Urinary Incontinence
Number: 0223
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses urinary incontinence.
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Medical Necessity
Aetna considers multi-channel urodynamic studies medically necessary when the member has both symptoms and physical findings of urinary incontinence/voiding dysfunctions (such as stress incontinence, overactive bladder, lower urinary tract symptoms) and there is consideration by the provider to perform invasive, potentially morbid or irreversible treatments after conservative management has been tried and failed.
Aetna considers the following urinary incontinence interventions medically necessary (unless otherwise specified) when criteria are met:
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Artificial Urinary Sphincter
Implantation of an artificial urinary sphincter (AUS) for the treatment of urinary incontinence (UI) due to intrinsic urethral sphincter deficiency (IUSD) for members with any of the following indications:
- Children with intractable UI due to IUSD who are refractory to behavioral or pharmacological therapies and are unsuitable candidates for other types of surgical procedures for correction of UI; or
- Members who are 6 or more months post-prostatectomy who have had no improvement in the severity of UI despite trials of behavioral and/or pharmacological therapies; or
- Members with epispadias-exstrophy in whom bladder neck reconstruction has failed; or
- Women with intractable UI who have failed behavioral or pharmacological, and other surgical treatments.
Aetna considers the artificial urinary sphincter experimental, investigational, or unproven for all other indications because its effectiveness for indications other than the ones listed above has not been established.
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Peri-Urethral Injections of Bulking Agents
Peri-urethral injections of bulking agents that are cleared by the Food and Drug Administration (FDA) for UI (e.g., Bulkamid (polyacrylamide hydrogel), Coaptite [calcium hydroxylapatite], Contigen [glutaraldehyde crossed-linked collagen], Durasphere [carbon-coated spheres/beads], Macroplastique [polydimethylsiloxane], Uryx [ethylene vinyl alcohol copolymer]) for the management of members with UI resulting from intrinsic sphincter deficiency that is refractory to conservative management (e.g., Kegel exercises, biofeedback, electrical stimulation, and/or pharmacotherapies).
Members whose incontinence does not improve after 3 treatments with bulking agents are considered treatment failures and are not likely to respond to this therapy. In such cases, further treatment with bulking agents is not considered medically necessary.
Aetna considers injection of peri-urethral bulking agents for UI experimental, investigational, or unproven for neurogenic bladder and all other indications.
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Implantable Sacral Nerve Stimulators (e.g., Axonics and InterStim)
Permanent implantation (sometimes referred to as Stage 2) of FDA-approved implantable sacral nerve stimulators (e.g., Axonics and InterStim) for the treatment of urge UI or symptoms of urge-frequency when all of the following criteria are met:
- Member has experienced urge UI or symptoms of urge-frequency for at least 6 months and the condition has resulted in significant disability (the frequency and/or severity of symptoms are limiting the member's ability to participate in daily activities); and
- Pharmacotherapies (i.e., at least 2 different anti-cholinergic drugs or an anti-cholinergic and a beta-3 adrenergic receptor agonist [mirabegron]) and behavioral treatments (e.g., pelvic floor exercise, biofeedback, timed voids, and fluid management) resulted in failure or inadequate response after 12-week trial, absent a contraindication to such a trial; and
- Temporary trial stimulation (sometimes referred to as basic percutaneous/peripheral nerve evaluation [PNE] or advanced Stage 1) provides at least 50% decrease in symptoms.
Aetna considers temporary trial stimulation (basic PNE or advanced Stage 1) of the device medically necessary for members who meet selection criteria 1 and 2 above.
Aetna also considers permanent implantation (Stage 2) of a sacral nerve stimulator medically necessary for the treatment of non-obstructive urinary retention when all of the following criteria are met:
- The member has experienced urinary retention for at least 6 months and the condition has resulted in significant disability (the frequency and/or severity of symptoms are limiting the member's ability to participate in daily activities); and
- Pharmacotherapies (e.g., alpha blockers and antibiotics for urinary tract infections) as well as intermittent catheterization have failed or are not well-tolerated; and
- A temporary trial stimulation (basic PNE or advanced Stage 1) of the device has provided at least 50% decrease in residual urine volume.
Aetna considers temporary trial stimulation (basic PNE or advanced Stage 1) of the right and left sides (where leads are placed bilaterally; and each side is tested sequentially during a single visit) medically necessary for members who meet selection criteria 1 and 2 above for treatment of urgent incontinence and non-obstructive urinary retention. No more than 6 total test stimulations (basic PNE or advanced Stage 1) are considered medically necessary. Aetna considers bilateral implantation of a permanent sacral nerve stimulator experimental, investigational, or unproven for the treatment of UI and non-obstructive urinary retention because the effectiveness of bilateral implantation of a permanent sacral nerve stimulator has not been established.
Aetna considers removal of an implantable sacral nerve stimulator medically necessary even where the initial implantation of the implantable sacral nerve stimulator was not indicated.
Aetna considers the use of implantable sacral nerve stimulator experimental, investigational, or unproven for all other indications because its effectiveness for indications other than the ones listed above has not been established.
According to the product labeling, implantable sacral nerve stimulator is contraindicated and has no proven value for individuals who have not demonstrated an appropriate response to a temporary trial stimulation (basic PNE or advanced Stage 1) or are unable to operate the neurostimulator.
Exclusions
Implantable sacral nerve stimulator has no proven value for individuals with mechanical obstruction such as benign prostatic hypertrophy, or urethral stricture; persons with stress incontinence; and individuals with neurologic disease origins, such as multiple sclerosis or diabetes with peripheral nerve involvement. Implantable sacral nerve stimulator has not been shown to be effective for urinary retention, urinary frequency-urgency syndrome or urge urinary incontinence due to these causes.
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Vaginal Cones
Aetna considers weighted vaginal cones (vaginal weights) medically necessary DME when they are used in combination with a structured pelvic floor muscle exercise (Kegel's exercise) program for the treatment of simple (pure) stress UI.
Aetna considers vaginal cones experimental, investigational, or unproven for other indications because their effectiveness for indications other than the ones listed above has not been established.
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Pessary (Bladder Neck Support Prosthesis)
Aetna considers a pessary, a plastic device that fits into the vagina to help support the uterus and bladder, medically necessary DME for the treatment of women with stress or mixed UI, and for the treatment of pelvic organ (uterine) prolapse.
Aetna considers a pessary experimental, investigational, or unproven for other indications because its effectiveness for indications other than the ones listed above has not been established.
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Tension-Free Vaginal Tape Procedure
Aetna considers the tension-free vaginal tape (TVT) procedure medically necessary for the treatment of stress UI when women with intractable UI have failed behavioral and/or pharmacological treatments.
Aetna considers the TVT procedure experimental, investigational, or unproven for other indications (except for the treatment of pelvic organ prolapse complicated by stress UI - see CPB 0858 - Organ Prolapse: Selected Procedures) because its effectiveness for indications other than the one listed above has not been established.
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Transobturator Tape Procedure
Aetna considers the transobturator tape (TOT) procedure medically necessary for the treatment of stress UI when women with intractable stress UI have failed behavioral and/or pharmacological treatments.
Aetna considers the TOT procedure experimental, investigational, or unproven for urge urinary incontinence and other indications because its effectiveness for indications other than the one listed above has not been established.
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Colposuspension and Sling Procedures
Aetna considers colposuspension and conventional sub-urethral sling procedures (e.g., the Solyx single-incision sling) medically necessary for persons with stress UI that is refractory to conservative management (e.g., pelvic floor muscle training, electrical stimulation, and biofeedback).
Aetna considers the colposuspension and sub-urethral sling procedures experimental, investigational, or unproven for other indications because their effectiveness for indications other than the one listed above has not been established.
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Biofeedback
For biofeedback for UI, see CPB 0132 - Biofeedback.
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Percutaneous Tibial Nerve Stimulation
Aetna considers percutaneous tibial nerve stimulation (PTNS) (e.g., the NURO Percutaneous Tibial Neuromodulation System (Medtronic, Minneapolis MN), and the Urgent PC Neuromodulation System [Uroplasty, Inc., Minneapolis, MN]) medically necessary for the treatment of members with idiopathic overactive bladder (urge UI or urge-frequency) when members meet the first 2 criteria listed for Implantable Sacral Nerve Stimulators (e.g., Axonics and InterStim) (for the treatment of urge urinary incontinence or symptoms of urge-frequency). In general, 12 treatments (once-weekly) with PTNS are needed for symptom relief. If the member fails to improve after 12 PTNS treatments, continued treatment is considered not medically necessary. If the member improves after 12 PTNS treatments, continued monthly treatments are considered medically necessary as long as the member’s symptoms remain improved.
Aetna considers percutaneous tibial nerve stimulation experimental, investigational, or unproven when criteria are not met.
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Transurethral Radiofrequency Therapy (Renessa Procedure)
Aetna considers transurethral radiofrequency therapy (Renessa procedure) medically necessary for the treatment of stress UI in non-pregnant women who are either not able or not willing to undergo surgery for their condition.
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Urethral Inserts
Aetna considers urethral inserts medically necessary for the treatment of female stress UI.
Aetna considers urethral inserts experimental, investigational, or unproven for other indications because their effectiveness for indications other than the one listed above has not been established.
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Cunningham Clamp
Aetna considers the Cunningham clamp medically necessary for the treatment of post-prostatectomy urinary incontinence in men with stress incontinence and good bladder storage function.
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Intravaginal Electrical Stimulation
Aetna considers intravaginal electrical stimulation of the pelvic floor medically necessary for women with stress, urgency or mixed urinary incontinence.
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Experimental, Investigational, or Unproven
Aetna considers the following UI interventions and management methods experimental, investigational, or unproven because the effectiveness of the treatment has not been established:
- Adjustable retropubic sub-urethral sling in the treatment of stress urinary incontinence
- Adjustable Trans-obturator Male System for the treatment of stress urinary incontinence (SUI)
- Autologous myoblast transplantation
- Autologous muscle-derived cell therapy
- Bariatric surgery as a treatment of urinary incontinence in persons who would otherwise not meet medical necessity criteria for obesity surgery in CPB 0157 - Obesity Surgery
- Collagen porcine dermis mesh
- Dynamometry for quantification of pelvic floor muscle strength in female urinary incontinence
- Electrical nerve stimulation for pelvic floor dysfunction in male stress incontinence
- Electro-acupuncture for the treatment of neurogenic bladder
- Flyte System (mechanotherapy) for the treatment of SUI
- Genetic testing for stress urinary incontinence
- High-intensity focused electromagnetic therapy for the treatment of stress urinary incontinence
- Implantable sacral nerve stimulator for the treatment of neurogenic bladder
- Laser Therapy: The Genityte Procedure (laser therapy) and FemiLift (CO2 laser)
- Magnetically controlled endo-urethral artificial urinary sphincter
- Magnetic stimulation for the treatment of women with SUI
- Micro-ablative radiofrequency for the treatment of over-active bladder
- Moxibustion for the treatment of post-stroke UI and SUI
- Neocontrol System, which uses extracorporeal magnetic innervation (ExMI)
- Platelet-rich plasma
- Protect PNS System (wireless microtechnology neuromodulation of the posterior tibial nerve) for the treatment of overactive bladder and the associated symptoms of urinary urgency, urinary frequency, and urge incontinence
- Pudendal nerve stimulation
- Radiofrequency micro-remodeling with the SURx System (paraurethral or transvaginal)
- Subcutaneous and subfascial tibial nerve stimulation (INTIBIA [Coloplast, Humlebaek, Denmark])
- Subcutaneous tibial nerve stimulation (e.g., the eCoin Peripheral Neurostimulator System [Valencia Technologies, Valencia, CA]; Altaviva Implantable Tibial Neuromodulation Device (ITNM) [Medtronic, Minneapolis, MN])
- Subfascial tibial nerve stimulation (e.g., BlueWind Revi) for the treatment of overactive bladder syndrome, and urge urinary incontinence
- Stem cell therapy (including mesenchymal stem/stromal cells)
- Transcutaneous electrical nerve stimulation (TENS) in the treatment of overactive bladder
- Transcutaneous tibial nerve stimulation (e.g., the Vivally System, and ZIDA Wearable Neuromodulation System) for the treatment of overactive bladder (OAB) and the associated symptoms of urinary urgency, urinary frequency, and urge incontinence
- Transperineal implantation of permanent adjustable balloon continence device (e.g., ACT, ProACT Therapy System, Uromedica, Inc.)
- Vibratory perineal stimulation
- Peri-urethral injections of bulking agents for any of the following circumstances:
- Members undergoing or planning to undergo desensitization injections to meat products; or
- Members with an acute condition involving cystitis, urethritis, or infection; or
- Members with severe allergies manifested by a history of anaphylaxis, or history or presence of multiple severe allergies; or
- Previous pelvic radiation therapy; or
- Unstable or noncompliant bladder.
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Policy Limitations and Exclusions
Pelvic Muscle Trainers
Note: Aetna does not cover the Athena pelvic muscle trainer, Gyneflex, Kegelmaster, or similar devices for the treatment of UI because these devices are considered exercise machines, and they do not meet Aetna's definition of covered durable medical equipment (DME). Most Aetna plans exclude coverage of exercise devices. Please check benefit plan descriptions for details. In addition, such exercise devices do not meet Aetna's definition of covered DME because they are not primarily medical in nature and/or are normally of use to persons who do not have an illness or injury.
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Related Policies
Background
- stress incontinence,
- urge incontinence,
- overflow incontinence, and
- mixed stress and urge incontinence.
Stress incontinence is more common but less difficult to control than urge incontinence. Mixed incontinence is more prevalent than urge incontinence in women while the latter is more commonly seen in men. In women, stress incontinence (SI) is generally caused by an incompetent urethral mechanism which arises from damage to the urethral sphincter or weakening of the bladder neck support that typically occurred during childbirth. Some women develop SI as a consequence of multiple anti-incontinence procedures resulting in a condition known as intrinsic urethral sphincter deficiency. In men, SI is usually a consequence of operations for benign prostatic hypertrophy or prostatic carcinoma. The mechanisms of post-prostatectomy UI may involve bladder dysfunction, sphincter incompetence, and mixed. Urge incontinence occurs when one senses the urge to void, but is unable to prevent leakage of urine before reaching the bathroom. It is usually associated with an overactivity of the detrusor muscle. Overflow incontinence is the result of the bladder's inability to empty normally. It may be due to an underactive detrusor muscle or obstruction of the urethra resulting in the overdistension of the bladder and therefore overflow of urine. Multi-channel urodynamics studies are not indicated in the first-line assessment of patients with urinary incontinence/voiding dysfunctions. Guidelines from the American Urological Association, the European Association of Urology and the National Institute for Health and Care Excellence are useful in determining when multi-channel urodynamics studies should be performed.
American Urological Association guidelines on adult (Winters et al., 2012) provided the following recommendations:
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Stress Urinary Incontinence (SUI) / Prolapse
- Clinicians may perform multi-channel urodynamics in patients with both symptoms and physical findings of stress incontinence who are considering invasive, potentially morbid or irreversible treatments. (Option; Evidence Strength: Grade C)
- Clinicians should perform stress testing with reduction of the prolapse in women with high grade pelvic organ prolapse (POP) but without the symptom of SUI. Multi-channel urodynamics with prolapse reduction may be used to assess for occult stress incontinence and detrusor dysfunction in these women with associated lower urinary tract symptoms (LUTS). (Option; Evidence Strength: Grade C)
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Overactive Bladder (OAB), Urgency Urinary Incontinence (UUI), Mixed Incontinence
Clinicians may perform multi-channel filling cystometry when it is important to determine if altered compliance, detrusor overactivity (DO) or other urodynamic abnormalities are present (or not) in patients with urgency incontinence in whom invasive, potentially morbid or irreversible treatments are considered. (Option; Evidence Strength: Grade C) -
LUTS (Lower Urinary Tract Symptoms)
Clinicians may perform multi-channel filling cystometry when it is important to determine if DO or other abnormalities of bladder filling/urine storage are present in patients with LUTS, particularly when invasive, potentially morbid or irreversible treatments are considered. (Expert Opinion)
European Association of Urology guidelines on urinary incontinence (EAU, 2013) stated that “'urodynamics is generally used as a collective term for all tests of bladder and urethral function. These guidelines will review both non-invasive estimation of urine flow, i.e., uroflowmetry, and invasive tests, including multichannel cystometry, ambulatory monitoring and video-urodynamics, and different tests of urethral function, such as urethral pressure profilometry, Valsalva leak point pressure estimation and retrograde urethral resistance measurement. Multichannel cystometry, ambulatory monitoring and video-urodynamics aim to observe the effects on intra-vesical and intra-abdominal pressures while reproducing a patient's symptoms. Bladder filling may be artificial or physiological and voiding is prompted. Any incontinence observed may be categorized as SUI, detrusor overactivity (DO) incontinence, a mixture of SUI/DO incontinence, or, rarely, urethral relaxation incontinence. A test may fail to reproduce a patient's symptoms because of poor diagnostic accuracy or because the symptoms are not directly attributable to a urodynamically measurable phenomenon. Urodynamic testing is widely used as an adjunct to clinical diagnosis, to direct decisions about treatment and to provide prognostic information. When clinical diagnosis is difficult because of an unclear history or inconclusive examination, urodynamics may provide the only 'diagnosis' available. Although it is unlikely that carrying out a test, in itself, would alter the outcome of treatment, it remains possible that the test results would influence treatment decisions to such an extent that better outcomes would be achieved. This has been the rationale for using urodynamics prior to surgery."
National Institute for Health and Care Excellence guideline "Urinary Incontinence: The Management of Urinary Incontinence in Women" (NICE, 2013) provided the following recommendations regarding urodynamic testing:
- Do not perform multi-channel cystometry, ambulatory urodynamics, or video-urodynamics before starting conservative management. [2006, amended 2013]
- After undertaking a detailed clinical history and examination, perform multi-channel filling and voiding cystometry before surgery in women who have:
- Symptoms of over-active bladder leading to a clinical suspicion of detrusor over-activity, or
- Symptoms suggestive of voiding dysfunction or anterior compartment prolapse, or
- Had previous surgery for stress incontinence [2006, amended 2013]
- Do not perform multi-channel filling and voiding cystometry in the small group of women where pure SUI is diagnosed based on a detailed clinical history and examination. [2006, amended 2013]
- Consider ambulatory urodynamics or videourodynamics if the diagnosis is unclear after conventional urodynamics. [2006, amended 2013]
Treatments for UI include pelvic muscle exercises (Kegel exercise), behavioral therapies such as bladder training and/or biofeedback, pharmacotherapies (e.g., anti-cholinergic agents, musculo-tropic relaxants, calcium channel blockers, tricyclic anti-depressants, or a combination of anti-cholinergic, anti-spasmodic medications and tricyclic anti-depressants), and a variety of surgical procedures including intra-urethral injection of collagen, and implantation of an artificial urinary sphincter. Specifically, urge incontinence is more effectively managed with peripherally acting receptor agonists or antagonists while stress incontinence is better controlled by pelvic muscle exercises, behavioral therapies, or corrective surgery.
Electrical stimulation has also been employed in the treatment of UI, especially in Europe. The mechanism of action of electrostimulation is still unclear, but it probably serves to provide a kind of muscular training similar to that of pelvic floor exercise. In this regard, Green and Laycock (1990) demonstrated that interferential currents produce increases in muscle activity, as indicated by pressure probes at the peri-vaginal and abdominal areas. It is also conceivable that electrical stimulation may improve re-innervation of partially damaged pelvic floor muscles by enhancing the sprouting of sensory motor axons. Additionally, repeated stimulation of the pelvic floor musculature may also help to strengthen the supporting ligaments. Examples of electrical stimulation devices include the Innova and Minnova systems (Empi, Inc., St. Paul, MN). An assessment of nonsurgical treatments for urinary incontinence prepared for the Agency for Healthcare Research and Quality (AHRQ) (Shamliyan et al., 2012) found that intravaginal electrical stimulation increased continence rates and improved stress urinary incontinence more often than sham stimulation. The AHRQ assessment stated that a high level of evidence suggests increased continence rates and improvement in UI with electrical stimulation. This conclusion was based upon nine studies that examined intravaginal electrical stimulation. The studies included women with predominant urgency UI, clinical or urodynamic stress UI, or urodynamic mixed UI. Electrical stimulation was described with different levels of detail and had variable stimulation parameters, depending on the UI type being treated, including the use of 4 Hz, 10 Hz, 20 Hz, or 50 Hz frequency for 4 weeks, 7 to 8 weeks, 12 weeks, or 15 weeks.
Peri-urethral injection of bulking agents has been shown to be safe and effective for the treatment of UI resulting from intrinsic sphincter deficiency. One of the first bulking agents available on the market is Contigen (Bard, Canada), which is a sterile, injectable gel composed of highly purified bovine collagen that has been minimally cross-linked with 0.0075% glutaraldehyde. All patients are required to undergo a pre-treatment skin test. Patients who exhibit local hypersensitivity will not be considered for treatment. Intra-urethral injections of glutaraldehyde-cross-linked (GAX) collagen are performed under local or general anesthesia. In men, the procedure is usually carried out trans-urethrally. The urethra and bladder are monitored by means of a 21F cystoscope, and the bladder is filled with fluid cystoscopically. A percutaneous 10F or 12F suprapubic catheter is inserted into the bladder, and its location is verified. This catheter drains the bladder during the implantation procedure. Aliquots of GAX collagen are injected in a circumferential manner around the sphincter. In patients in whom no sphincter could be seen or in whom no sphincter existed (after radical prostatectomy), GAX collagen is injected circumferentially around the bladder neck. Once the lumen is occluded with the water running through the cystoscope, the injections are terminated, and the cystoscope is not inserted past the area of injection again.
In women, intra-urethral injections of GAX collagen are performed transurethrally or periurethrally. In the latter approach, the proximal urethra and bladder neck are visualized under direct cystoscopy. A 22G spinal needle is advanced parallel to the urethra in the peri-urethral tissue up to the bladder neck, and its position is confirmed by cystoscopy. Aliquots of collagen are then injected cystoscopically into the peri-urethral tissues to occlude the urethra. If intraluminal extravasation occurs, the injection is stopped, and another injection site is chosen. At the end of the procedure performed under local anesthetics, the patient is asked to cough or strain while in the supine position and then in the upright position. If leakage still occurs, more collagen is injected. If no leakage occurs and there is no urinary retention, the patient is discharged from the hospital. When the procedure is performed under general anesthesia and the bladder is filled, an 8F feeding tube is inserted to empty the bladder and then removed. All patients receive perioperative antibiotics. If patients remain incontinent after treatment, re-injections of collagen are performed. Satisfactory results are usually obtained within three treatment sessions.
Angioli and colleagues (2008) stated that in recent years, they used a variety of bulking agents, including bovine collagen, Macroplastique (polydimethylsiloxane), calcium hydroxylapatite, ethylene vinyl alcohol copolymer, and dextranomer in the treatment of urinary incontinence. Urethral injections have a success rate of 40% to 90%. These investigators asserted that Macroplastique is the most effective and safe based on literature data and their experience. This surgical procedure, in fact, has a good percentage of success in accurately selected patients. In the authors' experience, Macroplastique can also be used in oncological patients, elderly women, and patients with significant comorbidities and high surgical risk, yielding good objective and subjective results.
In a prospective, randomized, controlled trial, Ter Meulen and associates (2009) evaluated the effectiveness of the Macroplastique (MPQ) Implantation System (MIS) in women with urodynamic stress UI (SUI) and urethral hypermobility after unsuccessful conservative treatment. These subjects had no prior incontinence surgery. A total of 24 women received MPQ; 21 controls underwent a pelvic floor muscle exercises home program. Follow-up was at 3 months and the MPQ group also at 12 months. At 3 months, pad usage decreased significantly more in the MPQ group than in the control group (p = 0.015). According to physician and patient self-assessment, respectively, 71% and 63% of women in the MPQ group were considered cured or markedly improved. This was significantly higher compared to controls. There was a significantly higher increase in Incontinence Quality-of-Life questionnaire score in the MPQ group compared to controls (p = 0.017). Improvements in the MPQ group at 3 months were sustained to 12 months. Adverse events were mild and transient. The authors concluded that the Macroplastique Implantation System is an acceptable option for women with SUI and urethral hypermobility.
Plotti et al. (2009) prospectively investigated the effectiveness and complications of Macroplastique transurethral implantation in cervical cancer patients affected by SUI after radical hysterectomy (RH). Patients affected by de novo SUI post-type 3 RH were considered for eligibility in this study. Pre-operative and post-operative assessments included a standardized urogynecological history, urogynecological and neurological physical examination, evaluation of the severity of SUI symptoms, a 3-day voiding diary, urine culture, and urodynamic assessment. All patients underwent transurethral implantation using the MIS. Patient follow-up was performed 6 and 12 months after surgery. A total of 24 consecutive patients were enrolled. At the 12-month follow-up, the SUI cure rate was 42% (10 of 24 patients), the improvement rate was 42% (10 of 24), and the failure rate was 16% (4 of 24). The overall success rate was 84% (10 patients cured and 10 improved). No intra-operative or post-operative early complications were found. The four patients in whom treatment was not successful had pre-operative urethral hypermobility. Subjective patient perception of SUI symptom severity showed significant improvement (mean severity of urinary loss perception 6.6 ± 1.8 versus 2.3 ± 3.3, p < 0.05). The frequency of incontinence on the 3-day voiding diary was significantly reduced at follow-up (14.5 ± 5.8 versus 4.3 ± 7.9 episodes per 3 days, p < 0.05). The authors concluded that bulking agent urethral injection could be a valid option with no surgical complications. This therapeutic strategy is able to treat SUI and improve the well-being of cervical cancer patients after radical surgery.
Ghoniem et al. (2009) evaluated the effectiveness and safety of Macroplastique as a minimally invasive endoscopic treatment for female SUI primarily due to intrinsic sphincter deficiency. A total of 247 females with intrinsic sphincter deficiency were randomized 1:1 and treated with a transurethral injection of Macroplastique or Contigen (which served as the control). Repeat treatment was allowed after the 3-month follow-up. Effectiveness was determined 12 months after the last treatment using Stamey grade, pad weight, and Urinary Incontinence Quality of Life Scale scores. Safety assessments were recorded throughout the study. After 12 patients were excluded from the study, 122 patients received Macroplastique injection and 125 received Contigen injection. The mean patient age was 61 years, and the average history of incontinence was 11.2 years. Of the patients, 24% had undergone prior incontinence surgery. At 12 months after treatment, 61.5% of patients who received Macroplastique and 48% of controls had improved by 1 Stamey grade. In the Macroplastique group, the dry/cure rate was 36.9% compared to 24.8% in the control group (p < 0.05). In the Macroplastique and control groups, the 1-hour pad weight decrease was 25.4 and 22.8 ml from baseline (p = 0.64), and the mean improvement in Urinary Incontinence Quality of Life Scale score was 28.7 and 26.4 (p = 0.49), respectively. The authors concluded that Macroplastique injection was statistically more effective than Contigen for SUI primarily due to intrinsic sphincter deficiency, with a 12.1% cure rate difference.
Available evidence indicates that intra-urethral injection of bulking agents is safe and effective for the treatment of UI, especially in women, resulting from intrinsic sphincter deficiency. Appropriate candidates should have no improvement in incontinence with conservative measures. For collagen-based products, a pre-treatment skin test for collagen should be performed, showing no evidence of local hypersensitivity. Patients whose incontinence does not improve after three treatment sessions are considered treatment failures. Periurethral injections of bulking agents should be avoided in the following individuals: those with previous pelvic radiation therapy (less likely to benefit); unstable or non-compliant bladder; patients with severe allergies manifested by a history of anaphylaxis or a history or presence of multiple severe allergies; patients with an acute condition involving cystitis, urethritis, or infection; and patients undergoing or planning to undergo desensitization injections to meat products (for collagen products).
The tension-free vaginal tape (TVT) procedure is an established treatment for intractable stress UI in persons who have failed behavioral and pharmacological treatments. An earlier assessment conducted by the Society of Obstetricians and Gynecologists of Canada (2003) concluded that “[t]he TVT procedure is promising but currently under evaluation in trials that will establish its efficacy and safety.”
Recent randomized trials and studies with long-term follow-up have indicated that the TVT procedure is safe and effective for the treatment of stress UI. In a randomized controlled study (n = 72), Paraiso et al. (2004) concluded that the TVT procedure results in greater objective and subjective cure rates for urodynamic SUI than does laparoscopic Burch colposuspension. This is in agreement with the results of those by Valpas et al. (2004) and Ward et al. (2004). In a multi-center randomized controlled trial (n = 128), Valpas and associates reported that treatment with TVT results in higher objective and subjective cure rates at 1 year than treatment by means of laparoscopic mesh colposuspension. In another multi-center randomized controlled study (n = 344), Ward and colleagues concluded that the TVT procedure appears to be as effective as colposuspension for the treatment of urodynamic stress UI at 2 years.
Based on the results of a controlled trial with a 2-year follow-up (n = 50), Meschia and colleagues (2004) stated that TVT can be recommended for patients with prolapse and occult SUI. In a comparison study (n = 61), deTayrac and co-workers (2004) concluded that trans-obturator sub-urethral tape appears to be equally efficient as TVT for the surgical treatment of SUI in women, with no reduction of bladder outlet obstruction at 1-year follow-up.
In a prospective observational, multi-center study (n = 90), Nilsson et al. (2004) reported that the TVT procedure for the treatment of female SUI is effective over a period of 7 years. This finding extends the observation of that by Abdel-Fattah and associates (2004), who concluded that the Pelvicol pubovaginal sling is a safe procedure in the surgical management of SUI, with a similar success rate and patient satisfaction rate to TVT up to 3 years of follow-up. An assessment by the National Institute for Clinical Excellence (NICE, 2003) concluded that “[t]he tension-free vaginal tape (TVT) procedure is recommended as one of a range of surgical options for women with uncomplicated urodynamic stress incontinence in whom conservative management has failed.” The Ontario Health Technology Advisory Committee (2004) concluded that TVT should be offered as one option to treat women who are affected by SUI severely enough to warrant a surgical treatment approach.
There is evidence that percutaneous tibial nerve stimulation (PTNS) (Urgent PC Neuromodulation System, Uroplasty, Inc., Minneapolis, MN) is an effective treatment for chronic non-neurogenic urinary voiding dysfunctions (e.g., overactive bladder/urge incontinence) in persons who have failed conservative treatments. In general, 3 to 12 treatments (once weekly) with PTNS are needed for symptom relief. If a patient fails to improve after 12 PTNS treatments, further treatments are unlikely to be effective.
Percutaneous tibial nerve stimulation is regarded as an intermediate therapy between pelvic muscle exercise and sacral nerve stimulation (e.g., InterStim). Treatments are usually administered in twelve 30-minute sessions. Van der Pal et al. (2006a) examined the relationship between QOL and voiding variables in patients with lower urinary tract dysfunction treated with PTNS (n = 30). These investigators concluded that PTNS is useful for treating refractory urge incontinence and should at least be considered as a therapeutic alternative before resorting to aggressive surgery. Patients must have a reduction of greater than or equal to 2 pads/day before their QOL improves, and this might be the best definition of successful therapy for patients with urge UI. De Gennaro and colleagues (2004) assessed pain tolerability and the preliminary results of PTNS in children with unresponsive lower urinary tract symptoms (n = 23). These researchers concluded that PTNS is safe, minimally painful, and feasible in children. It seems helpful for treating refractory non-neurogenic lower urinary tract symptoms. This is in agreement with the findings of Hoebeke et al. (2002), who reported that PTNS has a significant effect on voiding frequency, the uroflowmetry curve, and bladder capacity in children with non-neurogenic bladder sphincter dysfunction. Van Balken (2007) stated that PTNS is carried out in 12 weekly sessions of 30 minutes each, through a percutaneously placed needle cephalad to the medial malleolus. Success can be obtained in about 2/3 of patients.
Guidelines from the American Urologic Association (Gormley et al., 2012) have concluded: “Clinicians may offer peripheral tibial nerve stimulation (PTNS) as a third-line treatment in a carefully selected patient population. Option (evidence strength grade C; balance between benefits and risks/burdens uncertain).”
There is insufficient evidence to support the use of the Neocontrol system, which uses extracorporeal magnetic innervation (ExMI), for the treatment of urinary incontinence. The clinical role of this technology as a conservative incontinence therapy has not been defined, and longer follow-up than that reported is required to determine the durability of treatment results. An assessment prepared for the California Technology Assessment Forum (CTAF, 2004) concluded that pelvic floor magnetic stimulation for UI does not meet CTAF's criteria. The assessment concluded that “There is insufficient evidence from randomized clinical trials to conclude that pelvic floor magnetic stimulation is as beneficial as these alternative therapies.” Since the CTAF assessment was published, an additional randomized controlled clinical trial (Culligan et al., 2005) and an uncontrolled prospective study (Voorham - van der Zalm, 2006) found extracorporeal magnetic stimulation to be ineffective.
Radiofrequency (RF) energy has been used for various clinical applications. Characteristics of RF energy allow it to be used for precisely controlled thermal therapy directed at soft tissues to induce such changes as collagen deposition and tissue shrinkage. These soft tissue effects are currently being examined for the treatment of genuine SUI in women. Ross et al. (2002) evaluated the effectiveness of RF electrothermal energy in the treatment of genuine SUI (n = 94). The authors concluded that RF bipolar electrothermal energy appears to be a safe and efficient means of treating mild to moderate genuine SUI. It resulted in shrinkage and elevation of paravaginal connective tissue, stabilizing the urethra and bladder neck, thereby restoring continence. The authors stated, however, that long-term follow-up is necessary.
Sotomayor and Bernal (2003) studied the safety and quality of life impact of transurethral RF energy tissue micro-remodeling of the proximal urethra and bladder outlet in patients with SUI. Forty-one patients with SUI were sequentially enrolled into four treatment groups and then underwent rapid outpatient treatment under conscious sedation using an investigational RF energy delivery device. At 6 months, 75% to 80% of patients in all four groups demonstrated an improvement in quality of life. Two groups demonstrated statistical significance in both mean quality of life improvement and incontinence frequency reduction at 6 months. However, it is unclear if treatment resulted in clinically significant improvements in these parameters. Furthermore, long-term effectiveness of this approach is still unavailable.
Sotomayor and Bernal (2005) published longer follow-up findings of their 2003 study. They reported that significant incontinence episode frequency reduction was demonstrated by three of four treatment groups. They also noted that RF micro-remodeling demonstrated 12-month safety, quality of life improvement, and incontinence episode frequency reduction. No one treatment group demonstrated clear superiority in efficacy outcomes. Moreover, the authors stated that this pilot study had a number of limitations and weaknesses, namely, the trial was uncontrolled, and there were few subjects in any one treatment group. Also, diagnosis and follow-up evaluation lacked urodynamic testing.
Lenihan and colleagues (2005) examined the feasibility, safety, and patient comfort associated with RF tissue micro-remodeling in women with SUI given oral and local anesthesia. A total of 16 women with SUI and hypermobility (based on history and physical examination) with no history of previous definitive incontinence therapy were enrolled in this study. The women had a mean age of 49.7 years (range of 30 to 76 years) and a mean duration of incontinence of 7.6 years (range of 1 to 30 years). The non-surgical RF micro-remodeling treatment, which was previously shown to be of significant benefit when administered under intravenous (IV) sedation in an outpatient surgical center setting, was successfully completed in all 16 women. Either the treating physician or the patient had the option to convert to IV sedation during the procedure if there was too much discomfort; however, this did not occur in any of the 16 patients. Thus, neither the treating physician nor any patient determined that conversion to IV conscious sedation was needed for treatment completion. The first six patients received an oral sedative and oral analgesic, as well as a local peri-urethral anesthetic block with 10 ml of 2% lidocaine. The final 10 patients (63%) received only one oral sedative or analgesic and a total of 10 ml lidocaine local anesthetic. Two women who received the maximum oral regimen (both oral sedation and analgesics) experienced nausea and emesis when drinking immediately after treatment, and one of these women also experienced urinary retention, which resolved after 24 hours of catheterization. Immediately before discharge, subjects classified their pain on a scale from 0 ("no pain") to 10 ("terrible pain"). The mean score was 1.8, and 38% of subjects selected "0." The authors concluded that this pilot trial demonstrated the feasibility, safety, and patient comfort associated with performing a novel new successful technique of non-surgical RF of the urethra for the treatment of SUI in an office-based setting using oral plus local anesthesia. It should be noted that this study was not designed to evaluate the effectiveness of RF micro-remodeling in the treatment of SUI.
Lenihan (2005) examined the effect of menopause and hormone replacement therapy (HRT) on incontinence quality of life (I-QOL) score improvement in women with moderate-to-severe SUI after transurethral RF tissue micro-remodeling. A total of 173 women with genuine SUI with bladder outlet hypermobility were enrolled. Subjects were randomly assigned to undergo either RF micro-remodeling (n = 110) or sham treatment (n = 63). Participants were analyzed by menopausal status and HRT use for 10-point or greater I-QOL score improvement (an increase associated with subjective and objective SUI improvement). Radiofrequency micro-remodeling resulted in 81% of subjects achieving 10-point or greater I-QOL score improvement versus 49% of sham subjects at 12 months (p = 0.04). Outcomes did not differ statistically when pre-menopausal (85%), post-menopausal using HRT (70%), and post-menopausal not using HRT (71%) groups were compared. The authors concluded that menopausal status and HRT demonstrated no impact on the quality of life improvement experienced by women with moderate-to-severe SUI who underwent RF tissue micro-remodeling. They also stated that further studies in pre-menopausal and post-menopausal women with SUI that measure additional effectiveness outcomes after RF micro-remodeling may provide further information concerning the clinical impact of menopause and HRT on this collagen-based treatment modality.
Appell and co-workers (2006) performed a prospective, randomized, controlled trial to demonstrate the 12-month safety and effectiveness of transurethral RF collagen micro-remodeling in women with SUI. Women with SUI, bladder outlet hypermobility, and leak point pressure (LPP) greater than or equal to 60 cm H2O were randomized to RF micro-remodeling or "sham treatment." Adverse events (AEs) were recorded. Incidence of greater than or equal to 10-point I-QOL score improvement, a magnitude of improvement with a demonstrated responsiveness to patient satisfaction with treatment and to greater than or equal to 25% reduction in both incontinence episode frequency and stress pad weight, served as a subjective outcome measurement. Change in mean LPP served as an objective outcome measurement. The 12-month RF micro-remodeling safety profile was statistically no different than that of sham treatment (a brief bladder catheterization). Seventy-four percent of women with moderate-to-severe baseline SUI experienced greater than or equal to 10-point I-QOL score improvement at 12 months (p = 0.04). Women who underwent RF micro-remodeling demonstrated LPP elevation at 12 months, while sham-treated women demonstrated LPP reduction (p = 0.02). The authors concluded that transurethral RF micro-remodeling is a safe treatment for women with SUI. In women with moderate-to-severe SUI, this novel therapy resulted in statistically significant improvement in QOL of a magnitude associated with patient satisfaction with the treatment. Women who underwent RF micro-remodeling demonstrated a statistically significant elevation in mean LPP at 12 months. While this study found statistically significant improvement in frequency and severity of incontinence episodes, the criterion of greater than or equal to 25% reduction in both incontinence episode frequency and stress pad weight seems to be a "low bar" to clear. While RF micro-remodeling demonstrated a statistically significant elevation in mean LPP at 12 months, its clinical relevance is unclear. It is also interesting that the authors concluded that "transurethral RF micro-remodeling is a safe treatment for women with SUI" (effectiveness was not addressed). Furthermore, this study appeared to have the same group of subjects as reported by Lenihan (2005) -- 110 women underwent RF micro-remodeling and 63 underwent virtually identical "sham treatment."
In a retrospective study, Appell and associates (2007) evaluated long-term safety and effectiveness of RF collagen denaturation for SUI in 21 patients from a 12-month randomized controlled trial utilizing 3-day diaries and the I-QOL survey. Significant increases in overall I-QOL scores 3 years or more post-treatment was the primary endpoint. Secondary endpoints were reductions in frequency and severity of incontinence episodes. After 3 years, mean overall I-QOL score improvement was 12.7 (+/- 26); 56% of patients achieved 50% or more reduction in frequency. No new AEs occurred. These results indicated that RF collagen denaturation is safe and provides durable effectiveness. This was a longer follow-up (3 years) study of the previous studies reported (Lenihan, 2005; Appell et al., 2006). The authors also noted that additional studies of RF collagen denaturation are ongoing, including a study to expand the indication of RF collagen denaturation in patients who experienced suboptimal responses to a surgical intervention.
Vianello et al. (2007) reviewed recent literature on mini-invasive surgical techniques for the treatment of female SUI. Surgical aspects, intra-operative and peri-operative complications, and objective and subjective outcomes were analyzed and compared. Studies had to investigate at least 40 women with a minimum follow-up of 12 months. A total of 38 prospective studies were found: 27 of them were on mid-urethral slings; 8 assessed urethral injections; and 3 RF treatments. Fifteen studies were randomized. Follow-ups ranged from 12 to 60 months, except for sexual function, which had a 6-month follow-up. Ten out of 38 studies assessed patients who did not have pelvic organ prolapse or detrusor over-activity and had not undergone any previous anti-incontinence procedure. The authors concluded that mid-urethral slings showed good outcomes and are safe and brief to perform, with a relatively short learning curve. Urethral injections showed discouraging results, as they have poor outcomes and repetitive treatments are frequently necessary. Injections can be used in women with contraindications to major surgical procedures, with intrinsic sphincter deficiency as the main cause of incontinence. Radiofrequency showed worse results than mid-urethral slings but is a valuable choice in women who refuse more invasive procedures.
Appell (2008) stated that patients who received transurethral collagen denaturation by means of non-ablative RF energy applied through a transurethral probe have shown improvements in quality of life and in Valsalva leak point pressure. This procedure presents a beneficial non-surgical treatment option for women with SUI.
An assessment by the California Technology Assessment Forum (Karliner, 2008) on RF micro-remodeling for the treatment of female SUI stated that while RF micro-remodeling (Renessa) for SUI does not show as high success rates as the gold standard approaches (Burch and TVT), it does demonstrate a good safety profile and moderate improvement in objective urinary leakage and quality of life, particularly for women with moderate-to-severe SUI. It stated that RF micro-remodeling with the Renessa System meets its criteria for safety, effectiveness, and improvement in health outcomes for the treatment of moderate-to-severe female SUI in non-pregnant women who are either not able or not willing to undergo surgery for their condition.
In a continuing, prospective, 36-month, open-label, single-arm clinical trial, Elser et al. (2009) evaluated the effectiveness of non-surgical transurethral collagen denaturation (Renessa) in women with SUI caused by bladder outlet hypermobility. Twelve-month results from intent-to-treat (ITT) analysis were reported. Women with SUI secondary to bladder outlet hypermobility for 12 months or longer who failed earlier conservative treatment and had not received earlier surgical or bulking agent therapy were included in the study. Subjects were treated as outpatients and received an oral antibiotic and local peri-urethral anesthesia before undergoing Renessa therapy. Voiding diaries and in-office stress pad weight tests yielded objective assessments. Subjective measures include the Incontinence Quality of Life (I-QOL), Urogenital Distress Inventory (UDI-6), and Patient Global Impression of Improvement (PGI-I) instruments. A total of 136 women received treatment (ITT population). Patients experienced significant reductions versus baseline in median number of leaks caused by activity/day and activity/week (p < 0.0026 for both), with 50% of patients reporting 50% or more reduction. Pad weight tests revealed that 69% of women had 50% or more reduction in leakage (median reduction 15.2 g; p < 0.0001); 45% were dry (29% no leaks; 16% less than 1-g leakage). Significant improvements occurred in median scores on the I-QOL (+9.5 [range of -66.0 to 91.0]; p < 0.0001) and mean scores on the UDI-6 (-14.1 ± 24.7; p < 0.0001). Furthermore, 71.2% showed I-QOL score improvement, including 50.3% with 10-point or greater improvement, and 49.6% reported on the PGI-I that they were "a little," "much," or "very much" better. The authors concluded that at 12 months, treatment of SUI with non-surgical transurethral collagen denaturation resulted in significant improvements in activity-related leaks and quality of life.
It is also interesting to note that the transvaginal RF bladder neck suspension procedure for SUI has not been shown to provide satisfactory results. Buchsbaum and colleagues (2007) evaluated the outcome and patient acceptance of the transvaginal RF bladder neck suspension procedure. A retrospective chart review of 18 women treated with the transvaginal RF bladder neck suspension procedure for SUI was conducted. Data on demographics, urodynamics, daily leakage episodes, complications, patient satisfaction, and further intervention were collected. The mean number of leaks per day was 5.7. There were no complications. Post-operatively, 2 patients were continent, 4 were improved, and 10 were unimproved. The mean number of daily leaks was reduced to 2.7. Five patients reported to be extremely satisfied with the procedure; 1 patient was satisfied, and 10 were not satisfied. Seven patients sought additional treatment within 1 year. Low cure rate, low patient satisfaction, and high rate of additional treatment led these researchers to abandon the transvaginal RF bladder neck suspension procedure as a treatment option.
Ismail (2008) evaluated the safety and effectiveness of transvaginal RF remodeling of the endopelvic fascia as a primary procedure for SUI due to urethral hypermobility in women. It included 24 patients who had the procedure at 2 district general hospitals. Outcome measures included the pad test, urodynamic assessment, continence diary, pain scores, as well as operative and post-operative complications, and assessment was made on recruitment during hospital admission and at 3, 6, and 12 months follow-up. A rising failure rate was noted as early as 3 months, leading to a cumulative cure rate of 45.8% at 12 months follow-up. This low effectiveness could be attributed to inherent weakness of the endopelvic fascia. No major complications were encountered, and pain scores were mild. In this regard, a draft assessment by the California Technology Assessment Forum (2008) on RF micro-remodeling for the treatment of female SUI stated that RF micro-remodeling with the SURx System (paraurethral or transvaginal) does not meet its criteria for safety, effectiveness, and improvement in health outcomes for the treatment of female SUI.
Polypropylene meshed tape may be placed at the mid-urethra or bladder neck using retropubic or trans-obturator approaches. Various types of sub-urethral tapes inserted via the trans-obturator route (TVT obturator route [TVTO] and trans-obturator tape [TOT]) have been used for the treatment of SUI. In a systematic review, Latthe and co-workers (2007) evaluated the effectiveness and complications of TOTs as treatment for SUI. Randomized controlled trials (RCTs) that compared the effectiveness of TVTO or TOT with synthetic TVT by retropubic route for the treatment of SUI in all languages were included. Two reviewers extracted data on participants' characteristics, study quality, population, intervention, cure, and adverse effects independently. There were 5 RCTs that compared TVTO with TVT and 6 RCTs that compared TOT with TVT. When compared by subjective cure, TVTO and TOT at 2 to 12 months were no better than TVT (odds ratio [OR] 0.85; 95% confidence interval [CI]: 0.60 to 1.21). Adverse events such as bladder injuries (OR 0.12; 95% CI: 0.05 to 0.33) and voiding difficulties (OR 0.55; 95% CI: 0.31 to 0.98) were less common, whereas groin/thigh pain (OR 8.28; 95% CI: 2.7 to 25.4), vaginal injuries, or erosion of mesh (OR 1.96; 95% CI: 0.87 to 4.39) were more common after tape insertion by the trans-obturator route. The authors concluded that the evidence for short-term superiority of effectiveness of TOTs is currently limited. Bladder injuries and voiding difficulties are lower, but the risk of vaginal erosions and groin pain is higher with TVTO/TOT. Methodologically sound and sufficiently powered RCTs with long-term follow-up are needed, and the results of continuing trials are awaited.
In a prospective, single-blinded, multi-center RCT, Barry et al. (2008) compared the safety and effectiveness of the trans-obturator tape (Monarc) with the retropubic tape (tension-free vaginal tape, TVT) for the treatment of SUI. A total of 187 women with SUI were randomly allocated to undergo surgery with either the Monarc sling (n = 80) or TVT (n = 107). Outcome measures were intra-operative complications (especially bladder injury), peri-operative complications, symptomatology, quality of life, as well as urodynamic outcomes. At 3 months, data were available on 140 women, 82 (59%) TVT and 58 (42%) Monarc. The TVT group was significantly more likely to be complicated by bladder injury (7 TVT, 0 Monarc, p < 0.05). Blood loss and operative time were significantly less in the Monarc group, which was 49 ml (31) versus that of the TVT group, which was 64 ml (41) (p < 0.05); 18.5 mins (6.5) TVT versus 14.6 mins (6) Monarc (p < 0.001). The subjective and objective SUI cure rates were 86.6% (71) versus 72.4% (42) (p = 0.77) and 79.3% versus 84.5% (p = 0.51) for the TVT and Monarc groups, respectively. Both groups reported similar improvement in incontinence impact and satisfaction with their operation, although return to activity was significantly quicker with the trans-obturator route (p = 0.029). The authors concluded that the transobturator tape appears to be as effective as the retropubic tape in the short term, with a reduction in the risk of intra-operative bladder injury, shorter operating time, decreased blood loss, and quicker return to usual activities.
Barber et al. (2008) compared the safety and effectiveness of the trans-obturator tape to TVT in the treatment of SUI in patients with and without concurrent pelvic organ prolapse. A total of 170 women were randomized to receive TVT or trans-obturator tape. Subjects with detrusor over-activity or previous sling surgery were excluded. The primary outcome was the presence or absence of abnormal bladder function, a composite outcome defined as the presence of any of the following: incontinence symptoms of any type, a positive cough stress test, or re-treatment for SUI or post-operative urinary retention assessed 1 year following surgery. This study was a non-inferiority study design. Of the 180 women who enrolled in the study, 170 underwent surgery, and 168 returned for follow-up, with a mean follow-up of 18.2 ± 6 months. Mean operating time, length of stay, and post-operative pain scores were similar between the two groups. Bladder perforations occurred more frequently in the TVT group (7% compared with 0%, p = 0.02); otherwise, the incidence of peri-operative complications was similar. Abnormal bladder function occurred in 46.6% of TVT patients and 42.7% of trans-obturator tape patients, with a mean absolute difference of 3.9% favoring trans-obturator tape (95% CI: -11.0% to 18.6%). The "p" value for the 1-sided non-inferiority test was 0.006, indicating that trans-obturator tape was not inferior to TVT. The authors concluded that the trans-obturator tape is not inferior to TVT for the treatment of SUI and results in fewer bladder perforations. Moreover, they also noted that larger studies are needed to assess the relative risk of the less common but potentially severe complications that have been seen with both procedures. Furthermore, studies with longer follow-up are necessary to ascertain if the effectiveness of trans-obturator tape is durable.
Koch and Zimmern (2008) evaluated the evidence base for surgical management of SUI in women. Pubovaginal sling has a higher success rate than the Burch at the expense of a higher morbidity. A prophylactic Burch procedure at the time of an abdominal sacrocolpopexy can reduce secondary SUI and urge incontinence. Sub-urethral tapes have a higher cure rate for patients with predominant SUI and can safely be placed at the time of concomitant pelvic surgery. The TVT has a higher rate of lower urinary tract injury and voiding dysfunction when compared with trans-obturator tape. The authors concluded that the Burch and pubovaginal sling have a high success rate for treating SUI; prospective RCTs are needed to evaluate the long-term results of sub-urethral slings. This is in agreement with the observation of Rogers (2008), who stated that the use of the trans-obturator tape (one of the many newer techniques) entails the placement of polypropylene mesh through the obturator foramen rather than through the retropubic space, but large, randomized trials with adequate follow-up comparing these newer anti-incontinence procedures are limited.
A systematic evidence review by Sung et al. (2007) found that the trans-obturator approach was associated with a lower risk of complications than the retropubic approach to mid-urethral slings for the treatment of stress incontinence, but there was insufficient evidence to compare the effect of surgical approaches on objective and subjective outcomes.
Guidelines on the choice of surgery for SUI from the Society of Obstetricians and Gynecologists of Canada (Robert et al., 2005) concluded that there is insufficient evidence to support the use of the TOT procedure for stress urinary incontinence. Guidelines on UI from the National Collaborating Centre for Women's and Children's Health concluded that the TOT procedure is recommended as an alternative treatment option for SUI if conservative management has failed, "provided women are made aware of the lack of long-term outcome data." This was a "D" recommendation, based on consensus or low-quality evidence. Earlier guidance on the TOT procedure from the National Institute for Health and Clinical Excellence (NICE, 2005) was withdrawn when NICE was made aware that one of the main studies that was considered in the overview of evidence on the safety and efficacy of this procedure had been withdrawn by the journal that published it.
Tahseen and Reid (2009) estimated changes in overactive bladder (OAB) symptoms and urge UI in patients undergoing the TOT procedure for SUI and mixed UI. Telephone interviews were conducted using the International Consultation on Incontinence-Female Lower Urinary Tract Symptoms questionnaire, the International Consultation on Incontinence questionnaire-Overactive Bladder (ICIQ-OAB), and the Verbal Analogue Satisfaction (VeAS) scale. Pre-operative OAB scores were compared with post-operative scores in women with SUI only (group 1), mixed UI with predominant stress leakage (group 2), and mixed UI with predominant urge (group 3). Case notes were reviewed for pre-operative assessment and complications. At a median follow-up of 13 months, significant improvement was noted in ICIQ-OAB scores, from a median of 10 (1 to 15) pre-operatively to a median of 3 (0 to 11) post-operatively (p < 0.001). Overall, urge UI was cured in 19 of 44 (43%) patients, improved in a further 16 (36%), and was persistent in only 9 (21%). In group 2 (SUI predominant), urge UI was cured in 10 of 23 (43.5%) patients, improved in 10 (43.5%), and persistent in 3 (13%). In group 3 (urge UI predominant), urge UI was cured in 9 of 21 (43%) patients, improved in 6 (28.5%), and persistent in 6 (28.5%). Post-operative lower urinary tract symptom scores were low in all three groups (median 4/48 [0 to 18]). Stress incontinence was cured in 77%, improved in a further 19%, and unchanged in 4%. The median VeAS score was 9 (2 to 10); 21% (11/52) of participants had low satisfaction scores (less than 8) owing to persistent urge and slow voiding. The authors concluded that marked resolution or improvement (79%) in urge UI after the TOT procedure was noted, and no case of de novo urge UI was identified. Moreover, the authors noted that it is unclear how to predict who will benefit and remain free of urge following the surgery. Furthermore, they stated that larger outcome studies of TOT with longer follow-up are needed, ideally using standardized, validated assessment tools, focusing on the common problem of mixed UI, with clear reporting criteria, and assessment at baseline and after surgery.
On behalf of the Agency for Healthcare Research and Quality, the Vanderbilt Evidence-based Practice Center systematically reviewed evidence on the treatment of OAB, urge UI, and related symptoms. These investigators focused on prevalence and incidence, treatment outcomes, comparisons of treatments, modifiers of outcomes, and costs. They included studies published in English from January 1966 to October 2008 and excluded studies with fewer than 50 subjects, fewer than 75% women, or lack of relevance to OAB. Of 232 included publications, 20 were of good quality, 145 were fair, and 67 poor. These researchers calculated weighted averages of outcome effects and conducted a mixed-effects meta-analysis to examine outcomes of pharmacotherapies across studies.
Overactive bladder affects more than 10 to 15% of adult women, with 5 to 10% experiencing urge UI monthly or more often. Six available medications are effective in short-term studies: estimates from meta-analysis models suggest extended-release forms (taken once daily) reduce urge UI by 1.78 (95% CI: 1.61, 1.94) episodes per day, and voids by 2.24 (95% CI: 2.03, 2.46) per day. Immediate-release forms (taken twice daily or more) reduce urge UI by 1.46 (95% CI: 1.28, 1.64) and voids by 2.17 (95% CI: 1.81, 2.54). As context, placebo reduces urge UI episodes by 1.08 (95% CI: 0.86, 1.30) and voids by 1.48 (95% CI: 1.19, 1.71) per day. No one drug was definitively superior to others, including comparisons of newer, more selective agents to older antimuscarinics. Procedural and surgical treatments, such as sacral nerve stimulation (neuromodulation) and bladder instillation of oxybutynin or injections of botulinum toxin, were found to treat symptoms in select groups of women, though more information is needed to understand safety and effectiveness. Acupuncture was the sole complementary and alternative medicine treatment, among reflexology and hypnosis, with early evidence of benefit. The strength of the evidence is insufficient to fully inform the choice of these treatments. Select behavioral interventions were associated with symptom improvements comparable to medications. Limited evidence suggests no clear benefit from adding behavioral interventions at the time of initiation of pharmacotherapy. The authors concluded that OAB and associated symptoms are common; treatment effects are modest. Quality of life and treatment satisfaction measures suggest such improvements can be important to women. The amount of high-quality literature available is meager for helping guide women's choices. Gaps include weak or absent data about long-term follow-up, poorly characterized and potentially concerning harms, information about the best choices to minimize side effects, and study of how combinations of approaches may best be used. This is problematic since the condition is chronic, and a single treatment modality is unlikely to fully resolve symptoms for most women.
Sirls et al. (2002) reported the long-term results of the FemSoft urethral insert for the management of female SUI. This 5-year controlled multi-center study enrolled 150 women. Outcome measures included pad weight tests (PWT), voiding diary (VD), quality of life (QOL), and satisfaction questionnaires. Outcome measures during the baseline period were compared to evaluations during follow-up. Concurrent evaluations with and without device use were also performed. Safety evaluations included urinalysis and culture, LPP, and cystoscopy. Adverse events were recorded throughout the study. One to two years of follow-up were collected on all study participants (mean of 15 months). Statistically significant reductions in overall daily incontinence episodes (p < 0.001) and PWT urine loss (p < 0.001) were observed with the device at all follow-up intervals, and 93% of women had a negative PWT at 12 months. Women were satisfied with the ease of use of the device, comfort, and dryness, and significant improvements in QOL were observed (p < 0.001). Sub-group analysis revealed that the insert was effective, despite the presence of urgency, low LPP, failed surgery, and advanced age. Adverse events included symptomatic urinary tract infection in 31.3%, mild trauma with insertion in 6.7%, hematuria in 3.3%, and migration in 1.3% of women. The results of PWT and VD demonstrated device efficacy. Women were satisfied, and significant improvements in QOL were observed; adverse events were transient and required minimal or no treatment. The authors concluded that the urethral insert should be considered as an option for the management of SUI.
Robinson et al. (2003) evaluated the safety and efficacy of an urethral device (NEAT) and compared it with the Reliance Insert. The ease of use of both devices was then evaluated. A total of 24 women with mixed or SUI were enrolled in the study. Study subjects were blinded and randomly assigned to a device group. Device efficacy was assessed by pad weighing at 0 and 4 months. Success was defined as a 50% or greater reduction in urine loss using the formula 100 [(pad weight without device - pad weight with device)/pad weight with device]. Safety was evaluated using urinalysis and urine cultures. Ease of use assessment scales were also completed. Eleven patients were randomized to the Reliance Insert and 13 to the NEAT device. There were no significant differences between the two groups in age, height, weight, duration of incontinence, pad weight, leakage score, parity, or QOL score. Based on the pad weight success formula, there was no significant difference in device success between the two groups at 4 months. Women who were post-menopausal had a trend towards a higher level of success in the reduction of their pad weight. Previous treatment, diagnosis, and hormone replacement therapy all had no relationship to device success. Leakage score data showed that subjects had a significant decrease in urine leakage when using either device. There was no statistically significant difference in ease of use between the two devices. Adverse symptoms most commonly noted were awareness of the device (62.5%), urgency (29.2%), and urethral discomfort or pain (20.8%). One urinary tract infection (UTI) was observed. The most common finding on urinalysis was trace hematuria (15.8%). The authors concluded that the NEAT device appears to be at least as effective and safe as the Reliance Insert. Both devices are effective at decreasing urine leakage in patients with SUI or mixed UI. The risk of UTI is low, but these devices may cause trace hematuria.
The Genityte procedure is a novel approach for the treatment of SUI. It entails the use of laser that works in a similar fashion to skin tightening treatments. The treatment stimulates the skin’s natural production of collagen, making it more supple and elastic. Genityte works to regain bladder control by tightening the tissue around the urethra. The number of treatments needed to restore the function of a woman’s urethra supposedly depends largely on how much collagen is still present in her skin. The clinical value of the Genityte procedure needs to be validated by well-designed studies.
In a pilot study, Groen and colleagues (2005) evaluated the results of chronic pudendal nerve neuromodulation (CPNN) on women with idiopathic refractory detrusor over-activity incontinence. A percutaneous screening test (PST) was performed in patients with urodynamically demonstrated detrusor over-activity incontinence. Such a test includes the performance of a cystometrogram without and with percutaneous pudendal nerve stimulation and is considered positive if stimulation results in a more than 50% increase in the bladder volume at the first involuntary detrusor contraction or the maximum cystometric capacity. Patients with a positive PST qualified for the implantation of a mini-neurostimulator with an integrated electrode, a so-called Bion®, adjacent to the pudendal nerve at Alcock's Canal. Five-day voiding-incontinence diaries were the main tool for the evaluation of therapy. A PST was performed in 14 women; 6 patients responded positively and received a Bion®. The degree of incontinence decreased significantly in this group, which also included patients in whom sacral neuromodulation had failed. There were no severe adverse events. The authors concluded that CPNN may reduce the degree of detrusor over-activity incontinence, even in patients in whom sacral neuromodulation fails.
Spinelli et al. (2005) stated that pudendal nerve stimulation has beneficial effects on numerous pelvic floor function impairments such as urinary and/or fecal incontinence, retention, and constipation. In preceding literature, the implant technique required a fairly complex and invasive surgery, although recent advances with percutaneous placement of the lead through an introducer have made the procedure much less invasive. These researchers performed a staged procedure similar to that of sacral neuromodulation (SNM) to place a tined lead near the pudendal nerve, using neurophysiological guidance that allowed accurate pudendal nerve stimulation through either perineal or posterior approach. They have named this approach CPNN. A total of 15 neurogenic patients (8 males, 7 females) with symptoms of urge UI due to neurogenic over-active bladder underwent CPNN. All patients had complete neurophysiological and urodynamic evaluation at baseline and follow-up and were asked to complete voiding and bowel diaries for 7 days. During screening, the average number of incontinent episodes per day decreased from 7 ± 3.3 to 2.6 ± 3.3 (p < 0.02, paired t-test). Eight patients became continent, 2 improved by more than 88% (from 9 to 1 daily incontinence episode), and 2 patients reduced the number of incontinence episodes by 50%. The implantable pulse generator (IPG) was subsequently implanted in those 12 patients. Three patients without improvement did not continue to the second stage. In implanted patients with 6 months follow-up, urodynamic evaluation showed an objective improvement in the maximum cystometric capacity, which increased from 153.3 ± 49.9 to 331.4 ± 110.7 ml (p < 0.01, paired t-test). The maximum pressure decreased from 66 ± 24.3 to 36.8 ± 35.9 cm H2O (p = 0.059, paired t-test). Eight patients reported significant improvement in bowel function. The authors concluded that CPNN is feasible. Neurophysiological guidance is mandatory to place the lead near the pudendal nerve, either using a perineal or posterior approach. They stated that further studies must be carried out to identify the best stimulation parameters and to verify the long-term results.
Seif and associates (2005) noted that sacral neuromodulation is known to be an alternative therapeutic option for patients with anti-cholinergic resistant overactive bladder (OAB). For the same indication, a micro-stimulation system called BION has been available since last year. The BION stimulator, which measures only 2.8 x 0.3 cm, is designed for pudendal nerve stimulation. Its implantation technique, as well as the first clinical results, were presented and discussed. During an outpatient PST, a pudendal nerve stimulation is performed with a needle electrode under local anesthesia. A 50% increase in the urodynamic parameters (bladder capacity, first desire to void, compliance, etc.) is an indication for a chronic implantation of the BION stimulator, which can also be placed under local anesthesia. Two patients have been treated with a BION stimulator in the authors' clinic so far. Patient 1 suffered from OAB with frequent UI, and patient 2 had a sensory OAB with high voiding frequency. After the BION® implantation, patient 1 showed a reduction in incontinence episodes by 31.5% per day, and patient 2 had lowered voiding frequencies from 12.6 to 7 per day. The post-operative urodynamic investigations confirmed these clinical results. The authors concluded that the BION system and CPNN seem to be alternatives to sacral neuromodulation; however, patient selection is difficult as subchronic stimulation for a longer period of time is not possible so far.
Madjar et al. (2001) reviewed the evolution of appliances and devices used for treating post-prostatectomy UI. These investigators used MEDLINE to search the literature from 1966 to March 2000 and then manually searched bibliographies to identify studies that their initial search may have missed. The evolution of treatment for post-prostatectomy UI may be traced back to the 18th century. Two main schools of thought simultaneously evolved. The first fixed urethral compression devices were constructed to enable urethral obstruction by fixed resistance. This outlet resistance allows voiding after intra-abdominal and intra-vesical pressure is elevated, but it is sufficient to prevent leakage between urinations. The other school of thought preferred the creation of dynamic urethral compression, in which outlet resistance is not fixed but may be decreased when voiding is desired or elevated between urinations. Therapeutic fixed and dynamic urethral compression interventions may be further divided into external or internal compressive devices or procedures. External fixed compression devices may be traced back to antiquity. A penile clamp, similar to the later Cunningham clamp, and a truss designed to compress the urethra by external perineal compression were presented in the Heister textbook of surgery, Institutiones Chirurgicae, as early as 1750. Dynamic compressive devices applied externally were developed much later, such as the first artificial urinary sphincter, described by Foley in 1947, and the Vincent apparatus, described in 1960. The modern era of fixed urethral compression began in 1961 with Berry. Acrylic prostheses impregnated with bismuth to allow radiographic visualization were produced in various shapes and sizes and used to compress the urethra against the urogenital diaphragm. In 1968, the UCLA group under the direction of Kaufman began to use cavernous crural cross-over to compress the bulbous urethra (Kaufman I). Later, two other modifications were described, including approximation of the crura in the midline using a polytetrafluoroethylene mesh tape (Kaufman II) and an implantable silicone gel prosthesis (Kaufman III). With the advent of the artificial urinary sphincter pioneered by Scott in 1973, interest in passive urethral compression disappeared in favor of the implantation of an inflatable circumferential prosthetic sphincter. Recently, there has been a trend back to passive urethral compression. The authors concluded that much creativity has been dedicated to solving the complex and challenging problem of post-prostatectomy UI. Devices used for treating this condition may be grouped according to the mechanism of action and how they are applied. Passive urethral compression, long abandoned in favor of dynamic implantable sphincters, has re-emerged.
Moore et al. (2004) evaluated the safety, effectiveness, comfort, and patient satisfaction with three penile compression devices: the Cunningham clamp, C3, and U-Tex. The devices were tested in random order in a multiple-period, cross-over study design using a Latin squares configuration. The subjects had undergone radical prostatectomy 6 months or more before the study, had no neurologic or cognitive impairment, and had not undergone radiotherapy. Baseline penile Doppler ultrasonography was followed by ultrasound scanning with each device. In random order, subjects completed a 4-hour pad test, with and without each device, and the questionnaire. A total of 12 men completed the study. The mean Mini-Mental State Examination score was 29.6 (SD 1.2, range of 27 to 30). The mean urine loss at baseline was 122.8 g (SD 130.8). The mean urine loss with each device was 53.3 g (SD 65.7) with the U-Tex, 32.3 g (SD 24.3) with C3, and 17.1 g (SD 21.3) with the Cunningham clamp (p < 0.05). No device had an impact on the resistive index; the C3 and U-Tex allowed good cavernosal artery flow, and the Cunningham clamp significantly lowered the distal blood flow velocity (from 12.5 to 7.3 cm/s [left systolic velocity] to 9.5 cm/s [right systolic velocity]) even at the loosest setting. The Cunningham clamp was ranked positively by 10 of 12 men; 2 of 12 men rated the C3 positively; none rated the U-Tex positively. The authors concluded that the Cunningham device was the most effective and most acceptable to users, but it also contributed to reduced systolic velocity in all men. None of the devices completely eliminated urine loss when applied at a comfortable pressure. Individualized instruction to cognitively capable men is necessary to ensure appropriate application, comfort, and fit.
An UpToDate review on "Urinary incontinence in men" (Clemens, 2012) states that "[a]djunctive measures include incontinence pads, indwelling catheters, external urinary catheters, and penile incontinence clamps. The treatment of urinary incontinence with an indwelling catheter is usually a poor management choice, as it is associated with urethral trauma, infection, and nephrolithiasis. Incontinence pads and indwelling catheterization are discussed elsewhere. In men, external urinary catheters (condom catheters) can be useful in managing urinary incontinence, with less associated morbidity compared to indwelling catheterization. Successful use of an external catheter requires adherence of the condom sheath to the penis. Use of external catheters may not be possible in some patients who are unable to keep catheters in place (e.g., due to skin infections) or are not physically able to place catheters (e.g., obesity, neurologic impairment). In patients with neurogenic bladder dysfunction, the use of an external catheter may be associated with progressive renal damage unless it is confirmed with urodynamics that bladder storage pressures remain low... Another option is the use of a penile incontinence clamp. A clamp is most suitable for ambulatory men with stress incontinence and good bladder storage function. Clamps are meant to be used on an intermittent basis. Their use in men with sensory abnormalities should be avoided, as tissue damage from the clamp can occur with prolonged use."
The Athena pelvic muscle trainer is an electronic device designed to strengthen pelvic muscles in women. This would appear to be similar to Kegelmaster. Per CPB 223, Aetna does not cover the Kegelmaster, Gyneflex, or similar devices for the treatment of UI because these devices are considered exercise machines and do not meet Aetna's definition of covered durable medical equipment (DME). Furthermore, there is a clinical trial on the effectiveness of the Athena pelvic muscle trainer device in the treatment of stress, urge, or mixed incontinence in women (http://clinicaltrials.gov/ct2/show/NCT01073878).
Elmi et al. (2011) evaluated the effectiveness of endo-urethral autologous myoblast transplantation in the treatment of UI in children with bladder exstrophy-epispadias complex. Subjects were evaluated at 4 years of follow-up regarding the safety, efficacy, and durability of the procedure, and health-related quality of life. A total of 7 boys underwent autologous myoblast transplantation between May and December 2006. All patients had persistent UI after bladder neck reconstruction and bulking agent injection. Patients were followed for 4 years after autologous myoblast transplantation regarding clinical outcomes and cystometric, urodynamic, uroflowmetric, and urethrocystoscopic evaluations. Health-related quality of life was also measured before treatment and at final follow-up. No evidence of urinary obstruction was observed. Five children (71%) were completely continent, and 2 (29%) were socially dry with complete daytime dryness at final follow-up. Health-related quality of life improved significantly. Urodynamic studies revealed a progressive increase in bladder capacity (p < 0.001). Mean detrusor leak point pressure showed a 27 cm H2O (158%) increase during the 4-year follow-up. Uroflowmetry parameters of voided volume and average maximum flow rate were improved significantly (p < 0.001). The authors concluded that the 4-year outcomes demonstrate that autologous myoblast transplantation for UI in children with bladder exstrophy-epispadias complex is relatively reliable, reproducible, safe, and effective with minimal morbidity. This novel treatment represents a promising therapeutic approach in patients with UI. They stated that further randomized trials with larger numbers of patients and longer follow-up are needed.
According to the Interstim product labeling, the safety and effectiveness of bilateral sacral nerve stimulation have not been established (Medtronic, 2008).
In a pilot study, Marcelissen et al. (2011) examined if bilateral sacral nerve stimulation can be effective in restoring treatment efficacy in patients in whom unilateral sacral neuromodulation fails. Patients in whom unilateral sacral neuromodulation failed were included in the analysis. The percutaneous nerve evaluation test was used to evaluate the effect of contralateral and bilateral stimulation. The stimulation electrode was placed in the contralateral S3 foramen, and symptoms were self-recorded using a 3-day voiding diary. Clinical success was defined as more than a 50% improvement in at least one relevant voiding diary parameter versus baseline. The 15 study patients underwent test stimulation with percutaneous nerve evaluation. In 3 patients, lead migration was suspected and, thus, they were not included in the analysis. Four of the remaining 12 patients had a successful response to percutaneous nerve evaluation, of whom 3 were eventually implanted with a contralateral lead. After 12 months of treatment, 2 of the 3 patients had a successful outcome. The authors concluded that only a select group of patients appeared to benefit from bilateral stimulation after unilateral therapy failure. They stated that further investigation is needed to determine the predictive factors and cost-effectiveness of this treatment.
Guidelines from the American Urologic Association (Gormley et al., 2012) have concluded: “Clinicians may offer sacral neuromodulation (SNS) as a third-line treatment in a carefully selected patient population characterized by severe refractory OAB symptoms or patients who are not candidates for second-line therapy and are willing to undergo a surgical procedure. Recommendation (evidence strength grade C; benefits outweigh risks/burdens).”
Woodruff et al. (2008) stated that little is known about the host response to the various biologic and synthetic graft materials used as substitutes for autologous fascia. These researchers investigated the host response to sling graft materials in humans. A total of 24 women undergoing sling revision had a portion of the graft material removed for comparative analysis. At exploration, the degree of graft preservation (integrity), encapsulation, infection, and fibrosis was quantified. A histopathologic analysis was performed by systematically examining each specimen for the inflammatory response, neovascularity, and host fibroblast infiltration. A total of 24 grafts were explanted at 2 to 34 months after implantation. The indications for removal were a lack of sling efficacy in 2, urinary retention in 9, and sling obstruction in 13. The types of graft material were polypropylene mesh (PPM) in 10, autologous fascia in 5, porcine dermis in 4, cadaveric dermis in 3, and cadaveric fascia in 2. No graft degradation had occurred in PPM material. Autologous and cadaveric fascia had the most demonstrable graft degradation. No encapsulation had occurred with autologous fascia or PPM. The porcine dermis was the most encapsulated. No host infiltration had occurred with the encapsulated porcine grafts, and only peripheral infiltration of fibroblasts had occurred in the cadaveric grafts. The PPM grafts had the greatest number of fibroblasts throughout the entire graft. Neovascularity was most prevalent in mesh and was also present in the autologous fascia. Giant cells were seen in 2 mesh and 2 porcine grafts. The authors concluded that the results of this study have shown that porcine dermis has the potential to encapsulate. The degree of host tissue infiltration was greatest with PPM, and no degradation of the mesh material had occurred with time.
An UpToDate review on “Treatment of urinary incontinence” (DuBeau, 2012) does not mention the use of collagen porcine dermis mesh as a therapeutic option. Furthermore, an UpToDate review on “Overview of transvaginal placement of reconstructive materials (surgical mesh or biograft) for treatment of pelvic organ prolapse or stress urinary incontinence” (Trabuco and Gebhart, 2012) states that “Mid-urethral slings, using macroporous polypropylene mesh, are the most common procedures for treatment of SUI. A sling made of microporous material (ObTape) for mid-urethral slings was associated with high complication rates and was removed from the market.” It does not mention the use of collagen porcine dermis.
In an open, prospective, single-center study, Cornu et al. (2011) evaluated the safety of intrasphincteric injections of autologous muscular cells in patients with post-prostatectomy incontinence (PPI; n = 12). Patients underwent intrasphincteric injections of autologous muscular cells isolated from a biopsy of deltoid muscle. The primary endpoint was the Q(max) variation at the 3-month visit in order to assess potential bladder outlet obstruction. Secondary endpoints assessed side effects and efficacy parameters based on symptoms, quality of life score, voiding diary, pad test, and urethral pressure profile at 1, 2, 3, 6, and 12 months after injection. No immediate complications occurred, and no significant variation was noted on Q(max). The only side effects possibly product-related were 3 cases of urinary tract infection treated with antibiotics. An acceptable safety and tolerability of the procedure, regardless of the injected dose of muscular cells, was demonstrated. Results on efficacy after 1 year were heterogeneous, with 4/12 patients describing reduced urine leakage episodes, 1/12 patient presenting increased maximal closure pressure, and 8/12 patients showing improvement on the pad test. The authors concluded that cell therapy consisting of intrasphincteric injections of autologous muscular cells in patients with PPI was a feasible and safe procedure. They stated that these findings indicated that some subjects may positively respond to this procedure, but clinical efficacy remains to be confirmed.
In a prospective, dose-ranging, feasibility study, Carr et al. (2013) evaluated the 12-month safety and potential efficacy of autologous muscle-derived cells (Cook MyoSite Incorporated, Pittsburgh, PA) as therapy for SUI. A total of 38 women in whom SUI had not improved with conservative therapy for 12 or more months underwent intra-sphincter injection of low doses (1, 2, 4, 8, or 16 × 10^6) or high doses (32, 64, or 128 × 10^6) of autologous muscle-derived cells, which were derived from biopsies of their quadriceps femoris. All patients could elect a second treatment of the same dose after 3-month follow-up. Assessments were made at 1, 3, 6, and 12 months after the last treatment. The primary endpoint was the incidence and severity of adverse events. In addition, changes in SUI severity were evaluated by pad test, diary of incontinence episodes, and quality of life surveys. Of the 38 patients, 33 completed the study. Treatment-related complications were limited to minor events such as pain/bruising at the biopsy and injection sites. Of patients who received two treatments of autologous muscle-derived cells who were eligible for analysis, a higher percentage of those in the high-dose versus the low-dose group experienced a 50% or greater reduction in pad weight (88.9%, 8 of 9 versus 61.5%, 8 of 13), had a 50% or greater reduction in diary-reported stress leaks (77.8%, 7 of 9 versus 53.3%, 8 of 15), and had 0 to 1 leaks during 3 days (88.9%, 8 of 9 versus 33.3%, 5 of 15) at final follow-up. The authors concluded that injection of autologous muscle-derived cells in a wide range of doses appears safe, with no major treatment-related adverse events reported. They stated that treatment with autologous muscle-derived cells shows promise for relieving SUI symptoms and improving quality of life. Moreover, they noted that the most effective dose of cells has yet to be determined, and a placebo-controlled study powered to determine treatment efficacy is necessary. Two ongoing studies have been designed to address these issues.
Phe and colleagues (2014) described the minimally invasive adjustable continence therapy (ACT) balloon placement surgical technique and analyzed the results of ACT balloon in the treatment for female SUI. A review of the literature was performed by searching the PubMed database using the following search terms: ACT balloons, female urinary incontinence, and female continence. A total of 8 studies were published between 2007 and 2013. The mean follow-up of these studies was 1 to 6 years. The mean age of the patients ranged between 62 and 73 years; 40 to 100% of patients had already been treated surgically for their SUI. A significant reduction in the number of pads used per day was observed after ACT balloon placement, with improvement of short pad tests from 49.6 to 77.3 g pre-operatively to 11.2 to 25.7 g after ACT balloon placement; 15 to 44% of patients considered that their SUI had been cured, and 66 to 78.4% were satisfied with the result. The explantation rate ranged between 18.7 and 30.8%. Quality of life was significantly improved, and no major complications were reported. The authors concluded that ACT balloons constitute a reasonable, minimally invasive alternative for the treatment of female SUI due to intrinsic sphincter disorder, especially in patients who have already experienced failure of standard surgical treatment and in clinical settings incompatible with invasive surgical placement of an artificial urinary sphincter (especially women over the age of 80 years). Moreover, they stated that long-term results are essential to evaluate the effectiveness of this treatment.
Vij and Drake (2015) describe mirabegron as a β3 adrenoceptor agonist approved for treating symptoms of overactive bladder (OAB), including urinary urgency and urgency incontinence. By activating β3 adrenoceptors, mirabegron promotes relaxation of the detrusor muscle, but it may also interact with other targets in the bladder and decrease sensory nerve activity. Phase III clinical trials (SCORPIO, ARIES, and CAPRICORN) assessed various doses of mirabegron, showing significant reductions in mean incontinence episodes and the number of micturitions per 24 hours (the coprimary endpoints), as well as improvements in health-related quality of life and other secondary measures. The drug proved effective for many patients who had previously stopped antimuscarinic therapy due to ineffectiveness or poor tolerability. A long-term study (TAURUS) documented treatment-emergent adverse effects, primarily mild to moderate in severity, with the most common being hypertension, dry mouth, constipation, and headache; notably, the incidence of dry mouth was lower than that associated with the antimuscarinic comparator. Efficacy and safety profiles were similar in older patients, and a urodynamic safety study in men indicated no consistent impact on voiding function, although a slight increase in postvoid residual was observed. Combining mirabegron with α-adrenergic blockers did not appear to heighten adverse effects. The authors referenced the DRAGON study, a 12-week phase IIB dose-ranging trial conducted mainly in Europe, which randomized 919 patients into six groups: placebo, mirabegron at doses of 25, 50, 100, or 200 mg once daily, or tolterodine as an active comparator. Results showed a dose-dependent reduction in mean micturitions per 24 hours with mirabegron, significant at doses of 50 mg and above compared to placebo. Among those receiving 50 mg of mirabegron, 28% were classified as 'responders' with a reduction in voiding frequency to eight times daily or less, compared to 19% for both placebo and tolterodine. Significant improvements were also noted in secondary endpoints, including mean urgency and urgency incontinence episodes, nocturia, and mean voided volume, with responses evident as early as one week into treatment and maximum efficacy achieved at 8–12 weeks. The authors note that dose reductions are necessary for individuals with severe renal failure or moderate hepatic failure, while no adjustments are required based on food intake. Ongoing research is exploring the potential for combination therapy with antimuscarinics. The authors concluded that mirabegron is a first-in-class β3 agonist for treatment of OAB in women or men, which appears to have good efficacy and tolerability. It can be used in patients who have discontinued antimuscarinic therapy, or who have contraindications for antimuscarinics.
Frankel et al. (2022) discuss pharmacologic treatments for overactive bladder (OAB), which is characterized by bothersome symptoms such as urgency and urge urinary incontinence (UUI), including anticholinergics and β3-adrenergic receptor agonists. While anticholinergics can lead to adverse effects like dry mouth, constipation, cognitive impairment, and an increased risk of dementia, β3-adrenergic receptor agonists may offer a safer and effective alternative. Vibegron, a β3-adrenergic receptor agonist, received approval in Japan in 2018 and in the United States in 2020. Over the past three years, two phase 3 trials (EMPOWUR and its extension) have evaluated once-daily vibegron at a dose of 75 mg for treating OAB, with additional secondary and subgroup analyses confirming its efficacy and safety. In the international phase 3 EMPOWUR trial, vibegron treatment resulted in significant improvements compared to placebo in micturition frequency, UUI episodes, urgency episodes, and voided volume as early as week 2, with these benefits sustained throughout the 12-week trial. The 40-week EMPOWUR extension study further demonstrated sustained efficacy in patients receiving vibegron for a total of 52 weeks, along with enhancements in patient-reported quality of life measures. Overall, vibegron was found to be generally safe and well tolerated, with a dedicated ambulatory blood pressure monitoring study indicating no clinically meaningful effects on blood pressure or heart rate. Collectively, the studies suggest that vibegron is an effective, safe, and well-tolerated treatment option for patients with OAB, and this review summarizes the published data on its efficacy and safety nearly one year after its approval in the U.S.
Test Stimulation of the InterStim
The Medtronic InterStim system is an implantable sacral neuromodulation therapy used to treat overactive bladder, urinary urge incontinence, non‑obstructive urinary retention, and fecal incontinence by delivering mild electrical stimulation to the sacral nerves that regulate bladder and bowel function. By modulating aberrant neural signaling between the brain and pelvic organs, InterStim can reduce urgency, frequency, and incontinence episodes in patients who have not responded to conservative treatments. It includes an implantable neurostimulator and lead, preceded by an external evaluation phase to determine therapeutic response, and has demonstrated long‑term clinical durability and significant improvements in quality of life.
InterStim provides two types of trials—basic and advanced—before the implantation of a permanent sacral nerve stimulator. The basic trial, sometimes referred to as percutaneous/peripheral nerve evaluation (PNE), involves the placement of a temporary lead through a minimally invasive outpatient procedure, where the lead is inserted via the S3 foramen under local anesthesia. This lead is then externalized and connected to an external test stimulator, with the trial typically lasting between 3 to 7 days. The primary goal of this trial is to determine if the patient experiences a ≥50% improvement in symptoms such as urinary urgency, urge incontinence, or non-obstructive urinary retention. In contrast, the advanced trial, sometimes referred to as Stage 1 trial, employs a tined lead connected to the external test stimulator through a percutaneous extension, allowing for a longer trial period to assess the therapy's efficacy with the permanent tined lead. This procedure is performed in a hospital or surgical center and involves inserting the permanent tined lead through the S3 sacral foramen, with the trial lasting up to 14 days.
The InterStim product labeling states that, in clinical studies, subjects underwent anywhere from 1 to 6 test stimulation procedures before implantation of InterStim.
The Medtronic InterStim test stimulation lead kit manual stated that “Of the 260 patients (45.0%) who qualified for implantation,169 (65.0%) had a successful result (minimum of 50% improvement in dysfunctional voiding symptoms) during their first test stimulation procedure. Of the remaining 91 patients, 56 (21.5%) obtained a successful result during a second test stimulation, and 35 (13.5%) obtained a successful result during three or more test stimulations. Reasons for repeat test stimulation procedures included inadequate responses to test stimulation or technical problems …. The safety and effectiveness of this therapy has not been established for pediatric use (patients under the age of 16), patients with neurological disease origins, such as multiple sclerosis or diabetes, and bilateral stimulation”.
Axonics Neuromodulation System for the Treatment of Urinary Incontinence
The Axonics Sacral Neuromodulation (SNM) system is a long‑term, implantable neuromodulation therapy designed to treat symptoms of overactive bladder, including urinary urgency incontinence, by delivering gentle electrical stimulation to the sacral nerves that regulate bladder function. This miniaturized device helps restore normal communication between the brain and bladder, resulting in improved urinary control and symptom reduction.
Axonics provides two types of trials—basic and advanced—before the implantation of a permanent sacral nerve stimulator. The basic trial, sometimes referred to as percutaneous/peripheral nerve evaluation (PNE), involves the placement of a temporary lead through a minimally invasive outpatient procedure, where the lead is inserted via the S3 foramen under local anesthesia. This lead is then externalized and connected to an external test stimulator, with the trial typically lasting between 3 to 7 days. The primary goal of this trial is to determine if the patient experiences a ≥50% improvement in symptoms such as urinary urgency, urge incontinence, or non-obstructive urinary retention. In contrast, the advanced trial, sometimes referred to as Stage 1 trial, employs a tined lead connected to the external test stimulator through a percutaneous extension, allowing for a longer trial period to assess the therapy's efficacy with the permanent tined lead. This procedure is performed in a hospital or surgical center and involves inserting the permanent tined lead through the S3 sacral foramen, with the trial lasting up to 14 days.
Benson et al. (2020) noted that sacral neuromodulation (SNM) is a guideline-recommended treatment for voiding dysfunction, including urgency, urge incontinence (UI), and non-obstructive retention, as well as fecal incontinence. The Axonics System is a miniaturized, rechargeable SNM system designed to provide therapy for at least 15 years, which is expected to significantly reduce revision surgeries, as it will not require replacement as frequently as the non-rechargeable SNM system. The ARTISAN-SNM study is a pivotal study designed to treat patients with urgency UI (UUI). These researchers presented clinical results at 1 year. A total of 129 eligible UUI patients were treated. All subjects were implanted with a quadripolar tined lead and neurostimulator in a single procedure. Effectiveness data were collected using a 3-day bladder diary, a validated quality of life questionnaire (ICIQ-OABqol), and a participant satisfaction questionnaire. Therapy responders were defined as participants with a greater than or equal to 50% reduction in UUI episodes compared to baseline. Data were analyzed on all 129 subjects. At 1 year, 89% of the subjects were therapy responders. The average UUI episodes per day reduced from 5.6 ± 0.3 at baseline to 1.4 ± 0.2. Subjects experienced an overall clinically meaningful improvement of 34 points on the ICIQ-OABqol questionnaire. All study participants (100%) were able to recharge their device at 1 year, and 96% of participants reported that the frequency and duration of recharging were acceptable. There were no serious device-related adverse events (AEs). The authors concluded that the Axonics System was safe and effective at 1 year, with 89% of participants experiencing clinically and statistically significant improvements in UUI symptoms.
Geynisman-Tan et al. (2021) described factors associated with satisfaction with the Axonics SNM System at 1 year. This was a secondary analysis of data collected in the ARTISAN-SNM study—a prospective, single-arm, multi-center trial of the Axonics r-SNM System. ARTISAN-SNM recruited subjects with UUI to undergo a single, non-staged implant of the lead and rechargeable neurostimulator. Participants were considered therapy responders if they had a greater than or equal to 50% reduction in UUI episodes in a 3-day period at 1 month post-implant. Bladder diaries and satisfaction (7-point Likert scale) were evaluated at 1 year. A total of 124 participants (110 "responders" and 14 "non-responders") had complete data at baseline, 1 month, and 1 year following the implant. Most subjects were satisfied with Axonics at 1 year: 68.5% were "very satisfied," 25.8% were "moderately satisfied," and 2.4% were "slightly satisfied." At 1 year, treatment effectiveness, as measured by electronic bladder diaries, was significantly associated with satisfaction. Participants who were "very satisfied" had a larger reduction in voids per day (p = 0.01), leaks per day (p = 0.004), urgent leaks per day (p = 0.04), and voids in which the urgency was desperate per day (p = 0.03) compared to those less satisfied; 12 of the 14 "non-responders" continued to see improvements in symptom reduction from 1 month to 1 year; 9/14 (64%) were "responders" at 1 year, with 6 reporting being "very satisfied" and 1 reporting being "moderately satisfied." The authors concluded that satisfaction 1 year after implantation of Axonics SNM was extremely high and correlated with the degree of symptom improvement, which increased over time.
Pezzella et al. (2021) stated that SNM is a guideline-recommended treatment with proven therapeutic benefit for UUI patients. The Axonics System is the first Food and Drug Administration (FDA)-approved rechargeable SNM system and is designed to deliver therapy for a minimum of 15 years. The ARTISAN-SNM study was designed to evaluate UUI participants treated with the Axonics System. These researchers presented 2-year follow-up results. A total of 129 UUI participants underwent implantation with the Axonics System. Therapeutic response rate, participant quality of life (QOL), and satisfaction were determined using 3-day voiding diaries, ICIQ-OABqol, and satisfaction questionnaires. Participants were considered responders if they had a 50% or greater reduction in UUI episodes post-treatment. At 2 years, 93% of the participants (n = 121 completers at 2 years) were therapy responders, of which 82% achieved greater than or equal to 75% reduction in UUI episodes, and 37% were dry (100% reduction). Daily UUI episodes reduced from 5.6 ± 0.3 at baseline to 1.0 ± 0.2 at 2 years. Statistically significant improvements in ICIQ-OABqol were reported. All participants were able to recharge their device, and 94% of participants reported that the recharging frequency and duration were acceptable. Participant demographics and condition severity were not correlated with clinical outcomes or recharging experience. No unanticipated or serious device-related AEs occurred. The authors concluded that at 2 years, participants treated with the Axonics System demonstrated sustained safety and effectiveness, high levels of satisfaction with therapy and recharging. Participant-related factors were not associated with effectiveness or recharging outcomes, indicating the reported results were applicable to a diverse population.
Wang et al. (2021) noted that overactive bladder (OAB) and UUI affect millions of women and men and result in billions of dollars in healthcare expenses. First- and second-line therapy includes behavioral modifications and/or pharmacotherapies; however, many patients' symptoms remain or worsen on these treatments. There has been concern regarding the detrimental side effects of the most widely prescribed medications for managing these bladder symptoms. As a result, there has been increased interest in continuous sacral neuromodulation, an FDA-approved therapy for refractory UUI. These investigators reviewed current research on the effectiveness, patient/provider satisfaction, and safety profile of the Axonics System. Furthermore, they addressed the current state of SNM and potential future direction and applicability. The authors concluded that the Axonics system is a safe and effective device for the treatment of OAB and UUI. Additionally, it affords patients the convenience of a rechargeable, compact, MRI-safe system. It should be noted that the rechargeable system, while allowing for approximately 15 years of battery and lead life, may have its challenges in terms of charge burden. Furthermore, this system is easily adapted for experienced implanters of sacral neuromodulating devices.
Furthermore, an UpToDate review on “Urgency urinary incontinence/overactive bladder (OAB) in females: Treatment” (Lukacz, 2022) states that “Sacral neuromodulation—SNM is a minimally invasive surgical electrical stimulation option to treat OAB symptoms that is offered to patients whose symptoms do not respond to initial interventions and pharmacotherapy. Several devices are available, including InterStim micro system, InterStim II, and Axonics, which include MRI-compatible options. InterStim micro and Axonics have rechargeable implanted programmable device options, which can increase battery life to 15 years or more and may be more cost-effective than the non-rechargeable option. These devices require the patient to have the cognitive ability and desire to manage the technology, perform a testing procedure, monitor the impact of stimulation on urinary incontinence episodes, urgency, and pad usage for a week or two, and manage the recharging process should they select this option. The InterStim II device has a non-rechargeable battery that requires replacement every 3 to 5 years.”
Polyacrylamide Hydrogel (Bulkamid)
Kasi et al. (2016) performed a systematic review on the effectiveness of polyacrylamide hydrogel (PAHG, Bulkamid) in the treatment of female patients with SUI with regard to reproducibility, feasibility, safety, and clinical outcome. These investigators searched MEDLINE (1966 to 2015), Scopus (2004 to 2015), POPLINE (1974 to 2015), and ClinicalTrials.gov (2008 to 2015), along with reference lists of electronically retrieved studies. Observational studies, prospective, retrospective, and RCTs were included. Two reviewers independently selected studies, assessed the risk of bias, and tabulated data to structured forms. These researchers included 8 studies, which enrolled a total of 767 patients who received treatment with PAHG. They found that 186 of 767 women (24.3%, range of 12 to 35%) required re-injection in order to achieve adequate effectiveness. The most frequent adverse effects were pain at the site of injection (4 to 14%) and urinary tract infections (3 to 7%). Both the number of incontinence episodes per 24 hours and the number of ml per 24 hours were significantly reduced 1 year following treatment, and the quality of life of patients was significantly improved. The authors concluded that PAHG is a safe intervention for treating women with SUI, but repeat injections are often required. They stated that further research is needed to compare its effectiveness with other bulking agents.
In a prospective, observational study, Altman and colleagues (2017) examined the effects of transurethral polyacrylamide hydrogel injection in patients considered ineligible for mid-urethral sling surgery. A total of 81 patients received treatment with transurethral polyacrylamide hydrogel injection. Subjects were considered ineligible for placement of a mid-urethral sling based on significant comorbidity (48%), one or more previously failed invasive treatments (16%), mixed UI (27%), continuous incontinence (5%), or previous pelvic radiation therapy (4%). Longitudinal assessment of subjective treatment outcomes was performed using the validated UDI and the pelvic floor impact questionnaire (PFIQ) at baseline, 2 months, and 6 months. To deal with repeated measurements, mixed linear models were used to examine changes in the outcomes over time. There was a significant improvement in the overall UDI score from baseline to month 2 follow-up (FU) (p < 0.001). No major differences between the month 2 and 6 FUs were observed. The largest difference in effect was observed for the irritative and stress subscales; 25 patients (33%) requested a second injection at the month-2 FU visit. At month-6 FU, the UDI scores for patients having had only one injection were largely unchanged, whereas all UDI domains worsened further for patients having had a second injection at the month-2 visit. After the injection, there were 3 minor AEs (3.7%) and no serious AEs. The authors concluded that in patients considered ineligible for mid-urethral sling surgery, transurethral injection with polyacrylamide hydrogel may alleviate UI symptoms. Repeat injections did not improve outcomes in this complicated group of patients.
Mohr and associates (2017) noted that mixed UI (MUI), defined as mixed symptoms of SUI and OAB, is a difficult entity if conservative treatment has failed. Cure rates are low compared with SUI, particularly the OAB component, which may deteriorate after sling insertion. Bulking agents pose an appealing alternative for the treatment of MUI. They have shown beneficial effects in small case studies, but larger series are lacking. In a prospective study, these investigators examined the safety and efficacy profile of Bulkamid in female patients with MUI. A total of 154 women with MUI symptoms (components of SUI/OAB within the limits of 60 to 40% either way) received bulking therapy with Bulkamid. Patients were followed up 3 months post-operatively. The primary outcome was the domain "Incontinence impact" on the KHQ; secondary outcomes were the other KHQ domains, visual analog scale (VAS), and International Continence Society (ICS) standardized pad weight test as objective measurements of incontinence. Statistically significant improvements were found for all KHQ domains, pad weight test, and the VAS before and after bulking; the overall complication rate was 13%. The authors concluded that the findings of this study showed improvement in MUI after bulking therapy according to both subjective and objective outcomes. These investigators could advocate bulking therapy for treating MUI, as it is simple and safe and showed both objective and subjective improvement and relief. They stated that long-term results (up to 1 year) are awaited.
Hussain and Bray (2019) noted that urethral bulking agents (UBAs) to treat SUI were first described in the 1930s when paraffin was used to increase urethral resistance. Since then, several agents have been introduced to the market, with varying degrees of safety, efficacy, and durability. The agents currently available include calcium hydroxyl apatite (Coaptite), carbon-coated zirconium (Durasphere), polydimethylsiloxane elastomer (Macroplastique), and polyacrylamide hydrogel (Bulkamid). The latest product, PDMS-U (Urolastic), is a silicone gel that polymerizes when injected. The short-term efficacy of UBAs is generally encouraging; however, longer follow-up results show that the success rates are reduced and many women will require repeat treatment.
In a controlled clinical trial, Itkonen Freitas and co-workers (2020) examined if polyacrylamide hydrogel is non-inferior to tension-free vaginal tape in the treatment of women with primary SUI. Subjects were randomized to tension-free vaginal tape or polyacrylamide hydrogel treatment. The primary outcome was patient satisfaction, and secondary outcomes were effectiveness in reducing urinary leakage and complications at 1-year follow-up. For statistical power, significance was considered at 5%, power was set at 80%, and the non-inferiority limit was 20% with a 10% expected drop-out rate. A total of 224 women with primary SUI entered the study between September 28, 2015, and March 1, 2017. Of the women, 111 were randomized to tension-free vaginal tape and 113 were randomized to polyacrylamide hydrogel. At 1 year, a satisfaction score of 80 or greater on a VAS of 0 to 100 was reached in 95.0% and 59.8% of patients treated with tension-free vaginal tape and polyacrylamide hydrogel, respectively. Therefore, polyacrylamide hydrogel did not meet the non-inferiority criteria set in this study. As secondary outcomes, the cough stress test was negative in 95.0% of tension-free vaginal tape cases versus 66.4% of polyacrylamide hydrogel cases (difference 28.6%, 95% CI: 18.4 to 38.5). However, most peri-operative complications, including those in 19 tension-free vaginal tape cases versus 3 polyacrylamide hydrogel cases (difference 16.0%, 95% CI: 7.8 to 24.9), and all 6 re-operations due to complications (difference 5.9%, 95% CI: 1.2 to 12.4) were associated with tension-free vaginal tape. The authors concluded that mid-urethral tension-free vaginal tape slings were associated with better satisfaction and cure rates than polyacrylamide hydrogel in women with primary SUI. However, complications were mainly associated with tension-free vaginal tape. Therefore, tension-free vaginal tape should be offered as a first-line treatment in women who expect to be completely cured by the initial treatment and are willing to accept the complication risks. Since polyacrylamide hydrogel treatment also provides high satisfaction and cure rates, women with primary SUI can be offered polyacrylamide hydrogel as an alternative treatment.
Furthermore, an UpToDate review on “Stress urinary incontinence in women: Persistent/recurrent symptoms after surgical treatment” (Morgan, 2020) states that “Several materials are available for peri-urethral injection therapy. Products that are now commonly used include: Polyacrylamide hydrogel (Bulkamid): a homogeneous, stable hydrophilic polymer gel composed of 2.5% cross-linked dextranomer polyacrylamide and 97.5% water, available in Europe.”
On January 28, 2020, the Bulkamid Urethral Bulking System was approved by the FDA. It is indicated for urethral injection for the treatment of SUI due to ISD in adult women who have SUI or stress-predominant mixed incontinence.
Adjustable Retropubic Sub-Urethral Sling for Stress Urinary Incontinence
In a single-center, prospective study, Leizour and associates (2016) evaluated the safety and effectiveness of the adjustable sub-urethral sling Remeex in the treatment of male SUI. Participants were patients treated for SUI after radical prostatectomy (RP) or transurethral resection of prostate. The severity of incontinence was evaluated by the number of pads used per day. Success rate, complications and number of adjustments were studied. From February 2011 to May 2015, Remeex was implanted in 25 patients. The average pre-operative number of pads used per day was 3.8 (± 1.8). Sling tension has been adjusted the day after surgery in all patients. Mean follow-up was 31 months (± 15). During follow-up, 6 patients did not need any re-adjustment (24%) and 15 patients (60%) had to be re-adjusted. One Remeex system had to be completely removed because of a sub-occlusive syndrome; 3 patients had early infection requiring partial system removal (Varitensor). At the end of follow-up, 9 patients were cured (36%), 9 patients (36%) were significantly improved and 7 patients (28%) were not improved; 5 patients were waiting for a new re-adjustment. The authors concluded that in this short series of patients who had prostatic surgery, at mid-term follow-up, the placement of an adjustable sub-urethral sling was associated with an improvement or cure of UI symptoms in 2/3 of cases.
Magnetically Controlled Endo-Urethral Artificial Urinary Sphincter
Mazzocchi and colleagues (2016) stated that UI is a widespread dysfunction that affects more than 300 million people worldwide. At present, no technological solutions are able to restore continence in a minimally invasive and effective way. These researchers described the design, fabrication, and testing of a novel artificial endo-urethral urinary sphincter that attempts to fully restore continence. The device can be inserted/retracted in a minimally invasive fashion without hospital admission, does not alter the body scheme and can be applied to both women and men. The device core is a uni-directional polymeric valve and a magnetically activated system, which is able to modulate its opening pressure. Bench tests and ex-vivo tests on a human cadaver demonstrated that the device was able to fully restore continence and allowed urination when desired. The authors concluded that the proposed system showed a high potential as a technological solution that may restore a normal daily life in patients affected by UI. These preliminary findings need to be validated by well-designed studies.
Transcutaneous Electrical Nerve Stimulation (TENS) in the Treatment of Overactive Bladder
Sharma and colleagues (2016) stated that OAB accounts for 40 to 70% of cases of incontinence. The etiology is unknown, though detrusor instability is found in urodynamic evaluation of almost all cases. Detrusor instability or hyperreflexia can be inhibited by direct inhibition of impulses in the pre-ganglionic afferent neuron or by inhibition of bladder pre-ganglionic neurons of the efferent limb of the micturition reflex. Transcutaneous electrical nerve stimulation (TENS) is based on the gate control theory of abolishing the local micturition reflex arc. In a prospective experimental study, these researchers evaluated the safety and effectiveness of TENS in idiopathic OAB. They evaluated the effectiveness of TENS versus placebo in reducing OAB symptoms (n1 = 20, n2 = 20); 10 treatment sessions (5 sessions/week) of 30 minutes were conducted. There was a significant improvement in Overactive Bladder Symptom Scores (OABSS) in the TENS group, and 2 patients were completely dry following TENS therapy. The authors concluded that in elderly women with OAB, where other co-medications had their own anti-cholinergic side effects and impairment of cognition is a concern, TENS can be a useful intervention. The authors also noted that future advancements will likely emphasize the exact placement site of electrodes with less collateral stimulation. The main drawbacks of this study were: (i) small sample size (n = 20) for the TENS-treated group; (ii) all patients were uniformly treated with alternate high- and low-frequency TENS with burst therapy intermittently to prevent the development of tolerance; high intensity was used to achieve maximum effect; and (iii) the ideal stimulation protocol needs to be worked out.
In a randomized, double-blind, placebo-controlled study, Borch and associates (2017) evaluated the immediate effect on natural fill urodynamic parameters and bladder function during TENS in children with OAB and daytime UI (DUI). A total of 24 children with severe OAB and DUI (mean age of 8.5 ± 1.2 years) underwent 48-hour natural fill urodynamics. After 24 hours of baseline investigation, the children were randomized to either active continuous TENS (n = 12) or placebo TENS (n = 12) over the sacral S2-S3 outflow. The urodynamic recordings were analyzed manually for 3 different bladder contraction patterns resulting in a void. The number of bladder contractions not leading to a void was also calculated. Maximum voided volume (MVV) and average voided volume (AVV) were identified for both the baseline and the intervention day. It was found that TENS had no immediate objective effect on bladder capacity. The difference (before minus after treatment) in MVV/EBC in the active TENS group was 0.03 ± 0.23 versus the placebo TENS group at -0.01 ± 0.10 (p = 0.61). Furthermore, there was no significant difference in the proportion of different bladder contraction types between the two groups; TENS did not significantly influence the number of bladder contractions not leading to a void. Results were presented as mean ± SD. The authors concluded that there was no immediate objective effect of TENS on bladder activity assessed by natural fill urodynamics in children with OAB and DUI.
Transperineal Implantation of Permanent Adjustable Balloon Continence Device
There is insufficient evidence to support the use of extra-urethral (non-circumferential) retropubic adjustable compression devices (ProACT Therapy System) for the treatment of UI. The ProACT Therapy System (Uromedica, Inc.), an adjustable continence therapy, is a minimally invasive urological device designed to treat persons with SUI. A Horizon Scanning Report of the ProACT by the Australian Safety and Efficacy Register of New Interventional Procedures - Surgical (ASERNIPS, 2006) raised questions about the safety of the device. The report concluded that the currently available literature on the ProACT system suggested that the device is safe for implantation. However, as the studies presented suggest, there are recurring safety issues with the device, namely post-operative complications such as the migration of the device and erosion of the urethra or the bladder. Although these complications were able to be corrected through removal and later re-implantation of the device in most cases, this presents an added risk to the patient as a result of the re-implantation procedure. Intra-operatively, implantation of the device is not reported as overly difficult, and successful implantation may increase as surgeons familiarize themselves with the procedure. Further studies investigating the long-term (more than 2 years) effects of the ProACT Therapy System are needed to ascertain any long-term advantage of the ProACT Therapy System over other treatment options. Furthermore, randomized controlled trials or comparative studies are needed to compare differences in rates of complications between the ProACT Therapy System and other treatment options. The National Institute for Health and Clinical Excellence (2006) has concluded that current evidence on the safety and efficacy of insertion of extra-urethral (non-circumferential) retropubic adjustable compression devices for SUI does not appear adequate for this procedure to be used without special arrangements for consent and for audit and research.
Aboseif et al. (2009) examined the safety, effectiveness, adjustability, and technical feasibility of the adjustable continence therapy device (Uromedica, Plymouth, MN) for the treatment of recurrent female SUI. Female patients with recurrent SUI were enrolled in the study, and a defined set of exclusionary criteria were followed. Baseline and regular follow-up tests to determine eligibility and to measure subjective and objective improvement were performed. A trocar was passed fluoroscopically and with digital vaginal guidance to the urethro-vesical junction through small incisions between the labia majora and minora. The adjustable continence therapy device was delivered, and the balloons were filled with isotonic contrast. The injection ports for balloon inflation were placed in a subcutaneous pocket in each labia majora. Device adjustments were performed percutaneously in the clinic post-operatively. An approved investigational device exemption FDA protocol was followed to record all adverse events. A total of 162 subjects underwent implantation, with 1 year of data available on 140. Mean Stamey score improved by 1 grade or more in 76.4% (107 of 140) of subjects. Improvement in the mean incontinence quality of life questionnaire score was noted at 36.5 to 70.7 (p < 0.001). Reductions in mean Urogenital Distress Inventory (60.3 to 33.4) and Incontinence Impact Questionnaire (54.4 to 23.4) scores also occurred (p < 0.001). Mean provocative pad weight decreased from 49.6 to 11.2 gm (p < 0.001). Of the patients, 52% (67 of 130) were dry at 1 year (less than 2 gm on provocative pad weight testing), and 80% (102 of 126) were improved (greater than 50% reduction on provocative pad weight testing). Complications occurred in 24.4% (38 of 156) of patients. Explantation was required in 18.3% (28 of 153) of the patients during 1 year. In terms of the complications, 96.0% were considered to be mild or moderate. The authors concluded that the Uromedica adjustable continence therapy device is an effective, simple, safe, and minimally invasive treatment for recurrent female SUI. It can be easily adjusted percutaneously to enhance efficacy, and complications are usually easily manageable. Explantation does not preclude later repeat implantation. Moreover, the authors stated that additional studies are needed to determine the long-term durability of the device.
In an editorial that accompanied the aforementioned study, Gilling (2009) stated that the results appear superior to those of bulking agents, although comparison of these heterogeneous groups is difficult.
Kocjancic et al. (2010) evaluated the implantation procedure and assessed patient outcomes of adjustable continence therapy for severe intrinsic sphincter deficiency and recurrent female SUI. The adjustable continence device consists of 2 silicone balloons on either side of the proximal urethra under the bladder neck, each attached to a titanium port buried in the labia to allow post-operative titration. Urodynamic assessment was done in 57 female patients in whom previous pelvic surgery had failed. Pad use and an incontinence quality of life questionnaire were evaluated before ACT implantation, post-operatively at 1, 3, 6, and 12 months, and annually thereafter. Patients recorded their overall impression and percent of improvement post-operatively based on the Patient Global Impression Index and a visual analog scale. Mean follow-up was 72 months (range of 12 to 84). At 6-year follow-up in 29 patients, mean pad use improved from 5.6 daily at baseline to 0.41, and intrinsic sphincter deficiency improved from 27.2 to 78.6 (p < 0.001). As measured on the visual analog scale, 68% of patients considered themselves dry. On the Patient Global Impression Index questionnaire, 64% were very much improved, 23% were much improved, and 13% were only minimally improved or unchanged. No patients considered themselves worse after the procedure. Complications necessitating device removal developed in 21.1% of patients. The authors concluded that the relative ease of insertion and the ability to tailor this therapy to individual needs makes this an attractive option for the challenging treatment of recurrent SUI due to intrinsic sphincter deficiency. Furthermore, they noted that these findings are encouraging, especially in terms of patient subjective outcomes, but their study was limited by the number of patients treated, the modification in procedural technique during the study, and the lack of more objective data. More studies are needed to establish the actual ACT mechanism of action in previously failed surgical cases and to more closely monitor objective outcomes in light of procedural and post-operative management.
Dynamometry for Quantification of Pelvic For Muscle Strength
Deegan and colleagues (2018) stated that there remains no gold standard for quantification of voluntary pelvic floor muscle (PFM) strength, despite international guidelines that recommend PFM assessment in females with UI. In this study, methods currently reported for quantification of skeletal muscle strength across disciplines were systematically reviewed and their relevance for clinical and academic use related to the pelvic floor were described. These investigators performed a systematic review via Medline, PubMed, CINHAL, and the Cochrane database using key terms for pelvic floor anatomy and function were cross-referenced with skeletal muscle strength quantification from 1946 to 2016. Full text peer-reviewed articles in English having female subjects with UI were identified. Each study was analyzed for use of controls, type of methodology as direct or indirect measures, benefits, and limitations of the technique. A total of 1,586 articles were identified of which 50 met the inclusion criteria; 9 methodologies of determining PFM strength were described including: digital palpation, perineometer, dynamometry, electromyography (EMG), vaginal cones, ultrasonography, magnetic resonance imaging (MRI), urine stream interruption test, and the Colpexin pull test; 32% lacked a control group. The authors concluded that technical refinements in both direct and indirect instrumentation for PFM strength measurement are allowing for sensitivity. However, the most common methods of quantification remain digital palpation and perineometry; techniques that pose limitations and yield subjective or indirect measures of muscular strength. Moreover , they stated that dynamometry has potential as an accurate and sensitive tool, but is limited by inability to assess PFM strength during dynamic movements.
The Leva Pelvic Floor Trainer
The Leva pelvic floor trainer is intended for the purpose of rehabilitation and training of weak pelvic floor muscles for the treatment of stress, mixed, and mild to moderate urge incontinence in women. This device interacts with the user via smartphone technology. There is a lack of evidence that the use of this device provides better outcomes than conventional Kegel exercises.
Oliveira and colleagues (2017) noted that strengthening exercises for pelvic floor muscles (PFM) are considered the first approach in the treatment of SUI. Nevertheless, there is no evidence about training parameters. These researchers identified the protocol and/or most effective training parameters in the treatment of female SUI. A literature search was conducted in the PubMed, Cochrane Library, PEDro, Web of Science, and Lilacs databases, with publishing dates ranging from January 1992 to March 2014. The articles included consisted of English-speaking experimental studies in which strengthening exercises for PFM were compared with placebo treatment (usual or untreated). The sample had a diagnosis of SUI, and their age ranged between 18 and 65 years. The assessment of methodological quality was performed based on the PEDro scale. A total of 7 high methodological quality articles were included in this review. The sample consisted of 331 women, with a mean age of 44.4 ± 5.51 years, an average duration of urinary loss of 64 ± 5.66 months, and severity of SUI ranging from mild to severe. Strengthening exercise programs included different training parameters concerning the PFM. Some studies applied abdominal training and adjuvant techniques. Urine leakage cure rates varied from 28.6% to 80%, while the strength increase of PFM varied from 15.6% to 161.7%. The authors concluded that the most effective training protocol consists of strengthening exercises for PFM by digital palpation combined with biofeedback monitoring and vaginal cones, including 12-week training parameters and 10 repetitions per series in different positions compared with strengthening exercises for PFM alone or a lack of treatment.
In a randomized controlled trial (RCT), Weinstein et al. (2022) examined if pelvic floor muscle training (PFMT) using a motion-based digital intra-vaginal device is more effective than home PFMT for the treatment of stress urinary incontinence (SUI) or stress-predominant mixed UI (MUI). In a remote, virtually executed 8-week prospective superiority study, women with SUI or stress-predominant MUI were randomized to PFMT using a motion-based digital therapeutic device or a home training program using written and narrated instructions. Primary outcomes were change in UDI-6 (Urogenital Distress Inventory, Short Form) score and SUI episodes on a 3-day bladder diary. A sample size of 139 per group (n = 278) was planned to meet the power analysis requirements for the UDI-6 score (n = 278) and the bladder diary (n = 78). Pre-specified secondary outcomes included quality of life surveys and adherence reporting. From September 2020 to March 2021, a total of 5,353 participants were screened, and 363 were randomized: 182 in the intervention and 181 in the control group. There were no baseline clinicodemographic differences between groups. The mean change in UDI-6 score was significantly greater for the intervention group compared with the control group (18.8 versus 14.7, p = 0.01). The median (inter-quartile range [IQR]) number of SUI episodes on the 3-day bladder diary was significantly reduced from 5 (3 to 8) and 5 (3 to 8) episodes to 1 (0 to 3) and 2 (1 to 4) (p = 0.005) in the intervention group compared with the control group, respectively. A significantly greater number of participants in the intervention group than in the control group reported they were "much improved" or "very much improved" on the PGI-I (Patient Global Impression of Improvement) (63/143 [44.1%] versus 45/156 [28.8%], OR of 1.94, 95% CI: 1.21 to 3.15). There were no device-related severe adverse events (AEs). The authors concluded that in this all-remote, virtually conducted study, PFMT guided by a motion-based digital therapeutic device resulted in significantly improved UI symptoms and reduction of UI episodes compared with a home training program.
The authors stated that a drawback of this trial was the inability to carry out a physical examination before enrollment. For example, pelvic organ prolapse beyond the introitus was an exclusion criterion, and subjects were asked about “seeing or feeling a bulge,” a question that has been used in other epidemiologic studies. Baseline pelvic floor muscle strength assessment may have added value to a study of first-line UI treatment, although research and expert consensus supported digital health in the remote context, including initiation of PFMT in the absence of a physical examination. Moreover, these researchers stated that longer-term follow-up is underway to better understand the durability of the treatment regimen and examine the need for maintenance exercises to sustain the benefits of therapy.
Weinstein et al. (2023) examined the long-term effectiveness of an 8-week regimen of PFMT guided by a motion-based digital therapeutic device compared with a standard home program in the treatment of SUI and stress-predominant MUI. The primary virtual trial was carried out from October 2020 to March 2021; a total of 363 women with SUI or stress-predominant MUI were randomized to complete PFMT using the device (intervention group) or a standard home pelvic floor muscle training program (control group) for 8 weeks. Primary outcomes included change in UDI-6 score and SUI episodes on a 3-day bladder diary. The PGI-I was also assessed, with "much better" and "very much better" responses considered as improvement. In this planned secondary analysis, symptom and adherence data were collected in follow-up at 6 and 12 months. A modified intention-to-treat (ITT) analysis was carried out using Student's t-tests and χ² tests as appropriate. Of 299 subjects analyzed at 8 weeks, 286 (95.7%) returned 6- and 12-month data (151 in the control group, 135 in the intervention group). Mean age was 51.9 ± 12.8 years, and mean BMI was 31.8 ± 7.4; 84.6% of subjects were parous, and 54.9% were post-menopausal. Mean change in UDI-6 score from baseline to 6 and 12 months was significantly greater in the intervention group than in the control group (20.2 ± 20.9 versus 14.8 ± 19.5, p = 0.03 and 22.7 ± 23.3 versus 15.9 ± 20.3, p = 0.01, respectively). Subjects in the intervention group had more than twice the odds of reporting improvement on the PGI-I compared with subjects in the control group (OR 2.45, 95% CI: 1.49 to 4.00). The authors concluded that the use of this technology may facilitate remote access to PFMT for women with UI and represents an effective modality for scaling conservative first-line care above PFMT home programs. For women choosing first-line care at home for SUI or MUI, a motion-based digital therapeutic device may be considered to optimize durable treatment results.
The authors concluded that drawbacks of this trial included the lack of physical examination and other objective measures of pelvic floor muscle performance at baseline and follow-up. Furthermore, bladder diaries were not collected at 6 or 12 months to enable comparison of the number of UI episodes reported during the active study period. In addition, although these investigators were able to collect information regarding continued use for subjects in the intervention group due to reporting from the device, they were unable to collect parallel information for subjects in the control group. Although this limited their ability to understand the presence or absence of continued PFMT in the control group, it was inherent in the design of the control group and typical for the use of home PFMT.
In a retrospective cohort study, Keyser et al. (2023) examined the effectiveness of a prescription digital therapeutic (pDTx) in reducing UI symptoms in real-world users. This trial examined data from users of a pDTx designed to guide PFMT between July 1, 2020, and December 31, 2021. The primary outcome was UI symptom change as reported via in-app UDI-6. Included subjects were female, 18 years of age or older, with a diagnosis of SUI, urgency UI, or MUI who completed the UDI-6 at baseline and 8 weeks. Demographic, symptom, and adherence data were summarized. Paired t-tests and Wilcoxon signed rank tests were used to analyze change in outcomes from baseline to 8 weeks across adherence and UI diagnosis groups. Of 532 women with UI, 265 (50%) met criteria and were included in the analysis. Mean age was 51.2 ± 11.5 years (range of 22 to 84, n = 265). Mean BMI was 27.3 ± 6.2 kg/m² (range of 15.2 to 46.9, n = 147). Most subjects had SUI (59%), followed by MUI (22%), urgency UI/OAB (11%), and unspecified UI (8%). UDI-6 scores improved by 13.90 ± 15.53 (p ≤ 0.001); 62% met or exceeded the minimum clinically important difference (MCID). Device-reported PFMT adherence was 72% at 4 weeks and 66% at 8 weeks (100% = 14 uses/week). Subjects in each diagnosis category reported significant improvement on UDI-6 score from baseline to 8 weeks. No association between UDI-6 score improvement and adherence category, age, BMI, or UI subtype was identified. The authors concluded that the findings of this study showed the effectiveness of a pDTx in reducing UI symptoms among this cohort of users in a real-world setting. Users with stress, mixed, and urgency UI achieved statistically and clinically significant symptom improvement over an 8-week period. These researchers stated that enhanced data collection of relevant demographic and clinical information will further add to the value and applicability of the data. They stated that these findings may inform additional research and development, including efforts to improve in-app data collection and promote adherence. These investigators stated that given the opportunity of pDTx, further investigation designed to present larger patient cohorts is planned, including the application of machine learning to expanded data sets. Clinically validated pDTx designed to treat UI in women may help to scale treatment and management of this significant, yet undertreated health condition.
Weinstein et al. (2024) noted that there are sparse data regarding the long-term effectiveness of PFMT for the treatment of UI. These researchers examined the impact of an 8-week PFMT program guided by a motion-based intra-vaginal device versus a standard home program over 24 months. Between October 2020 and March 2021, a total of 363 women with stress or mixed UI were randomized and completed an 8-week PFMT program using a motion-based intra-vaginal device (intervention group) or a home program following written/video instructions (control group). Participants were not asked to continue training after the 8-week program. At 18 and 24 months’ follow-up, the UDI-6 and PGI-I were collected. In the original trial, a total of 139 subjects in each arm were needed to detect a 0.3 effect size (alpha = 0.05, power 0.8, 1-tailed t-test) in the difference in UDI-6 scores. A total of 231 subjects returned 24-month data. Mean age at 24 months was 51.7 ± 14.5 years, and mean BMI was 31.8 ± 7.4 kg/m². Mean change in UDI-6 scores from baseline to 24 months was greater in the intervention group than the control group (−21.1 ± 24.5 versus −14.8 ± 19.4, p = 0.04). Reported improvement using PGI-I was greater in the intervention group than in the control group at 24 months (35% versus 22%, p = 0.03, OR 1.95 [95% CI: 1.08 to 3.57]). The authors concluded that PFMT guided by a motion-based prescription intra-vaginal device yielded durable and significantly greater UI symptom improvement than a standard home program, even in the absence of continued therapy.
The authors stated that drawbacks of this study included the lack of bladder diaries at these time points, and the limitations inherent to a remotely conducted study, including the absence of a physical examination. These researchers noted that although a more robust, in-person follow-up containing these additional data points may be ideal, ease of access to remotely obtained surveys may have resulted in a larger percentage of participants who engaged in follow-up. They stated that the balance between the ease of access for research participants using remote or app-based data collection tools and the value of in-person evaluation is an ongoing discussion among researchers.
Vaginal Laser Therapy
Pergialiotis and co-workers (2017) presented available evidence related to vaginal laser therapy as a treatment option for SUI. These investigators searched the Medline (1966 to 2017), Scopus (2004 to 2017), ClinicalTrials.gov (2008 to 2017), and Cochrane Central Register of Controlled Trials (CENTRAL) (1999 to 2017) databases for relevant studies in this field. They included all observational studies (prospective and retrospective, randomized and non-randomized) that reported outcomes on vaginal laser therapy as a therapeutic option for SUI. A total of 13 studies were included that recruited 818 patients who underwent laser therapy for SUI. The methodological quality of most included studies was low, as they were either individual case-control studies, case series, or poor-quality cohorts (Oxford Level of Evidence 3b and 4). According to the existing evidence, laser therapy may be a useful, minimally invasive approach for treating SUI. However, the methodological limitations of included studies rendered them prone to significant bias, limiting their scientific integrity. The authors concluded that as the demand for minimally invasive approaches for treating SUI increases, it is expected that more patients will seek alternative treatments over current standards (mid-urethral slings). They stated that given the limitations of the existing studies, it appeared that conducting future trials is needed to elucidate this field.
Alsulihem and Corcos (2021) examined the available literature to evaluate the safety, efficacy, and outcomes of lasers in the treatment of female SUI and OAB. A PubMed search was performed up to May 2020, including observational and investigational human studies that documented the effects of laser treatment in SUI and OAB. A total of 27 studies, recording subjective or objective measures in SUI or OAB, were included. Lasers used included Er:YAG and Fractional CO2 lasers. The overall quality of studies was poor, and 23 out of 27 studies were case-series studies (Level of Evidence [LOE] = 4). The Er:YAG laser showed a modest reduction in mild SUI cases, with benefits lasting a maximum of 13 to 16 months. The Er:YAG laser for OAB showed conflicting results, with a trend to improve OAB symptoms for up to 12 months. The Fractional CO2 laser showed an improvement in mild SUI in a few studies; however, no long-term data are available. For OAB symptoms, studies showed minimal improvement that was examined in short-term studies. When reported, adverse events (AEs) were insignificant; however, they were not reported systematically. Several drawbacks have been noted in the current literature on vaginal lasers, including large variation in laser settings and protocols, short-term follow-up, lack of urodynamic evaluation, and appropriate objective measures. The authors concluded that based on the available literature, lasers cannot be recommended as a therapeutic option at this time. These researchers stated that future better-quality studies are needed to document the exact mechanism of action, longevity, safety, and its eventual place in the current treatment algorithms of SUI and OAB.
Vibratory Perineal Stimulation
Rodrigues and associates (2018) noted that PFM play an important part in the urinary continence mechanism. Changes in their structure and functionality may lead to a predisposition to pelvic floor dysfunction such as UI. Some techniques for conservative treatment of UI are already well documented. However, new approaches have been found that require scientific proof of their effectiveness, such as vibratory stimulation (VS). These researchers performed a systematic review of studies that investigated the use of perineal VS (PVS) for the treatment of SUI. This study followed the recommendations of the Cochrane Collaboration for systematic reviews. Studies that used PVS for the treatment of female UI were eligible. A total of 56 studies were found, of which ten were duplicates and were excluded. Analysis of the titles and abstracts led to the exclusion of 30 studies, leaving 16 for detailed analysis. Of these, only 3 were included as they fulfilled all the eligibility criteria previously established for the present study. In spite of the heterogeneity of the protocols, all the studies had the goal of assessing the effects of vibration on the PFM, and the stimulation was found to be effective in reducing urinary leakage, improving muscle strength and consequently the patients' QOL. The authors concluded that because of the heterogeneity and the small number of studies, it is not possible to draw a conclusion as to the effectiveness of PVS for the treatment of SUI, and further studies are needed to provide scientific support for its use.
Stem Cell Therapy
Goldman et al. (2012) reviewed the current state of research in the use of stem cells (SCs) for SUI and assessed the likelihood of this becoming a relevant treatment option. The peer-reviewed literature consisting of relevant clinical and animal studies on the topic of SUI was surveyed and reviewed. Animal studies have demonstrated the potential utility of SCs in promoting functional recovery of the urethra after simulated childbirth injury. Research in animals suggests similar urethral recovery after injection of bone marrow-derived mesenchymal SC secretions as after injection of the SCs themselves. Therefore, whether the improvements result from the injection of the SCs themselves or from their secretion of specific proteins is unclear. Early clinical trials have demonstrated the feasibility and short-term safety of injecting muscle-derived SCs into the urethra to treat SUI. The authors concluded that larger and longer-term clinical trials are needed.
Burdzinska and associates (2018) noted that cell therapy constitutes an attractive alternative to treat SUI. Although promising results have been demonstrated in this field, the procedure requires further optimization. The most commonly proposed cell types for intra-urethral injections are muscle-derived cells (MDCs) and mesenchymal stem/stromal cells (MSCs). These investigators evaluated the effects of MDC-MSC co-transplantation into the urethra. Autologous transplantation of labeled MDCs, bone marrow MSCs, or co-transplantation of MDC-MSC were performed in aged multiparous female goats (n = 6 in each group). The mean number of cells injected per animal was 29.6 × 10^6 (± 4.3 × 10^6); phosphate-buffered saline (PBS)-injected animals constituted the control group (n = 5). Each animal underwent urethral pressure profile (UPP) measurements before and after the injection procedure. The maximal urethral closure pressure (MUCP) and functional area (FA) of UPPs were calculated. The urethras were collected at the 28th or the 84th day after transplantation. The marker fluorochrome (DID) was visualized and quantified using an in-vivo imaging system in whole explants. Myogenic differentiation of the graft was immunohistochemically evaluated. The grafted cells were identified in all urethras collected at day 28, regardless of injected cell type. At this time point, the strongest DID-derived signal (normalized to the number of injected cells) was noted in the co-transplanted group. There was a distinct decline in signal intensity between day 28 and day 84 in all types of transplantation. Both MSCs and MDCs contributed to striated muscle formation if transplanted directly to the external urethral sphincter. In the MSC group, those events were rare. If cells were injected into the submucosal region, they remained undifferentiated, usually packed in clearly distinguishable depots. The mean increase in MUCP after transplantation in comparison to the pre-transplantation state in the MDC, MSC, and MDC-MSC groups was 12.3% (± 11.2%, not significant [ns]), 8.2% (± 9.6%, ns), and 24.1% (± 3.1%, p = 0.02), respectively. The mean increase in FA after transplantation in the MDC, MSC, and MDC-MSC groups amounted to 17.8% (± 15.4%, ns), 15.2% (± 12.9%, ns), and 17.8% (± 2.5%, p = 0.04), respectively. The authors concluded that the findings of this study suggested that MDC-MSC co-transplantation provided a greater chance of improvement in urethral closure than transplantation of each population alone.
Fazeli and colleagues (2019) stated that in recent years, the administration of stem cells has been considered a new therapeutic option for UI. These researchers examined the efficacy of MSC transplantation in the treatment of UI. Combinations of the keywords “mesenchymal stem cells,” “MSCs,” “urinary incontinence,” “urethral sphincter,” and “involuntary urination” were searched in PubMed and Science Direct databases. Following the application of exclusion criteria to the 1,946 papers obtained and review, duplicate articles were removed, and 23 articles were considered further. The search was limited to animal model studies. The data obtained from the evaluation of different studies indicated that the injected MSCs play an important role in the neovascularization and the recovery of muscle cells in UI models through the paracrine process. The authors concluded that the available evidence suggested that further trials are needed to focus on the clinical phase of MSC therapy for patients affected by UI.
In a systematic review and meta-analysis, Mariotti et al. (2023) examined clinical trials on the use of autologous stem cell (SC) injection for the treatment of SUI. These investigators analyzed the effect in terms of UI improvement and continence recovery following SC treatment. They carried out a literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Entry into the analysis was restricted to data collected from prospective studies on humans, including female and male patients with SUI. These researchers performed a cumulative meta-analysis to examine the trend in the effect size across different groups at follow-up. Available data were compared in terms of event rate (ER) for the percentage of pad-free patients. A total of 12 studies were included in the analysis. The sample size of patients with SUI ranged from 5 to 123 cases, mainly female cases. Autologous muscle-derived SC (MDSC) was used in 9 studies, and adipocyte-derived SC (ADSC) in 3 trials. Considering a random effect model, the ER of continence recovery was 0.41 (95% CI: 0.29 to 0.54), with similar results between the ADSC (ER, 0.40; 95% CI: 0.12 to 0.69) and the MDSC group (ER 0.41; 95% CI: 0.27 to 0.55) [I² = 84.69%; Q 104.69 – p < 0.01] (Test of group differences; p = 0.96). The authors concluded that autologous MDSC or ADSC injection for the treatment of SUI showed to be a safe procedure, and a 41% mean rate of continence recovery was described. These researchers stated that a higher effort should be made to design better clinical trials, objectively examining either modifications inside the urethral sphincter or long-term functional results in terms of pad tests and UI questionnaires.
Artificial Urinary Sphincter (AMS 800)
The artificial urinary sphincter (AUS) has been shown to be effective for urinary incontinence (UI) due to intrinsic urethral sphincter deficiency (IUSD) and is a useful alternative when conservative interventions have failed. Implantation of an AUS is a commonly used surgical option for the management of male urethral deficiency, especially following prostatectomy. A clinical practice guideline for UI in adults by the Agency for Healthcare Policy and Research (1992) recommends that post-prostatectomy patients wait at least 6 to 12 months before AUS placement and try behavioral and pharmacologic therapies first. To be considered for AUS implantation, the patient must be motivated and have enough dexterity and ability to operate the device.
The AUS (AS 800, American Medical Systems, Minnetonka, MN) is an externally controlled urethral occlusion device. The transfer of fluid within the device is controlled by a pressure-regulating balloon placed extra-peritoneally in the patient's pelvis or abdominal cavity and a control pump placed in a subcutaneous pocket in the scrotum or labium. Squeezing the pump allows the fluid within the closed-loop system to be transferred from the cuff to the balloon. It takes a few minutes before the cuff re-inflates automatically to the preset level, thus allowing the urethra to remain open for voiding. The AS 800 has the option of primary deactivation. Primary deactivation is performed to limit the cuff compression during the early post-operative healing period, thus minimizing the risk of cuff erosion and infection. In males, the preferred site of cuff placement is around the bladder neck because erosion is less likely. When implantation of the device at the bladder neck is precluded by previous surgery, the cuff is placed around the bulbous urethra. In females, the AUS cuff is placed around the bladder neck. The device is implanted abdominally or vaginally.
Aetna's selection criteria for AUS are consistent with the AHCPR clinical practice guidelines for urinary incontinence in adults. Potential candidates for AUS implantation should be evaluated preoperatively to exclude severe detrusor instability as well as to ensure adequate bladder stability and compliance prior to implantation of the AUS. Appropriate candidates for implantation of an AUS must have adequate motivation and sufficient manual dexterity to operate the device. Post-prostatectomy patients should wait 6 to 12 months and attempt behavioral and pharmacologic therapies first. AUS may also be indicated in patients with epispadias-exstrophy in whom bladder neck reconstruction has failed; women in whom behavioral or pharmacologic therapies, or other surgical options have failed; and children with intractable UI who are refractory to pharmacologic therapies or unsuitable for other types of operation.
Peyronnet and associates (2019a) performed a systematic review of studies reporting the outcomes of AMS-800 AUS implantation in women with SUI resulting from intrinsic sphincter deficiency (ISD). A systematic literature search of the Medline and Embase databases was performed in June 2018 in accordance with the PRISMA statement; no time limit was used. Study selection and data extraction were performed by two independent reviewers. Of 886 records screened, 17 were included. All were retrospective or prospective non-comparative case series; one study reported on vaginal AUS implantation, 11 on open AUS implantation, two on laparoscopic AUS implantation, two on robot-assisted AUS implantation, and one compared open and robot-assisted implantations. The vast majority of patients had undergone at least one anti-incontinence surgical procedure prior to AUS implantation (69.1% to 100%). The intra-operative bladder neck injury rates ranged from 0% to 43.8%, and the intra-operative vaginal injury rates ranged from 0% to 25%. After mean follow-up periods ranging from 5 to 204 months, the complete continence rates ranged from 61.1% to 100%. The rates of explantation, erosion, and mechanical failure varied from 0% to 45.3%, 0% to 22.2%, and 0% to 44.1%, respectively. The authors concluded that AMS-800 AUS could provide excellent functional outcomes in women with SUI resulting from ISD but at the cost of relatively high morbidity. These researchers stated that high-level evidence studies are needed to help better define the role of AUS in the SUI armamentarium in women.
Reus and colleagues (2020) stated that the use of the AUS for non-neurogenic severe SUI in women due to sphincter deficiency is either not specifically registered and/or reimbursed in some countries worldwide, as opposed to severe SUI in men, in whom it is considered the gold standard. With the waning popularity of synthetic mid-urethral slings for the treatment of SUI, evidence-based assessment of AUS performance and safety is mandatory for patient counseling. These investigators carried out a systematic review of studies evaluating short- to long-term AUS performance and safety outcomes in non-neurogenic women with severe SUI. PubMed/Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from 1987 to 2018, without language restriction. Included studies had to report outcomes after AUS implantation in at least five women with non-neurogenic SUI, after a minimum follow-up of 6 months. A total of 12 articles collecting data from 886 patients were identified, with no study being randomized or prospective. The reported zero pad rates ranged from 42% to 86%, revision rates from 6% to 44%, and mechanical failure rates from 2% to 41%. Procedure serious adverse event (AE) rates ranged from 2% to 54%, and rates of serious adverse device effects such as explantation ranged from 2% to 27%. The authors concluded that the level of evidence supporting the use of an AUS for non-neurogenic SUI in women is very low; AUS outcome assessments necessitate well-designed randomized trials, in accordance with current evidence-based medicine requirements.
Peyronnet and co-workers (2019b) stated that widespread adoption of the AMS-800 AUS in female patients has been hampered by the surgical morbidity of its implantation through an open approach. These researchers described a standardized technique of robotic bladder neck AUS implantation in female patients and reported the peri-operative and functional outcomes obtained by multiple surgeons with this technique. They retrospectively reviewed the charts of all female patients who underwent robotic AUS implantation for UI due to ISD between March 2012 and March 2017 in five institutions. Most of the 10 surgeons involved were not highly experienced in female AUS implantation and/or in robotic surgery. The AUS was implanted at the bladder neck through a trans-peritoneal robotic approach. The finger placed by the assistant surgeon in the vagina is paramount to expose the vesico-vaginal space and guide the robotic surgeon throughout the bladder neck dissection. The primary endpoint was the incontinence categorized as complete continence (i.e., no pads used), improved incontinence, or unchanged incontinence. A total of 49 women underwent robotic AUS implantation. There were eight intra-operative complications (16.3%): five bladder neck injuries and three vaginal injuries; nine patients experienced post-operative complications (18.3%), but only two were Clavien greater than or equal to 3 (4.1%). After a median follow-up of 18.5 months, one explantation (vaginal erosion, 2.1%) and three revisions (one mechanical and two non-mechanical failures, 6.1%) were needed. At last follow-up, 40 patients were fully continent (81.6%), six had improved incontinence (12.2%), and three had unchanged incontinence (6.1%). The authors concluded that in this first multi-center series of robot-assisted AUS implantation, this technique appeared feasible, safe, and reproducible, with peri-operative and functional outcomes in the early learning curve not inferior to those reported in large series of open AUS implantation from tertiary referral centers. These investigators stated that the findings of this study suggested that this technique is feasible and reproducible by surgeons with various levels of surgical expertise; however, further data are needed to confirm the findings of the present report.
The authors stated that this study had several drawbacks. First, it had numerous biases inherent to its retrospective design. The lack of a control group did not allow a proper assessment of the value of robotic female AUS implantation compared with the open or laparoscopic approaches or other therapeutic options (e.g., pubovaginal sling, bulking agents, etc.). The relatively small sample size (n = 49) was another drawback of the present series. Lastly, opening of the bladder dome performed in challenging cases introduced significant, although isolated, heterogeneity in the technique used, but was part of a “patient-first” policy and had certainly contributed to the safe development of this new surgical technique. Opening of the bladder dome was felt less and less necessary with increasing experience.
Screening for Urinary Incontinence in Women
In a systematic review, Nelson and colleagues (2018) examined if screening for urinary incontinence (UI) in women not previously diagnosed would improve outcomes (symptoms, quality of life [QOL], and function) and assessed the accuracy of screening methods and potential harms of screening. English-language searches of Ovid Medline, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (January 1, 1996, to March 30, 2018); ClinicalTrials.gov (April 2018); and reference lists of studies and reviews were carried out. Randomized trials, cohort studies, systematic reviews of studies that enrolled non-pregnant women without previously diagnosed UI, and compared clinical outcomes and adverse effects between women who were and were not screened, and diagnostic accuracy studies that reported performance measures of screening tests were included. No studies evaluated the overall effectiveness or harms of screening. A total of 17 studies evaluated the diagnostic accuracy of 18 screening questionnaires against a clinical diagnosis or results of diagnostic tests. Of these, 14 poor-quality studies were based in referral clinics, enrolled only symptomatic women, or had other limitations; one good-quality and two fair-quality studies (evaluating four methods) enrolled women not recruited on the basis of symptoms. Areas under the receiver-operating characteristic curve for stress, urge, and any type of incontinence in these studies were 0.79, 0.88, and 0.88 for the Michigan Incontinence Symptom Index; 0.85, 0.83, and 0.87 for the Bladder Control Self-Assessment Questionnaire; and 0.68, 0.82, and 0.75 for the Overactive Bladder Awareness Tool. The Incontinence Screening Questionnaire had a sensitivity of 66% and specificity of 80% for any type of incontinence. The authors concluded that available evidence is insufficient on the overall effectiveness and harms of screening for UI in women, and limited evidence in general populations suggested fairly high accuracy for some screening methods. The main drawbacks of this review were that studies enrolled few participants, often from symptomatic referral populations; used various reference standards; and infrequently reported confidence intervals (CIs).
Despite the lack of studies determining the benefits and harms of UI screening, the Women's Preventive Services Initiative (WPSI) recommended that doctors screen women of all ages, including adolescents, for UI yearly by using a questionnaire. The WPSI recommended referring women with UI for further evaluation if it affects their activities and QOL. These recommendations were based on indirect evidence that UI is common, treatment may be effective, and the harms of screening are unlikely to be serious. The recommendations might change if studies directly evaluating the benefits and harms of screening for UI become available. There are no data to support that the correct frequency of screening is yearly (no authors listed, 2018).
Bariatric Surgery for the Treatment of Urinary Incontinence in Obese Women
Shimonov and colleagues (2017) examined the effect of bariatric surgery on female pelvic floor disorders (PFDs). A total of 80 consecutive obese women who underwent laparoscopic sleeve gastrectomy were prospectively enrolled. Four validated questionnaires (ICIQ-UI, BFLUTS-SF, PFDI-20, PISQ-12) were used to evaluate pelvic floor symptoms before and 6 months after surgery. Outcome results were analyzed according to the presence of pre-operative urinary incontinence (UI), defined as a positive answer to the question "How often do you leak urine?" on the ICIQ-UI questionnaire. A total of 77 women (aged 41.3 ± 11.5 years; parity 1.9 ± 1.6) completed all pre- and post-operative questionnaires. Mean body mass index (BMI) before and 6 months after surgery was 42 ± 4.7 and 33 ± 4.7, respectively. Pre-operatively, 29 (37.7%) women (mean age of 45.6 ± 11, mean BMI 42.3 ± 5.2) had UI, 17 (59%) of whom had stress urinary incontinence (SUI). Surgically induced weight loss was associated with statistically significant improvement in UI and filling symptoms, pelvic organ prolapse and colorectal-anal scores, and condition-specific sexual function and QOL parameters. Specifically, the total score of the ICIQ-UI questionnaire decreased from 9.28 ± 3.6 pre-operatively to 2.9 ± 3.8 post-operatively (p < 0.001), and the urinary score of the PFDI-20 questionnaire decreased from 31.4 ± 17.9 pre-operatively to 9.3 ± 12.3 post-operatively (p < 0.001). Furthermore, 15 (51.7%) women reported complete resolution of UI following weight loss. The authors concluded that surgically induced weight loss resulted in resolution of UI in up to 52% of pre-operatively incontinent women and subsequent improvement in other pelvic floor symptoms. Moreover, they stated that larger studies with longer follow-up are required to examine the possible impacts of bariatric surgery on various aspects of pelvic floor function.
In a meta-analysis, Lian and associates (2017) evaluated the effects of bariatric surgery on PFD in obese women. These researchers carried out a systematic search of PubMed, Cochrane Library, CNKI, and CBM databases up to October 2016, and studies reporting pre-operative and post-operative outcomes in obese women undergoing bariatric surgery were included. The Pelvic Floor Distress Inventory (PFDI-20), the Pelvic Floor Incontinence Questionnaire (PFIQ-7), the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, Female Sexual Function Index, and the International Consultation on Incontinence Questionnaire-Urinary Incontinence short form score were used for evaluating pelvic floor dysfunction after bariatric surgery. A total of 11 cohort studies were finally included. Pooled results revealed that bariatric surgery was associated with a significant improvement in PFD for obese women overall [PFDI-20: standard mean difference (SMD) = 0.89, 95% CI: 0.44 to 1.34, p < 0.001; PFIQ-7: SMD = 1.23, 95% CI: 0.17 to 2.29, p = 0.023]. In the subscale analysis, there was significant improvement in UI and pelvic organ prolapse. However, no significant improvement was found in fecal incontinence and sexual function. The authors concluded that bariatric surgery is associated with significant improvement in UI and has a benefit on pelvic organ prolapse for obese women. However, there is no significant improvement in fecal incontinence and sexual function. These investigators stated that further multi-center, large-scale, and longer-term randomized controlled trials (RCTs) are needed to confirm these findings.
In another meta-analysis, Zhang and colleagues (2020) examined the effectiveness of bariatric surgery in obese women with UI. Searches of PubMed, the Cochrane Library, and Embase databases were performed using "weight loss surgery/bariatric surgery/gastric bypass surgery" and "incontinentia urinae / uracratia / urinary incontinence / uroclepsia" in the title/abstract before January 2018. Meta-analysis was conducted using Review Manager 5.3 (Cochrane Collaboration, Oxford, United Kingdom). The SMD and odds ratio (OR) were used to describe results of continuous variables and dichotomous variables, respectively. Pooled data showed that bariatric surgery reduced the incidence of UI in obese women at the follow-up of 6 months (OR, 3.27; 95% CI: 2.55 to 4.21; p < 0.00001) and 12 months (OR, 4.04; 95% CI: 2.62 to 6.22; p < 0.00001) and significantly reduced the BMI at 6 months (SMD, 1.86; 95% CI: 1.19 to 2.53; p < 0.00001) and 12 months (SMD, 2.04; 95% CI: 1.44 to 2.64; p < 0.00001). In addition, bariatric surgery could also significantly increase QOL (SMD, 0.53; 95% CI: 0.27 to 0.80; p < 0.00001) and improve the function of pelvic floor disorders (SMD, 0.55; 95% CI: 0.38 to 0.72; p < 0.00001) based on QOL questionnaires and the Pelvic Floor Distress Inventory 20, respectively. The authors concluded that this meta-analysis demonstrated that bariatric surgery is an effective choice for obese women with UI; however, more RCTs are needed to confirm these findings.
Furthermore, UpToDate reviews on “Treatment of urinary incontinence in women” (Lukacz, 2018a) and “Treatment of urgency incontinence/overactive bladder in women” (Lukacz, 2018b) do not mention bariatric surgery as a therapeutic option.
FemiLift (CO2 Laser) for the Treatment of Urinary Incontinence in Women
In an observational study, Pitsouni et al. (2016) examined the effect of micro-ablative fractional carbon dioxide (CO2) laser therapy on vaginal pathophysiology and the symptoms of the genitourinary syndrome of menopause (GSM). Post-menopausal women with moderate-to-severe symptoms of GSM underwent three sessions of CO2 laser therapy at monthly intervals. Participants were evaluated at baseline and 4 weeks after the last treatment. The primary outcomes were Vaginal Maturation Value (VMV) and Vaginal Health Index Score (VHIS). Secondary outcomes included symptoms of GSM, Female Sexual Function Index (FSFI), International Consultation on Incontinence Questionnaire of Female Urinary Tract Symptoms (ICIQ-FLUTS), Urinary Incontinence Short Form (ICIQ-UI SF), Urogenital Distress Inventory (UDI-6), and King's Health Questionnaire (KHQ). A total of 53 post-menopausal women completed this study; VMV, VHIS, and FSFI increased significantly. Dyspareunia, dryness, burning, itching, dysuria, frequency, urgency, urgency incontinence, stress incontinence, and scores on the ICIQ-FLUTS, ICIQ-UI SF, UDI-6, and KHQ decreased significantly. Factors predicting which women the CO2 laser therapy was more effective for were not identified. The authors concluded that the findings of this study suggested that intravaginal CO2 laser therapy for post-menopausal women with clinical signs and symptoms of GSM may be effective in improving both vaginal pathophysiology and reported symptoms. This was an observational study, with a relatively small (n = 53) sample size and short-term follow-up (4 weeks). These preliminary findings need to be validated in well-designed studies.
Gonzalez et al. (2018) examined the long-term effect of thermo-ablative fractional CO2 laser (TACO2L) as an alternative treatment for early stages of stress urinary incontinence (SUI) in post-menopausal women with genitourinary syndrome of menopause. A total of 161 post-menopausal patients (age of 53.38 ± 5.1 years, range of 45 to 65 years) with a clinical diagnosis of mild SUI were prospectively enrolled in the study. Patients received one treatment with TACO2L every 30 to 45 days, each treatment comprising four sessions, followed in all patients by a yearly treatment session at 12, 24, and 36 months. SUI was evaluated using the International Continence Society 1-hour pad test and the ICIQ-UI SF before and after TACO2L treatment. TACO2L treatment was associated with a significant improvement in ICIQ-UI SF scores and 1-hour pad weight test at 12 months (both p < 0.001), 24 months (both p < 0.001), and 36 months (both p < 0.001). Improvements were maintained for up to 36 months without the need for any further intervention. The results were confirmed by significant histological changes related to trophic restoration of the vagina, responsible for extrinsic and intrinsic mechanisms involved in urinary continence. The authors concluded that these findings suggested that TACO2L was a safe and efficient novel treatment strategy in patients with mild SUI. These researchers stated that further investigation to confirm the long-term results presented here is still needed. They also noted that this was a prospective, non-randomized study of an observational nature with no control group. Since all patients enrolled were relatively young (45 to 65 years), the results of this particular study could not be translated into older populations.
Lin and associates (2018) noted that female pelvic floor disorders, including female SUI or sexual dysfunction, are notorious for affecting the quality of life (QOL) in women. It has been reported that laser therapy might result in collagen remodeling and improvement in tissue firmness. These investigators evaluated the short-term outcome of female pelvic floor disorders treated by laser therapy. Women with self-reported symptoms of female pelvic floor disorders (limited to SUI and sexual dysfunction) were included in the study. Participants were treated with the Er:YAG laser or the fractional micro-ablative CO2 laser. The therapeutic effect was focused on SUI symptoms and sexual dysfunction. There were 31 women who underwent laser treatment, including 21 patients treated with Erbium:YAG laser and 10 treated with CO2 laser. In the Erbium:YAG laser group, ICIQ-SF scores dropped from 8.25 ± 5.66 to 5.00 ± 3.99 (p = 0.007); and in the CO2 laser group, scores dropped from 11.11 ± 6.85 to 6.44 ± 4.25 (p = 0.035), contributing to the drop of ICIQ-SF scores from 9.14 ± 6.08 to 5.45 ± 4.05 for all enrolled patients (p = 0.001). However, objective measures using the pad test did not show a statistically significant difference between before and after treatment (from 3.20 ± 5.84 g to 1.54 ± 3.18 g, p = 0.224). Sexual dysfunction was improved in 13 patients (44.83%), but Female Sexual Function Index (FSFI) scores were not different before and after laser treatment (44.22 ± 23.36 versus 44.09 ± 24.51, p = 0.389). The authors concluded that laser therapy, either by Erbium:YAG laser or CO2 laser, appeared to be useful for female pelvic floor disorders, especially in improving SUI symptoms; however, the effectiveness needs further confirmation in large prospective and randomized studies. This was a small (n = 10 in the CO2 laser group), non-randomized study with short-term follow-up (2 months).
Furthermore, an UpToDate review on “Treatment of urinary incontinence in women” (Lukacz, 2019) states that “There is insufficient evidence to support the use of vaginal laser (CO2 or erbium) for the treatment of urinary incontinence in the setting of genitourinary syndrome of menopause.”
Hafidh et al. (2023) stated that CO2 laser therapy is an emerging treatment for women with SUI. In a systematic review and meta-analysis, these investigators examined the effectiveness of CO2 laser therapy for the management of SUI-related symptoms in women. A total of four databases were screened until January 2023. All effectiveness continuous endpoints were examined via subtraction of the post-treatment from pre-treatment values; data were summarized as mean difference (MD) with 95% CI using the random-effects model. A total of 15 studies with 700 patients were analyzed. CO2 laser therapy significantly decreased the 1-hour pad weights at 3 months (n = 5 studies, MD = -3.656 g, 95% CI: -5.198 to -2.113, p < 0.001), 6 months (n = 6 studies, MD = -6.583 g, 95% CI: -11.158 to -2.008, p = 0.005), and 12 months (n = 6 studies, MD = -3.726 g, 95% CI: -6.347 to -1.106, p = 0.005). Moreover, CO2 laser therapy significantly decreased the ICIQ-Urinary Incontinence Short Form Scores at 3 months (n = 10 studies, MD = -4.805, 95% CI: -5.985 to -3.626, p < 0.001), and 12 months (n = 6 studies, MD = -3.726, 95% CI: -6.347 to -1.106, p = 0.005). Furthermore, CO2 laser therapy significantly decreased the PFIQ scores at 6 months (n = 2 studies, MD = -11.268, 95% CI: -18.671 to -3.865, p = 0.002), and 12 months (n = 2 studies, MD = -10.624, 95% CI: -18.145 to -3.103, p = 0.006). In addition, CO2 laser therapy significantly decreased the UDI-6 scores at 3 months (n = 2 studies, MD = -21.997, 95% CI: -32.294 to -11.699, p < 0.001), but not at 6 months (n = 3 studies, MD = -3.034, 95% CI: -7.357 to 1.259, p = 0.169). Finally, CO2 laser therapy significantly increased the VHIS at 6 months (n = 2 studies, MD = 2.826, 95% CI: 0.013 to 5.638, p = 0.047), and 12 months (MD = 1.553, 95% CI: 0.173 to 2.934, p = 0.027). The authors concluded that CO2 laser therapy improved SUI-related symptoms in women. Moreover, these researchers stated that to obtain solid conclusions, well-designed studies (large-sized, randomized, double-blinded, controlled trials) with standardized settings, consistent therapeutic protocols, and long-term follow-up periods are needed. Furthermore, outcome evaluations should be carried out in a uniform manner to ensure the reliability of the results.
The authors stated that this study had several drawbacks. First, the small number of studies and corresponding sample size. Indeed, there was a reduced number of studies that have examined the safety and effectiveness of CO2 laser treatment (specifically for SUI) compared to those examining its application for genitourinary syndrome of menopause (GSM). In certain studies, urinary symptoms, including SUI, were considered as components of the broader symptom profile associated with GSM, and these researchers decided to exclude them to maintain a uniform and strict inclusion criterion. Additionally, some outcomes did not report the long-term effectiveness of the intervention. Second, these investigators also observed heterogeneity across several endpoints, which could have impacted the validity of the meta-analyzed results. Moreover, some studies were single-arm studies without randomization, which could have potentially subjected the results to selection bias. Third, the lack of uniformity of CO2 laser application. Fourth, some studies did not provide adequate information on the technique and related parameters. Fifth, the lack of retrospectively recording the research protocol in the International Prospective Register of Systematic Reviews (PROSPERO); thus, potential bias could not be certainly excluded.
Gene Testing for Stress Urinary Incontinence
In a systematic review, Isali and colleagues (2020) provided insight into the genetic pathogenesis of stress urinary incontinence (SUI) by gathering and synthesizing the available data from studies evaluating differential gene expression in SUI patients and identifying possible novel therapeutic targets and leads. A systematic literature search was conducted through September 2017 for the concepts of genetics and SUI. Gene networking connections and gene-set functional analyses of the identified genes as differentially expressed in SUI were performed using GeneMANIA software. Of 3,019 studies, four were included in the final analysis. A total of 13 genes were identified as being differentially expressed in SUI patients; 11 genes were over-expressed: skin-derived antileukoproteinase (SKALP/elafin), collagen type XVII alpha 1 chain (COL17A1), plakophilin 1 (PKP1), keratin 16 (KRT16), decorin (DCN), biglycan (BGN), protein bicaudal D homolog 2 (BICD2), growth factor receptor-bound protein 2 (GRB2), signal transducer and activator of transcription 3 (STAT3), apolipoprotein E (APOE), and Golgi SNAP receptor complex member 1 (GOSR1), while two genes were under-expressed: fibromodulin (FMOD) and glucocerebrosidase (GBA). GeneMANIA revealed that these genes are involved in intermediate filament cytoskeleton and extracellular matrix organization. The authors concluded that many genes are involved in the pathogenesis of SUI. Furthermore, whole-genome studies are needed to identify these genetic connections. These researchers stated that this study laid the groundwork for future research and the development of novel therapies and SUI biomarkers in clinical practice.
An UpToDate review on “Evaluation of women with urinary incontinence” (Lukacz, 2019) states that “The risk of urinary incontinence, particularly urgency incontinence, may be higher in patients with a family history. One study found that the risk of incontinence was increased for both daughters (relative risk [RR] 1.3, 95% CI 1.2-1.4) and sisters (RR 1.6, 95% CI 1.3-1.9) of women with incontinence. Twin studies attribute a 35% to 55% genetic contribution to urgency incontinence/overactive bladder but only 1.5% for stress incontinence.”
Furthermore, an UpToDate review on “Urinary incontinence in men” (Clemans, 2019) does not mention genetic testing as a management option.
The Adjustable Trans-Obturator Male System for the Treatment of Stress Urinary Incontinence
In a systematic review and meta-analysis, Esquinas and Angulo (2019) examined the effectiveness of the Adjustable Trans-Obturator Male System (ATOMS) device to treat male stress urinary incontinence (SUI). Two independent reviewers identified studies eligible for a systematic review and meta-analysis from various sources written in English, German, and Spanish, using the databases PubMed, Embase, and Web of Science. They excluded studies on female incontinence. These researchers employed the DerSimonian and Laird method for defining heterogeneity and calculating the grouped standardized mean difference (SMD). The primary objective of this review was the evaluation of clinical efficacy based on the achievement of dryness following device adjustment, defined as the use of no pad or one safety pad per day (PPD). The secondary objective focused on analyzing improvement of incontinence with the device. The magnitude of effect was calculated by analyzing the decrease in PPD and/or in the 24-hour pad test. The number and severity of complications according to the Clavien-Dindo classification were also reviewed. The pooled data of 1,393 patients from 20 studies (13 retrospective and 7 prospective) showed that treatment with ATOMS resulted in a mean 67% dryness rate and 90% improvement after adjustment. The mean total number of system fillings per patient was 2.4. The mean pad count and 24-hour pad test decrease were -4.14 PPD and -443 cc, respectively. There was significant heterogeneity in the sample analyzed, mainly based on variable baseline severity of incontinence, the proportion of patients treated with irradiation, and different generation devices. The proportion of irradiated patients affected the dryness rate (p = 0.0014), together with baseline severity of incontinence (p = 0.0035) and different generation devices used (p < 0.0001). The standardized mean follow-up was 20.9 months, with complications occurring in 16.4% (major complications 3.0%) and explantation in 5.75%. No randomized study has been developed so far to compare ATOMS to other devices for treating male SUI. The authors concluded that despite the evidence being exclusively based on descriptive studies and limited follow-up, ATOMS has proven to be a safe alternative to treat different degrees of male SUI following prostate surgery; better results were observed for patients with less than 6 PPD before implantation, non-irradiated patients, and the use of a 3rd-generation device with a silicone-covered pre-attached scrotal port. These researchers stated that ATOMS appeared to be a safe and effective procedure, with pooled data showing high objective effectiveness and a low rate of complications in the short- and medium-term. They noted that it would be of great interest to develop comparative prospective studies in the future among ATOMS and other devices, not only regarding effectiveness but also including patient-reported outcomes.
The authors stated that the main drawbacks of this systematic review and meta-analysis lay in the scant level of evidence provided by the design and nature of the non-controlled, and mainly retrospective, studies available, and in their relatively short follow-up. The variable nature and severity of SUI and the different proportion of patients receiving radiation likely explained the high heterogeneity observed. Combining the results of individual studies increased the total number of participants, and more participants imply more statistical power. However, combining studies with differences among participants could also reduce statistical power and make real effects more difficult to identify.
In a systematic review and meta-analysis, Angulo and colleagues (2019) examined the safety and efficacy of ATOMS compared to ProACT for male SUI according to literature findings; studies on female or neurogenic incontinence were excluded. Differences between ATOMS and ProACT in the primary objective: dryness status (no pad or 1 safety pad/day) after initial device adjustment, and in secondary objectives: improvement, satisfaction, complications, and device durability, were estimated using a random-effects model. Statistical heterogeneity among studies included in the meta-analysis was assessed using tau², Higgins’s I² statistics, and Cochran’s Q test. Combined data from 41 observational studies with 3,059 patients showed higher dryness (68% versus 55%; p = 0.01) and improvement (91% versus 80%; p = 0.007) rates for ATOMS than ProACT. The mean pad count (-4 versus -2.5 pads/day; p = 0.005) and pad-test decrease (-425.7 versus -211.4 cc; p < 0.0001) were also significantly lower. Satisfaction was higher for ATOMS (87% versus 56%; p = 0.002), and the explant rate was higher for ProACT (5% versus 24%; p < 0.0001). The complication rate for ProACT was also higher, but not statistically significant (17% versus 26%; p = 0.07). The mean follow-up was 25.7 months, lower for ATOMS than ProACT (20.8 months versus 30.6 months; p = 0.02). The rate of working devices favored ATOMS at 1 year (92% versus 76%; p < 0.0001), 2 years (85% versus 61%; p = 0.0008), and 3 years (81% versus 58%; p = 0.0001). Significant heterogeneity was evidenced due to variable incontinence severity at baseline, difficulties in common reporting of complications, different numbers of adjustments, time of follow-up, and the absence of randomized studies. The authors concluded that despite the limitations that studies available were exclusively descriptive and the follow-up was limited, literature findings confirmed that ATOMS was more effective, with higher patient satisfaction and better durability than ProACT to treat male SUI.
The authors stated that the main drawbacks of this meta-analysis included the short-term follow-up (mean of 25.7 months), especially in the ATOMS arm, and the very high heterogeneity observed between studies; this likely reflects a variable severity of sphincteric damage included and the absence of randomized controlled trials (RCTs). Furthermore, the criteria to report complications appeared variable between the studies analyzed. The drawbacks highlighted were in consonance with the publication bias identified according to Egger’s linear regression. It should also be noted that the ATOMS studies had shorter follow-up than the ProACT studies (20.8 months versus 30.6 months).
Furthermore, an UpToDate review on “Urinary incontinence in men” (Clemens, 2019) does not mention the Adjustable Trans-obturator Male System as a therapeutic option.
Magnetic Stimulation for Women with Stress Urinary Incontinence
In a meta-analysis of studies with short-term follow-up, Peng and colleagues (2019) examined the efficacy of magnetic stimulation (MS) in female patients with stress urinary incontinence (SUI) by investigating peer-reviewed randomized controlled trials (RCTs). PubMed, Embase, and the Cochrane Library were searched for any peer-reviewed original articles in English. Databases were searched up to July 2018. Included studies examined the effects of MS on SUI. The data were analyzed using Review Manager 5.3 software (Cochrane Collaboration, Oxford, UK). A total of four studies involving 232 patients were identified and included in the present meta-analysis. Compared with the sham stimulation, the MS group had statistically significantly fewer leaks per 3 days (mean difference [MD] = -1.42; 95% CI: -2.42 to -0.59; p = 0.007), less urine loss on the pad test (g/24 hours) (MD = -4.99; 95% CI: -8.46 to -1.53; p = 0.005), higher quality of life (QOL) scores (MD = 0.42; 95% CI: 0.02 to 0.82; p = 0.009), and lower International Consultation on Incontinence Questionnaire (ICIQ) scores (MD = -4.60; 95% CI: -5.02 to -4.19; p < 0.001). MS presented a higher cure or improvement rate, with a statistically significant improvement in Urogenital Distress Inventory (UDI) and Incontinence Impact Questionnaire Short Form (IIQ-SF) scores compared to sham stimulation. No MS-related adverse events (AEs) were reported in the study. The authors concluded that MS led to an improvement in SUI without any reported safety concerns and an improvement in patient QOL; however, the long-term outcome of this technique remains unclear and is the subject of ongoing research.
The authors stated that the drawbacks of this present study were: First, its small sample size and insufficient statistical power. Second, the stimulation parameters and duration of the studies were not consistent, which made these investigators doubt whether a meta-analysis could be performed. However, the results based on RCTs were excellent despite inconsistent variables. Third, when analyzing the data of the pad test, a high heterogeneity that was most likely caused by incomplete experimental design was recorded if these researchers added the study by Manganotti et al. (2007) to the analysis. Therefore, this study's data were finally excluded by performing sensitivity analysis. These researchers stated that further well-designed RCTs with long-term follow-up and a large sample size are needed.
Lukanovic et al. (2021) noted that urinary incontinence (UI) is becoming an increasingly common health problem, and its treatment can be conservative or surgical. In a systematic review, these researchers examined the effectiveness of MS in the treatment of UI. They compared results with findings from their clinical study—a prospective, non-randomized study conducted at the Ljubljana University Medical Center's Gynecology Division. It included 82 randomly selected female patients, irrespective of their UI type. The success rate of using MS in treating UI was based on standardized ICIQ-UI SF questionnaires. Subjects completed 10 therapy sessions on MS, and follow-up was carried out 3 months after the last therapy session. UI improved following treatment with MS. The ICIQ-UI SF score improved in patients regardless of the type of UI; however, the greatest decrease in post-treatment assessment ICIQ-UI SF scores was observed in subjects with SUI. The authors concluded that MS is a successful non-invasive conservative method for the treatment of patients with UI. Moreover, these researchers stated that future studies are needed, all of which should include a large sample size, a control group, an optimal research protocol, pre-treatment analyses, standardization, and longer follow-ups.
The authors stated that this review had several drawbacks. First, and perhaps most importantly, the sample was non-randomized. Although this non-probability sampling method was the most applicable and widely used method in clinical research, the sampling method did not guarantee equal chances for each subject in the target population, it was less representative of the target population, and it decreased the ability to draw completely impartial conclusions regarding the effectiveness of MS. Second, the power of this study was low, as was the power of most studies in this systematic review. An ideal study is one that has high power, which means that the study has a high chance of detecting a difference between groups if it exists, and consequently, if the study demonstrates no difference between groups, the researcher can be reasonably confident in concluding that none exists. According to the literature review, the ideal power for any study is considered to be 80%. For this study to achieve a significance level of 95% and a power of 80%, the sample size should equal 189; in this study, the sample size of 76 accounted for a power of 57%. This meant that this study had low power, and studies with lower power increase the likelihood that a statistically significant finding represents a false positive result. These investigators stated that future studies may address all of the above drawbacks and test the robustness of these findings in an extended environment. One drawback could also be that this study included only the ICIQ-UI SF as the tool for measuring the effectiveness of MS in the treatment of UI; however, this questionnaire was the only available validated questionnaire in Slovenian. These researchers were convinced that patient-reported outcomes were the most appropriate when describing treatment success or failure. As these investigators also concluded in the systematic review, they were aware that outcome measurements to generate comparable data should be standardized.
The Neocontrol™System
In a systematic review and meta-analysis, Ho and colleagues (2020) examined the effectiveness of extracorporeal magnetic stimulation for the treatment of stress urinary incontinence (SUI). Data sources included four electronic databases from inception to May 18, 2019. Two authors independently carried out the search, evaluated the methodological quality, and extracted data. The final studies included in the analysis were selected after reaching consensus with the third author. A total of 20 studies were included in the systematic review, and 12 of these were included in the meta-analysis. Quality assessment indicated that only 8 of 17 randomized controlled trials (RCTs) had a low risk of overall bias, whereas all controlled trials had a serious risk of bias. The weighted mean effect size of magnetic stimulation on quality of life (QOL), number of leakages, pad test outcomes, and number of incontinence events was 1.045 (95% CI: 0.409 to 1.681), -0.411 (95% CI: 0.178 to 0.643), -0.290 (95% CI: 0.025 to 0.556), and -0.747 (95% CI: -1.122 to -0.372), respectively. Subgroup analysis revealed a significant difference in the type of QOL measurement used. Sensitivity analyses revealed that a high degree of heterogeneity persisted even after omitting studies individually. The authors concluded that extracorporeal magnetic stimulation may be effective in treating urinary incontinence and improving QOL without major safety concerns; however, because of a high degree of heterogeneity among studies, inferences from the results must be made with caution. These investigators encouraged researchers to conduct further qualitative and quantitative studies to develop consistent content and dosage for the intervention.
In a systematic review, Stroje et al. (2023) examined the available evidence on the effectiveness of extracorporeal magnetic stimulation (ExMI) in the treatment of female patients with urinary incontinence (UI). These investigators carried out an analysis using the following electronic databases: Medline, PubMed, ScienceDirect, and the Cochrane Library (data published between 2008 and 2023). Searches of the aforementioned databases were performed in April 2023. Only RCTs in English studies were eligible for inclusion in this review and were evaluated with the Downs and Black checklist. A total of 11 studies met the inclusion criteria. Among these, 2 trials examined the use of ExMI and pelvic floor muscle training (PFMT); 3 studies compared active ExMI versus sham ExMI; and 4 studies examined only ExMI. Moreover, there was no control group in 2 of these studies. One study compared the effects of Kegel exercises with ExMI, while another study compared electro-stimulation with ExMI. The reviewed studies exhibited significant differences in interventions, populations, and outcome measures. The authors concluded that ExMI has shown promise as a treatment for female UI. These researchers stated that whether used alone or as a component of combination therapy, ExMI has the potential to enhance patients' QOL without significant safety concerns. Moreover, these researchers stated that more in-depth investigations are needed to examine the long-term effectiveness of this promising treatment for UI.
Moxibustion
Li and colleagues (2021) noted that urinary incontinence (UI) is a frequently identified complication among stroke survivors. Moxibustion is commonly used to treat post-stroke UI in Asian countries. In a systematic review and meta-analysis, these researchers examined the evidence of using moxibustion for post-stroke UI management. A total of 12 databases were searched to identify randomized controlled trials (RCTs) using moxibustion to improve post-stroke UI management; four Chinese journals were also manually screened for potentially eligible articles. A total of 10 studies with 719 subjects and one completed trial without published results were included. Compared with "routine methods of treatment and/or care," the meta-analyses revealed that moxibustion had superior effects in improving UI symptoms and alleviating the severity of UI. The authors concluded that this systematic review identified preliminary research evidence that moxibustion may be effective in managing the symptoms of post-stroke UI; these investigators stated that more rigorously designed, large-scale RCTs are needed to provide more robust evidence in this area.
Zhou et al. (2024) noted that stress urinary incontinence (SUI) significantly impacts women's health and imposes substantial mental and socio-economic burdens. These researchers examined the effectiveness of various treatments for women with SUI using network meta-analysis (NMA). They systematically searched databases up until June 30, 2022, to identify relevant RCTs focusing on SUI in women. Subsequently, the quality of the included studies was assessed, and NMA was carried out using STATA 14.0 software. A total of 31 RCTs involving 2,922 participants were included in the analysis. A total of 18 treatment plans were identified. The treatment plan consisting of moxibustion + pelvic floor muscle training (PFMT) + electromyographic biofeedback (EB) showed the most significant reduction in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF) scores. Due to a lack of consistency across studies, an NMA was not carried out for the outcomes of effectiveness and the 1-hour pad test. The authors concluded that the combined intervention of moxibustion + PFMT + EB appeared to be the most effective in reducing patients' reported symptoms and improving their quality of life (QOL). Moreover, these investigators stated that due to the drawbacks of the included studies, more high-quality, large sample-size RCTs are needed to reinforce the current evidence.
Cervico-Sacropexy or Vagino-Sacropexy for the Treatment of Urinary Incontinence and Apical Prolapse
Page et al. (2022) noted that several anatomic theories suggest that lax utero-sacral ligaments may result in apical prolapse and urinary incontinence (UI); thus, prolapse repair, such as cervico-sacropexy (CESA) or vagino-sacropexy (VASA), may resolve UI. Shortcomings in current therapeutic options endorse further exploration of the potential benefit of a surgical alternative. In a systematic review, these investigators examined the evidence on the safety and effectiveness of CESA and VASA as alternative surgical therapeutic options for urge and/or mixed UI and apical prolapse. The PRISMA 2020 statement was followed. Studies from inception to September 2021 were systematically reviewed and included. Data collection, risk of bias, and certainty of evidence were evaluated using the standard Cochrane methods. The primary outcome measures were improvements in prolapse and urinary symptoms. Secondary outcomes included surgical safety and re-intervention rates for complications and recurrence. The included studies showed a moderate-to-high risk of bias and low certainty of evidence. Owing to their heterogeneity, no meta-analysis was carried out. Cure rates for mixed and urge UI and apical prolapse were 47.5% (95% CI: 42.4 to 52.6), 73.8% (95% CI: 61.9 to 85.7), and 97% to 100%, respectively, at a mean follow-up of 9.7 ± 7.3 months. Additional incontinence surgery was performed in 38.9% (216/555) of women with initial UI, and concomitant or subsequent surgery for prolapse was performed in 4.4% (13/299). The authors concluded that CESA or VASA may remedy symptoms of urge and mixed UI and appeared to correct apical prolapse in the short term; moreover, the overall level of evidence was low. These researchers stated that further clinical trials, integrated into the IDEAL framework, targeting better-identified patient selection and using validated outcome measures, are needed to guide further research and implementation in practice.
Trans-Perineal Ultrasound for the Diagnosis of Stress Urinary Incontinence
In a case-control, single-center study, Keshavarz et al. (2021) examined the use of trans-perineal ultrasonography (TPUS) for the diagnosis of stress urinary incontinence (SUI). This trial involved married women who were referred to the gynecologic and ultrasound (US) wards with negative urinalysis and culture results. Patients with positive cough signs based on the urodynamic testing data were considered cases, whereas control women showed no cough symptoms and were recruited from the same ward. There was a significant difference (p < 0.001) in bladder neck descent (BND; mean ± SD, 10.89 ± 5.51 mm versus 7.08 ± 2.60 mm, respectively; p = 0.0001) and the retro-vesical (β) angle with the Valsalva maneuver (144.22° ± 19.63° versus 111.81° ± 24.47°; p < 0.001) between the case and control groups. Furthermore, the β angle without the Valsalva maneuver was higher in the case group (112.35° ± 23.10°) than in the control group (120.17° ± 25.16°; p = 0.001). There were no cases of urinary leak, urethral diverticulitis, bladder stone or mass, or cysto-urethrocele in the patients of either group. The results of multivariate logistic regression with a backward method showed that BND (OR, 1.24; 95% CI: 1.09 to 1.40) and the β angles with and without the Valsalva maneuver (OR, 1.1; 95% CI: 1.06 to 1.13; and OR, 1.04; 95% CI: 1.01 to 1.06) were predictors of SUI. A β angle higher than 127° with the Valsalva maneuver, with an area under the curve (AUC) of 0.89 (95% CI: 0.75 to 0.96), could very well predict the SUI response. This finding showed that TPUS could effectively distinguish between normal and non-normal responses, with 89% sensitivity and 79% specificity. The authors concluded that the β angle with the Valsalva maneuver could effectively predict the SUI response. Moreover, these researchers stated that since TPUS may also be an appropriate tool for post-surgical assessments of patients with SUI, more focus on the diagnostic accuracy of TPUS for recovery of SUI after surgery should be conducted in further studies.
The authors stated that this study had several drawbacks. First, it is recognized that findings on the Valsalva maneuver will vary with the quality of the maneuver. However, standardization of pressure would probably require invasive monitoring, as efforts at non-invasive standardization have been largely unsuccessful. Second, the SUI diagnoses and TPUS findings were not connected to the urodynamic findings, such as maximal urethral closure pressure and urodynamic stress incontinence. Moreover, US examinations carried out on different bladder volumes might yield different results. Third, the limited sample size prohibited stratification of subjects into several groups that incorporated certain variables, such as body mass index (BMI), parity, and type of delivery, as these variables may affect the threshold value of the main variables examined. Fourth, this study was a single-center study and only included Iranian women. These investigators stated that further studies with different methods in different age groups and parities are needed to validate these findings.
In a prospective, observational study, Turkoglu et al. (2022) examined the use of TPUS while diagnosing SUI by comparing the urethral angle (α), posterior urethra-vesical angle (β), and BND during rest and the Valsalva maneuver in continent women and women with SUI. This trial was carried out with 50 women with SUI and 50 continent women. TPUS was conducted at rest and during the Valsalva maneuver, and the Q-tip test was performed. During the Valsalva maneuver, both α and β angles were significantly higher in women with SUI (p < 0.001). The difference between Valsalva and rest measurements of α and β angles (Rα, Rβ) was also significantly higher in women with SUI (p < 0.001). The cut-off point determined for Rα in the diagnosis of SUI was 16° (80% sensitivity, 98% specificity). A statistically significant strong correlation was found between the Q-tip test angle and Rα value (p = 0.000; r = 0.890). Q-tip visual analog scale (VAS) pain scores were significantly higher than US VAS pain scores (p < 0.001). In relation to the BND comparison between the two groups, BND was significantly higher in the SUI group (p < 0.001). The cut-off point determined for BND in the diagnosis of SUI was > 11 mm (90% sensitivity, 98% specificity). The authors concluded that TPUS was a practical, reliable, non-invasive, and comfortable method for the evaluation of SUI. It has the advantage of dynamic evaluation during the Valsalva maneuver. Rotation angles and BND exhibited high sensitivity and specificity for the detection of SUI. Moreover, these researchers noted that the change in the α angle with Valsalva (Rα) could be used as an alternative to the Q-tip test.
The authors stated that this study had several drawbacks. First, there was a lack of urodynamic proof for SUI. SUI patients were all surgery candidates with observed SUI based on the cough test. These investigators were strict about not including patients with pelvic organ prolapse in either group. They also excluded complicated SUI patients who required urodynamic studies according to ACOG guidelines, such as those with prior pelvic surgery, urgency, post-void residual volume greater than 150 cc, and Q-tip test results of less than 30. Second, there was a lack of standardization of the Valsalva maneuver, which was the case in the majority of studies since measurement of intra-abdominal pressure is not easily done and can require rectal probes. Third, these researchers did not examine levator ani muscle (LAM) injury, which is better observed with three-dimensional (3D) US. LAM injury is important in the pathogenesis of bladder neck mobility. Fourth, the use of the vaginal probe instead of the convex probe was noted, as the majority of related literature used the latter. The authors chose to use the vaginal probe with a curved array tip since they observed the same anatomical structures in the same plane with a clearer view.
In a systematic review and meta-analysis, Chen et al. (2023) examined the diagnostic value of TPUS in patients with SUI using evidence-based methods. These investigators carried out a comprehensive search of studies on the diagnosis of SUI by TPUS in PubMed, Embase, Medline, Cochrane Library, Medicine, Web of Science, and clinicaltrials.gov databases on August 1, 2022. Studies were included if they met the inclusion criteria and were evaluated by different quality evaluation methods according to study types. Various US parameters were collected and analyzed to judge the diagnostic value of TPUS in patients with SUI. A total of 13 studies with 1,563 subjects were finally included. The combined statistics showed no significant difference in age and parity among the included patients, and the BMI of the SUI group was slightly higher than that of the normal population (MD 1.20, 95% CI: 0.68 to 1.72). The results indicated that compared with the normal population, the α angle (MD 15.56, 95% CI: 9.93 to 21.90), β angle (at rest: MD 10.02 mm, 95% CI: 1.95 to 18.09; at Valsalva: MD 22.40 mm, 95% CI: 13.79 to 31.01), BND (MD 6.82 mm, 95% CI: 4.49 to 9.14), area of hiatus (MD 2.83 cm², 95% CI: 0.71 to 4.94), and bladder neck funneling (RR 4.71, 95% CI: 1.08 to 20.62) of SUI patients were significantly different, which showed the potential value of TPUS in the diagnosis of SUI. The authors concluded that evidence-based medicine was employed to statistically analyze published studies on the diagnostic value of TPUS in patients with SUI. The results suggested that TPUS has application value in the diagnosis of SUI and has the potential to become a routine examination method to aid in clinical decision-making.
Platelet-Rich Plasma for the Treatment of Stress Urinary Incontinence
Dankova et al. (2023) stated that there is no clear clinical evidence that platelet-rich plasma (PRP) injections improve female sexual dysfunction (FSD) and stress urinary incontinence (SUI). In a systematic review, these researchers examined the safety and effectiveness of PRP injections in women with FSD and SUI, and explored the optimal dosing, frequency, area of injections, and duration of treatment. They carried out a systematic search on PubMed, Embase, and the Cochrane Library database, as well as sources of grey literature from the date of database or source creation to January 2023. After title/abstract and full-text screening, clinical studies on humans examining the effectiveness of PRP in gynecological disorders using standardized tools were included. Risk of bias was assessed using RoB-2 for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for observational studies. A total of 4 prospective and 1 retrospective study examined FSD, while 6 prospective and 1 RCT examined SUI. A total of 327 women with a mean age of 51 ± 12 years were included. For FSD, PRP significantly improved the Female Sexual Function Index (FSFI), the Vaginal Health Index (VHI), and the Female Sexual Distress Score (FSDS). For SUI, PRP resulted in a significant improvement in the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and the Urogenital Distress Inventory-6 (UDI-6). The identified RCT reported a significantly higher mean score of ICIQ-SF (p < 0.05) and UDI-6 (p < 0.01) in the mid-urethral sling group compared to the PRP injections group. Regarding the risk of bias, the RCT was characterized by high risk, whereas the observational studies were of moderate risk. The protocol for PRP injections for FSD involved the injection of 2 ml of PRP into the distal anterior vaginal wall once monthly for 3 months. For SUI, 5 to 6 ml of PRP should be injected into the peri-urethral area once monthly for 3 months. The authors concluded that despite the promising initial results of PRP injections, the level of evidence for all outcomes was deemed low due to the methodological concerns raised in most of the included studies. These investigators stated that there is an emerging need for high-quality RCTs examining PRP injections for the treatment of FSD and SUI.
The authors stated that this study had two main drawbacks. First, the included studies displayed significant heterogeneity in terms of PRP preparation technique, dose, injected area, and duration of treatment; thus, a meta-analysis could not be carried out. Second, most included studies raised methodological concerns. This problem predominantly stemmed from the small number of included subjects, suboptimal methods of reporting randomization, relatively short follow-up, restricted number of events, and the implementation of non-recognized scales. Accordingly, some important parameters, such as PRP preparation technique, dose of PRP, injected area, and the percentage of patients with improvement in underlying disease symptoms, remained unreported in some of the included studies.
Subcutaneous Tibial Nerve Stimulation (eCoin)
Short-term data on subcutaneous nerve stimulation have shown promising results for the treatment of overactive bladder (OAB) and urinary incontinence (UI). The eCoin is a small, coni-shaped device that can be implanted adjacent to the tibial nerve to provide pre-programmed stimulation.
In a prospective, single-arm, open-label, multi-center study, MacDiarmid et al. (2019) examined the safety and effectiveness of a fully implanted, primary battery-powered, nickel-sized and shaped neuromodulation device known as the eCoin for tibial nerve stimulation for the treatment of refractory urge urinary incontinence (UUI). This feasibility trial included 46 subjects with refractory UUI and was carried out at multiple sites in the U.S. and New Zealand. The device was implanted in the lower leg over the tibial nerve and activated after 4 weeks. Bladder diary data and validated quality of life (QOL) instruments were collected 3 and 6 months after activation and compared to baseline values. The mean ± SD age of participants was 63.4 ± 11.5 years, and 45 (98%) were women. Episodes of UUI were reduced by a relative median of 71% after 3 months of treatment (4.2 versus 1.7 daily episodes at 3 months, p = 0.001). A 50% or greater decrease in reported episodes of UUI was observed in 32 of 46 participants (69.6%) at 3 months, with more than 20% dry at 3 and 6 months. Incontinence Quality of Life (I-QOL) scores improved by an average of 25.9 points, and 33 of 46 patients (72%) indicated improvement in symptoms. A single serious adverse event (AE) secondary to wound care resolved with intravenous (IV) antibiotics. The authors concluded that the implantable neuromodulation device was a safe and effective treatment for UUI associated with OAB syndrome, with a significant reduction or resolution of symptoms and no significant safety concerns.
Rogers and Sen (2021) stated that the treatment of OAB with UUI symptoms follows an algorithmic pathway. Patients who fail first- and second-line treatments may be offered percutaneous tibial nerve stimulation (PTNS), onabotulinumtoxinA injections (BOTOX), or sacral neuromodulation as a third-line treatment. An implantable tibial nerve stimulator may present a more convenient and effective treatment than these options. The coin-sized neurostimulator is subcutaneously implanted in a single visit using only local anesthesia. These researchers presented an instructional video showing the brief placement of the eCoin device for the treatment of OAB with UUI. The eCoin placement technique was demonstrated on a patient in an ambulatory surgery center procedure room setting. A custom marking template was provided to indicate the location of the incision and final eCoin placement. Once the markings were made, the patient was prepped for the procedure with local anesthesia. The lower leg was then sterilized and draped. The custom marking tool was used again to remark the incision site and eCoin placement location. Once the incision was made, a custom sizing blunt dissection tool was used to create a pocket for device placement. The eCoin was then easily inserted into the pocket, located above the tibial nerve. A layered closure technique was completed. The patient was then fitted with an ankle support to provide gentle compression for 4 weeks. During this period, the patient was instructed to comply with provided after-care instructions and materials to prevent infection or eCoin device migration. After the 4-week healing duration, the eCoin device was activated. A total of 133 patients across 15 study sites were implanted with the eCoin device in a clinical trial. The mean implant time from incision to closure was 20.77 minutes (SD 9.08). The median implant time was 18 minutes. All of the patients were evaluated for wound healing approximately 2 weeks post-implant. There was 1 related severe AE, an infection resulting in uncomplicated explant at a hospital setting. At the time of this writing, patients in the study had the device implanted for an average of 56.9 weeks. The treatment was effective and sustainable, as described in other abstract submissions. The authors showed the use of a safe method of subcutaneous tibial nerve stimulation implant placement that was performed in the office under local anesthesia. The procedure time was relatively brief, resulting in minimal AEs in a large cohort.
Rogers et al. (2021) reported on a prospective, open-label, single-arm trial of the eCoin device carried out at 15 U.S. medical centers involving 137 subjects with refractory UUI. After implantation in the lower leg above the fascia over the tibial nerve, eCoin delivered automated stimulation sessions for the duration of the study. The primary effectiveness measure was the proportion of subjects who achieved a 50% or greater reduction from baseline in UUI episodes after 48 weeks of therapy. The primary safety measure was device-related AEs at the same time point. Of the 137 subjects enrolled, 133 were implanted with eCoin, and 132 were included in the intention-to-treat (ITT) population. Of those 132 subjects, 98% were female, the mean ± SD age was 63.9 ± 10.9 years, and baseline daily UUI episodes were 4.3 ± 3.1. The primary effectiveness analysis showed that 68% (95% CI: 60% to 76%) of subjects experienced at least a 50% reduction in UUI episodes at 48 weeks post-activation; 16% of implanted subjects experienced device-related AEs through 52 weeks post-implantation.
Kaaki et al. (2022) reported on a prospective, single-arm, open-label study, including 23 participants with refractory UUI who were previously participants in the eCoin clinical feasibility trial. This follow-on study was conducted at 7 sites in the U.S. and New Zealand. Participants were re-implanted with a new eCoin device and activated after 4 weeks. Bladder diary data and validated QOL instruments, collected at 12 weeks and 24 weeks post-activation, were compared with baseline. Participants of the study were considered responders if they reported a 50% or greater reduction from baseline in episodes of UUI on a 3-day voiding diary. At 12 weeks of treatment, 74% (95% CI: 52% to 90%) of participants were considered responders. At 24 weeks of treatment, 82% (95% CI: 60% to 95%) of participants were considered responders, with 36% (95% CI: 20% to 57%) of participants achieving complete continence. There were no device-related serious AEs reported during the study.
Gilling et al. (2022) reported on a study to evaluate the safety and effectiveness of the eCoin. A feasibility clinical trial was conducted, and the results after 1 year of treatment with the eCoin were presented. A total of 46 participants with refractory UUI were included in this prospective, single-arm, open-label study. This study was conducted at 7 sites in the U.S. and New Zealand. Participants in this study were implanted with the eCoin in the lower leg over the tibial nerve and activated after 4 weeks. Bladder diary data and validated QOL instruments, collected at 3, 6, and 12 months post-activation, were compared to baseline values. Responders were defined as those who had a 50% or greater reduction in reported episodes of UUI. At 12 months, 65% of participants were considered responders, with 26% of participants achieving complete continence. The median number of UUI episodes per day decreased from 4.2 at baseline to 1.7 at 12 months; 70% of participants reported feeling "better," "much better," or "very much better" on the Likert 7-point maximum scale. One participant experienced a related serious AE.
Smith (2022) stated that implantable tibial nerve stimulation (ITNS) is promising, with a variable number of days and duration of stimulation possible, creating less burden on the patient. The author noted that long-term safety, effectiveness, and tolerability are unknown at this time but are expected to be acceptable. With all the interest conveyed by the biotech companies, there is sure to be more to come on these technologies.
Al-Danakh et al. (2022) stated that PTNS techniques have dramatically grown after approval to manage OAB. This review focused on the most current data on PTNS types (percutaneous, transcutaneous, and implant) and their mechanism of action, safety, effectiveness, advantages, drawbacks, limitations, and clinical applications. These investigators described the recent studies that addressed the role of tibial nerve stimulation in OAB management. The BlueWind RENOVA system, Bioness StimRouter, and eCoin are examples of emerging technologies that have evolved from interval sessions (percutaneous PTNS and transcutaneous PTNS) to continuous stimulation (implants). These can be efficiently managed at home by patients with minimal burden on the health system and fewer visits, especially during the COVID-19 pandemic. The authors concluded that the advancements in tibial nerve stimulation for OAB treatment have been rapidly increasing over recent years. It is minimally invasive and effective, similar to sacral nerve stimulation (SNM), but less aggressive. Implantable PTNS has shown promise in terms of safety, effectiveness, and high acceptance rate; however, evidence is still limited to short-term trials, and tolerability, method, and drawbacks remain challenges.
Bessington et al. (2023) reviewed the literature on eCoin implantation, from proof-of-concept to mid-term data, with the longest period of follow-up being 12 months. The authors found that the eCoin device showed promising early data for effectiveness in managing OAB symptoms. Complication rates remained low and were mostly related to wound healing following the initial placement of the device. Research into the continued improvement and modification of the device appeared optimistic; however, longer-term data still need to be obtained. Indeed, implantable PTNS has a role in the future management of OAB, and devices such as eCoin will still need to prove a long-term benefit to be a mainstay of management.
In a prospective, single-arm, multi-center study, Lucente et al. (2024) examined the continued safety and effectiveness of the eCoin ITNS for urgency urinary incontinence (UUI) in patients with OAB. The 1-year pivotal study was extended through 2 years. The ITNS is a novel and recently FDA-approved therapy. This trial was carried out on 137 subjects with refractory UUI to evaluate eCoin ITNS therapy. A 3-day voiding diary was collected along with the OAB questionnaire, Patient Global Impression of Improvement, and a custom Likert scale on subject satisfaction. The primary effectiveness measure was the proportion of subjects who achieved at least a 50% reduction from baseline in the number of UUI episodes. The primary safety measure was device-related AEs. A total of 72 subjects completed the 96-week evaluation. Around 78% (95% CI: 67% to 87%) experienced at least a 50% reduction in UUI episodes; 48% (95% CI: 36% to 60%) experienced at least a 75% reduction, and 22% (95% CI: 13% to 33%) were dry on a 3-day diary. Subjects reported a decrease from baseline in their UUI episodes per day of 2.61 (SD 2.97) and 2.97 (SD 2.64) at 48 weeks and 96 weeks, respectively. Approximately 91.3% did not require additional medications for OAB. No serious or unanticipated AEs were reported in this extension phase. The authors concluded that eCoin ITNS showed consistent continuing safety and effectiveness in treating OAB patients with UUI. The findings supported it as an excellent therapeutic option for refractory patients.
The authors stated that the study faced common challenges in neuromodulation research, precluding the implementation of a blinded, comparative trial. Furthermore, patient withdrawals and loss to follow-up were influenced by the COVID-19 pandemic, potentially impacting data reliability.
Lucente et al. (2025) stated that UUI, an important subset of OAB, manifests with symptoms such as urgency, frequency, and incontinence, severely impacting quality of life (QOL). Neuromodulation therapies, including sacral nerve stimulation (SNM), percutaneous tibial nerve stimulation (PTNS), and implanted tibial nerve stimulation (ITNS), are FDA-approved for the treatment of UUI. Traditional neuromodulation entails sensory and motor response evoking amplitudes; however, emerging evidence suggests that sensory and sub-sensory settings might enhance treatment outcomes by influencing brain activation. These investigators examined the effectiveness of sensory and sub-sensory programming of the eCoin ITNS in reducing UUI episodes. The eCoin ITNS is a fully implantable device providing low-duty cycle tibial nerve stimulation. The ESSENCE (Effectiveness of Sensory and Sub-sensory Stimulation Amplitudes Using eCoin Implantable Tibial Nerve Stimulation in Reducing Urgency Urinary Incontinence Episodes) Trial was carried out as a double-blind RCT, and 36 subjects with UUI across 5 U.S. centers were enrolled, aiming to assess changes in UUI episodes and QOL over 3 months. Subjects were randomized to sensory or sub-sensory stimulation groups, with the sensory group activated to the amplitude at which stimulation was first felt and the sub-sensory group set 25% below this threshold. UUI episodes were recorded using 3-day voiding diaries, and QOL was assessed via the Overactive Bladder Symptom Quality of Life Questionnaire (OABq) to evaluate the primary endpoint of reduction from baseline in the number of UUI episodes per day on the 3-day voiding diary. Results showed a mean reduction in UUI episodes of 2.1 per day for the sensory group and 2.73 per day for the sub-sensory group from a pooled baseline of 5.53. Both groups reported improvements in health-related quality of life (HR-QOL) and patient satisfaction. These findings aligned with previous studies on SNM, showing that both sub-sensory and sensory settings were effective, potentially enhancing patient comfort and device longevity. The authors concluded that the ESSENCE Trial demonstrated that both sensory and sub-sensory amplitude settings of eCoin ITNS showed a reduction in UUI episodes, improved QOL, and increased patient satisfaction, offering the potential for optimizing neuromodulation therapies. Moreover, these researchers noted that while the study design lacked sufficient power to demonstrate statistical significance and establish the non-inferiority of the sub-sensory group compared to the sensory group, the observed data trends support the potential benefits of sub-sensory programming. These researchers stated that further investigations are needed to solidify these findings and confirm the non-inferiority of sub-sensory settings compared to sensory programming. Larger-scale studies with sufficient power for comparative analysis could better outline the differences between these two approaches. Nevertheless, the results highlighted the promising potential of sub-sensory stimulation as a refined strategy in ITNS therapy, balancing effective UUI management with long-term patient-centered care.
The authors stated that a drawback of this trial was the lack of a statistically significant comparison between groups. Although both groups showed a reduction in UUI, improvement in QOL, and patient satisfaction, it is unclear if the effects observed in the sub-sensory group were non-inferior to the sensory group.
Amundsen et al. (2025) stated that implantable tibial neuromodulation (iTNM) systems have recently become commercially available in the U.S. and offer a new method of neurostimulation for the treatment of OAB. In the absence of head-to-head studies, this meta-analysis indirectly compared the safety and effectiveness of sacral nerve stimulation (SNM) and iTNM for the treatment of OAB. These investigators carried out a comprehensive search using terms for OAB and neuromodulation. Primary effectiveness measures included a 50% or greater reduction in UUI episodes, urinary frequency, and/or OAB symptoms. Primary safety measures included the rate of device-related AEs. A total of 20 studies met selection criteria, encompassing 1,416 patients treated with SNM and 350 patients treated with iTNM. No comparative or placebo-controlled studies for SNM and iTNM were identified; thus, the analysis was completed using single-arm results. Weighted averages showed that the UUI responder rate was similar for both SNM and iTNM (71.8% and 71.3%, respectively). Similarly, weighted averages of OAB responder rates were 73.9% for SNM and 79.4% for iTNM. Similar rates of device-related AEs were also observed. The authors concluded that this meta-analysis found similar safety and effectiveness of SNM and iTNM for the treatment of OAB and UUI, including UUI and OAB symptom response rates, reduction in UUI episodes, significant improvements in QOL, and low rates of procedure and device-related AEs. Notably, this comparable effectiveness was observed without the use of a trial phase of neuromodulation in the iTNM studies versus SNM studies. Moreover, these researchers stated that current results suggest that iTNM may also have lower surgical re-intervention rates; however, additional follow-up time is needed to confirm if this trend will continue.
The authors stated that this meta-analysis had several drawbacks. First, while this meta-analysis featured a large number of studies and corresponding patients, 11 studies were considered to have a moderate risk of potential bias, most often related to challenges with randomization and blinding due to patient sensation of neurostimulation, along with the retrospective and single-center design of several of these studies. Differences in study populations, geography, study methods, effectiveness definitions, and stage of device development (i.e., pilot study versus pivotal study versus study completed post-marketing) may also impact the generalizability of the results. Patient-level data were unavailable for analysis; thus, data for all endpoints were not always available for each study even if they had been collected. These elements, though possible with any meta-analysis and not specific to this review, should be considered when interpreting the presented results. Second, the expected difference between the length of follow-up observed in the selected iTNM and SNM studies (weighted average of 13.0 and 39.2 months, respectively) was noted. While SNM devices have been available for commercial use in the U.S. for almost 30 years (since 1996), iTNM was first FDA-approved less than 2 years ago (December 2022); accordingly, the average length of follow-up data available for SNM was much longer than for iTNM. More importantly, most device- and procedure-related AEs notably occurred within the first several months following implantation for both iTNM and SNM devices. Further comparability between later revisions and/or explant rates will certainly need to be assessed. Clearly, devices designed with implanted batteries—both iTNM and SNM—will require eventual surgical replacement. Both the original implant and surgical revisions result in costs to medical systems and patients; published data comparing costs between iTNM and SNM are not yet available. Third, challenges in comparing the frequency of urination were also identified in this analysis, primarily because of consistent differences in urinary frequency reported in the studies completed in Asia, which ultimately may describe a more severe population of patients with OAB. While the reason for this difference is unclear, the frequency was reported with a range of 10 to 14.9 in iTNM and SNM studies completed in North America, Europe, and the Middle East, compared with 21.6 to 29.2 in SNM studies in Asia, resulting in challenges in comparison of results related to urinary frequency. The impact of iTNM on urinary frequency needs to be further examined in future studies. Fourth, none of the studies identified were head-to-head trials, limiting the ability for direct comparisons. Future RCTs are needed to provide additional clarity regarding comparative differences in safety and effectiveness and to provide further guidance regarding ideal patient selection for both methods of neuromodulation, tibial versus sacral.
Subcutaneous Tibial Nerve Stimulation (Altaviva)
The Altaviva Implantable Tibial Neuromodulation (ITNM) device was developed as a leadless implantable neuromodulation device placed above the fascia in the lower leg that delivers electrical stimulation to the tibial nerve. This design may reduce the need for recurring office visits for therapy maintenance compared to percutaneous tibial neuromodulation. On September 18, 2025, the FDA approved our Altaviva rechargeable Implantable Tibial Neuromodulation device for the treatment of urge urinary incontinence (UUI).
In 2021, the FDA granted Investigational Device Exemption (IDE) approval to begin a clinical trial (TITAN 1) exploring a novel ITNM device designed to relieve symptoms of bladder incontinence. TITAN 1, a feasibility study completed in 2022, was a prospective, multicenter study that enrolled 24 subjects from 7 sites, 20 of whom were implanted with an investigational ITNM device (Lee, et al., 2023). The primary objective of the TITAN 1 study was to characterize procedural learnings through 14-days post-implant using a series of questions about the implant procedure. Subject responses to stimulation, including the lowest stimulation at which a motor response could be observed (motor threshold), the lowest stimulation amplitude at which the subject reported sensation of stimulation (sensory threshold), type of sensation (e.g., tapping), and type of motor response (e.g., great toe flexion) were collected at implant and follow-ups. Stimulation was delivered for 60 min every other day at 20 Hz, 200 μs with a stimulation amplitude set to a comfortable level above the motor and/or sensory threshold. All 20 subjects completed the 14-day visit and all 8 implanting physicians from 7 sites completed the procedural learnings questionnaire. All respondents reported the training conducted prior to the first implant was adequate. For each procedural step (identifying landmarks, dissecting to the level of the fascia, creating the subcutaneous pocket, inserting the implantable neurostimulator, and pocket closure), 90–95% of respondents rated these “easy” or “somewhat easy.” Safety data in this early phase of the study (time between study start and last subject's 14-day follow-up visit) are as follows: 5 device-, procedure-, and/or therapy-related adverse events (AEs) were reported in three subjects including 1 serious adverse event (wound infection) which resulted in device explant 6 weeks after implant. During this timeframe, no AEs were reported for suspected device migration. Motor and sensory threshold testing data were collected in the TITAN 1 study to understand responses to nerve stimulation. All twenty study subjects demonstrated motor and/or sensory response to stimulation at two implant timepoints (intra-operative and post-operative) and at the 7-day follow-up visit. Eighteen of nineteen subjects demonstrated motor and/or sensory response at the 14-day follow-up visit; for one subject, the threshold assessment was not performed.
The Evaluation of Implantable Tibial Neuromodulation (TITAN 2) pivotal study (NCT05226286), which began in 2022, is a prospective multicenter investigational device exemption (IDE) study conducted in the US with 126 subjects evaluating the safety and effectiveness of the Medtronic Altaviva ITNM system for the treatment of OAB symptoms. Early learnings from the TITAN 1 feasibility study were used to inform the pivotal study protocol (Lee, et al., 2023).
Lee et al. (2026) reported the results of the TITAN 2 pivotal study which evaluated the safety and effectiveness of the Medtronic implantable tibial neuromodulation (ITNM) system. The study enrolled adults with overactive bladder symptoms who had failed or were intolerant to at least two medications. Conducted as a prospective, multicenter, single‑arm trial, it followed 126 implanted subjects through 6‑ and 12‑month outcomes, with symptoms assessed using voiding diaries and validated patient‑reported outcome tools. The primary outcome was the proportion of subjects achieving at least a 50% reduction in daily UUI episodes at 6 months. The study found that 59% of participants met the primary endpoint at 6 months, and 61% met it at 12 months, demonstrating sustained improvement. Significant reductions were observed in UUI episodes per day, urinary frequency among those with baseline ≥10 voids/day, and urgency symptoms as measured by the Urgency Perception Scale. Improvements in health‑related quality of life were robust and maintained through 12 months, with most subjects reporting that their condition had improved and that they were satisfied with treatment. Adverse device effects occurred in 20% of subjects over 12 months, most commonly mild or moderate pain or infection at the implant site, with only one serious adverse event reported, which resolved. Important limitations include the absence of a blinded or sham‑controlled comparator group, which may introduce placebo effects; however, the durability of results over 12 months offers some reassurance. The performance goal used for statistical comparison was derived from other neuromodulation studies and is not widely standardized, and the study does not identify reasons why some patients preferred medications they had previously failed. Additionally, optimal stimulation parameters and cadence remain unknown, as all implantable tibial neuromodulation studies use protocols more intensive than traditional percutaneous approaches. The investigators concluded that, despite these limitations, TITAN 2 demonstrates clinically meaningful improvements in UUI and related symptoms with a favorable safety profile, supporting ITNM as a viable therapeutic option for patients seeking alternatives to medication or office‑based neuromodulation.
An accompanying editorial comment (Peters, 2026) reflected a clinician’s perspective on the evolving landscape of tibial neuromodulation for overactive bladder (OAB) and expresses both optimism and frustration about current implantable technologies. The author describes an ideal “nirvana” device, which is safe for office implantation, well reimbursed, highly effective, and capable of achieving patient satisfaction comparable to botulinum toxin or sacral neuromodulation, while noting that such a device does not yet exist. They review the anatomical and historical context of tibial nerve modulation and highlight a key unresolved question: whether devices placed above the fascia, such as eCoin and the device evaluated in the TITAN 2 study, stimulate the tibial nerve as effectively as systems with electrodes placed directly at the nerve. The author argues that this fundamental question could have been answered with a sham‑controlled trial, which was not conducted. They also raise concerns about comparative effectiveness, noting that different implantable systems report variable responder rates and that patient satisfaction in the TITAN 2 study declined from 74% at 6 months to 65% at 12 months, with only 50% of patients reporting that they were “much better” or “very much better.” The comment further emphasized the robust sham effect observed in neuromodulation, citing a recent double‑blind, sham‑controlled trial of a noninvasive tibial nerve stimulator that demonstrated a high sham response rate (59.5%), underscoring the necessity of sham controls when evaluating new implantable devices. The author argues that above‑the‑fascia systems, which automatically cycle on and off, were especially well suited for such study designs, making the lack of sham‑controlled trials a missed scientific opportunity. Despite welcoming additional treatment options for OAB, the author calls for more rigorous comparative research, specifically, an NIH‑sponsored randomized sham‑controlled trial directly comparing above‑ and below‑fascia devices, to enable clinicians to properly counsel patients and move closer to achieving the “nirvana” device.
Subcutaneous and Subfascial Tibial Nerve Stimulation (INTIBIA)
The INTIBIA system (Coloplast,[Humlebaek, Denmark]) is an investigational implantable tibial nerve stimulator designed to treat urgency urinary incontinence (UUI). The device consists of a lead implanted near the ankle and a wireless ankle stimulator to deliver electrical pulses to the tibial nerve to reduce UUI symptoms. A pivotal clinical trial of the INTIBIA system is ongoing (NCT05250908).
ZIDA Wearable Neuromodulation System (Transcutaneous Electrical Nerve Stimulation) for the Treatment of Idiopathic Non-Obstructive Urinary Retention
Coolen et al. (2021) noted that TENS and PTNS provide minimally invasive ways for the treatment of idiopathic non-obstructive urinary retention (NOUR). In a systematic review, these investigators examined the effectiveness of TENS and PTNS for the treatment of idiopathic NOUR. They carried out a systematic review in accordance with the PRISMA guidelines. Embase, Medline, Web of Science Core Collection, and the Cochrane CENTRAL register of trials were searched for all relevant publications until April 2020. A total of 3,307 records were screened based on the title and abstract; 8 studies met the inclusion criteria and none of the exclusion criteria. A total of 5 studies, all from the same group, reported the effectiveness of PTNS, and 2 that of TENS in adults with idiopathic NOUR. One study reported the effectiveness of TENS in children with idiopathic NOUR. Objective success was defined as a 50% or larger decrease in the number of catheterizations per 24 hours or in the total catheterized volume in 24 hours. The objective success rate of PTNS ranged from 25% to 41%. Subjective success was defined as the patient's request for continued chronic treatment with PTNS and ranged from 46.7% to 59%; 80% of women who underwent trans-vaginal stimulation reported an improvement, such as a stronger stream when voiding. TENS in children reduced post-void residual (PVR) volume and urinary tract infections (UTIs). The authors concluded that the effectiveness of TENS and PTNS in the treatment of idiopathic NOUR was limited and should be verified in larger randomized studies before its use in clinical practice.
Smith et al. (2022) stated that bladder symptoms are common in Parkinson's disease (PD), affecting 50% of all patients. These symptoms have a significant impact on quality of life (QOL) as well as implications for morbidity, contributing to falls and hospital admission. The treatment of bladder symptoms can be complicated by the tendency to experience side effects in patients with PD, including cognitive impairment and gait instability with anti-muscarinic agents; thus, the development of new, better treatments is needed. Tibial nerve stimulation is a form of neuromodulation demonstrated to improve overactive bladder (OAB) symptoms in non-neurogenic cohorts. Previously requiring hospital attendance, these researchers examined the use of this intervention employing a simple device that can be used by patients at home. The STRIPE Trial is a phase-II randomized controlled trial (RCT) of transcutaneous nerve stimulation (TNS) delivered by the Geko device, a small, self-adhesive neuromuscular stimulation device currently used for thromboembolism prophylaxis post-surgery. Active TNS will be compared to sham stimulation, with subjects blinded to treatment allocation and undertaking outcome assessment while still blinded. Subjects will be asked to self-administer stimulation at home twice weekly for 30 minutes per session over the course of 3 months. The primary outcome measure will be the International Consultation on Incontinence Overactive Bladder Questionnaire at week 12. Secondary outcomes will include pre- and post-intervention bladder diary (frequency, urgency episodes, nocturia), patient perception of global change, bowel function, as well as bladder-related QOL. Subjects will be recruited from the Proactive Integrated Management and Empowerment (PRIME) cross-sectional trial in which subjects have been screened for bladder symptoms and invited to take part, as well as clinician referral from around the region. The authors concluded that this trial entails an RCT of a novel and easy-to-use method of delivering TNS for the treatment of PD-related bladder symptoms in the patient's own home. This may potentially have huge benefits, avoiding the problems with side effects that can be associated with anti-muscarinic agents and providing a new potential modality of treatment.
Bapir et al. (2022) noted that OAB symptoms of frequency, urgency, and urinary incontinence (UI) are often associated with known neurological diseases like multiple sclerosis (MS), spinal cord injury (SCI), PD, and stroke. In a systematic review, these investigators examined the effectiveness of pharmacological and non-pharmacological treatments for the treatment of neurogenic OAB. They searched 2 electronic databases (PubMed and Embase) for RCTs focusing on pharmacological and non-pharmacological treatments for OAB symptoms associated with neurological diseases published up to April 30, 2022. A total of 157 studies were retrieved; 94 were selected by title and abstract screening; after the removal of 17 duplicates, 77 records were evaluated by full-text examination. A total of 62 studies were finally selected. The studies selected for review focused on the following interventions: anti-cholinergics (n = 9), mirabegron (n = 5), comparison of different drugs (n = 3), cannabinoids (n = 2), intravesical instillations (n = 3), botulinum toxin (n = 16), transcutaneous TNS (TTNS) (n = 6), acupuncture (n = 2), TENS (n = 4), pelvic floor muscle training (PFMT) (n = 10), and others (n = 2). Anti-cholinergics were more effective than placebo in decreasing the number of daily voids in patients with PD (mean difference [MD] - 1.16, 95% CI: -1.80 to -0.52, 2 trials, 86 patients, p < 0.004), but no significant difference from baseline was found for incontinence episodes and nocturia. Mirabegron was more effective than placebo in increasing the cystometric capacity in patients with MS (MD 89.89 mL, 95% CI: 29.76 to 150.01, 2 trials, 98 patients, p < 0.003), but no significant difference was observed for symptom scores and bladder diary parameters. TTNS was more effective than its sham control in decreasing the number of nocturia episodes (MD -1.40, 95% CI: -2.39 to -0.42, 2 trials, 53 patients, p < 0.005), but no significant changes in OAB symptom scores were reported. PFMT was more effective than conservative advice in decreasing the ICIQ symptom score (MD -1.12, 95% CI: -2.13 to -0.11, 2 trials, 91 patients, p = 0.03), although the number of incontinence episodes was not significantly different between groups. The authors concluded that the findings of this meta-analysis revealed a moderate effectiveness of all considered treatments without proving the superiority of one therapy over the others. Combination treatment using different pharmacological and non-pharmacological therapies could achieve the best clinical effectiveness due to the favorable combination of the different mechanisms of action. This could be associated with fewer side effects due to drug dosage reduction. Moreover, these researchers stated that these findings were only provisional and should be considered with caution due to the few studies included in the meta-analysis and the small number of patients.
Ghavidel-Sardsahra et al. (2022) stated that PTNS and TTNS showed a promising effect on OAB and interstitial cystitis/painful bladder syndrome. In a systematic review and meta-analysis, these investigators examined the safety and effectiveness of these therapeutic methods. They searched studies available on PubMed, Embase, Cochrane, Scopus, Web of Science, and ProQuest on March 31, 2021, to find both published and unpublished studies. The retrieved studies were screened by 2 independent researchers, and then the selected studies were critically appraised using the Cochrane risk-of-bias tool for randomized trials and Joanna Briggs Institute's checklist for quasi-experimental studies. The results of studies were synthesized using Review Manager (RevMan) 5.4 statistical software when the data were homogenous. The meta-analysis was carried out by calculating the effect size (MD) and their 95% confidence intervals (CIs). Of a total of 3,194 publications, 68 studies were included in the qualitative evaluation, and 9 studies (11 trials) in the quantitative stage. When TTNS or PTNS were compared to sham, placebo, no treatment, or conservative management, a decrease in the frequency of urination was observed in both TTNS (MD: -3.18, 95% CI: -4.42 to -1.94, p < 0.00001) and PTNS (MD: -2.84, 95% CI: -4.22 to -1.45, p < 0.00001), and overall TTNS or PTNS (MD: -2.95, 95% CI: -4.01 to -1.88, p < 0.00001). Significant improvements in mean voiding volume (MVV) and decreasing nocturia were also observed. The authors concluded that nerve stimulations with either PTNS or TTNS appeared to be effective interventions in the treatment of refractory idiopathic OAB in terms of daily voiding frequency, MVV, urgency episodes, and nighttime voiding frequency. Moreover, these researchers noted that these findings did not show any improvement in terms of urinary incontinence, PVR volume, or UI, and maximum cystometric capacity, which emphasized the effectiveness of these modalities on dry OAB rather than wet OAB.
In a scoping review, Sayner et al. (2022) examined the feasibility and outcomes of TTNS as a first-line therapeutic option for OAB. These investigators searched 6 electronic databases to identify full-text studies from 2015 that examined the impact of TTNS on OAB and bladder dysfunction in individuals aged 18 years and older. A total of 15 studies met the inclusion criteria. TTNS was compared with sham treatment, para-sacral stimulation, PFMT, anti-cholinergic medication, and PTNS. Heterogeneity in treatment application and parameters existed, with variations in treatment duration, frequency of use, and treatment settings such as pulse width (μs) and frequency (Hz). Results indicated that TTNS has effectiveness equal to PFMT and PTNS in the management of OAB; however, it was not as effective as anti-cholinergic medication. The authors concluded that TTNS is a promising first-line therapeutic option for individuals with OAB, especially in the older population and for those with neurogenic bladder. It could provide symptomatic relief from urinary incontinence, frequency, urgency, and nocturia while avoiding the bothersome side effects of more invasive or pharmaceutical therapies. Moreover, these researchers stated that heterogeneity in treatment parameters limited generalizability and translation of the most appropriate clinical application and should be considered in future trials.
In a systematic review and meta-analysis, Tahmasb et al. (2023) examined the available evidence on the effects of TTNS and PTNS on multiple sclerosis (MS)-induced neurogenic lower urinary tract dysfunction. Medical databases including PubMed, Scopus, Embase, and Web of Science were systematically searched from inception to September 2022. Meta-analysis was performed using the comprehensive meta-analysis tool. The inclusion criteria were fulfilled by 12 studies examining the effects of PTNS/TTNS on MS-induced neurogenic lower urinary tract dysfunction. Comparing the post-intervention results to the baseline showed that the rate of frequency was decreased in both PTNS and TTNS groups after intervention. The overall mean change of TNS on frequency was -2.623 (95% CI: -3.58 to -1.66; p < 0.001, I²: 87.04) among 6 eligible studies. The post-void residual (PVR) was decreased after treatment in both methods of TNS, with an overall MD of -31.13 mL (95% CI: -50.62 to -11.63; p = 0.002, I²: 71.81). The other urinary parameters, including urgency (MD: -4.69; 95% CI: -7.64 to -1.74; p < 0.001, I²: 92.16), maximum cystometric capacity (MD: 70.95; 95% CI: 44.69 to 97.21; p < 0.001, I²: 89.04), and nocturia (MD: -1.41; 95% CI: -2.22 to 0.60; p < 0.001, I²: 95.15), were improved after intervention, too. However, the results of subgroup analysis showed no effect of TTNS on urinary incontinence (MD: -2.00; 95% CI: -4.06 to 0.06; p = 0.057, I²: 95.22) and nocturia (MD: -0.39; 95% CI: -1.15 to 0.37; p = 0.315, I²: 84.01). In terms of mean voided volume, the evidence was related to only PTNS with a mean change of 75.01 mL (95% CI: -39.40 to 110.61; p < 0.001, I²: 85.04). The authors concluded that although the available evidence suggested that TNS might be an effective method for the treatment of neurogenic lower urinary tract dysfunction, the evidence base was poor and derived from small, mostly non-randomized studies with a high risk of bias and confounding. Moreover, these researchers stated that the long-term effects of TNS therapy and its cost-effectiveness need to be addressed by future high-quality controlled trials.
Chen et al. (2023) compared and ranked the safety and effectiveness of oral medications, 3 doses of onabotulinumtoxinA, and TTNS on improving urodynamic outcomes in patient-reported outcomes and safety outcomes in patients with detrusor overactivity (NDO). These investigators searched PubMed, Embase, Medline, Cochrane Library, Medicine, and clinicaltrials.gov from their inception to October 2022 and included RCTs on the drug, onabotulinumtoxinA, and TTNS for the treatment of patients with NDO. Outcomes included urodynamic parameters, voiding diary, QOL changes, AE rate, and PVR. A total of 26 studies and 2,938 patients were included in the statistics. Regarding effectiveness, all interventions except TTNS and alpha-blockers were statistically different from the placebo group. The urodynamic outcome and patient-reported outcome suggested that onabotulinumtoxinA injection (urodynamic outcome: onabotulinumtoxinA 200 U, the mean surface under the cumulative ranking curve [SUCRA]: 87.4; patient-reported outcome: onabotulinumtoxinA 100 U, mean SUCRA: 89.8) was the most effective treatment, and the safety outcome suggested that TTNS (SUCRA: 83.3) was the safest. Cluster analysis found that anti-muscarinic agents and β3-adrenoceptor agonists possessed good safety and effectiveness. The authors concluded that onabotulinumtoxinA injection was probably the most effective way for the treatment of patients with NDO, with increasing effectiveness but decreasing safety as the dose rises. The effectiveness of alpha-blockers and TTNS was not statistically different from the placebo group. Anti-muscarinic agents and β3-adrenoceptor agonists exhibited good safety and effectiveness.
Yildiz and Sonmez (2023) examined the effectiveness of transcutaneous medial plantar nerve stimulation (T-MPNS) on QOL and clinical parameters associated with incontinence in women with idiopathic OAB. A total of 21 women were included in this study; all subjects received T-MPNS. Two self-adhesive surface electrodes were positioned with the negative electrode near the metatarsal-phalangeal joint of the great toe on the medial aspect of the foot and the positive electrode 2 cm inferior-posterior of the medial malleolus (in front of the medio-malleolar-calcaneal axis). T-MPNS was carried out 2 days a week, 30 minutes a day, for a total of 12 sessions over 6 weeks. Subjects were evaluated for incontinence severity (24-hour pad test), 3-day voiding diary, symptom severity (Overactive Bladder Questionnaire [OAB-V8]), QOL (Quality of Life-Incontinence Impact Questionnaire [IIQ-7]), positive response and cure-improvement rates, as well as treatment satisfaction at baseline and at the 6th week. Statistically significant improvement was found in the severity of incontinence, frequency of voiding, incontinence episodes, nocturia, number of pads, symptom severity, and QOL parameters at the 6th week compared with baseline. Treatment satisfaction, treatment success, and cure or improvement rates were found to be high at the 6th week. The authors concluded that T-MPNS was effective on both clinical parameters and QOL associated with incontinence in women with idiopathic OAB. Moreover, these researchers stated that randomized, placebo/sham-controlled, multi-center studies are needed to validate the effectiveness of T-MPNS. These investigators stated that this trial had several drawbacks. First, this was a single-center study. Second, the study was not controlled; thus, the findings could be influenced by a placebo effect. Third, there was a lack of data on urodynamics and long-term follow-up of women.
In a 12-week, open-label, single-arm, multi-center study, Goudelocke et al. (2024) examined the safety and effectiveness of a novel, wearable neuromodulation system incorporating embedded EMG evaluation, representing the first closed-loop wearable therapy for bladder control. This trial of patients with OAB examined the response of bladder diary parameters and QOL metrics. Subjects used the TTNS system, either once or thrice weekly, with evaluations at weeks 1, 4, 8, and 12. Enrolled subjects (n = 96) were assessed for changes in urinary frequency, urgency, and urgency urinary incontinence episodes, and QOL changes using various questionnaires. In the intention-to-treat (ITT) population (n = 96, mean age of 60.8 ± 13.0 years, 88.5% women), significant reductions in 3-day diary parameters were observed for daily voids, incontinence, as well as urgency episodes at 12 weeks. QOL improvements exceeded the minimal clinically important difference (MCID) for all QOL questionnaires. Long-term results remained robust at 12 months. Device-related AEs were mild, and there were no device-related serious AEs. Mean therapy compliance at 12 weeks was 88.5%; and high satisfaction rates were reported for the device overall. The authors concluded that the Avation device showed promising effectiveness in the treatment of adults with OAB and urge UI. At 12 weeks, both diary parameters and QOL indicators demonstrated significant improvement and remained robust at 12 months. The device had a favorable safety profile with high compliance and patient satisfaction. These investigators stated that this novel, closed-loop wearable TNS system represents a significant advancement in bladder control therapy, offering a non-invasive, patient-centered alternative with improved accessibility and ease of use.
Parodi et al. (2024) stated that OAB affects millions of patients globally, and its treatment is challenging but improves the patient's QOL. Besides standard techniques for neuromodulation (sacral and pudendal neuromodulation and PTNS), several new techniques have been examined for the treatment of symptoms of refractory OAB. These investigators described the state of the art of new neuromodulation techniques for lower urinary tract dysfunction (LUTD). They carried out a comprehensive Medline, Embase, and Scopus search in March 2023 (keywords: LUTD, new technologies, neuromodulation, LUTS, OAB, painful bladder syndromes, etc.). Studies were included according to inclusion (RCTs, prospective trials, large retrospective studies) and exclusion (case reports, outcomes not clearly expressed in full text, animal studies) criteria. The reference lists of the included studies were also scanned. Both adult and pediatric populations were included, in addition to both neurogenic and non-neurogenic OAB. A narrative review was then carried out. Peroneal neuromodulation, TENS, magnetic nerve stimulation, and para-sacral transcutaneous neuromodulation were the most studied investigative techniques and were shown to yield promising results in treating OAB symptoms. Most studies showed promising results even in the complex scenarios of patients with OAB refractory to standard treatments. Comparing investigational techniques with standard of care (SOC) and their respective clinical outcomes and safety profiles, and confronting their pros and cons, these researchers believed that once such treatment modalities are further developed, they could play a role in the OAB treatment algorithm. The authors concluded that although the described neuromodulation techniques are being intensely studied, the available results are not yet sufficient for any guidelines to recommend their use.
Subfascial Tibial Nerve Stimulation (e.g., BlueWind Revi) for the Treatment of Overactive Bladder Syndrome and Urgency Urinary Incontinence
Heesakkers et al. (2018) stated that overactive bladder (OAB) is a chronic condition affecting lower urinary tract function that has a significant negative impact on quality of life (QOL). In a prospective, 6-month, multi-center study, these investigators examined the performance and safety of the BlueWind implantable tibial nerve system in the treatment of refractory OAB. Objective assessment was carried out by voiding diary parameters, including voids per day, volume voided per day, urgency assessment, leaking episodes per day, pads used per day, leak severity, and clinical success defined as a 50% or greater reduction in the number of leaks per day, the number of voids per day, or the number of episodes with a degree of urgency greater than 2, or a return to less than 8 voids per day on a 3-day diary. Subjective assessment was based on the OAB-q, including health-related quality of life (HRQL) and symptom severity score. Safety was evaluated by adverse event (AE) analysis. A total of 34 of the 36 implanted subjects completed the study; 1 subject withdrew voluntarily, and 1 developed inflammation necessitating removal of the system. In the remaining subjects, 71% experienced clinical success at 6 months. Leaks per day, leak severity, and pad changes per day decreased significantly over time, with 27.6% of urge incontinence subjects becoming "dry." Voids per day, degree of urgency, volume per void, and pads changed improved significantly. All QOL aspects (concern, coping, sleep, and social) improved, as well as symptom severity scores measured by the OAB-q. AEs included implant site pain (13.9%), suspected infection (22.2%), and procedural wound complications (8.3%). The authors concluded that the BlueWind implantable tibial nerve stimulator was a safe, minimally invasive system that afforded OAB patients significant improvements. These researchers stated that these preliminary findings showed that the system exhibited a low-risk safety profile and may be considered an effective therapeutic option for OAB management.
Dorsthorst et al. (2020) examined the 3-year safety and effectiveness of the BlueWind Medical RENOVA iStim system for the treatment of OAB syndrome. All patients who previously underwent implantation with the RENOVA system were offered continued participation. The primary long-term study endpoint was to examine the safety profile based on the incidence of serious AEs (system- and/or procedure-related), which was measured by the impact and frequency of serious AEs. The secondary endpoints included clinical improvement compared to baseline and QOL improvement compared to baseline at 36 months, which was measured by a 3-day voiding diary and QOL questionnaires at certain time points. Of the 34 patients with OAB syndrome who previously underwent implantation with the RENOVA system, 20 consented to continuation in this 3-year follow-up study. Mean patient age was 56.1 years, and 16 (80%) of the study cohort were women. The overall treatment success rate was 75% at 36 months in the per protocol (16) and the intention-to-treat (ITT) (20) analyses. A total of 73% of the patients reported improvement in health-related QOL (HR-QOL) scores above the minimal important difference of 10 points. The authors concluded that this 3-year follow-up study using the BlueWind RENOVA iStim system for the treatment of OAB syndrome symptoms confirmed the long-term good safety profile, with no technical failures reported. Lasting treatment effectiveness is mirrored by a sustained positive impact on patient QOL.
Dorsthorst et al. (2022) reported on features that may be predictive of treatment response for patient-tailored OAB intervention with an implantable tibial neurostimulator using patient and technical prediction factors. This study was designed as a follow-up study based on parameter settings and patients' preferences during the pilot and extended study of the implantable tibial nerve stimulator (RENOVA iStim system). For this study, these investigators compared all treatment parameters (stimulation amplitude, frequency, and pulse width) and usage data (duration of treatment) during the different follow-up visits. They obtained usage data from a total of 32 patients who were implanted with the system between February and September 2015. Age, sex, body mass index (BMI), and previous experience with PTNS treatment were considered as possible prediction factors for treatment success; however, only BMI was considered a statistically significant prediction factor (p = 0.042). A statistically significant increase in mean treatment level was observed in the responder group during the 3-month follow-up visit (mean: 6.7 mA, SD 0.416) as compared with the initial system activation visit (mean: 5.8 mA, SD 0.400) (p = 0.049). No other visits showed statistically significant changes in both groups (responders and non-responders) during the defined time points. The authors concluded that these findings underscored the need to use patient-tailored OAB treatment; BMI was found to be a negative predictive factor for treatment success. However, it was not possible to develop a specific responder model. These researchers stated that the need for patient-tailored healthcare is important and might improve the long-term treatment outcome and compliance for each patient. They stated that multi-center studies with a larger number of patients will shed light on a better predictive model in the treatment of OAB using an implantable tibial neurostimulation device.
The authors stated that a drawback of this trial was the small sample size (n = 32). A larger sample size perhaps would have allowed delineation of predictive factors correlated with treatment success. Having predictive factors could be of great importance in counseling the patient for personalized OAB treatment. These predictive factors, in combination with further ongoing research in the onset of OAB, could be the cornerstone of personalized OAB treatment instead of the “one-treatment-fits-all” theory, perhaps allowing earlier utilization of this therapy in the treatment paradigm.
Heesakkers et al. (2024) noted that OAB affects 1 in 6 adults in Europe and the U.S. and impairs the QOL of millions of individuals globally. When conservative management fails, third-line treatments, including tibial neuromodulation (TNM), are often pursued. TNM has traditionally been accomplished percutaneously in clinic. A minimally invasive implantable device activated by a battery-operated external wearable unit has been developed for the treatment of urge urinary incontinence (UUI), mitigating the burden of frequent clinic visits and more invasive therapies that are currently commercially available. In a prospective, single-arm, open-label, multi-center study, these researchers examined the safety and effectiveness of the BlueWind Implantable Tibial Neuromodulation (iTNM) system in adult females with UUI (i.e., wet OAB). Results with the device were previously published under the name RENOVA iStim, which has since been renamed as the Revi System. Approximately 1 month post-implantation of the device, subjects delivered therapy at their convenience and completed a 7-day voiding diary before visits at 6 and 12 months post-treatment initiation. The primary safety and effectiveness endpoints were the proportion of responders to therapy (50% or greater improvement in the average number of urgency-related incontinence episodes) and the incidence of AEs from implantation to 12 months post-activation. A total of 151 subjects, mean age of 58.8 years (SD: 12.5), were implanted; 144 and 140 completed the 6- and 12-month visits, respectively. Subjects demonstrated a mean baseline of 4.8 UUI episodes per day (SD 2.9) and 10 voids per day (SD 3.3). Six and 12 months post-activation, 76.4% and 78.4% of participants, respectively, were responders to therapy in an ITT analysis. Of the 139 participants with completed 12-month diaries, 82% were responders, 50% were classified as "dry" (on at least 3 consecutive diary days), and 93.5% of participants reported that their symptoms improved. No implanted participant experienced a serious AE related to the procedure or device. The authors concluded that iTNM, delivered and powered by a patient-controlled external wearable communicating with an implant, showed clinically meaningful and statistically significant improvement in UUI symptoms and a high safety profile. This therapy highlighted the value of patient-centric therapy for the treatment of UUI. It should be noted that this study was funded by BlueWind Medical Inc.
Kapur et al. (2024) noted that third-line therapies for OAB that are currently recommended include intravesical onabotulinumtoxin-A injections (BTX-A), PTNS, and sacral neuromodulation (SNM). The implantable tibial nerve stimulator (ITNS) is a novel therapy that is now available to patients with OAB. These investigators analyzed shifts in patient preference for third-line therapies for OAB after introducing ITNS as an option among the previously established therapies for non-neurogenic OAB. A survey was designed and distributed via SurveyMonkey to the platform's audience of U.S. adults aged 18 years and older. Screening questions were asked to include only subjects who reported symptoms of OAB. Descriptions of current AUA/SUFU guideline-approved third-line therapies (BTX-A, PTNS, and SNM) were provided, and participants were asked to rank these therapies in order of preference (stage A). Subsequently, ITNS was introduced with a description, and participants were then asked to rank their preferences among current guideline-approved therapies and ITNS (stage B). Absolute and relative changes in therapy preferences between stage A and stage B were calculated. Associations between ultimate therapy choice in stage B and participant characteristics were analyzed. A total of 485 participants completed the survey (62.5% female); the mean age was 49.1 ± 36.5 years (SD). The most common OAB symptoms reported were UUI (73.0%) and urinary urgency (68.0%); 29.2% of patients had tried medication for OAB in the past, and 8.0% to 10.3% of patients were previously treated with a third-line therapy for OAB. In stage A, participants ranked their first choice of third-line therapy as follows: 28% BTX-A, 27% PTNS, and 13.8% SNM; 26.6% of participants chose no therapy, and 4.5% chose all three equally. In stage B, participants ranked their first choice as follows: 27.6% BTX-A, 19.2% PTNS, 7.8% SNM, and 19.2% ITNS; 21.9% of participants chose no therapy, and 4.3% chose all four equally as their first choice. There were both absolute and relative declines in proportions of patients interested in BTX-A, SNM, and PTNS as their first choice of third-line therapy with the introduction of ITNS. Patients originally interested in PTNS in stage A had the greatest absolute change following the introduction of ITNS, with 7.8% of participants opting for ITNS in stage B. Those interested in SNM in stage A had the largest relative change in interest, with 43.5% of those originally interested in SNM opting for ITNS in stage B. Lastly, with the introduction of ITNS, the number of participants initially not interested in any third-line therapy declined by an absolute change of 4.7% and a relative change of 17.6%. Participants experiencing concurrent stress urinary incontinence (SUI) symptoms were more likely to choose a current guideline-approved third-line therapy than ITNS or no therapy at all (p = 0.047). Those who had previous experience with third-line therapies were more likely to choose a third-line therapy other than ITNS as their ultimate choice of therapy in stage B. Of those who had chosen a guideline-approved third-line therapy in stage B (not ITNS), 13.6% had previous experience with BTX-A, 14.7% with PTNS, and 32 (11.2%) with SNM (p < 0.001, p < 0.001, p = 0.009, respectively). The authors concluded that from this study, it appeared that ITNS may attract a subset of patients who would not have otherwise pursued current guideline-approved third-line therapies for OAB. When patients were provided with descriptions of third-line OAB therapies, including ITNS as an option, ITNS appeared to compete with SNM and PTNS. It is possible that ITNS will provide patients with a different phenotype of neuromodulation therapy that can appeal to a niche OAB population. Given that ITNS devices have been introduced relatively recently to the market, their application will largely depend on cost and payer coverage, provider bias, and patient comorbidities. These researchers stated that further investigation is needed to understand how these factors interact with and influence patient preference for advanced OAB therapy to understand which patients will most benefit from this treatment modality. Furthermore, these investigators stated that long-term studies on ITNS devices are also needed to ascertain the effectiveness of ITNS over time in treating OAB and UUI compared to established and guideline-approved third-line therapies.
The authors stated that this study had several drawbacks. First, this trial did not include all types of ITNS devices that are currently available. Although names of devices were not mentioned in the survey, the type of ITNS described in stage B was based on the technology that was FDA-approved at the time of survey distribution, namely eCoin, which is leadless and has an intrinsic battery within the implant. Since then, another ITNS device called Revi (BlueWind Medical) has recently gained FDA approval for the treatment of UUI. This technology has an external pulse generator that is worn around the ankle during treatment. While not included in this study, this form of ITNS may lead to further declines in patient preference for the other guideline-approved third-line therapies. Second, survey distribution was stopped after reaching a critical response rate by participants; however, study generalization may have been more feasible with a larger sample size. Additionally, this trial under-represented some racial/ethnic minorities, such as African Americans and Hispanics. This distribution may reflect the convenience sampling utilized by SurveyMonkey, which may result in demographic distributions that do not reflect the overall U.S. population. There may also be a component of selection bias since the survey participants were limited to those who are members of SurveyMonkey Audience. Future studies should expand sampling to include more participants or account for key factors such as race/ethnicity. Third, with SurveyMonkey being a digital platform with no interactive interface, any questions that participants may have had that would affect their choice of therapy could not be answered, unlike in the authors’ previous study that provided time for any questions regarding therapy after patients were shown the counseling video at an office visit appointment. Physician counseling on OAB therapies heavily influences patient preference and choice of treatment. This component was not considered in this survey, which may affect these findings. Fourth, this study was designed and distributed as a market research study to gauge interest in a novel treatment modality for idiopathic OAB; thus, the influence of provider bias, medical comorbidities, and cost/coverage of the procedure on patient preference could not be assessed. These findings were based on patient perception of each therapy via the information these researchers provided within the survey, independent of the influence of physician counseling and provider bias, cost and payer coverage, and individual patient comorbidities. However, these confounding factors play a significant role in influencing patient perception of third-line therapies for OAB and can impact follow-through with therapy. Therefore, this should be considered when interpreting these findings and in designing future relevant studies.
Heesakkers et al. (2025) reported on the long‑term (2-year) effectiveness, safety, and patient satisfaction associated with the Revi implantable tibial neuromodulation system for women with urgency urinary incontinence (UUI). This prospective, multicenter, single‑arm, open-label pivotal trial implanted the device in 151 female participants and followed them for up to 24 months. Primary clinical outcomes, including reductions in UUI episodes documented by voiding diaries, were assessed at 6 and 12 months, with participants optionally continuing into a long-term extension. Ninety-seven women completed the 24‑month assessment. Of these, 79% achieved the primary efficacy endpoint of ≥50% reduction in UUI episodes, and 56% achieved ≥75% reduction. Symptom improvement was durable, with response rates at 6, 12, and 24 months remaining stable (78%, 82%, and 79%, respectively). Additional benefits included reductions in urgency-related large leaks, improvements in voiding frequency, and meaningful improvements across all domains of the OAB‑Q, alongside very high satisfaction rates; 97% of participants reported being satisfied, and all indicated willingness to continue therapy. Safety outcomes were favorable, with no device‑ or procedure‑related serious adverse events and a low explant rate of 2%, none due to device complications. Study limitations included its nonrandomized, unblinded design, raising the possibility of bias, although the durability and magnitude of clinical improvements reduce concerns regarding placebo effects. Long-term follow-up began after some participants had completed the initial 12‑month protocol, contributing to loss to follow-up and potential selection bias. While a last‑observation‑carried‑forward analysis supported overall findings, missing data and reliance on per‑protocol analyses may still underestimate nonresponder rates. Notably, no men were included in the study. Despite these limitations, the authors conclude that the Revi System provides a durable, safe, and less invasive neuromodulation alternative for women with UUI, with efficacy comparable to sacral neuromodulation and percutaneous tibial nerve stimulation but with fewer device‑related complications.
Flyte System (Mechanotherapy)
The Flyte System, an FDA-cleared device, is a mechanotherapy that guides users through Kegel exercises (pelvic floor muscle contractions) for the treatment of stress urinary incontinence (SUI). The Flyte device is inserted into the vagina and delivers vibrations while the user contracts and relaxes their pelvic floor muscles. The device's controller has a light that indicates when to contract and relax; the standard treatment time is 5 minutes per day for 12 weeks.
Nakib et al. (2024) noted that SUI presents as unintentional urine leakage associated with activities. It significantly affects QOL and is the most common type of incontinence in women. Current therapeutic options, especially non-surgical therapies, are lacking. In a randomized, controlled, double-blinded study, these researchers examined the effectiveness of mechanotherapy provided by the Flyte intra-vaginal device during pelvic floor muscle training (PFMT). Flyte is a repeat-use device for conditioning and strengthening the pelvic floor muscles (PFMs). It provides 2-part mechanotherapy. Part 1 is the stretching and pre-loading of the PFM from the internal wand. Part 2 integrates mechanical pulses that elicit muscle cellular and tissue-level responses that trigger cellular regeneration, improve neuromuscular facilitation, and enhance motor learning. Subjects used the device for 5 minutes per day for 12 weeks. Subjects (n = 144) were randomized and evaluated at 6 and 12 weeks. Arm A (72) received both Part 1 and Part 2 mechanotherapy for 12 weeks, whereas Arm B (72) received Part 1 therapy for 6 weeks, then crossed over to full therapy. Mean age was 50 and 49 years, respectively; prior pelvic/abdominal surgery was reported in 26% and 46%, and previous incontinence treatments in 13% and 22%. The primary endpoint was 24-hour pad weight (24-HR PW) at 6 weeks. Secondary endpoints were 24-HR PW at 12 weeks and QOL [International Consultation on Incontinence Questionnaire (ICIQ), Urinary Incontinence Quality of Life (UI-QOL)]. Part 1 therapy had a greater than anticipated therapeutic effect; therefore, the study was under-powered to identify differences between study arms. Consequently, data were pooled to examine the effects of mechanotherapy. Twenty-four-hour PW was significantly reduced at 6 weeks (p < 0.0001), with further reduction from 6 to 12 weeks (p < 0.0001). Data were stratified based on 24-HR PW severity. Significant reductions were noted in all severity groups (mild p < 0.0001, moderate p < 0.0001, severe p < 0.01). QOL was similarly improved at 6 weeks (ICIQ p < 0.0001, UI-QOL p < 0.0001) and 12 weeks (ICIQ p < 0.0001, UI-QOL p < 0.0001). Compliance was greater than 80% at 6 weeks and 70% at 12 weeks. The authors concluded that 2-part mechanotherapy significantly improved 24-HR PW and QOL across all severities of SUI. Improvements were noted in as little as 2 weeks and appeared to be sustained through 2-year follow-up. Moreover, these researchers stated that further investigations are needed to determine optimal therapy protocols and to evaluate the effectiveness of this promising therapy in other pelvic floor disorders or in skeletal muscle abnormalities such as postpartum SUI, mixed incontinence, urge incontinence, and fecal incontinence.
The authors stated that this study had several drawbacks. First, it was found that the sample size was under-powered to identify the superiority of mechanical pulses (Part 2 mechanotherapy) added to the muscle stretch and pre-loading provided by the wand itself (Part 1 mechanotherapy). Therefore, the study design was not adequate due to the larger than expected positive effect of the wand alone. Post-hoc calculation indicated that 50 additional subjects (25 in each arm) were needed to show superiority of the added mechanical vibratory effect. The practical consequence of this distinction between study arms was uncertain, as the commercial device provides both components of the mechanotherapy. When the study data were pooled for both groups, the benefit of this therapy over baseline was highly significant for both objective and subjective endpoints. Second, some participants experienced discomfort using the wand. While this was anticipated, as with muscle soreness noted after any muscle exercise, a smaller wand configuration is now the standard product available. Third, the study did not examine variations in therapy delivery (e.g., duration of muscle contraction against the device, length of each therapy session, and length of therapy beyond 12 weeks).
Furthermore, an UpToDate review on “Female urinary incontinence: Treatment” (Lukacz, 2024) does not mention mechanotherapy as a management/therapeutic tool.
Electro-Acupuncture for the Treatment of Neurogenic Bladder
Zeng and Li (2024) noted that neurogenic bladder dysfunction is a common consequence of stroke, and it substantially impacts the QOL and functional independence of affected individuals. Traditional treatment modalities have limitations in achieving optimal outcomes. In a retrospective, single-center study, these researchers examined the effectiveness of electro-acupuncture on bladder function and neurogenic bladder urodynamic characteristics in stroke patients. This trial was carried out on 100 stroke patients with neurogenic bladder admitted to the authors’ hospital from January 2020 to October 2023. It compared traditional treatment (n = 51) with electro-acupuncture treatment (n = 49). Baseline characteristics, urodynamic parameters, bladder function parameters, bladder symptoms, QOL assessments, AEs as well as patient satisfaction were collected from medical records and compared between the 2 groups. No significant difference was observed in age, sex distribution, BMI, duration of stroke, and alcohol intake between the 2 groups (p > 0.05). Compared with the traditional treatment group, the electro-acupuncture group showed significant improvements in urodynamic parameters such as maximum cytometric capacity (MCC), detrusor pressure at maximum capacity, post-void residual (PVR) volume, bladder compliance, Qmax, and average flow rate, and the differences were significant between groups (p < 0.05). The electro-acupuncture treatment group showed a significant reduction in bladder symptoms such as frequency of micturition and incontinence episodes (p < 0.001) and a significant improvement in cognitive function and social return function (p < 0.05). The incidence rates of UTI, hematuria, skin allergy and treatment discontinuation in the electro-acupuncture treatment group (6.12%, 2.04%, 4.08%, and 12.24%, respectively) were significantly lower than those in the traditional treatment group (23.53%, 27.45%, 29.41%, and 35.29%, respectively) (p < 0.05). The patient satisfaction score in the electro-acupuncture treatment group (97.96%) was significantly higher than that in the traditional treatment group (70.58%) (p < 0.001). The authors concluded that electro-acupuncture exhibited certain clinical value and holds promise as an adjunctive treatment for the treatment of neurogenic bladder dysfunction in stroke patients. Well-designed studies are needed to validate these preliminary findings.
High-Intensity Focused Electromagnetic Therapy in the Treatment of Stress Urinary Incontinence
In a single-center study, Long et al. (2024) examined the effectiveness of high-intensity focused electromagnetic (HIFEM) technology in the treatment of female stress urinary incontinence (SUI). A total of 20 women with SUI received a treatment course with HIFEM technology. Patients attended 6 therapies scheduled twice weekly. Validated questionnaires were assessed, including the Overactive Bladder Symptom Score (OABSS), Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire-7 (IIQ-7), International Consultation on Incontinence Questionnaire (ICIQ), and Valued Living Questionnaire (VLQ). Some urodynamic parameters, such as maximum flow rate (Qmax), residual urine (RU), and bladder volume at first sensation to void (Vfst), were also collected. Bladder neck mobility in ultrasound (US) topography was assessed pre- and post-treatment at 1- and 6-month follow-up visits. HIFEM treatment significantly improved SUI symptoms on pad tests from 4.2 ± 5.5 to 0.6 ± 1.3, and patients' self-assessment at the 6-month follow-up. Furthermore, the data from urinary-related questionnaires, including OABSS (5.3 ± 3.9 to 3.9 ± 3.6), UDI-6 (35.7 ± 22.3 to 15.2 ± 10.6), IIQ-7 (33.1 ± 28.7 to 14.3 ± 17.2), and ICIQ (9.4 ± 5.0 to 5.4 ± 3.6), all showed a significant reduction. The analysis of the urodynamic study showed that only maximum urethral closure pressure (MUCP) (46.4 ± 25.2 to 58.1 ± 21.2) and urethral closure angle (UCA) (705.3 ± 302.3 to 990.0 ± 439.6) significantly increased after the 6 sessions of HIFEM treatment. The urethral and vaginal topography assessments indicated that HIFEM mainly worked on pelvic floor muscles (PFMs) and enhanced their function and integrity. The authors concluded that the findings of this study suggested that HIFEM technology was an effective therapy for the treatment of SUI. Moreover, these investigators noted that future studies should examine several areas to strengthen the clinical implications of HIFEM technology in the treatment of SUI. Longer follow-up periods should be included, and the observation period should be extended to 1 or more years, which could provide more robust data regarding the long-term effectiveness of HIFEM treatment effects. Furthermore, a comparative study could also be conducted with other non-invasive or minimally invasive treatments, such as fractional CO2 laser therapy or platelet-rich plasma (PRP), which could contextualize its relative benefits as well as limitations. Lastly, investigating the accurate molecular and cellular mechanisms by which HIFEM affects PFMs might be beneficial for its application in other pelvic floor disorders.
The authors stated that this trial had several drawbacks. First, the small sample size (n = 20) might reduce the statistical power and may not represent the whole population of SUI patients. Second, the lack of a control group might limit the attribution of observed improvements solely to the HIFEM treatment. Third, the observation period was short (up to 6 months). Fourth, the study was carried out in a single center, which may have introduced selection bias and limited the generalizability of findings to other settings.
Leonardo et al. (2025) noted that many treatments have been employed to treat urinary incontinence (UI); however, all these therapeutic approaches have limitations. Recently, a new non-invasive treatment for pelvic floor muscles (PFM) using a HIFEM field was unveiled. In a systematic review and meta-analysis, these investigators examined the available evidence on the safety and effectiveness of HIFEM. The databases used were PubMed, Cochrane, Embase, and SCOPUS. The literature search was performed using strategic keywords: (women) AND ((High Intensity Electromagnetic Field) OR (Electromagnetic Stimulation)) AND ((urinary incontinence) OR (overactive bladder) OR (pelvic floor dysfunction)). Studies that met the inclusion and exclusion criteria were then analyzed. A total of 7 studies were included in this review, and most of the studies concluded that the usage of HIFEM could significantly reduce the symptoms related to UI and improve QOL. There was a higher decrease in UI episodes (MD: -4.10, 95% CI: -7.34 to -0.85, p = 0.01) and improvement of ICIQ-UI Short Form (ICIQ-UI SF) score (MD: -3.03, 95% CI: -3.27 to -2.79, p < 0.00001) in the HIFEM group compared to the control. Sub-group analyses showed better QOL parameters (MD -3.40; p = 0.01, MD -0.70; p = 0.04) compared to the control, albeit statistically comparable overall (p = 0.09). However, both pooled analyses for contraction and resting tone changes showed that there were no significant differences between the two groups (SMD: 0.98, 95% CI: -0.70 to 2.66, p = 0.25; and SMD: 0.20, 95% CI: -0.18 to 0.58, p = 0.30, respectively). Lastly, there were no safety issues highlighted in most of the studies included. The authors concluded that available evidence suggested that HIFEM may be a safe and effective non-invasive treatment for female UI by promoting QOL. Moreover, these researchers stated that as a consequence of high heterogeneity and possible bias, future well-designed studies with proper blinding and standardized outcomes are needed to ascertain the applicability of HIFEM for the treatment of UI.
Implantable Sacral Nerve Stimulators for the Treatment of Neurogenic Bladder
In a meta-analysis, Sun and Song (2025) examined the safety and effectiveness of sacral nerve stimulation (SNM) in the treatment of neurogenic bladder (NB) and neurogenic bowel dysfunction (NBD). These investigators carried out a systematic literature search using PubMed and Web of Science up to August 2024, focusing on studies related to SNM treatment for NB or NBD. After assessing the quality of the studies, data were extracted and analyzed using Review Manager 5.3. A total of 15 studies involving 573 patients were included. After SNM treatment, the patients showed significant improvements in key outcome measures, including voiding frequency per 24 hours (V24) (weighted mean difference [WMD] -4.08; 95% CI: -6.80 to -1.35; p = 0.003), mean urine volume per micturition (MUV) (WMD 123.60; 95% CI: 93.17 to 154.03; p < 0.001), number of leakage episodes per 24 hours (L24) (WMD -4.27; 95% CI: -5.79 to -2.74; p < 0.001), number of nocturia episodes (WMD -2.48; 95% CI: -2.62 to -2.35; p < 0.001), clean intermittent self-catheterization per 24 hours (WMD -2.35; 95% CI: -2.98 to -1.71; p < 0.001), bladder compliance (WMD 9.09; 95% CI: 2.31 to 15.87; p = 0.009), maximum detrusor pressure (MDP) during the storage phase (WMD -14.76; 95% CI: -18.63 to -10.88; p < 0.001), maximum urine flow rate (Qmax) (WMD 6.50; 95% CI: 4.21 to 8.80; p < 0.001), maximum cystometric capacity (MCC) (WMD 66.28; 95% CI: 2.83 to 129.73; p = 0.04), Wexner score (WMD -9.98; 95% CI: -13.65 to -6.31; p < 0.001), and NBD score (WMD -6.31; 95% CI: -6.89 to -5.73; p < 0.001). The authors concluded that these findings indicated that SNM was safe and effective in treating NB or NBD.
In a meta-analysis, Yu et al. (2025) examined available evidence of non-invasive or minimally invasive neuromodulation therapies in improving urodynamic outcomes, voiding diaries, and quality of life (QOL) in patients with neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI). These researchers carried out a comprehensive search of 10 databases from inception until August 30, 2023. Randomized controlled trials (RCTs) examining the effects of conventional treatment (CT) and CT combined with sham stimulation (SS), transcranial magnetic stimulation (TMS), sacral nerve magnetic stimulation (SNMS), TMS+SNMS, sacral pulsed electromagnetic field therapy (SPEMFT), sacral transcutaneous electrical nerve stimulation (STENS), sacral dermatomal transcutaneous electrical nerve stimulation (SDTENS), bladder & sacral transcutaneous electrical nerve stimulation (B&STENS), transcutaneous tibial nerve stimulation (TTNS), transcutaneous electrical acupoint stimulation (TEAS), pelvic floor electrical stimulation (PFES), or pelvic floor biofeedback therapy (PFBFBT) on post-void residual (PVR) volume, maximum cystometric capacity (MCC), V24, MUV, Qmax, MDP, maximum voiding volume (MVV), L24, lower urinary tract symptoms (LUTS) score, and spinal cord injury-QOL (SCI-QOL) score in patients with NLUTD after SCI were included. Two researchers independently extracted data on study characteristics and outcomes following the PRISMA statement. The Cochrane risk of bias tool (2.0) was used to assess the quality of RCTs. A total of 52 RCTs with 2,884 participants were included. CT+TMS was able to remarkably decrease PVR (mean difference [MD], -132.14; 95% CI: -230.97 to -33.31) and increase MUV (MD, 147.79; 95% CI: 64.51 to 231.06). CT+SNMS ranked high in improving V24 (MD, 2.76; 95% CI: 1.26 to 4.25) and reducing L24 (MD, -2.73; 95% CI: -4.46 to -1.01); CT+TMS+SNMS maximized the reduction of SCI-QOL scores (MD, -1.52; 95% CI: -2.97 to -0.25) and ranked second in both reducing PVR and improving MCC; CT+SPEMFT had a significant advantage in improving MCC (MD, 83.31; 95% CI: 39.73 to 126.88) and increasing Qmax (MD, 5.91; 95% CI: 2.99 to 8.84); improvement in MDP was highly ranked by CT+TTNS (MD, 9.46; 95% CI: 2.15 to 16.76). The authors concluded that CT combined with magnetic stimulation therapy provided more benefits than its combination with electrical stimulation. These researchers stated that TMS+SNMS appeared to be a promising non-invasive neuromodulation technique in managing NLUTD after SCI. Moreover, these researchers stated that high-quality RCTs are needed to validate these findings.
Buford et al. (2024) stated that NLUTD is highly prevalent among patients with neurologic disorders. Some studies have reported that implantable neuromodulation could improve symptoms of NLUTD. In a retrospective, single-center study, these investigators described their experience with sacral and pudendal neuromodulation in patients with NLUTD. They carried out a retrospective chart review of patients with the "neurogenic bladder" ICD-9/10 (International Classification of Diseases, 9th Revision/10th Revision) code at a single institution. This included patients from 2008 to 2020 who underwent stage 1 neuromodulation trial. Demographic and clinical information was collected, including neurologic diagnosis, the character of patients' voiding symptoms, the presence or absence of fecal incontinence, the need for intermittent catheterization, and whether patients had sufficient (greater than 50%) improvement in their symptoms to undergo stage 2 implantable pulse generator (IPG) placement. These researchers identified 82 patients with neurologic diagnoses who underwent stage 1 neuromodulation. The most common diagnoses were diabetic cystopathy (17.07%), spinal surgery (17.07%), and SCI (12.20%). The most commonly reported symptoms were urinary urgency and urge urinary incontinence. Overall, 59 patients (71.95%) advanced to stage 2 IPG placement, including 72% of patients with sacral leads and 76% with pudendal leads. The authors concluded that neuromodulation was feasible and effective in the treatment of NLUTD. Moreover, these researchers stated that further investigations into its utilization are needed.
The authors stated that drawbacks of this trial included its retrospective design; thus, they could not examine potential causality, delve deeply into patient history, and standardize data collection. The small sample size (n = 82 subjects; 10 patients with SCI) limited the generalizability of the findings. However, the sample size was on par with similar studies that examined neuromodulation for the management of NLUTD. Furthermore, the study was carried out at a single center, which may have restricted the diversity of the patient population. These investigators also stated that it was important to acknowledge that due to the focus of this study on the short trial phase, long-term effectiveness and adverse events (AEs) were not specifically recorded or analyzed. In a subsequent meta-analysis that included SNM for non-neurogenic voiding symptoms, the incidence of AEs was comparable to those reported in the van Ophoven meta-analysis; thus, it was reasonable to assume potential long-term AEs would be consistent with other studies. This highlighted the need for future research with prospective designs, larger sample sizes, multi-center collaborations, validated questionnaires, and longer follow-up periods to provide more robust and comprehensive evidence.
Furthermore, an UpToDate review on “Chronic complications of spinal cord injury and disease” (Abrams and Wakasa, 2024) states that “Studies of implanted sacral nerve modulators show promise as a treatment for urinary incontinence following SCI. For patients with unsatisfactory responses to medical and catheter management, other treatments, bladder augmentation, urinary diversion, sphincterotomy, urethral stent, and electrical implantation devices can be considered in selected cases, although there is limited evidence of their comparative efficacy.”
Micro-Ablative Radiofrequency for the Treatment of Over-Active Bladder
Slongo et al. (2025) stated that energy therapies have been suggested as potential treatments for OAB; however, there are few studies examining their effectiveness. In a pilot study, these researchers compared the effects of fractional micro-ablative RF to sham treatment. This trial was carried out with 77 women diagnosed with OAB, randomized into 2 groups: one receiving 3 monthly sessions of fractional micro-ablative RF and the other receiving sham treatment, both combined with behavioral therapy. Assessments were carried out at baseline and 30 days after therapy using validated questionnaires for urinary symptoms (ICIQ-Short Form, ICIQ-OAB, and ICIQ-QOL), as well as vaginal and sexual function, and pelvic floor muscle functionality. Both treatment groups showed significant improvements in all validated questionnaires evaluating urinary and vaginal symptoms (p < 0.001), with no significant differences between them. The ICIQ-OAB scores improved significantly in both the RF group (-4.5 points; p < 0.001) and the sham group (-4.5 points; p < 0.001), with no significant differences between the groups (p = 0.812). Furthermore, there were no improvements noted in sexual function or vaginal trophism in the RF group. However, assessments of endurance, resistance, and fast contractions of the pelvic floor muscles revealed improvement only in the RF group, with no changes observed in power or perineometer measurements. The authors concluded that micro-ablative RF treatment combined with behavioral therapy did not show benefits over sham treatment with behavioral therapy for the treatment of OAB symptoms.
Percutaneous Tibial Nerve Stimulation (PTNS) for the Treatment of Idiopathic Overactive Bladder
Jericevic et al. (2024) stated that overactive bladder (OAB) patients who do not achieve satisfactory results with second-line OAB medications should be offered third-line therapies (e.g., botulinum toxin A [BTX-A], percutaneous tibial nerve stimulation [PTNS], and sacral nerve stimulation [SNM]). These researchers determined which clinical factors affect progression from second- to third-line OAB therapy. Between 2014 and 2020, the American Urological Association (AUA) Quality Registry was queried for adult patients with idiopathic OAB. For the primary outcome, patient and provider factors associated with increased odds of progression from second- to third-line therapy were assessed. Secondary outcomes included median time for progression to third-line therapy and third-line therapy utilization across subgroups. A total of 641,122 patients met inclusion criteria and were included in the analysis. Of these, only 7,487 (1.2%) received third-line therapy after receiving second-line therapy. On multivariate analysis, patients aged 65 to 79, women, White race, a history of dual anticholinergic and β3 agonist therapy, metropolitan area, government insurance, and single specialty practice had the greatest odds of progressing to third-line therapy. Black and Asian race, male gender, and rural setting had lower odds of progressing to third-line therapy. BTX-A was the most common therapy overall (40% BTX-A, 32% SNM, 28% PTNS). The median time of progression from second- to third-line therapy was 15.4 months (IQR 5.9 to 32.4). Patients less than 50 years old and women progressed fastest to third-line therapy. The authors concluded that very few patients received third-line therapies, and the time to progression from second- to third-line therapies was greater than 1 year. These researchers stated that the findings of this study highlighted a potential need to improve third-line therapy implementation.
The American Urological Association/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (AUA/SUFU) guideline on the "Diagnosis and Treatment of Idiopathic Overactive Bladder" (Cameron et al., 2024) recommends that clinicians offer sacral nerve stimulation (SNM), percutaneous tibial nerve stimulation (PTNS), and/or intra-detrusor botulinum toxin A (BTX) injection to patients with overactive bladder (OAB) who either do not respond adequately to pharmacotherapy or behavioral therapy or experience intolerable side effects from these treatments. This recommendation is classified as moderate, with an evidence level of Grade A.
Jefferson et al. (2025) stated that procedural therapies for OAB most often include intra-detrusor BTX injections, SNM, and PTNS. Despite their proven effectiveness, real-world data regarding therapy continuation and crossover rates between these modalities remain limited. In a retrospective, multi-center study, these investigators examined longitudinal patterns of treatment continuation and therapy crossover among women receiving procedural OAB treatments. This trial enrolled women with idiopathic OAB who underwent index BTX, SNM, or PTNS between 2014 and 2022. Subjects were identified using electronic medical records, and follow-up data were collected through December 31, 2023. The primary outcomes included the duration of maintenance treatments and crossover to another procedural therapy for OAB. Kaplan-Meier survival analysis estimated rates of continued treatment, and a log-rank test examined differences in crossover rates among treatment groups. A total of 506 women met inclusion criteria: 266 (52.6%) received BTX, 114 (22.5%) underwent SNM, and 126 (24.9%) received PTNS. Ongoing treatment rates were lowest for PTNS, with only 17.1% maintaining therapy between 3 and 5 years and 26.1% crossing over to another procedure within 3 years. Among BTX patients, 65.2% underwent repeat treatment within 3 years, and 9.5% of patients crossed over to another procedure within 3 years. Of those with 5 or more years of follow-up, 39.1% of patients continued with BTX procedures in the 3- to 5-year follow-up time point. Among SNM patients, the cumulative revision rates were 7.6% at 1 year and 10.9% at 2 years; and 13.1% of patients crossed over from SNM to another procedure within 3 years (the vast majority to BTX). The authors concluded that PTNS had the lowest ongoing therapy rates and the highest crossover rates. BTX and SNM showed similar crossover rates. These researchers stated that these findings underscored the importance of individualized patient counseling and treatment selection based on expectations of therapy persistence.
Furthermore, an UpToDate review on “Urgency urinary incontinence/overactive bladder (OAB) in females: Treatment” (Lukacz, 2025) states that “Patients who have persistent urgency urinary incontinence or other irritative symptoms despite an adequate trial of initial treatments and pharmacotherapies, are unable to tolerate pharmacologic therapy, or decline the above treatments after discussion of risks and benefits, can be referred to a specialist to discuss further options for treatment. Advanced therapies range from noninvasive office-based acupuncture-like nerve stimulation (PTNS) and office-based injections of botulinum toxin A to surgically implanted nerve stimulation devices (tibial nerve stimulation and SNM).”
Protect PNS System for the Treatment of Overactive Bladder
Protect PNS (Uro Medical, Boca Raton, FL) is a minimally invasive, wirelessly powered, micro-technology neurostimulator currently being studied for the treatment of overactive bladder (OAB) and is under regulatory review by the FDA.
Sirls et al. (2023) noted that tibial nerve stimulation is an effective treatment for OAB and has been employed as an in-person recurring session therapeutic option for many years. In a pilot study, these investigators examined the safety and effectiveness of a long-term implantable device and the method of using a retrograde approach to place the device (a percutaneous implantable pulse generator [pIPG] with integrated quadripolar electrodes) at the tibial nerve (Protect PNS; Uro Medical). This novel retrograde implant technique was developed via multiple cadaveric dissections to percutaneously implant a chronic, wireless, minimally invasive pIPG device with integrated quadripolar electrodes at the tibial nerve. A proof-of-concept (POC) pIPG device approved as part of an FDA Investigational Device Exemption (IDE) was designed to gain early experience in subjects with refractory OAB. The pIPG was implanted in the office under local anesthesia using the novel retrograde approach, and stimulation was activated by means of an external wireless energy source. Initially, a pilot study was designed to compare outcomes in subjects randomized to either PTNS or Protect PNS. However, due to the small sample sizes available at this time, it was not possible to compare the two groups; therefore, the objective of this manuscript was to describe the outcomes of subjects who underwent implantation of the Protect PNS system; 12-month safety and effectiveness were evaluated. A total of 9 subjects were enrolled in the randomized pilot study: 5 in the pIPG group and 4 in the PTNS group, and all completed the 13-week primary endpoint. Subsequently, 2 subjects in the PTNS group chose to cross over and had the pIPG implanted after 13 weeks. Outcomes of the 7 subjects who underwent implantation of the pIPG were described. No complications related to the office procedure were noted. Two of the older model pIPG devices became non-responsive at 1 and 4 weeks and were replaced. Six minor adverse events (AEs) were reported and resolved. Participants reported improvement in urge urinary incontinence (UUI) episodes, OAB symptoms, and quality of life (QOL). Subjects implanted with a pIPG reported a 50% reduction in UUI as early as 1 week. The authors concluded that the findings of this pilot study suggested that retrograde percutaneous implantation of a pIPG was a safe, minimally invasive, one-stage office procedure for the treatment of urge incontinence-related OAB symptoms, without significant complications after 12 months of follow-up. These researchers stated that future studies are needed to compare outcomes among treatment modalities.
The PROTECT Trial is a prospective, randomized-controlled, non-inferiority, multi-center clinical trial of the Protect PNS System of the tibial nerve versus sacral nerve stimulation (SNS) in the treatment of urinary urgency and incontinence resulting from refractory OAB. Another clinical trial, entitled “Guardian,” is designed to examine the safety and effectiveness of Protect PNS in the treatment of OAB compared to traditional medical management. The Guardian Trial enrolls about 600 subjects with refractory OAB at multiple centers across the U.S. While the GUARDIAN Trial has been completed, the Protect PNS is still considered investigational and is not yet available for general use. Uro Medical is expected to use the study results to support long-term, nationwide payor reimbursement coverage for the Protect PNS System as a mainline therapeutic option for OAB.
Amundsen et al. (2025) stated that implantable tibial nerve neuromodulation (iTNM) systems have recently become commercially available in the U.S. and offer a new method of neurostimulation for the treatment of OAB. In the absence of head-to-head studies, the objective of this meta-analysis was to indirectly compare the safety and effectiveness of sacral nerve stimulation (SNM) and iTNM for the treatment of OAB. These investigators carried out a comprehensive search using terms for OAB and neuromodulation. Primary effectiveness measures included a 50% or greater reduction in UUI episodes, urinary frequency, and/or OAB symptoms. Primary safety measures included the rate of device-related AEs. A total of 20 studies fulfilled selection criteria, totaling 1,416 patients treated with SNM and 350 patients treated with iTNM. No comparative or placebo-controlled studies for SNM and iTNM were identified; thus, the analysis was completed using single-arm results. Weighted averages showed that the UUI responder rate was similar for both SNM and iTNM (71.8% and 71.3%, respectively). Similarly, weighted averages of OAB responder rates were 73.9% for SNM and 79.4% for iTNM. Similar rates of device-related AEs were also observed. The authors concluded that this meta-analysis found similar safety and effectiveness of SNM and iTNM for the treatment of OAB and UUI, including UUI and OAB symptom response rates, reduction in UUI episodes, significant improvements in QOL, and low rates of procedure and device-related AEs. Notably, this comparable effectiveness was observed without the use of a trial phase of neuromodulation in the iTNM studies versus SNM studies. These researchers stated that current findings suggested that iTNM may also have lower surgical re-intervention rates; however, additional follow-up time is needed to confirm if this trend will continue.
The authors stated that this meta-analysis had several drawbacks. First, while this meta-analysis featured a large number of studies and corresponding patients, 11 studies were considered to have a moderate risk of potential bias, most often related to challenges with randomization and blinding due to patient sensation of neurostimulation, along with the retrospective and single-center nature of several of these studies. Differences in study populations, geography, study methods, effectiveness definitions, and stage of device development (i.e., pilot study versus pivotal study versus study completed post-marketing) may also impact the generalizability of the results. Patient-level data were not available for analysis; thus, data for all endpoints were not always available for each study even if they had been collected. These elements, though possible with any meta-analysis and not specific to this review, should be considered when interpreting the presented results. Second, the expected difference between the length of follow-up observed in the selected iTNM and SNM studies (weighted average of 13.0 months and 39.2 months, respectively) should be noted. While SNM devices have been available for commercial use in the U.S. for almost 30 years, iTNM was first FDA-approved less than 2 years ago. Accordingly, the average length of follow-up data available for SNM is much longer than for iTNM. More importantly, most device- and procedure-related AEs notably occurred within the first several months following implantation for both iTNM and SNM devices. Further comparability between later revisions and/or explant rates will certainly need to be assessed. Clearly, devices designed with implanted batteries—both iTNM and SNM—will require eventual surgical replacement. Both the original implant and surgical revisions result in costs to medical systems and patients; published data comparing costs between iTNM and SNM are not yet available. Third, challenges in comparing the frequency of urination were also identified in this analysis, primarily because of consistent differences in urinary frequency reported in the studies completed in Asia, which ultimately may describe a more severe population of patients with OAB. While the reason for this difference is unclear, the frequency was reported with a range of 10 to 14.9 in iTNM and SNM studies completed in North America, Europe, and the Middle East, compared with 21.6 to 29.2 in SNM studies in Asia, resulting in challenges in the comparison of results related to urinary frequency. The impact of iTNM on urinary frequency needs to be further examined in future studies. Fourth, none of the studies identified were head-to-head trials, limiting the ability for direct comparisons. Future randomized controlled trials (RCTs) are needed to provide additional clarity regarding comparative differences in safety and effectiveness and to provide further guidance regarding ideal patient selection for both methods of neuromodulation, tibial versus sacral.
Electrical Nerve Stimulation for Pelvic Floor Dysfunction in Male Stress Incontinence
Berghmans et al. (2013) examined the use of electrical stimulation with non-implanted devices for treating various types of urinary incontinence, including urgency, frequency, and nocturia, specifically in men. The review aimed to evaluate the effectiveness of this treatment compared to no treatment, placebo, or other single interventions, as well as to assess the combined effect of electrical stimulation with another intervention versus that intervention alone. Additionally, it compared different methods of electrical stimulation. The authors conducted a comprehensive search of the Cochrane Incontinence Group Specialized Trials Register, which includes trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, and other sources, up to January 21, 2012. They included randomized and quasi-randomized controlled trials in their analysis. Two reviewers independently assessed the trials for eligibility and evaluated the risk of bias using the Cochrane tool, resolving disagreements through discussion and involving a third reviewer when necessary. The review included six randomized controlled trials (five full papers and one abstract) with considerable variability in interventions, study protocols, electrical stimulation parameters, devices, populations, and outcome measures, encompassing a total of 544 men—305 receiving electrical stimulation and 239 receiving control treatments. Most trials were small, and there was insufficient information to adequately assess bias, with only two employing secure randomization methods. Some evidence suggested that electrical stimulation had a short-term effect in reducing incontinence compared to sham treatment (risk ratio [RR] at six months: 0.38, 95% CI 0.16 to 0.87), but not at 12 months. Four trials compared the effects of adding pelvic floor muscle training (PFMT) to electrical stimulation against PFMT alone or with biofeedback, finding no statistically significant difference in the number of men with urinary incontinence at three months (61% for combined treatment versus 63% for PFMT alone; RR 0.93, 95% CI 0.82 to 1.06). However, the combined treatment resulted in more adverse effects (17% versus 2% with PFMT alone; RR 7.04, 95% CI 1.51 to 32.94), and quality of life appeared to be better with PFMT alone. One small trial found no significant differences between two methods of transcutaneous electrical stimulation (anal versus perineal), although the anal stimulation group reported a lower (better) quality of life score.
In the 2021 "Pelvic, Obstetric and Gynaecological Physiotherapy (POGP) Good Practice Statement" regarding the safety and best practices for neuromuscular electrical stimulation (NMES) in treating pelvic floor muscle dysfunction, the authors note that “many randomized trials have been published on the use of NMES in the treatment of stress urinary incontinence (SUI); however, optimal stimulation parameters and treatment protocols have not yet been established.” A systematic review by Stewart et al. (2017) evaluated 56 studies on the role of NMES in treating SUI. The authors reported that the evidence was of low quality and inadequate, preventing any firm conclusions about the impact of NMES on quality of life (QoL) and cure rates. Furthermore, Stewart et al. (2017) could not determine whether NMES provides additional benefits over pelvic floor muscle training (PFMT), although they did find that NMES was more effective than no active treatment or a sham intervention.
The 2022 National Institute for Health and Care Excellence (NICE) guidelines on "Transcutaneous Electrical Neuromuscular Stimulation for Urinary Incontinence" indicate that the evidence supporting its efficacy is limited in both quantity and quality, necessitating that this procedure be conducted only under special arrangements that ensure clinical governance, informed consent, and appropriate audit or research. Furthermore, they recommend that future research should focus on randomized controlled trials comparing the effectiveness of transcutaneous neuromuscular electrical stimulation combined with pelvic floor muscle exercises against pelvic floor muscle exercises alone.
The American Urological Association (AUA, 2024) does not mention electrical nerve stimulation as a treatment option in the guideline on incontinence after prostate treatment.
Li et al. (2025) investigated electrical pudendal nerve stimulation (EPNS) as a potential clinic-based treatment for post-prostatectomy incontinence (PPI), noting that comparative evidence is scarce. They conducted a retrospective cohort study across three medical centers from 2018 to 2022, comparing EPNS (24 sessions over eight weeks) with pelvic-floor muscle training plus transrectal electrical stimulation (PFMT + TES). The primary outcomes measured were changes from baseline to the end of treatment in the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) score and 24-hour pad-test urine loss, while the Incontinence Impact Questionnaire-7 (IIQ-7) score served as a secondary outcome, with pad-free status recorded six months post-treatment. In adjusted analyses using propensity-score overlap weighting of 389 men, EPNS demonstrated significantly greater improvements than PFMT + TES in ICIQ-UI SF (β -4.34, 95% CI -6.65 to -2.02), 24-hour pad-test urine loss (β -631.26 g, 95% CI -750.81 to -511.70), and IIQ-7 (β -2.86, 95% CI -5.14 to -0.58). Unweighted within-group changes were consistent in direction. At the final follow-up, 32.6% of men in the EPNS group achieved pad-free status compared to 7.0% in the PFMT + TES group. These results suggest that eight weeks of EPNS can significantly alleviate symptom burden and urine loss, leading to noticeable quality-of-life improvements, although further research is necessary to assess long-term effects. The study has several limitations, including a short six-month follow-up that does not determine the persistence of improvements, potential background recovery during this period, and the influence of post-baseline care changes that were not accounted for. Additionally, due to patient circumstances (24% experienced PSA recurrence during follow-up) and the use of phone consultations, a comprehensive symptom reassessment was not feasible for all participants, limiting the data to the presence of ongoing urinary incontinence at the last visit. This binary endpoint lacks the detail of continuous measures, potentially reducing precision and statistical power. Furthermore, as this was not a randomized controlled trial, treatment selection was based on routine patient-clinician choices, which may introduce residual confounding despite overlap weighting. No subjects met the ICS continence standard, although some patients in both groups were pad-free, and the accuracy of the pad test may be compromised despite its common use. The limited sample size in certain subgroups also restricted subgroup analysis. In conclusion, for the overlap-weighted population, EPNS was associated with greater short-term improvements in continence outcomes compared to PFMT + TES, and future research should focus on long-term efficacy and comparative effectiveness in diverse populations through prospective randomization to refine treatment guidelines for PPI.
Tang et al. (2025) highlight that postoperative urinary incontinence (UI) is a common consequence of prostatectomy, which can greatly diminish patients' quality of life. While pelvic floor muscle exercises (PFMEs) are widely used, the effectiveness of electrical stimulation (ES) as a non-invasive adjunct treatment remains a topic of debate. This systematic review and meta-analysis aimed to assess the effectiveness of ES combined with PFME compared to PFME alone for managing UI following radical prostatectomy. A thorough search of databases including PubMed, MEDLINE, EMBASE, Cochrane Library, and ResearchGate identified 10 randomized controlled trials that met the inclusion criteria. The outcomes measured included the 24-hour pad test, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), quality of life (QOL), and incontinence control rates, with data analyzed using Review Manager 5.4.1 through fixed- and random-effects models. The results indicated that short-term ES (≤3 months) significantly improved ICIQ-SF scores (mean difference [MD] = -3.50; 95% confidence interval: -5.11 to -1.89, P <0.0001) and doubled the incontinence control rates (risk ratio = 2.01; P = 0.01), although no significant improvement was found in the 24-hour pad test (MD = -50.07; P = 0.30) or QOL. In contrast, long-term ES (≥6 months) showed significant reductions in urinary leakage as measured by the 24-hour pad test (MD = -21.64; P = 0.02), but did not demonstrate significant differences in ICIQ-SF scores or control rates compared to PFME alone. In conclusion, electrical stimulation therapy appears to be an effective treatment option for patients with post-radical prostatectomy UI, providing significant short-term improvements in UI symptoms and long-term reductions in urinary leakage.
References
The above policy is based on the following references:
General References
- California Technology Assessment Forum (CTAF). Biofeedback as an adjunct to pelvic floor muscle exercises for stress urinary incontinence in women. Technology Assessment. San Francisco, CA: CTAF; June 21, 2006.
- Cody JD, Richardson K, Moehrer B, et al. Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database Syst Rev. 2009;(4):CD001405..
- Eustice S, Roe B, Paterson J. Prompted voiding for the management of urinary incontinence in adults. Cochrane Database Syst Rev. 2000;(2):CD002113.
- Frankel J, Staskin D, Varano S, et al. An evaluation of the efficacy and safety of vibegron in the treatment of overactive bladder. Ther Clin Risk Manag. 2022;18:171-182.
- Glazener CMA, Cooper K. Anterior vaginal repair for urinary incontinence in women. Cochrane Database Syst Rev. 2001;(1):CD001755.
- Glazener CMA, Cooper K. Bladder neck needle suspension for urinary incontinence in women. Cochrane Database Syst Rev. 2004;(2):CD003636.
- Hay-Smith EJC, Bo K, Berghmans LCM, et al. Pelvic floor muscle training for urinary incontinence in women. Cochrane Database Syst Rev. 2006;(1):CD001407.
- Hay-Smith EJC, Dumoulin C. Pelvic floor muscle training versus no treatment, or inactive control treatments, for urinary incontinence in women. Cochrane Database Syst Rev. 2006;(1):CD005654.
- Hay-Smith J, Herbison P, Mørkved S. Physical therapies for prevention of urinary and faecal incontinence in adults. Cochrane Database Syst Rev. 2007;(4):CD003191.
- Holroyd-Leduc JM, Straus SE. Management of urinary incontinence in women: Scientific review. JAMA. 2004;291(8):986-995.
- Hunter KF, Moore KN, Glazener CMA, et al. Conservative management for postprostatectomy urinary incontinence. Cochrane Database Syst Rev. 2007;(2):CD001843.
- Macdonald R, Fink HA, Huckabay C, et al. Pelvic floor muscle training to improve urinary incontinence after radical prostatectomy: A systematic review of effectiveness. BJU Int. 2007;100(1):76-81.
- National Institute for Health and Clinical Excellence (NICE). Urinary Incontinence: The management of urinary incontinence in women. Clinical Guideline 40. London, UK: NICE; 2006.
- Onwude J. Stress incontinence. In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; December 2006.
- Ostaszkiewicz J, Johnston L, Roe B. Habit retraining for the management of urinary incontinence in adults. Cochrane Database Syst Rev. 2004;(2):CD002801.
- Ostaszkiewicz J, Johnston L, Roe B. Timed voiding for the management of urinary incontinence in adults. Cochrane Database Syst Rev. 2004;(1):CD002802.
- Shamliyan T, Wyman J, Kane RL. Nonsurgical treatments for urinary incontinence in adult women: Diagnosis and comparative effectiveness. Comparative Effectiveness Review No. 36. Prepared by the University of Minnesota Evidence-based Practice Center under Contract No. HHSA 290-2007-10064-I. AHRQ Publication No. 11(12)-EHC074-EF. Rockville, MD. Agency for Healthcare Research and Quality; April 2012.
- Thomas LH, Cross S, Barrett J, et al. Treatment of urinary incontinence after stroke in adults. Cochrane Database Syst Rev. 2008;(1):CD004462.
- Vij M, Drake MJ. Clinical use of the β3 adrenoceptor agonist mirabegron in patients with overactive bladder syndrome. Ther Adv Urol. 2015;7(5):241-248.
- Wallace SA, Roe B, Williams K, Palmer M. Bladder training for urinary incontinence in adults. Cochrane Database Syst Rev. 2004;(1):CD001308.
Multichannel Urodynamic Studies
- Assessment and diagnosis. In: Lucas MG, Bedretdinova D, Bosch JLHR, Burkhard F, Cruz F, Nambiar AK, de Ridder DJMK, Tubaro A, Pickard RS. Guidelines on urinary incontinence. Arnhem, The Netherlands: European Association of Urology (EAU); March 2013.
- National Collaborating Centre for Women's and Children's Health. Urinary incontinence: The management of urinary incontinence in women. London, UK: National Institute for Health and Care Excellence (NICE); September 2013.
- Winters JC, Dmochowski RR, Goldman HB, et al. Adult urodynamics: American Urological Association (AUA)/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) guideline. Linthicum, MD: American Urological Association (AUA); April 2012.
Colposuspension and Sling Procedures
- Dean NM, Ellis G, Wilson PD, Herbison GP. Laparoscopic colposuspension for stress urinary incontinence in women. Cochrane Database Syst Rev. 2006;(3):CD002239.
- Lapitan MC, Cody DJ, Grant AM. Open retropubic colposuspension for urinary incontinence in women. Cochrane Database Syst Rev. 2009;(4):CD002912.
- Leizour B, Chevrot A, Wagner L, et al. Adjustable retropubic suburethral sling Remeex®in the treatment of male stress urinary incontinence: One-year results. Prog Urol. 2017;27(4):238-243.
- National Institute for Health and Clinical Excellence (NICE). Insertion of biological slings for stress urinary incontinence in women. Interventional Procedure Guidance 157. London, UK: NICE; 2006.
- Ogah J, Cody JD, Rogerson L. Minimally invasive synthetic suburethral sling operations for stress urinary incontinence in women. Cochrane Database Syst Rev. 2009;(4):CD006375.
- Ontario Ministry of Health and Long Term Care, Medical Advisory Secretariat (MAS). Midurethral slings for women with stress urinary incontinence. Health Technology Policy Assessment. Toronto, ON: MAS; February 2006.
- Rehman H, Bezerra C, Bruschini H, Cody JD. Traditional suburethral sling operations for urinary incontinence in women. Cochrane Database Syst Rev. 2011;(1):CD001754.
- Stav K, Dwyer PL, Rosamilia A, et al. Repeat synthetic mid urethral sling procedure for women with recurrent stress urinary incontinence. J Urol. 2010;183(1):241-246.
Artificial Urinary Sphincter
- Agency for Healthcare Policy and Research (AHCPR). Urinary incontinence in adults. Clinical Practice Guideline. AHCPR Pub. No. 92-0038. Rockville, MD: AHCPR; March 1992.
- Fulford SC, Sutton C, Bales G, et al. The fate of the 'modern' artificial urinary sphincter with a follow-up of more than 10 years. Br J Urol. 1997;79(5):713-716.
- Haab F, Trockman BA, Zimmern PE, Leach GE. Quality of life and continence assessment of the artificial urinary sphincter in men with minimum 3.5 years of followup. J Urol. 1997;158(2):435-439.
- Kreder KJ, Webster GD. Evaluation and management of incontinence after implantation of the artificial urinary sphincter. Urol Clin North Am. 1991;18(2):375-381.
- Leo ME, Barrett DM. Success of the narrow-backed cuff design of the AMS800 artificial urinary sphincter: Analysis of 144 patients. J Urol. 1993;150:1412-1414.
- Levesque PE, Bauer SB, Atala A, et al. Ten-year experience with artificial urinary sphincter in children. J Urol. 1996;156(2 Pt 2):625-628.
- Peyronnet B, Capon G, Belas O, et al. Robot-assisted AMS-800 artificial urinary sphincter bladder neck implantation in female patients with stress urinary incontinence. Eur Urol. 2019b;75(1):169-175.
- Peyronnet B, O'Connor E, Khavari R, et al. AMS-800 Artificial urinary sphincter in female patients with stress urinary incontinence: A systematic review. Neurourol Urodyn. 2019a;38 Suppl 4:S28-S41.
- Pichon Riviere A, Augustovski F, Cernadas C, et al. AMS 800 artificial urinary sphincter for children with urinary incontinence [summary]. Report IRR No. 3. Buenos Aires, Argentina: Institute for Clinical Effectiveness and Health Policy (IECS); 2002.
- Reus CR, Phe V, Dechartres A, et al. Performance and safety of the artificial urinary sphincter (AMS 800) for non-neurogenic women with urinary incontinence secondary to intrinsic sphincter deficiency: A systematic review. Eur Urol Focus. 2020;6(2):327-338.
- Singh G, Thomas DG. Artificial urinary sphincter for post-prostatectomy incontinence. Br J Urol. 1996;77(2):248-251.
Periurethral Injections of Bulking Agents
- Altman D, Ghilotti F, Bellocco R, et al. Transurethral polyacrylamide hydrogel injection therapy in women not eligible for midurethral sling surgery. Female Pelvic Med Reconstr Surg. 2017;23(5):318-323.
- Angioli R, Muzii L, Zullo MA, et al. Use of bulking agents in urinary incontinence. Minerva Ginecol. 2008;60(6):543-550.
- Dmochowski RR, Appell RA. Injectable agents in the treatment of stress urinary incontinence in women: Where are we now? Urology. 2000;56(6 Suppl 1):32-40.
- Eckford SD, Abrams P. Para-urethral collagen implantation for female stress incontinence. Br J Urol. 1991;68:586-589.
- Food and Drug Administration. Bulkamid Urethral Bulking System - P170023. FDA: Silver Spring, MD. Available at: https://www.fda.gov/medical-devices/recently-approved-devices/bulkamid-urethral-bulking-system-p170023. Accessed October 1, 2020.
- Ghoniem G, Corcos J, Comiter C, et al. Cross-linked polydimethylsiloxane injection for female stress urinary incontinence: Results of a multicenter, randomized, controlled, single-blind study. J Urol. 2009;181(1):204-210.
- Herschorn S, Steele DJ, Radomski SB. Followup of intraurethral collagen for female stress urinary incontinence. J Urol. 1996;156(4):1305-1309.
- Hussain SM, Bray R. Urethral bulking agents for female stress urinary incontinence. Neurourol Urodyn. 2019;38(3):887-892.
- Itkonen Freitas A-M, Mentula M, Rahkola-Soisalo P, et al. Tension-free vaginal tape surgery versus polyacrylamide hydrogel injection for primary stress urinary incontinence: A randomized clinical trial. J Urol. 2020;203(2):372-378.
- Kasi AD, Pergialiotis V, Perrea DN, et al. Polyacrylamide hydrogel (Bulkamid®) for stress urinary incontinence in women: A systematic review of the literature. Int Urogynecol J. 2016;27(3):367-375.
- Keegan PE, Atiemo K, Cody J, et al. Periurethral injection therapy for urinary incontinence in women. Cochrane Database Syst Rev. 2007;(3):CD003881.
- Kieswetter H, Fischer M, Wober L, Flamm J. Endoscopic implantation of collagen (GAX) for the treatment of urinary incontinence. Br J Urol. 1992;69(1):22-25.
- McGuire EJ, English SF. Periurethral collagen injection for male and female sphincteric incontinence: Indications, techniques, and results. World J Urol. 1997;15(5):306-309.
- Mohr S, Marthaler C, Imboden S, et al. Bulkamid (PAHG) in mixed urinary incontinence: What is the outcome? Int Urogynecol J 2017;28(11):1657-1661.
- Morgan DM. Stress urinary incontinence in women: Persistent/recurrent symptoms after surgical treatment. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed August 2020.
- National Institute for Clinical Excellence (NICE). Intramural urethral bulking procedures for stress urinary incontinence in women. Interventional Procedure Guidance 138. London, UK: NICE; 2005.
- Plotti F, Zullo MA, Sansone M, et al. Post radical hysterectomy urinary incontinence: A prospective study of transurethral bulking agents injection. Gynecol Oncol. 2009;112(1):90-94.
- Sanchez-Ortiz RF, Broderick GA, Chaikin DC, et al. Collagen injection therapy for post-radical retropubic prostatectomy incontinence: Role of Valsalva leak point pressure. J Urol. 1997;158(6):2132-2136.
- Smith DN, Appell RA, Winters JC, Rackley RR. Collagen injection therapy for female intrinsic sphincteric deficiency. J Urol. 1997;157(4):1275-1278.
- Stricker P, Haylen B. Injectable collagen for type 3 female stress incontinence: The first 50 Australian patients. Med J Aust. 1993;158(2):89-91.
- Tamanini JT, D'Ancona CA, Netto NR Jr. Treatment of intrinsic sphincter deficiency using the Macroplastique Implantation System: Two-year follow-up. J Endourol. 2004;18(9):906-911.
- Ter Meulen PH, Berghmans LC, Nieman FH, van Kerrebroeck PE. Effects of Macroplastique((R)) Implantation System for stress urinary incontinence and urethral hypermobility in women. Int Urogynecol J Pelvic Floor Dysfunct. 2009;20(2):177-183.
- Winters JC, Appell R. Periurethral injection of collagen in the treatment of intrinsic sphincteric deficiency in the female patient. Urol Clin North Am. 1995;22(3):673-678.
Implantable Sacral Nerve Stimulators (e.g., Axonics and InterStim)
- Abrams GM, Wakasa M. Chronic complications of spinal cord injury and disease. UpToDate Inc., Waltham, MA. Last reviewed January 2025.
- Benson K, McCrery R, Taylor C, et al. One-year outcomes of the ARTISAN-SNM study with the Axonics System for the treatment of urinary urgency incontinence. Neurourol Urodyn. 2020;39(5):1482-1488.
- Bosch J, Groen J. Sacral (S3) segmental nerve stimulation as a treatment for urge incontinence in patients with detrusor instability: Results of chronic electrical stimulation using an implantable neural prosthesis. J Urol. 1995;154:504-507.
- Buford K, Eisner H, Vollstedt A, et al. Implantable neuromodulation for neurogenic lower urinary tract dysfunction: A single-institution retrospective study. Int Neurourol J. 2024;28(4):278-284.
- Burrows E, Harris A, Gospodarevskaya E. Sacral nerve stimulation for refractory urinary urge incontinence or urinary retention. MSAC Application 1009. Canberra, ACT: Medicare Services Advisory Committee (MSAC); 2000.
- Canadian Coordinating Office for Health Technology Assessment (CCOHTA). Sacral nerve stimulation device for urinary incontinence. Pre-assessment No. 4. Ottawa, ON: CCOHTA; 2002.
- Dijkema H, Weil EH, Mijs PT, Janknegt RA. Neuromodulation of sacral nerve for incontinence and voiding dysfunction. Eur Urol. 1993;24(1):72-77.
- Elabbady AA, Hassouna MM, Elhilali MM. Neural stimulation for chronic voiding dysfunction. J Urol. 1994;152(6 Pt 1):2076-2080.
- Geynisman-Tan J, Mueller MG, Kenton KS. Satisfaction with a rechargeable sacral neuromodulation system -- A secondary analysis of the ARTISAN-SNM study. Neurourol Urodyn. 2021;40(1):549-554.
- Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU Guideline. Linthicum, MD: American Urologic Association (AUA); 2012.
- Hartmann KE, McPheeters ML, Biller DH, et al. Treatment of overactive bladder in women. Evidence Report/Technology Assessment No. 187. Prepared by the Vanderbilt Evidence-based Practice Center under Contract No. 290-2007-10065-I. AHRQ Publication No. 09-E017. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); August 2009.
- Herbison GP, Arnold EP. Sacral neuromodulation with implanted devices for urinary storage and voiding dysfunction in adults. Cochrane Database Syst Rev. 2009;(2):CD004202.
- Janknegt RA, Weil EH, Eerdmans PH. Improving neuromodulation techniques for refractory voiding dysfunctions: Two-stage implant. Urology. 1997;49(3):358-362.
- Leroi AM, Lenne X, Dervaux B, et al. Outcome and cost analysis of sacral nerve modulation for treating urinary and/or fecal incontinence. Ann Surg. 2011;253(4):720-732.
- Lukacz ES. Urgency urinary incontinence/overactive bladder (OAB) in females: Treatment. UpToDate Inc., Waltham, MA. Last reviewed September 2022.
- Marcelissen TA, Leong RK, Serroyen J, et al. The use of bilateral sacral nerve stimulation in patients with loss of unilateral treatment efficacy. J Urol. 2011;185(3):976-980.
- Medtronic, Inc. Medtronic InterStim Therapy. Information for Prescribers. Minneapolis, MN: Medtronic; 2008.
- National Institute for Clinical Excellence (NICE). Sacral nerve stimulation for urge incontinence and urgency-frequency. Interventional Procedure Guidance 64. London, UK: NICE; June 2004.
- Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat (MAS). Sacral nerve stimulation for urinary urge incontinence, urgenc.y-frequency, urinary retention, and fecal incontinence. Health Technology Literature Review. Toronto, ON: MAS; 2005.
- Palmetto GBA, LLC. Sacral nerve stimulation for the treatment of urinary and fecal incontinence. Local Coverage Determination (LCD) L39543. Medicare Administrative Contractor (MAC) A and B. Columbia, SC: Palmetto GBA; effective November 5, 2023.
- Pezzella A, McCrery R, Lane F, et al. Two-year outcomes of the ARTISAN-SNM study for the treatment of urinary urgency incontinence using the Axonics rechargeable sacral neuromodulation system. Neurourol Urodyn. 2021;40(2):714-721.
- Pichon Riviere A, Augustovski F, Garcia Marti S, et al. Sacral nerve stimulation for the treatment of voiding dysfunction. Summary. IRR No. 225. Buenos Aires, Argentina: Institute for Clinical Effectiveness and Health Policy (IECS); 2011.
- Schmidt RA, Jonas U, Oleson KA, et al. Sacral nerve stimulation for the treatment of refractory urinary urge incontinence. J Urol. 1999;162(2);352-357.
- Shaker HS, Hassouna M. Sacral nerve root neuromodulation: An effective treatment for refractory urge incontinence. J Urol. 1998;159:1516-1519.
- Sun P, Song W. A meta-analysis on the efficacy and safety of sacral neuromodulation for neurogenic bladder or bowel dysfunction. Neuromodulation. 2025;28(5):727-736.
- Thiruchelvam N, Cruz F, Kirby M, et al. A review of detrusor overactivity and the overactive bladder after radical prostate cancer treatment. BJU Int. 2015;116(6):853-861.
- Thon W, et al. Neuromodulation of voiding dysfunction and pelvic pain. World J Urol. 1991;9:138-141.
- Wang A, Rourke E, Sebesta E, Dmochowski R. Axonics® system for treatment of overactive bladder syndrome and urinary urgency incontinence. Expert Rev Med Devices. 2021;18(8):727-732.
- Yu Z, Yang X, Ma T, et al. Effects of non-invasive or minimally invasive neuromodulation techniques on neurogenic lower urinary tract dysfunction after spinal cord injury: A network meta-analysis. Arch Phys Med Rehabil. 2025;106(6):961-972.
Electrical Muscle Stimulation
- Caputo RM, Benson JT, McClellan E. Intravaginal maximal electrical stimulation in the treatment of urinary incontinence. J Reprod Med. 1993;38(9):667-671.
- Dougall DS. The effects of interferential therapy on incontinence and frequency of micturition. Physiotherapy. 1985;71(3):135-136.
- Eriksen BC, Eik-Nes SH. Long-term electrostimulation of the pelvic floor: Primary therapy in female stress incontinence? Urol Int. 1989;44(2):90-95.
- Fall M, Lindstrom S. Electrical stimulation: A physiologic approach to the treatment of urinary incontinence. Urologic Clin North Am. 1991;18(2):393-407.
- Fantl JA, Newman DK, Colling J, et al. Urinary incontinence in adults: Acute and chronic management. Clinical Practice Guideline No. 2. 1996 Update. AHCPR Publication No. 96-0682. Rockville, MD: Agency for Health Care Policy and Research (AHCPR); March 1996.
- Indrekvam S, Hunskaar S. Side effects, feasibility, and adherence to treatment during home-managed electrical stimulation for urinary incontinence: A Norwegian national cohort of 3,198 women. Neurourol Urodyn. 2002;21(6):546-552.
- Peeker I, Peeker R. Early diagnosis and treatment of genuine stress urinary incontinence in women after pregnancy: Midwives as detectives. J Midwifery Womens Health. 2003;48(1):60-66.
- Sand PK, Richardson DA, Staskin DR, et al. Pelvic floor electrical stimulation in the treatment of genuine stress incontinence: A multicenter, placebo-controlled trial. Am J Obstet Gynecol. 1995;173(1):72-79.
- Smith JJ. Intravaginal stimulation randomized trial. J Urol. 1996;155:127-130.
The Neocontrol™System
- Culligan PJ, Blackwell L, Murphy M, et al. A randomized, double-blinded, sham-controlled trial of postpartum extracorporeal magnetic innervation to restore pelvic muscle strength in primiparous patients. Am J Obstet Gynecol. 2005;192(5):1578-1582.
- Feldman MD. Magnetic stimulation for the treatment of urinary incontinence in women. Technology Assessment. San Francisco, CA: California Technology Assessment Forum; October 20, 2004.
- Galloway N, et al. Multicenter trial: Extracorporeal magnetic innervation (ExMI) for the treatment of stress urinary incontinence. Proceedings of the 1st International Continence Society Meeting, hosted by the World Health Organization, Monaco, June 1998.
- Galloway NT, El-Galley RE, Sand PK, et al. Update on extracorporeal magnetic innervation (EXMI) therapy for stress urinary incontinence. Urology. 2000;56(6 Suppl 1):82-86.
- Hou W-H, Lin P-C, Lee P-H, et al. Effects of extracorporeal magnetic stimulation on urinary incontinence: A systematic review and meta-analysis. J Adv Nurs. 2020;76(9):2286-2298.
- Strojek K, Strączynska A, Radziminska A, Weber-Rajek M. The effects of extracorporeal magnetic innervation in the treatment of women with urinary incontinence: A systematic review. J Clin Med. 2023;12(17):5455.
- Sun MJ, Sun R, Chen LJ. The therapeutic efficiency of extracorporeal magnetic innervation treatment in women with urinary tract dysfunction following radical hysterectomy. J Obstet Gynaecol. 2015;35(1):74-78.
- Unsal A, Saglam R, Cimentepe E. Extracorporeal magnetic stimulation for the treatment of stress and urge incontinence in women -- results of 1-year follow-up. Scand J Urol Nephrol. 2003;37(5):424-428.
- Voorham-van der Zalm PJ, Pelger RC, Stiggelbout AM, et al. Effects of magnetic stimulation in the treatment of pelvic floor dysfunction. BJU Int. 2006;97(5):1035-1038.
- Yokoyama T, Fujita O, Nishiguchi J, et al. Extracorporeal magnetic innervation treatment for urinary incontinence. Int J Urol. 2004;11(8):602-606.
- Yokoyama T, Nishiguchi J, Watanabe T, et al. Comparative study of effects of extracorporeal magnetic innervation versus electrical stimulation for urinary incontinence after radical prostatectomy. Urology. 2004;63(2):264-267.
Vaginal Cones
- Agency for Healthcare Policy and Research (AHCPR). Urinary incontinence in adults. Clinical Practice Guideline. AHCPR Pub. No. 92-0038. Rockville, MD: AHCPR; March 1992.
- Fischer W, Linde A. Pelvic floor findings in urinary incontinence -- results of conditioning using vaginal cones. Acta Obstet Gynecol Scand. 1997;76(5):455-460.
- Herbison P, Plevnik S, Mantle J. Weighted vaginal cones for urinary incontinence. Cochrane Database Syst Rev. 2002;(1):CD002114.
- Kato K, Kondo A. Clinical value of vaginal cones for the management of female stress incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 1997;8(5):314-317.
- Olah KS, Bridges N, Denning J, Farrar DJ. The conservative management of patients with symptoms of stress incontinence: A randomized, prospective study comparing weighed vaginal cones and interferential therapy. Am J Obstet Gynecol. 1990;162(1):87-92.
Pessaries
- Bash KL. Review of vaginal pessaries. Obstet Gynecol Surv. 2000;55(7):455-460.
- Davila GW, Neal D, Horbach N, et al. A bladder-neck support prosthesis for women with stress and mixed incontinence. Obstet Gynecol. 1999;93(6):938-942.
- Davila GW, Ostermann KV. The bladder neck support prosthesis: A nonsurgical approach to stress incontinence in adult women. Am J Obstet Gynecol. 1994;171(1):206-211.
- Kondo A, Yokoyama E, Koshiba K, et al. Bladder neck support prosthesis: A nonoperative treatment for stress or mixed urinary incontinence. J Urol. 1997;157(3):824-827.
- Mouritsen L. Effect of vaginal devices on bladder neck mobility in stress incontinent women. Acta Obstet Gynecol Scand. 2001;80(5):428-431.
- Shaikh S, Ong EK, Glavind K, et al. Mechanical devices for urinary incontinence in women. Cochrane Database Syst Rev. 2006;(3):CD1756.
- Viera AJ, Larkins-Pettigrew M. Practical use of the pessary. Am Fam Physician. 2000;61(9):2719-2726, 2729.
Tension-Free Vaginal Tape Procedure
- Abdel-Fattah M, Barrington JW, Arunkalaivanan AS. Pelvicol pubovaginal sling versus tension-free vaginal tape for treatment of urodynamic stress incontinence: A prospective randomized three-year follow-up study. Eur Urol. 2004;46(5):629-635.
- Aggressive Research Intelligence Facility (ARIF). Tension free vaginal tape (TVT). Female urinary incontinence. Requests for Information -- Completed. Birmingham, UK: University of Birmingham; November 1999.
- Bezerra CA, Bruschini H, Cody DJ. Traditional suburethral sling operations for urinary incontinence in women. Cochrane Database Syst Rev. 2005;(3):CD001754.
- Boustead GB. The tension-free vaginal tape for treating female stress urinary incontinence. BJU Int. 2002;89(7):687-693.
- Canadian Coordinating Office for Health Technology Assessment (CCOHTA). Tension-free vaginal tape (TVT) for urinary incontinence. Pre-assessment No. 5. Ottawa, ON: CCOHTA; 2002.
- Cody J, Wyness L, Wallace S, et al. Systematic review of the clinical effectiveness of tension-free vaginal tape for treatment of urinary stress incontinence. Health Technol Assess. 2003;7(21):1-202.
- deTayrac R, Deffieux X, Droupy S, et al. A prospective randomized trial comparing tension-free vaginal tape and transobturator suburethral tape for surgical treatment of stress urinary incontinence. Am J Obstet Gynecol. 2004;190(3):602-608.
- Farrell SA, Beckerson L, Epp A, et al., and the Sub-Committee on Urogynaegology, Society of Obstetricians and Gynaecologists of Canada (SOGC). Tension-free vaginal tape (TVT) procedure. SOGC Technical Updates. J Obstet Gynaecol Can. 2003;25(8):692-694.
- He P, Zou J, Gong B, et al. Systematic review and meta-analysis of the efficacy of tension-free vaginal tape on pelvic organ prolapse complicated by stress urinary incontinence. Ann Palliat Med. 2021;10(12):12589-12597.
- L'Agence Nationale d'Accreditation d'Evaluation en Sante (ANAES). Evaluation en Sante. Assessment of tension-free vaginal tapes in patients with urinary incontinence during efforts. Paris, France: ANAES; 2002.
- Merlin T, Arnold E, Petros P, et al. A systematic review of tension-free urethropexy for stress urinary incontinence: Intravaginal slingplasty and the tension-free vaginal tape procedures. BJU Int. 2001;88(9):871-880.
- Meschia M, Pifarotti P, Spennacchio M, et al. A randomized comparison of tension-free vaginal tape and endopelvic fascia plication in women with genital prolapse and occult stress urinary incontinence. Am J Obstet Gynecol. 2004;190(3):609-613.
- Mundy L, Merlin T, Hodgkinson B, Parrella A. Gynecare TVT Obturator System for the treatment of female stress urinary incontinence. Horizon Scanning Prioritising Summary - Volume 3. Adelaide, SA: Adelaide Health Technology Assessment (AHTA) on behalf of National Horizon Scanning Unit (HealthPACT and MSAC); 2004.
- National Horizon Scanning Centre (NHSC). Tension free vaginal tape for urinary incontinence -- Horizon scanning review. New and Emerging Technology Briefing. Birmingham, UK: NHSC; 2000.
- National Institute for Clinical Excellence (NICE). Guidance on the use of tension-free vaginal tape (Gynecare TVT) for stress incontinence. Technology Appraisal Guidance 56. London, UK: NICE; 2003.
- Nilsson CG, Falconer C, Rezapour M. Seven-year follow-up of the tension-free vaginal tape procedure for treatment of urinary incontinence. Obstet Gynecol. 2004;104(6):1259-1262.
- Novara G, Ficarra V, Boscolo-Berto R, et al. Tension-free midurethral slings in the treatment of female stress urinary incontinence: A systematic review and meta-analysis of randomized controlled trials of effectiveness. Eur Urol. 2007;52(3):663-678.
- Novara G, Galfano A, Boscolo-Berto R, et al. Complication rates of tension-free midurethral slings in the treatment of female stress urinary incontinence: A systematic review and meta-analysis of randomized controlled trials comparing tension-free midurethral tapes to other surgical procedures and different devices. Eur Urol. 2008;53(2):288-308.
- Nygaard IE, Heit M. Stress urinary incontinence. Obstet Gynecol. 2004;104(3):607-620.
- Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat. Tension-free vaginal tape for stress urinary incontinence. Health Technology Literature Review. Toronto. ON: Ontario Ministry of Health and Long-Term Care; 2004.
- Paraiso MF, Walters MD, Karram MM, Barber MD. Laparoscopic Burch colposuspension versus tension-free vaginal tape: A randomized trial. Obstet Gynecol. 2004;104(6):1249-1258.
- Rentzhog L, Hellström A-L, Kinn A-C, et al. Evidence-based treatment of stress urinary incontinence. SBU Reports. Stockholm, Sweden: Swedish Council on Technology Assessment in Health Care (SBU); January 2000.
- UK National Health Service (NHS). What is 'Tension free vaginal tape procedure' for urinary stress incontinence in women? What is the evidence for its effectiveness? ATTRACT Database. Wales, UK; NHS; 2001.
- Valpas A, Kivela A, Penttinen J, et al. Tension-free vaginal tape and laparoscopic mesh colposuspension for stress urinary incontinence. Obstet Gynecol. 2004;104(1):42-49.
- Ward KL, Hilton P; UK and Ireland TVT Trial Group. A prospective multicenter randomized trial of tension-free vaginal tape and colposuspension for primary urodynamic stress incontinence: Two-year follow-up. Am J Obstet Gynecol. 2004;190(2):324-331.
Radiofrequency Electrothermal Energy
- Appell RA, Davila GW. Treatment options for patients with suboptimal response to surgery for stress urinary incontinence. Curr Med Res Opin. 2007;23(2):285-292.
- Appell RA, Juma S, Wells WG, et al. Transurethral radiofrequency energy collagen micro-remodeling for the treatment of female stress urinary incontinence. Neurourol Urodyn. 2006;25(4):331-336.
- Appell RA, Singh G, Klimberg IW, Graham C, Juma S, Wells WG, Kanellos A, Reilley SF. Nonsurgical, radiofrequency collagen denaturation for stress urinary incontinence: Retrospective 3-year evaluation. Expert Rev Med Devices. 2007;4(4):455-461.
- Appell RA. Transurethral collagen denaturation for women with stress urinary incontinence. Curr Urol Rep. 2008;9(5):373-379.
- Buchsbaum GM, McConville J, Korni R, Duecy EE. Outcome of transvaginal radiofrequency for treatment of women with stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18(3):263-265.
- Dmochowski R, Appell RA. Advancements in minimally invasive treatments for female stress urinary incontinence: Radiofrequency and bulking agents. Curr Urol Rep. 2003;4(5):350-355.
- Elser DM, Mitchell GK, Miklos JR, et al. Nonsurgical transurethral collagen denaturation for stress urinary incontinence in women: 12-month results from a prospective long-term study. J Minim Invasive Gynecol. 2009;16(1):56-62.
- Ismail SI. Radiofrequency remodelling of the endopelvic fascia is not an effective procedure for urodynamic stress incontinence in women. Int Urogynecol J Pelvic Floor Dysfunct. 2008;19(9):1205-1209.
- Karliner L. Radiofrequency micro-remodeling for the treatment of female stress urinary incontinence. A Technology Assessment. San Francisco, CA: California Technology Assessment Forum (CTAF); October 15, 2008.
- Lenihan JP, Palacios P, Sotomayor M. Oral and local anesthesia in the nonsurgical radiofrequency-energy treatment of stress urinary incontinence. Minim Invasive Gynecol. 2005;12(5):415-419.
- Lenihan JP. Comparison of the quality of life after nonsurgical radiofrequency energy tissue micro-remodeling in premenopausal and postmenopausal women with moderate-to-severe stress urinary incontinence. Am J Obstet Gynecol. 2005;192(6):1995-1998; discussion 1999-2001.
- Ribeiro FC, Silva MLA, da Silva MAPS, et al. Use of radiofrequency for the treatment of urinary incontinence in women: A systematic review. Rev Assoc Med Bras (1992). 2021;67(12):1857-1862.
- Ross JW, Galen DI, Abbott K, et al. A prospective multisite study of radiofrequency bipolar energy for treatment of genuine stress incontinence. J Am Assoc Gynecol Laparosc. 2002;9(4):493-499.
- Sotomayor M, Bernal GF. Transurethral delivery of radiofrequency energy for tissue micro-remodeling in the treatment of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2003;14(6):373-379.
- Sotomayor M, Bernal GF. Twelve-month results of nonsurgical radiofrequency energy micro-remodeling for stress incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2005;16(3):192-196; discussion 196.
- Vianello A, Costantini E, Del Zingaro M, Porena M. Mini-invasive techniques for the treatment of female stress urinary incontinence. Minerva Ginecol. 2007;59(6):557-569.
Percutaneous Tibial Nerve Stimulation
- Amundsen CL, Sutherland SE, Kielb SJ, Dmochowski RR. Sacral and implantable tibial neuromodulation for the management of overactive bladder: A systematic review and meta-analysis. Adv Ther. 2025;42(1):10-35.
- BlueCross BlueShield Association (BCBSA), Technology Evaluation Center (TEC). Percutaneous tibial nerve stimulation for the treatment of voiding dysfunction. TEC Assessment Program. Chicago, IL: BCBSA; March 2011;25(8).
- Cameron AP, Chung DE, Dielubanza EJ, et al. The AUA/SUFU guideline on the diagnosis and treatment of idiopathic overactive bladder. J Urol. 2024;212(1):11-20.
- De Gennaro M, Capitanucci ML, Mastracci P, et al. Percutaneous tibial nerve neuromodulation is well tolerated in children and effective for treating refractory vesical dysfunction. J Urol. 2004;171(5):1911-1913.
- Govier FE, Litwiller S, Nitti V, et al. Percutaneous afferent neuromodulation for the refractory overactive bladder: Results of a multicenter study. J Urol. 2001;165(4):1193-1198.
- Hoebeke P, Renson C, Petillon L, et al. Percutaneous electrical nerve stimulation in children with therapy resistant nonneuropathic bladder sphincter dysfunction: A pilot study. J Urol. 2002;168(6):2605-2607; discussion 2607-2608.
- Jefferson FA, Hanson KT, Khan AA, et al. Patterns of care following procedural intervention among women with overactive bladder. Neurourol Urodyn. 2025 Jun 3 [Online ahead of print].
- Jericevic D, Shapiro K, Bowman M, et al. Who progresses to third-line therapies for overactive bladder? Trends from the AQUA registry. Urol Pract. 2024;11(2):394-401.
- Kobashi K, Nitti V, Margolis E, et al. A prospective study to evaluate efficacy using the Nuro percutaneous tibial neuromodulation system in drug-naive patients with overactive bladder syndrome. Urology. 2019;131:77-82.
- Krivoborodov GG, Mazo EB, Shvarts PG. Afferent stimulation of the tibial nerve in patients with hyperactive bladder. Urologiia. 2002;(5):36-39.
- Lukacz ES. Urgency urinary incontinence/overactive bladder (OAB) in females: Treatment. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed June 2025.
- MacDiarmid SA, Peters KM, Shobeiri SA, et al. Long-term durability of percutaneous tibial nerve stimulation for the treatment of overactive bladder. J Urol. 2010;183(1):234-240.
- Peters KM, Carrico DJ, Wooldridge LS, et al. Percutaneous tibial nerve stimulation for the long-term treatment of overactive bladder: 3-year results of the STEP study. J Urol. 2013;189(6):2194-2201.
- Sirls LT, Schonhoff A, Waldvogel A, Peters KM. Development of an implant technique and early experience using a novel implantable pulse generator with a quadripolar electrode array at the tibial nerve for refractory overactive bladder. Neurourol Urodyn. 2023;42(2):427-435.
- U.S. Food and Drug Administration (FDA), Center for Devices and Radiologic Health (CDRH). Urgent PC Neurostimulation System. Summary of Safety and Effectiveness Data. 510(k) No. K052025. Rockville, MD: FDA; October 17, 2005.
- van Balken MR. Percutaneous tibial nerve stimulation: The Urgent PC device. Expert Rev Med Devices. 2007;4(5):693-698.
- van der Pal F, van Balken MR, Heesakkers JP, et al. Correlation between quality of life and voiding variables in patients treated with percutaneous tibial nerve stimulation. BJU Int. 2006a;97(1):113-116.
- van der Pal F, van Balken MR, Heesakkers JP. Percutaneous tibial nerve stimulation in the treatment of refractory overactive bladder syndrome: Is maintenance treatment necessary? BJU Int. 2006b;97(3):547-550.
- Vandoninck V, van Balken MR, Finazzi Agro E, et al. Percutaneous tibial nerve stimulation in the treatment of overactive bladder: Urodynamic data. Neurourol Urodyn. 2003;22(3):227-232.
Subcutaneous Tibial Nerve Stimulation (eCoin)
- Al-Danakh A, Safi M, Alradhi M, et al. Posterior tibial nerve stimulation for overactive bladder: Minechanism, classification, and management outlines. Parkinsons Dis. 2022;2022:2700227.
- Bressington MJ, Scholtz D, Hooshiary A, et al. Device evaluation: eCoin #x2013; implantable tibial nerve stimulator for overactive bladder. Expert Rev Med Devices. 2023;20(11):899-904.
- Kaaki B, English S, Gilling P, et al. Six-month outcomes of reimplantation of a coin-sized tibial nerve stimulator for the treatment of overactive bladder syndrome with urgency urinary incontinence. Female Pelvic Med Reconstr Surg. 2022;28(5):287-292. in
- Gilling P, Meffan P, Kaaki B, et al. Twelve-month durability of a fully-implanted, nickel-sized and shaped tibial nerve stimulator for the treatment of overactive bladder syndrome with urgency urinary incontinence: A single-arm, prospective study. Urology. 2021;157:71-78.
- Lucente V, Giusto L, MacDiarmid S. Two-year pivotal study analysis of the safety and efficacy of implantable tibial nerve stimulation with eCoin® for urgency urinary incontinence. Urology. 2024;194:17-23.
- Lucente V, Morrisroe S, Schiff W, Barber N. A prospective study on the effectiveness of sensory and sub-sensory stimulation amplitudes Using eCoin® implantable tibial nerve stimulation in reducing urgency urinary incontinence episodes and enhancing quality of life. Cureus. 2025;17(3):e81121.
- MacDiarmid S, Staskin DR, Lucente V, et al. Feasibility of a fully implanted, nickel sized and shaped tibial nerve stimulator for the treatment of overactive bladder syndrome with urgency urinary incontinence. J Urol. 2019;201(5):967-972.
- Rogers A, Bragg S, Ferrante K, et al. Pivotal study of leadless tibial nerve stimulation with eCoin® for urgency urinary incontinence: An open-label, single arm trial. J Urol. 2021;206(2):399-408.
- Rogers A, Sen SK. Placement of a coin-sized implantable tibial neurostimulator (eCoin device) for urgency urinary incontinence. Urology Video Journal. 2021;10:100079. Available at: https://www.ics.org/2020/abstract/614.
- Smith A. What’s on the horizon for implantable tibial nerve stimulation? American Urological Association. June 1, 2022. Available at: https://auanews.net.
Subcutaneous Tibial Nerve Stimulation (Altaviva)
- Lee UJ, Xavier K, Benson K, et al. Rationale and design of an implant procedure and pivotal study to evaluate safety and effectiveness of Medtronic's tibial neuromodulation device. Contemp Clin Trials Commun. 2023;35:101198.
- Lee U, Xavier K, Carey J, et al. Implantable tibial neuromodulation therapy improves symptoms of urge urinary incontinence from the TITAN 2 pivotal study. J Urol. 2026 Jan 26. Epub ahead of print.
- Peters KM. Editorial comment. J Urol. 2026 Feb 13. Epub ahead of print.
Extraurethral (Non-Circumferential) Retropubic Adjustable Compression Devices (The ProACT Therapy System)
- Aboseif SR, Franke EI, Nash SD, et al. The adjustable continence therapy system for recurrent female stress urinary incontinence: 1-year results of the North America Clinical Study Group. J Urol. 2009;181(5):2187-2191.
- Australian Safety and Efficacy Register of New Interventional Procedures - Surgical (ASERNIP-S). ProACT Therapy for male stress urinary incontinence. Horizon Scanning Prioritizing Summary. Canberra, ACT; ASERNIP-S for HealthPACT and MSAC; September 2006.
- Gilling PJ. New treatments for recurrent stress incontinence. J Urol. 2009;181(5):1992-1993.
- Kocjancic E, Crivellaro S, Ranzoni S, et al. Adjustable continence therapy for severe intrinsic sphincter deficiency and recurrent female stress urinary incontinence: Long-term experience. J Urol. 2010;184(3):1017-1021.
- National Institute for Health and Clinical Excellence (NICE). Insertion of extraurethral (non-circumferential) retropubic adjustable compression devices for stress urinary incontinence in women. Interventional Procedure Guidance 133. London, UK: NICE; July 2005.
- National Institute for Health and Clinical Excellence (NICE). Insertion of extraurethral (non-circumferential) retropubic adjustable compression devices for stress urinary incontinence in men. Interventional Procedure Consultation Document. London, UK: NICE; March 2007.
- Phe V, Nguyen K, Roupret M, et al. A systematic review of the treatment for female stress urinary incontinence by ACT® balloon placement (Uromedica, Irvine, CA, USA). World J Urol. 2014;32(2):495-505.
Transobturator Tape Procedure
- Barber MD, Kleeman S, Karram MM, et al. Transobturator tape compared with tension-free vaginal tape for the treatment of stress urinary incontinence: A randomized controlled trial. Obstet Gynecol. 2008;111(3):611-621.
- Barry C, Lim YN, Muller R, et al. A multi-centre, randomised clinical control trial comparing the retropubic (RP) approach versus the transobturator approach (TO) for tension-free, suburethral sling treatment of urodynamic stress incontinence: The TORP study. Int Urogynecol J Pelvic Floor Dysfunct. 2008;19(2):171-178.
- Hartmann KE, McPheeters ML, Biller DH, et al. Treatment of overactive bladder in women. Evidence Report/Technology Assessment No. 187. Prepared by the Vanderbilt Evidence-based Practice Center under Contract No. 290-2007-10065-I. AHRQ Publication No. 09-E017. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); August 2009.
- Koch YK, Zimmern P. A critical overview of the evidence base for the contemporary surgical management of stress incontinence. Curr Opin Urol. 2008;18(4):370-376.
- Latthe PM, Foon R, Toozs-Hobson P. Transobturator and retropubic tape procedures in stress urinary incontinence: A systematic review and meta-analysis of effectiveness and complications. BJOG. 2007;114(5):522-531.
- National Collaborating Centre for Women's and Children's Health. Urinary incontinence: Management of urinary incontinence in women. Clinical Guideline 40. Commissioned by the National Institute for Health and Clinical Excellence. London, UK: RCOG Press; October 2006.
- National Institute for Health and Clinical Excellence (NICE). Transobturator foramen procedures for stress urinary incontinence. Interventional Procedures Guidance 107 [withdrawn]. London, UK: NICE; January 2005.
- Robert M, Farrell SA, Easton WA, et al; Society of Obstetricians and Gynaecologists of Canada. Choice of surgery for stress incontinence. J Obstet Gynaecol Can. 2005;27(10):964-980.
- Rogers RG. Clinical practice. Urinary stress incontinence in women. N Engl J Med. 2008;358(10):1029-1036.
- Sivanesan K, Sathiyathasan S, Ghani R. Transobturator tension free vaginal tapes and bladder injury. Arch Gynecol Obstet. 2009;279(1):5-7.
- Sung VW, Schleinitz MD, Rardin CR, et al. Comparison of retropubic vs transobturator approach to midurethral slings: A systematic review and meta-analysis. Am J Obstet Gynecol. 2007;197(1): 3-11.
- Tahseen S, Reid P. Effect of transobturator tape on overactive bladder symptoms and urge urinary incontinence in women with mixed urinary incontinence. Obstet Gynecol. 2009;113(3):617-623.
Urethral Inserts
- Miller JL, Bavendam T. Treatment with the Reliance urinary control insert: One-year experience. J Endourol. 1996;10(3):287-292.
- Robinson H, Schulz J, Flood C, et al. A randomized controlled trial of the NEAT expandable tip continence device. Int Urogynecol J Pelvic Floor Dysfunct. 2003;14(3):199-203; discussion 203.
- Sirls LT, Foote JE, Kaufman JM, et al. Long-term results of the FemSoft urethral insert for the management of female stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2002;13(2):88-95; discussion 95.
- Staskin D, Bavendam T, Miller J, et al. Effectiveness of a urinary control insert in the management of stress urinary incontinence: Early results of a multicenter study. Urology. 1996;47(5):629-636.
Pudendal Nerve Stimulation
- Groen J, Amiel C, Bosch JL. Chronic pudendal nerve neuromodulation in women with idiopathic refractory detrusor overactivity incontinence: Results of a pilot study with a novel minimally invasive implantable mini-stimulator. Neurourol Urodyn. 2005;24(3):226-230.
- Seif C, van der Horst C, Naumann CM, et al. Pudendal nerve stimulation therapy of the overactive bladder -- an alternative to sacral neuromodulation? Aktuelle Urol. 2005;36(3):234-238.
- Spinelli M, Malaguti S, Giardiello G, et al. A new minimally invasive procedure for pudendal nerve stimulation to treat neurogenic bladder: Description of the method and preliminary data. Neurourol Urodyn. 2005;24(4):305-309.
Cunningham Clamp
- Clemens JQ. Urinary incontinence in men. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed January 2012.
- Madjar S, Raz S, Gousse AE. Fixed and dynamic urethral compression for the treatment of post-prostatectomy urinary incontinence: Is history repeating itself? J Urol. 2001;166(2):411-415.
- Moore KN, Schieman S, Ackerman T, et al. Assessing comfort, safety, and patient satisfaction with three commonly used penile compression devices. Urology. 2004;63(1):150-154.
Autologous Myoblast Transplantation
- Elmi A, Kajbafzadeh AM, Tourchi A, et al. Safety, efficacy and health related quality of life of autologous myoblast transplantation for treatment of urinary incontinence in children with bladder exstrophy-epispadias complex. J Urol. 2011;186(5):2021-2026.
Pelvic Floor Electrical Stimulation
- American Urological Association (AUA). Incontinence after prostate treatment: AUA/GURS/SUFU guideline. Amended 2024. Available at: https://www.auanet.org/guidelines-and-quality/guidelines/incontinence-after-prostate-treatment. Accessed January 21, 2026.
- Berghmans B, Hendriks E, Bernards A, et al. Electrical stimulation with non-implanted electrodes for urinary incontinence in men. Cochrane Database Syst Rev. 2013;2013(6):CD001202.
- Campbell SE, et al. Conservative management for postprostatectomy urinary incontinence. Cochrane Database Syst Rev, 2012;1:CD001843.
- Carlson K, Nitti V. Prevention and management of incontinence following radical prostatectomy. Urol Clin North Am. 2001;28(3).
- Grise P, Thurman S. Urinary incontinence following treatment of localized prostate cancer. Cancer Control. 2001;8(6):532-539.
- Li T, Wang S, Chen Q, et al. Electrical pudendal nerve stimulation versus pelvic floor muscle training with transrectal electrical stimulation for post-radical prostatectomy incontinence: A cohort study. Sci Rep. 2025;15(1):41603.
- Pelvic, Obstetric and Gynaecological Physiotherapy (POGP) Good Practice Statement: Safety and best practice in neuromuscular electrical stimulation for pelvic floor muscle dysfunction. 2021. Available at: https://thepogp.co.uk/_userfiles/pages/files/journals/128/11_good_practice_statement.pdf. Accessed January 21, 2026.
- National Institute for Health and Care Excellence (NICE). Transcutaneous electrical neuromuscular stimulation for urinary incontinence. 2021. Available at: https://www.nice.org.uk/guidance/ipg735. Accessed January 21, 2026.
- Richardson DA, Miller KL, Siegel SW, et al. Pelvic floor electrical stimulation: A comparison of daily and every-other-day therapy for genuine stress incontinence. Urology. 1996;48(1):110-118.
- Sand PK, Richardson DA, Staskin DR, et al. Pelvic floor electrical stimulation in the treatment of genuine stress incontinence: A multicenter, placebo-controlled trial. Am J Obstet Gynecol. 1995;173(1):72-79.
- Siegel SW, Richardson DA, Miller KL, et al. Pelvic floor electrical stimulation for the treatment of urge and mixed urinary incontinence in women. Urology. 1997;50(6):934-940.
- Tang G, Liu M, Chen X, et al. Effectiveness of electrical stimulation for treating male urinary incontinence after prostatectomy: A meta-analysis and systematic review. Int J Surg. 2025;111(9):6351-6361.
- Wille S, et al. Pelvic floor exercises, electrical stimulation and biofeedback after radical prostatectomy: Results of a prospective randomized trial. Urololgy. 2003;170(2 Pt 1):490-493.
- Yamanishi T et al. Randomized, placebo controlled study of electrical stimulation with pelvic floor muscle training for severe urinary incontinence after radical prostatectomy. J Urol. 2010;184(5):2007-2012.
- Zhu VP et al. Pelvic floor electrical stimulation for postprostatectomy urinary incontinence: A meta-analysis. Urology. 2012;79(3).
Other Experimental, Investigational, or Unproven Interventions for Urinary Incontinence
- Alsulihem A, Corcos J. The use of vaginal lasers in the treatment of urinary incontinence and overactive bladder, systematic review. Int Urogynecol J. 2021;32(3):553-572.
- Angulo JC, Schonburg S, Giammò A, et al. Systematic review and meta-analysis comparing Adjustable Transobturator Male System (ATOMS) and Adjustable Continence Therapy (ProACT) for male stress incontinence. PLoS One. 2019;14(12):e0225762.
- Borch L, Rittig S, Kamperis K, et al. No immediate effect on urodynamic parameters during transcutaneous electrical nerve stimulation (TENS) in children with overactive bladder and daytime incontinence - A randomized, double-blind, placebo-controlled study. Neurourol Urodyn. 2017;36(7):1788-1795.
- Burdzinska A, Dybowski B, Zarychta-Wiśniewska W, et al. Intraurethral co-transplantation of bone marrow mesenchymal stem cells and muscle-derived cells improves the urethral closure. Stem Cell Res Ther. 2018;9(1):239.
- Carr LK, Robert M, Kultgen PL, et al. Autologous muscle derived cell therapy for stress urinary incontinence: A prospective, dose ranging study. J Urol. 2013;189(2):595-601.
- Chen Y, Peng L, Liu M, et al. Diagnostic value of transperineal ultrasound in patients with stress urinary incontinence (SUI): A systematic review and meta-analysis. World J Urol. 2023;41(3):687-693.
- Clemens JQ. Urinary incontinence in men. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed May 2017; December 2019.
- Cornu JN, Doucet C, Sebe P, et al. Prospective evaluation of intrasphincteric injections of autologous muscular cells in patients with stress urinary incontinence following radical prostatectomy. Prog Urol. 2011;21(12):859-865.
- Dankova I, Pyrgidis N, Tishukov M, et al. Efficacy and safety of platelet-rich plasma injections for the treatment of female sexual dysfunction and stress urinary incontinence: A systematic review. Biomedicines. 2023;11(11):2919.
- Deegan EG, Stothers L, Kavanagh A, Macnab AJ. Quantification of pelvic floor muscle strength in female urinary incontinence: A systematic review and comparison of contemporary methodologies. Neurourol Urodyn. 2018;37(1):33-45.
- DuBeau CE. Treatment of urinary incontinence. UpToDate [serial online]. Waltham, MA: UpToDate; reviewed October 2012.
- Esquinas C, Angulo JC. Effectiveness of adjustable transobturator male system (ATOMS) to treat male stress incontinence: A systematic review and meta-analysis. Adv Ther. 2019;36(2):426-441.
- Fazeli Z, Faramarzi S, Ahadi A, et al. Efficiency of mesenchymal stem cells in treatment of urinary incontinence: A systematic review on animal models. Regen Med. 2019;14(1):69-76.
- Freites J, Stewart F, Omar MI, et al. Laparoscopic colposuspension for urinary incontinence in women. Cochrane Database Syst Rev. 2019;12:CD002239.
- Goldman HB, Sievert KD, Damaser MS. Will we ever use stem cells for the treatment of SUI? ICI-RS 2011. Neurourol Urodyn. 2012;31(3):386-389.
- Gonzalez Isaza P, Jaguszewska K, Cardona JL, Lukaszuk M. Long-term effect of thermoablative fractional CO2 laser treatment as a novel approach to urinary incontinence management in women with genitourinary syndrome of menopause. Int Urogynecol J. 2018;29(2):211-215.
- Hafidh B, Baradwan S, Latifah HM, et al. CO2 laser therapy for management of stress urinary incontinence in women: A systematic review and meta-analysis. Adv Urol. 2023;15:17562872231210216.
- Isali I, Mahran A, Khalifa AO, et al. Gene expression in stress urinary incontinence: A systematic review. Int Urogynecol J. 2020;31(1):1-14.
- Keshavarz E, Pouya EK, Rahimi M, et al. Prediction of stress urinary incontinence using the retrovesical (β) angle in transperineal ultrasound. J Ultrasound Med. 2021;40(8):1485-1493.
- Keyser LE, McKinney JL, Pulliam SJ, Weinstein MM. A digital health program for treatment of urinary incontinence: Retrospective review of real-world user data. Int Urogynecol J. 2023;34(5):1083-1089.
- Leonardo K, Rahardjo HE, Afriansyah A. Noninvasive high-intensity focused electromagnetic therapy in women with urinary incontinence: A systematic review and meta-analysis. Neurourol Urodyn. 2025;44(2):424-433.
- Li X, Li Z-M, Tan J-Y, et al. Moxibustion for post-stroke urinary incontinence in adults: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Clin Pract. 2021;42:101294.
- Lian W, Zheng Y, Huang H, et al. Effects of bariatric surgery on pelvic floor disorders in obese women: A meta-analysis. Arch Gynecol Obstet. 2017;296(2):181-189.
- Lin HY, Tsai HW, Tsui KH, et al. The short-term outcome of laser in the management of female pelvic floor disorders: Focus on stress urine incontinence and sexual dysfunction. Taiwan J Obstet Gynecol. 2018;57(6):825-829.
- Liu Z, Liu Y, Xu H, et al. Effect of electroacupuncture on urinary leakage among women with stress urinary incontinence: A randomized clinical trial. JAMA. 2017;317(24):2493-2501.
- Long C-Y, Lin K-L Yeh J-L, et al. Effect of high-intensity focused electromagnetic technology in the treatment of female stress urinary incontinence. Biomedicines. 2024;12(12):2883.
- Lukacz ES. Evaluation of women with urinary incontinence. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2019.
- Lukacz ES. Treatment of urgency incontinence/overactive bladder in women. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2018b.
- Lukacz ES. Treatment of urinary incontinence in women. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed May 2017; December 2018a; September 2019.
- Lukanovic D, Kunic T, Batkoska M, et al. Effectiveness of magnetic stimulation in the treatment of urinary incontinence: A systematic review and results of our study. J Clin Med. 2021;10(21):5210.
- Mariotti G, Salcicci S, Viscuso P, et al. Regenerative medicine-based treatment of stress urinary incontinence with stem cells: A systematic review and meta-analysis. Curr Stem Cell Res Ther. 2023;18(3):429-437.
- Mazzocchi T, Ricotti L, Pinzi N, Menciassi A. Magnetically controlled endourethral artificial urinary sphincter. Ann Biomed Eng. 2016;45(5):1181-1193.
- Medina CA, Costantini E, Petri E, et al. Evaluation and surgery for stress urinary incontinence: A FIGO working group report. Neurourol Urodyn. 2017;36(2):518-528.
- Oliveira M, Ferreira M, Azevedo MJ, et al. Pelvic floor muscle training protocol for stress urinary incontinence in women: A systematic review. Rev Assoc Med Bras (1992). 2017;63(7):642-650.
- Page A-S, Page G, Deprest J. Cervicosacropexy or vaginosacropexy for urinary incontinence and apical prolapse: A systematic review. Eur J Obstet Gynecol Reprod Biol. 2022;279:60-71.
- Paik SH, Han SR, Kwon OJ, et al. Acupuncture for the treatment of urinary incontinence: A review of randomized controlled trials. Exp Ther Med. 2013;6(3):773-780.
- Peng L, Zeng X, Shen H, Luo DY. Magnetic stimulation for female patients with stress urinary incontinence, a meta-analysis of studies with short-term follow-up. Medicine (Baltimore). 2019;98(19):e15572.
- Pergialiotis V, Prodromidou A, Perrea DN, Doumouchtsis SK. A systematic review on vaginal laser therapy for treating stress urinary incontinence: Do we have enough evidence? Int Urogynecol J. 2017;28(10):1445-1451.
- Pitsouni E, Grigoriadis T, Tsiveleka A, et al. Microablative fractional CO2-laser therapy and the genitourinary syndrome of menopause: An observational study. Maturitas. 2016;94:131-136.
- Pokrywczynska M, Adamowicz J, Czapiewska M, et al. Targeted therapy for stress urinary incontinence: A systematic review based on clinical trials. Expert Opin Biol Ther. 2016;16(2):233-242.
- Rodrigues MP, Paiva LL, Ramos JGL, Ferla L. Vibratory perineal stimulation for the treatment of female stress urinary incontinence: A systematic review. Int Urogynecol J. 2018;29(4):555-562.
- Sharma N, Rekha K, Srinivasan KJ. Efficacy of transcutaneous electrical nerve stimulation in the treatment of overactive bladder. J Clin Diagn Res. 2016;10(10):QC17-QC20.
- Shimonov M, Groutz A, Schachter P, Gordon D. Is bariatric surgery the answer to urinary incontinence in obese women? Neurourol Urodyn. 2017;36(1):184-187.
- Slongo H, Lunardi ALB, Fazzolari JC, et al. Microablative radiofrequency versus sham for overactive bladder: A randomized controlled trial. Menopause. 2025;32(3):191-196.
- Song P, Wen Y, Huang C, et al. The efficacy and safety comparison of surgical treatments for stress urinary incontinence: A network meta-analysis. Neurourol Urodyn. 2018;37(4):1199-1211.
- Trabuco EC, Gebhart JB. Overview of transvaginal placement of reconstructive materials (surgical mesh or biografts) for treatment of pelvic organ prolapse or stress urinary incontinence. UpToDate [serial online]. Waltham, MA: UpToDate; reviewed October 2012.
- Turkoglu A, Coskun ADE, Arinkan SA, Vural F. The role of transperineal ultrasound in the evaluation of stress urinary incontinence cases. Int Braz J Urol. 2022;48(1):70-77.
- Weinstein MM, Dunivan GC, Guaderrama NM, Richter HE. Digital therapeutic device for urinary incontinence: A randomized controlled trial. Obstet Gynecol. 2022;139(4):606-615.
- Weinstein MM, Dunivan GC, Guaderrama NM, Richter HE. Digital therapeutic device for urinary incontinence: A longitudinal analysis at 6 and 12 months. Obstet Gynecol. 2023;141(1):199-206.
- Weinstein MM, Dunivan GC, Guaderrama NM, Richter HE. A motion based device urinary incontinence treatment: A longitudinal analysis at 18 and 24 months. Int Urogynecol J. 2024;35(4):803-810.
- Wiafe B, Metcalfe PD, Adesida AB. Stem cell therapy: Current applications and potential for urology. Curr Urol Rep. 2015;16(11):77.
- Woodruff AJ, Cole EE, Dmochowski RR, et al. Histologic comparison of pubovaginal sling graft materials: A comparative study. Urology. 2008;72(1):85-89.
- Zeng X, Li Q. Effect of electroacupuncture treatment on bladder function and urodynamic features of neurogenic bladder in stroke: A retrospective study. Arch Esp Urol. 2024;77(10):1195-1201.
- Zhang J, Gao L, Liu M, Liu C. Effect of bariatric surgery on urinary incontinence in obese women: A meta-analysis and systematic review. Female Pelvic Med Reconstr Surg. 2020;26(3):207-211
- Zhou S, Zhang K, Atala A, et al. Stem cell therapy for treatment of stress urinary incontinence: The current status and challenges. Stem Cells Int. 2016;2016:7060975.
- Zhou Z, Zhang Y, Deng H, et al. Comparison of acupuncture and moxibustion related non-surgical therapies for women with stress urinary incontinence: A systematic review and network meta-analysis of randomized controlled trials. Explore (NY). 2024;20(4):493-500.
Screening for Urinary Incontinence in Women
- Nelson HD, Cantor A, Pappas M, Miller L. Screening for urinary incontinence in women: A systematic review for the women's preventive services initiative. Ann Intern Med. 2018;169(5):311-319.
- No authors listed. Screening for urinary incontinence in women: A recommendation from the Women's Preventive Services Initiative. Ann Intern Med. 2018;169(5).
Transcutaneous Electrical Nerve Stimulation (e.g., ZIDA Wearable Neuromodulation System) for the Treatment of Idiopathic Non-Obstructive Urinary Retention
- Bapir R, Bhatti KH, Eliwa A, et al. Efficacy of overactive neurogenic bladder treatment: A systematic review of randomized controlled trials. Arch Ital Urol Androl. 2022;94(4):492-506.
- Chen Y, Peng L, Zhang C, et al. The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: A systematic review and network meta-analysis. Int J Surg. 2023;109(5):1430-1438.
- Coolen RL, Groen J, Scheepe JR, Blok BFM. Transcutaneous electrical nerve stimulation and percutaneous tibial nerve stimulation to treat idiopathic nonobstructive urinary retention: A systematic review. Eur Urol Focus. 2021;7(5):1184-1194.
- Ghavidel-Sardsahra A, Ghojazadeh M, Rahnama'I MS, et al. Efficacy of percutaneous and transcutaneous posterior tibial nerve stimulation on idiopathic overactive bladder and interstitial cystitis/painful bladder syndrome: A systematic review and meta-analysis. Neurourol Urodyn. 2022;41(2):539-551.
- Goudelocke C, Sobol J, Poulos D, et al. A multicenter study evaluating the frequency of use and efficacy of a novel closed-loop wearable tibial neuromodulation system for overactive bladder and urgency urinary incontinence (FREEOAB). Urology. 2024;183:63-69.
- Parodi S, Kendall HJ, Terrone C, Heesakkers JPFA. What is in the pipeline on investigational neuromodulation techniques for lower urinary tract dysfunction: A narrative review. Neuromodulation. 2024;27(2):267-272.
- Sayner AM, Rogers F, Tran J, et al.Transcutaneous tibial nerve stimulation in the management of overactive bladder: A scoping review. Neuromodulation. 2022;25(8):1086-1096.
- Smith MD, Tenison E, Drake MJ, et al. Stimulation of the tibial nerve repetitively to improve incontinence in Parkinson's electronically (STRIPE Trial): A randomised control trial of tibial nerve stimulation for bladder symptoms in Parkinson's disease using a self-contained wearable device. Trials. 2022;23(1):912.
- Tahmasbi F, Hosseini S , Hajebrahimi A, et al. Efficacy of tibial nerve stimulation in neurogenic lower urinary tract dysfunction among patients with multiple sclerosis: A systematic review and meta-analysis. Urol Res Pract. 2023;49(2):100-111.
- Yildiz N, Sonmez R. Transcutaneous medial plantar nerve stimulation in women with idiopathic overactive bladder. Investig Clin Urol. 2023;64(4):395-403.
Implantable / Subfascial Tibial Nerve Stimulation (e.g., BlueWind Revi) for the Treatment of Overactive Bladder Syndrome and Urgency Urinary Incontinence
- Dorsthorst MJT, Digesu GA, Tailor V, et al. 3-year followup of a new implantable tibial nerve stimulator for the treatment of overactive bladder syndrome. J Urol. 2020;204(3):545-550.
- Dorsthorst MT, Digesu A, van Kerrebroeck P, et al. Patient-tailored healthcare and tibial nerve neuromodulation in the treatment of patients with overactive bladder symptoms. Neurourol Urodyn. 2022;41(2):679-684.
- Heesakkers JPFA, Digesu GA, van Breda J, et al. A novel leadless, miniature implantable tibial nerve neuromodulation system for the management of overactive bladder complaints. Neurourol Urodyn. 2018;37(3):1060-1067.
- Heesakkers JPFA, Toozs-Hobson P, Sutherland 3 SE, et al. A prospective study to assess the effectiveness and safety of the BlueWind System in the treatment of patients diagnosed with urgency urinary incontinence. Neurourol Urodyn. 2024;43(7):1491-1503.
- Kapur A, Harandi AA, Hartman-Kenzler J, Kim J. Shifts in patient preference of third-line overactive bladder therapy after introduction of the implantable tibial nerve stimulator. Neurourol Urodyn. 2024;43(4):959-966.
Flyte System (Mechanotherapy)
- Lukacz ES. Female urinary incontinence: Treatment. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed September 2024.
- Nakib N, Sutherland S, Hallman K, et al. Randomized trial of mechanotherapy for the treatment of stress urinary incontinence in women. Ther Adv Urol. 2024;16:17562872241228023.
