Chronic Pelvic Pain, Endometriosis, and Other Indications: Selected Treatments
Number: 0754
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses selected treatments for chronic pelvic pain, endometriosis, and other indications.
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Experimental and Investigational
The following procedures are considered experimental and investigational because the effectiveness of these approaches has not been established:
- Uterine nerve ablation (UNA), laparoscopic uterine nerve ablation (LUNA) and presacral neurectomy (PSN; both open and laparoscopic) for the treatment of chronic pelvic pain or other indications;
- Hypogastric plexus neurolysis for the treatment of chronic pelvic pain associated with endometriosis;
- Peritoneal excision (stripping) for the treatment of endometriosis.
Background
Approximately 15 to 20 % of women between 18 to 50 years of age have chronic pelvic pain of more than a year's duration. The American College of Obstetricians and Gynecologists (ACOG, 2004) defined chronic pelvic pain as non-cyclical pain of at least 6 months' duration that appears in locations such as the pelvis, anterior abdominal wall, lower back, or buttocks, and is serious enough to cause disability or lead to medical care. Chronic pelvic pain includes primary and secondary dysmenorrhea. Primary dysmenorrhea occurs in the absence of an identifiable cause, while secondary dysmenorrhea describes menstrual pain associated with a physical cause. Endometriosis is the most common gynecological cause of chronic pelvic pain. Other causes of chronic pelvic pain include pelvic inflammatory disease, pelvic congestion syndrome, nerve entrapment, interstitial cystitis, emotional stress, and pelvic floor pain related to muscular spasm.
Treatment for chronic pelvic pain depends on the underlying cause, severity of symptoms, the extent and location of disease, the desire for pregnancy, and the age of the patient. Conservative medical treatments for endometriosis include non-steroidal anti-inflammatory drugs and oral contraceptives. If these fail to relieve symptoms, second-line pharmacologics, such as danazol and gonadotropin-releasing hormone analogs, may be indicated. Conservative surgery involves excision, fulguration, or laser vaporization of endometriotic implants and removal of associated adhesions. Hysterectomy may be considered for patients with severe symptoms that do not respond to conservative treatment.
The use of nerve transection procedures have been investigated for the treatment of chronic pelvic pain. They are often carried out during the course of other surgical treatment for endometriosis. The most common of these nerve transection procedures are laparoscopic uterine nerve ablation (LUNA) and pre-sacral neurectomy (PSN). Laparoscopic uterine nerve ablation involves the destruction of the uterine nerve fibers that exit the uterus through the uterosacral ligament. Pre-sacral neurectomy refers to the interruption of the sympathetic innervation of the uterus at the level of the superior hypogastric plexus. Pre-sacral neurectomy is technically more challenging than LUNA because of the presence of large vessels and the ureters near the field of dissection.
Three randomized controlled trials (RCTs) using PSN along with other surgical treatment of endometriosis have been published (Tjaden et al, 1990; Candiani et al, 1992; Zullo et al, 2003). A RCT comparing outcomes of PSN to LUNA has also been published (Chen et al, 1996).
Tjaden et al (1990) found that the addition of PSN to standard surgical therapy by laparotomy enhanced pain relief for midline pain. However, only 8 of 26 patients were randomized and the study was terminated before completion because of significant reduction in midline pain by the patients undergoing PSN.
Candiani and colleagues (1992) randomly assigned 71 women with moderate to severe endometriosis and midline dysmenorrhea to conservative surgery alone or conservative surgery with PSN. The addition of PSN markedly reduced the midline component of menstrual pain, but no statistically significant differences were observed between the 2 groups in the frequency and severity of dysmenorrhea, pelvic pain, and dyspareunia in the long-term follow-up. Furthermore, constipation developed or worsened in 13 of 35 patients and urinary urgency developed in 3. The authors concluded that PSN should be considered only in selected cases (e.g., women with severe incapacitating dysmenorrhea, recurrent disease, or symptoms that did not respond to initial treatment).
Zullo et al (2003) randomly assigned 141 women aged 26 to 39 years with severe dysmenorrhea due to endometriosis to laparoscopic electrocautery ablation or excision, enucleation of endometriomas, lysis of adhesions, and uterosacral ligament resection of deep ligamentous lesions (group A) or these treatments plus PSN (group B). The addition of PSN significantly improved cure rates (defined as significant relief of dysmenorrhea) at both 6 months (87 % versus 60 %) and 12 months (86 % versus 57 %); the improvement occurred across all stages. Although the severity of dysmenorrhea, dyspareunia, and pelvic pain was lower in group B than group A, there was no difference between groups in the frequency of these symptoms. Surgical complications were uncommon and equivalent; constipation and urgency only occurred in women who had PSN (at 12 months: constipation 14 % and urgency 5 %). Of note, conservative surgery alone (i.e., without PSN) led to most of the reduction in severity of dysmenorrhea, as measured by a visual analog scale (VAS) (baseline score: 82, after conservative surgery: 54, after conservative surgery and PSN: 46). The authors concluded that PSN with conservative surgery was an effective treatment for pelvic pain related to endometriosis.
In a RCT of 68 patients with primary dysmenorrhea assigned to either PSN or LUNA, Chen et al (1996) reported that both groups were equal in terms of symptom relief (87.9 % versus 89.9 %), but the efficacy of PSN was better than LUNA at 12 months (81.8 % versus 51.4 %).
A Cochrane review on laparoscopic surgery for pelvic pain associated with endometriosis identified a RCT that reported positive results from a combined surgical approach of laparoscopic laser ablation, adhesiolysis, and uterine nerve ablation in women with pelvic pain associated with endometriosis. The authors concluded that since only 1 trial was identified, these results should be "interpreted with caution" (Jacobson, 2001).
An expert panel comprised of practicing gynecologists from the United States (Gambone et al, 2002) concluded that: "[t]here is some evidence that adjuvant presacral neurectomy adds benefit for midline pain, but currently, there is inadequate evidence to support the use of uterosacral nerve ablation."
Vercellini et al (2003) randomly assigned 180 women with endometriosis and pelvic pain to laparoscopic treatment of endometriosis lesions or laparoscopic treatment of endometriosis lesions plus an utero-sacral ligament resection. These investigators reported that the prevalence of recurrent dysmenorrhea was similar for both groups (approximately 28 % after 1 year and approximately 34 % after 3 years). Other studies showed the same lack of efficacy of adding LUNA to the surgical treatment of endometriosis (Sutton et al, 2001). Only 1 small clinical trial suggested any efficacy for LUNA, and that trial evaluated only patients with primary dysmenorrhea (Lichten and Bombard, 1987).
A Cochrane systematic evidence review of clinical trials on surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhea found there was only limited evidence to support the use of LUNA for primary dysmenorrhea. The comparison between LUNA and laparoscopic PSN (LPSN) for primary dysmenorrhea showed no significant difference in pain relief in the short-term; however, long-term LPSN was shown to be significantly more effective than LUNA. The treatment of LUNA combined with surgical treatment of endometrial implants versus surgical treatment of endometriosis alone showed that the addition of LUNA did not aid pain relief. For PSN combined with endometriosis treatment versus endometriosis treatment alone there was an overall difference in pain relief although the data suggested this may be specific to laparoscopy and for midline abdominal pain only. Adverse events were significantly more common for PSN; however, the majority were complications such as constipation, which may spontaneously improve. The authors' concluded, "[t]here is insufficient evidence to recommend the use of nerve interruption in the management of dysmenorrhea, regardless of cause" (Proctor et al, 2005).
A Cochrane review on treatment of chronic pelvic pain in women (2005) found that "LUNA is not shown to be effective" (Stones et al, 2005).
Guidelines on chronic pelvic pain from ACOG (2004) concluded: "[a]dding uterine nerve ablation to surgical treatment of endometriosis-associated pelvic pain or dysmenorrhea does not improve the outcome of surgical treatment. No evidence demonstrates that uterine nerve ablation improves nonmenstrual chronic pelvic pain." The guidelines recommended the following: "presacral neurectomy may be considered for treatment of centrally located dysmenorrhea but has limited efficacy for chronic pelvic pain or pain that is not central in its location. Uterine nerve ablation or transection of the uterosacral ligament also can be considered for centrally located dysmenorrhea, but it appears to be less effective than presacral neurectomy. Combining uterine nerve ablation or presacral neurectomy with surgical treatment of endometriosis does not further improve overall pain relief."
The Society for Obstetricians and Gynaecologists of Canada clinical practice guideline (2005) stated: "[t]here is limited evidence for use of presacral neurectomy in the management of primary dysmenorrhea, the risks must be carefully weighed against the expected benefits. Laparoscopic uterosacral ligament resection has not been shown to reduce dysmenorrhea and therefore should not be advocated as a mainstream treatment option."
Guidelines from the Royal College of Obstetricians and Gynaecologists (2006) concluded: "[t]here is no evidence that laparoscopic uterine nerve ablation is necessary when ablating endometriotic lesions and laparoscopic uterine nerve ablation by itself has no effect on dysmenorrhea associated with endometriosis. In cases that have failed to respond to conservative laparoscopic surgery, there may be a role for presacral neurectomy, especially in severe dysmenorrhoea, although the evidence is inconclusive."
Latthe and colleagues (2007) performed a systematic review of 9 RCTs to assess the effectiveness of surgical interruption of pelvic nerve pathways. The inclusion criteria were RCTs of utero-sacral nerve ablation or PSN (both open and laparoscopic procedures) for the treatment of dysmenorrhea. The main outcome measures were pain relief and adverse effects. There were 2 trials with open PSN; all other trials used laparoscopic techniques. For the treatment of primary dysmenorrhea, LUNA at 12 months was better when compared to a control or no treatment (odd ratio [OR] 6.12; 95 % confidence interval [CI]: 1.78 to 21.03). The comparison of LUNA with PSN for primary dysmenorrhea showed that at 12 months follow-up, PSN was more effective (OR 0.10; 95 % CI: 0.03 to 0.32). In secondary dysmenorrhea, along with laparoscopic surgical treatment of endometriosis, the addition of LUNA did not improve the pain relief (OR 0.77; 95 % CI: 0.43 to 1.39), while PSN did (OR 3.14; 95 % CI: 1.59 to 6.21). Adverse events were more common for PSN. These investigators concluded that the evidence for nerve interruption in the management of dysmenorrhea is limited.
A recently published guidance on "Laparoscopic Uterine Nerve Ablation (LUNA) for Chronic Pelvic Pain" from the National Institute for Health and Clinical Excellence (NICE, 2007) concluded: "[t]he evidence on laparoscopic uterine nerve ablation (LUNA) for chronic pelvic pain suggests that it is not efficacious and therefore should not be used."
While Gambone et al (2002) concluded that patients with dysmenorrhea who have not responded to medical therapy may be offered PSN, a Cochrane systematic evidence review of clinical trials on surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhea concluded, "[t]here is insufficient evidence to recommend the use of nerve interruption in the management of dysmenorrhea, regardless of cause (Proctor et al, 2005)". In addition, Latthe's more recent systematic review of the evidence (2007) concluded that the evidence for nerve interruption in the management of dysmenorrhea is limited. It should also be noted that the procedures reported by Candiani et al (1992) and Zullo et al (2003) were performed by a single, highly experienced surgeon, which limited the generalizability of their findings.
Thus, methodologically sound and sufficiently powered RCTs are needed to assess the effectiveness of both LUNA and PSN for chronic pelvic pain in women.
In a RCT, Daniels et al (2009) evaluated the effectiveness of LUNA in patients with chronic pelvic pain. A total of 487 women with chronic pelvic pain lasting longer than 6 months without or with minimal endometriosis, adhesions, or pelvic inflammatory disease were included in this study. Follow-up was carried out by questionnaires mailed at 3 and 6 months and at 1, 2, 3, and 5 years. Patients received bilateral LUNA or laparoscopy without pelvic denervation (no-LUNA); participants were blinded to the treatment allocation. The primary outcome was pain, which was assessed by a VAS. Data concerning the 3 types of pain (non-cyclical pain, dysmenorrhea, and dyspareunia) were analyzed separately as was the worst pain level experienced from any of these 3 types of pain. The secondary outcome was health-related quality of life, which was measured using a generic instrument (EuroQoL EQ-5D and EQ-VAS). After a median follow-up of 69 months, there were no significant differences reported on the visual analog pain scales for the worst pain (mean difference between the LUNA group and the no-LUNA group, -0.04 cm [95 % CI: -0.33 to 0.25 cm]; p = 0.80), non-cyclical pain (-0.11 cm [95 % CI: -0.50 to 0.29 cm]; p = 0.60), dysmenorrhea (-0.09 cm [95 % CI: -0.49 to 0.30 cm]; p = 0.60), or dyspareunia (0.18 cm [95 % CI: -0.22 to 0.62 cm]; p = 0.40). No differences were observed between the LUNA group and the no-LUNA group for quality of life. The authors concluded that among women with chronic pelvic pain, LUNA did not result in improvements in pain, dysmenorrhea, dyspareunia, or quality of life compared with laparoscopy without pelvic denervation.
Jedrzejczak et al (2009) assessed and compared the effectiveness of PSN in the presence and absence of endometriosis. A total of 23 women with midline chronic pelvic pain (aged 30.3 +/- 7.9 years, range of 21 to 46) unresponsive to medical therapy were recruited to the study. Endometriosis was absent in 7 and present in 16 subjects. Laparoscopic PSN using a harmonic scalpel was performed in all subjects; simultaneous excision of endometriotic lesions was also performed in subjects with endometriosis. Intensity of dysmenorrhea and pelvic pain was measured by visual analog pain scale at 3 and 12 months post-operatively. Dysmenorrhea decreased at 3 months by 75 % (p = 0.018) in those without endometriosis and by 78 % (p = 0.001) in those with endometriosis. At 12-month, dysmenorrhea increased in women with endometriosis (p = 0.008), but not in those without endometriosis. Pelvic pain not related to menses decreased by 67 % (p = -0.0007) and by 87 % (p = 0.028), respectively, in women with and without endometriosis. Dyspareunia, declined dramatically at 3 and 12 months to a median score of 0 (the majority of subjects had no discomfort; p < 0.001); the change in dyspareunia between 3 and 12 months was in favor of patients without endometriosis (p = 0.02). The authors concluded that PSN using a harmonic scalpel results in long-term pain relief, especially in patients without endometriosis. The findings of this small study need to be validated by well-designed stuides.
A review of treatments for endometriosis in Clinical Evidence (Ferrero et al, 2009) found that LUNA alone or PSN alone or with removal of endometriotic deposits is of unknown effectiveness. The review found that removal of endometrial deposits plus LUNA was more effective than diagnostic laparoscopy, but LUNA plus removal of endometriotic deposits was not more effective than removal of endometriotic deposits alone.
An UpToDate review on "Treatment of chronic pelvic pain in women" (Howard, 2014) states that "there is evidence that LUNA is not effective in the treatment of CPP and more evidence is needed before LPSN can be recommended for treatment of CPP".
Noor and Garely (2015) noted that chronic pelvic pain (CPP) is a commonly encountered condition that often is multi-factorial. Etiologies include gynecologic, urologic, gastro-intestinal, and neurologic conditions. Laboratory tests, imaging, and surgical intervention are not always helpful in identifying the etiology of pelvic pain. For appropriate management of this complex disease process, a detailed history and physical examination, and a multi-disciplinary approach are needed. Pelvic pain may be caused by endometriosis, pelvic inflammatory disease, adenomyosis, interstitial cystitis/painful bladder syndrome, or other factors. Evaluation may include keeping a pain diary; laboratory tests, such as a pregnancy test, urinalysis, or tests for sexually transmitted infections; ultrasonography of abnormalities detected on physical examination; and laparoscopy. Specific first-line treatments include non-steroidal anti-inflammatory drugs (NSAIDs) and oral contraceptives for endometriosis; progestins, gonadotropin-releasing hormone (GnRH) analogs, aromatase inhibitors, or hysterectomy for adenomyosis; and education, food avoidance, and behavioral modifications for interstitial cystitis/painful bladder syndrome. Surgical options include nerve transection procedures, LUNA, and PSN, although data on effectiveness are limited.
Speer and colleagues (2016) stated that CPP in women is defined as persistent, non-cyclic pain perceived to be in structures related to the pelvis and lasting more than 6 months. Often no specific etiology can be identified, and it can be conceptualized as a chronic regional pain syndrome or functional somatic pain syndrome. It is typically associated with other functional somatic pain syndromes (e.g., irritable bowel syndrome, non-specific chronic fatigue syndrome) and mental health disorders (e.g., post-traumatic stress disorder, depression). Diagnosis is based on findings from the history and physical examination. Pelvic ultrasonography is indicated to rule out anatomic abnormalities. Referral for diagnostic evaluation of endometriosis by laparoscopy is usually indicated in severe cases. Curative treatment is elusive, and evidence-based therapies are limited. Patient engagement in a biopsychosocial approach is recommended, with treatment of any identifiable disease process such as endometriosis, interstitial cystitis/painful bladder syndrome, and co-morbid depression. Potentially beneficial medications include depot medroxyprogesterone, gabapentin, NSAIDs, and GnRH agonists with add-back hormone therapy. Pelvic floor physical therapy may be helpful. Behavioral therapy is an integral part of treatment. In select cases, neuromodulation of sacral nerves may be appropriate. Hysterectomy may be considered as a last resort if pain appears to be of uterine origin, although significant improvement occurs in only about 50 % of cases. The authors stated that CPP should be managed with a collaborative, patient-centered approach; LUNA and PSN were not mentioned as therapeutic options.
Flyckt and colleagues (2017) noted that surgical approaches to endometriosis patients with chronic pelvic pain are multi-modal and require individualization. Laparoscopic approaches are preferred over laparotomy when conservatively treating endometriosis via excision or ablation/fulguration of lesions. The available data support cystectomy over fenestration or fulguration for endometriomas; however, there may be associated decreases in ovarian reserve with endometrioma treatment. Pre-sacral neurectomy may be useful in patients with midline pain and LUNA is not effective for the treatment of pelvic pain related to endometriosis. Appendectomy may be considered prophylactically at the time of the surgery for pelvic pain, although more studies are needed. For deep infiltrating endometriosis, the risks of aggressive bowel surgery must be weighed against the benefits of clear pain reduction. Post-operative medical suppressive therapy is strongly recommended to prolong symptom-free intervals of this chronic disease. As definitive therapy, hysterectomy can be helpful especially when combined with endometriosis excision. When performing hysterectomy, bilateral oophorectomy should be given careful consideration, as this procedure leads to premature surgical menopause and may not decrease the possibility of re-operation and persistence of symptoms in patients aged 30 to 39 years with chronic pain.
Currently, there is insufficient evidence regarding the effectiveness of open UNA for the treatment of dysmenorrhea. Well-designed studies with long-term follow-up are needed to ascertain the effectiveness of open UNA for the treatment of chronic pelvic pain or other indications.
Api and colleagues (2017) examined the correlation between the number of excised neural fibers and degree of pain relief following LPSN. In this before and after study, a total of 20 patients with severe mid-line dysmenorrhea (VAS greater than 80 mm) unresponsive to medical therapy were consecutively enrolled; all patients underwent LPSN. The superior hypogastric plexus was excised and sent for histologic confirmation. Two pathologists counted the number of neural fibers in the surgically removed tissue; VAS was used for pain assessment before and second, third, sixth, and 12th months after the operations. Of the initial 20 participants undergoing LPSN, 8 were excluded from the final analysis due to intra-operative diagnosis of endometriosis; therefore, the remaining 12 patients were evaluated. The pain scores significantly decreased at each follow-up visit compared with the pre-operative period (p = 0.002). The pathologists, who were blinded, reported the median (minimum-maximum) neural fiber count as 46 (20 to 85) and 47 (18 to 83). No significant correlation was demonstrated between the number of excised neural fibers and the amount of pain relief following LPSN. The authors concluded that LPSN was an effective surgical procedure to control primary dysmenorrhea. Moreover, these researchers stated that these preliminary findings revealed that the degree of pain relief in cases of severe mid-line dysmenorrhea was not related to the amount of excised neural tissue in LPSN. They stated that the pathophysiology of pain transmission and perception, and the underlying mechanism of the effectiveness of neurectomy need to be further elucidated. This study had 2 main drawbacks. First, the hypothesis was tested in a small number of cases (n = 12); second, the subtypes of the neural fibers were not differentiated.
An UpToDate review on "Treatment of chronic pelvic pain in women" (Tu and As-Sanie, 2018) states that "Women with CPP that is refractory to the above non-pharmacologic and medical therapies often ask about surgical options to reduce their pain. Potential procedures include presacral neurectomy, lysis of adhesions, and hysterectomy. Data supporting a role of these surgeries for the treatment of CPP are limited. For each of these surgeries, we counsel women about the risk of continued pain, and new postsurgical pain, in addition to the standard surgical risks".
The College National des Gynecologues et Obstetriciens Francais (CNGOF) guidelines on "The Management of Endometriosis" (Ploteau et al, 2018) stated that minimal and mild endometriosis (stage 1 and 2 Revised American Fertility Society [AFSR]) can lead to chronic pelvic pain and infertility but can also exist in asymptomatic patients. The prevalence of asymptomatic patients with minimal and mild endometriosis is not clear but typical endometriosis lesions are found in about 5 to 10 % of asymptomatic women and more than 50 % of painful and/or infertile women. Laparoscopic treatment of minimal and mild endometriotic lesions is justified in case of pelvic pain because their destruction decrease significatively the pain compared with diagnostic laparoscopy alone. In this context, ablation and excision give identical results in terms of pain reduction. Moreover, literature showed no interest in UNA in case of dysmenorrhea due to minimal and mild endometriosis. Then, it is recommended to treat these lesions during a laparoscopy realized as part of pelvic pain. On the other hand, it is not recommended to treat asymptomatic patients. With regard to treatment of minimal and mild endometriosis in infertile patients, only 2 studies can be selected and both showed that laparoscopy with excision or ablation and ablation of adhesions is superior to diagnostic laparoscopy alone in terms of pregnancy rate. However, it is not recommended to treat these lesions when they are asymptomatic because there is no evidence that they can progress with symptomatic disease. There is no study assessing the interest to treat these lesions when they are found fortuitously. Adhesion barrier utilization permits to reduce post-operative adhesions, however literature failed to demonstrate the clinical benefit in terms of reduction of the risk of pain or infertility.
In a systematic review and meta-analysis, Miller and colleagues (2020) compared the safety and efficacy of conservative surgery with or without adjunctive presacral neurectomy (PN) for chronic endometriosis-related pelvic pain; RCTs or non-RCTs of conservative endometriosis surgery with or without adjunctive PN were included. Main outcomes were treatment failure (the proportion of women in which surgery failed to adequately resolve mid-line pain) and the frequency of operative and post-operative complications. A total of 7 studies with 8 group comparisons (3 randomized) representing 503 women (250 PN; 253 control) were included. Over 34 months median follow-up, crude rates of treatment failure were 15.0 % with PN and 40.9 % with controls (risk ratio [RR] = 0.43, 95 % CI: 0.30 to 0.60, p < 0.001). The risk of post-operative constipation was higher with PN versus controls (12.5 % versus 0 %, p = 0.024). No treatment group differences were observed for the risk of operative complications (0.6 % versus 0 %, p = 0.498), re-operation (4.1 % versus 3.0 %, p = 0.758) or urinary incontinence (5.0 % versus 0 %, p = 0.195). Overall, in well-selected patients, conservative surgery with adjunctive PN may provide greater relief from mid-line pain and a similarly low rate of operative complications relative to conservative surgery alone but may increase the risk of constipation post-operatively. However, results were derived from mainly older and lower quality studies. Since then, surgical techniques to treat endometriosis have been improved and the effect of PN observed in prior studies should be confirmed in future studies in women in whom radical excision of deep infiltrating lesions was obtained.
The authors stated that this meta-analysis had several drawbacks pertaining to the quality of studies available for analysis that may influence interpretation. Heterogeneity in study design and surgical techniques was observed, which may have confounded data interpretation. These investigators were unable to determine the influence of surgical access (laparoscopy versus laparotomy) in treatment outcomes due to the small number of studies available for analysis. Inclusion of data from non-randomized studies may have introduced bias into the results. Indeed, most included studies were classified as intermediate- or high-risk of bias. However, study design differences did not impact overall conclusions since pain relief with PN persisted when analyzing only randomized trials. There was also considerable variation in the completeness of data reported among studies such that only weak conclusions could be derived from outcomes that were reported in few studies. Patient selection criteria and surgeon experience were under-reported and, thus, generalizability of these results may be limited. Further, the bulk of the results of this review were derived from older studies that utilized laparotomy. Yet, contemporary surgical management of endometriosis-related pain entails laparoscopic techniques that allow a more radical excision of endometriotic lesions with better long-term outcomes. Despite the fact that scientific reports on PN have decreased over the past 10 years, PN is widely promoted by specialized endometriosis treatment centers as a relatively safe and effective adjunct to conservative surgery, a conclusion that is debatable based on numerous factors including surgeon experience and limited evidence derived from studies with unclear generalizability to current practice. It appeared there may be a lack of concordance of the role of PN between scientific reports and in clinical practice at specialized centers where PN is aggressively promoted. These researchers stated that given the relative paucity of controlled studies on PN despite its continued use in clinical practice, additional randomized trials and high-quality non-randomized studies with long-term follow-up are needed to better characterize the benefits and harms associated with this procedure.
Hypogastric Plexus Neurolysis for the Treatment of Chronic Pelvic Pain Associated with Endometriosis
Possover et al (2007) presented different aspects and advantages of the laparoscopic approach to the pelvic nerves aimed at treating intractable pelvic neuralgia. These investigators reported on a non-consecutive series of 7 patients with different types and etiologies of chronic pelvic neuralgia, all of whom underwent laparoscopy. In all 7 cases, the neuralgia was refractory to medical management and had profound socioeconomic consequences for the patients. Techniques of laparoscopic transperitoneal neurolysis of several pelvic somatic nerves were described but also the authors’ technique of laparoscopic implantation of neuro-prothesis for neuromodulation on somatic pelvic nerves or on autonomic pelvic nerves as the superior hypogastric plexus. The authors concluded that laparoscopic approach to the pelvic nerves opened new possibilities for the diagnosis and treatment of pelvic neuralgia; and offered new curative surgical techniques. Moreover, these researchers stated that further carefully controlled studies with longer periods of follow-up are needed to determine the effectiveness of laparoscopic transperitoneal neurolysis for the treatment of refractory pelvic neuralgia.
Mohamed et al (2013) noted that various interventions, including the superior hypogastric plexus block and ganglion impar block, are commonly used for the treatment of pelvic or perineal pain caused by cancer. The inferior hypogastric plexus block (carried out using a trans-sacral approach under fluoroscopy and using a local anesthetic ⁄ steroid combination) for the diagnosis and treatment of chronic pain conditions involving the lower pelvic viscera was first described in 2007. Neurolysis of the inferior hypogastric plexus may be useful for the treatment of pelvic and perineal pain caused by cancer. These researchers examined the feasibility, safety and effectiveness of the newly introduced inferior hypogastric plexus block, carried out using a trans-sacral approach, for the relief of cancer-related pelvic and perineal pain. A total of 20 patients with cancer pain in the pelvis and ⁄ or perineum were injected with 6 ml to 8 ml of 10 % phenol bilaterally by passing a spinal needle through the sacral foramen to perform the inferior hypogastric block. Pain intensity (measured using a VAS), sleep score, activity score, psychological score and oral morphine consumption pre- and post-procedure were measured. Two of the 20 patients died during the follow-up period; thus, they were excluded from the study. All patients presented with cancer-related pelvic, perineal or pelvic/perineal pain. Pain scores were reduced from a mean (± SD) of 7.22 ± 1.31 pre-procedurally to 4.06 ± 1.73 1 week post-procedurally (p < 0.05). Furthermore, the mean consumption of morphine (delivered via 30 mg sustained-release morphine tablets) was reduced from 106.67 ± 32.90 mg to 61.67 ± 40.48 mg after 1 week (p < 0.05). No complications or serious side effects were encountered during or after the block. The authors concluded that the approach provided a good alternative technique for the treatment of low pelvic and perineal cancer-related pain. Moreover, these researchers stated that large, well-controlled studies and refinement of the technique using other radiological methods are needed to improve the safety and effectiveness of this new neurolytic technique.
Rocha et al (2020) stated that the superior hypogastric plexus block has been indicated for the treatment of visceral pelvic pain associated with malignancy. The 1st international report of this technique was published by Plancarte et al, in which a posterior percutaneous approach guided by fluoroscopy was described by applying neurolytic agents. The considerable variability in the data reported gave rise to 2 clinical approaches to those who performed the blockade early and those who executed it at a later stage of cancer. In a retrospective, longitudinal, single-center study, these researchers provided more evidence regarding the effectiveness of this procedure. A non-probabilistic sample was selected; the data collection took place from January 2006 to December 2016 with patients diagnosed with pelvic pain, confirmed by imaging and biopsy studies. Patients who received any other type of intervention of the sympathetic axis, patients with a different approach than the classic or para-vertebral technique, and patients with low survival rate were excluded. The Student t-test was employed to measure the significant difference between VAS and morphine equivalent daily dose (MEDD). The Cochran-Mantel-Haenszel test and the Gamma test were used to measure the association between the initial Karnofsky and blockade success. The study included a total of 180 patients. The success rate was 59.4 % at 1 month, 55.5 % at 3 months, and 48.8 % at 6 months. There was a sustained and significant VAS reduction that was 49.55 % at 3 months. A significant reduction in opioid consumption of 12.55 % was found at 3 months. There was no significant statistical evidence related to either opioid consumption or the functionality of the patient before the blockade as an influential variable in the success of the procedure. The authors concluded that although opioids remained the cornerstone of cancer pain treatment, they produced many deleterious side effects. The superior hypogastric plexus neurolysis represented a reproducible and effective alternative in the management of pain in this group of patients. Moreover, these researchers stated that prospective, randomized studies are needed to better understand the role of superior hypogastric plexus neurolysis in this and other cancer-related pain.
The authors stated that the main drawbacks of this study were its retrospective design as well as its single-center setting. In addition, survival of the oncological patient represented a critical limitation, especially if the study was a follow-up like this. To reduce the confounding factors, all patients who had received any other type of intervention on the sympathetic axis were eliminated from the sample. In the records, only VAS and MEDD scores were described as markers of effectiveness, functional outcome data were barely reported in the follow-ups. Moreover, the clinical stage of each type of cancer was not quantified because it would have added variables by subgroup that would not be significant because of the low representation of some types of cancer. It was decided to consider the patient’s functionality when assessing them by the Karnofsky performance, which was suitable for all oncological subgroups.
The American College of Obstetricians and Gynecologists' practice bulletin on “Chronic pelvic pain” (ACOG, 2020) did not mention hypogastric plexus neurolysis as a therapeutic option for chronic pelvic pain associated with endometriosis.
Furthermore, UpToDate reviews on “Endometriosis: Treatment of pelvic pain” (Schenken, 2022) and “Chronic pelvic pain in adult females: Treatment” (Tu and As-Sanie, 2022) do not mention hypogastric plexus neurolysis as a management / therapeutic option.
Peritoneal Excision (Stripping) for the Treatment of Endometriosis
Budden et al (2020) reported on RCTs that examined the surgical treatment of endometriosis-associated pelvic pain and highlighted their strengths and weaknesses. These investigators carried out a systematic review of English-language, full-text articles addressing the surgical management of pain symptoms associated with endometriosis. The terms endometriosis, pain, surgery, laparoscopy, plasma, and laser were used for searches in Cochrane, Medline, Embase, and clinical trial databases. Additional studies were identified from references in electronically located articles. The literature search was carried out by 2 independent authors, and abstracts were i screened for inclusion, with the resolution of any discrepancy by a 3rd author. Randomized studies that reported pain before and after surgery were eligible for inclusion. Supporting data from non-randomized trials were used for discussion. The Cochrane risk-of-bias assessment was performed on included studies. Search results for available articles from 1996 to October 2019 revealed 594 potential studies, with 20 studies meeting the inclusion criteria. Comparative studies of surgery versus no surgery for an effect on pain, surgical approach, the effect of different locations of disease on pain, nerve-dividing techniques for pain, and nerve-sparing effects for pain were studied. RCTs reported a substantial reduction in pain compared with no surgery in up to 80 % of women; however, up to a 1/3 of women in these studies reported a placebo response . There was no evidence of a difference in pain reduction with the mode of surgery (laparoscopy, laparotomy, or robot-assisted laparoscopy). There was limited evidence stating that excision was superior to ablative surgery; however, there were confounders in the reporting of disease location and depth and the pain symptoms most affected. These researchers stated that they need to reconsider the hypothesis that disc excision resulted in fewer complications and exhibited superior outcomes to those of segmental resection in light of the 1st RCT on this subject. Nerve-dividing surgery for pain has been demonstrated to be of no value for utero-sacral nerve ablation and/or division and of limited (if any) value for pre-sacral neurectomy. The authors concluded that although surgical RCTs had always been difficult to carry out, there were 16 RCTs on endometriosis-associated pain. Ethical considerations, the equipoise of surgeons and participants, and follow-up duration were important parameters in establishing RCTs. Furthermore, investigators must be willing to accept and adopt the evidence when it does demonstrate a particular outcome, such as the fact that surgical utero-sacral nerve disruption does not improve pain or that disc excision does not substantially reduce complications compared with segmental resection for bowel disease, as suggested by previous non-randomized studies.
Based on the best available evidence, Ouazana et al (2021) provided guidelines from the French College of Obstetricians and Gynecologists (CNGOF) for the prophylactic procedures associated with gynecological surgery for benign disease such as superficial endometriosis lesions and adhesions. The CNGOF has decided to adopt the AGREE II and GRADE systems for grading scientific evidence. Each recommendation for practice was allocated a grade that reflects the quality of evidence (QE) (clinical practice guidelines).
Endometriosis and Pelvic Pain: Superficial endometriosis could be entirely asymptomatic. Surgical treatment of asymptomatic superficial peritoneal endometriosis is not recommended in women of child-bearing age for the prevention of pelvic pain, especially in case of proximity to noble organs (e.g., the ureters, rectum and sigmoid, and ovaries in nulligravida) as there is no evidence that the disease will progress to become symptomatic (low level of evidence). In case of accidental discovery of superficial endometriosis in women of child-bearing age with pelvic pain, it is recommended that the lesions are excised, if surgically accessible. Removal of superficial endometriosis lesions in patients with painful symptoms improves quality of life (QOL) and pain (low level of evidence).
Endometriosis and Infertility: It appeared that women with isolated superficial endometriosis diagnosed by laparoscopy with histological confirmation have a significantly higher incidence of primary infertility than patients without endometriosis. However, there are no data regarding the impact of treatment of these lesions on the fertility in these women or on the natural course of their disease (low level of evidence). It is recommended that excision is performed rather than monopolar coagulation of superficial endometriosis lesions in infertile women, as this results in a higher spontaneous pregnancy rate (low level of evidence).
Adhesions and Pelvic Pain: There are limited data in the literature regarding the benefit of performing systematic adhesiolysis during laparoscopy to prevent pelvic pain when incidental pelvic adhesions are discovered. For patients with pelvic pain, it is probably better not to perform adhesiolysis to prevent pelvic pain, although this could be decided on a case-by-case basis depending on the extent of the adhesions, the topography, and the type of surgery considered (low level of evidence). For asymptomatic patients, it is recommended not to perform adhesiolysis to prevent pelvic pain due to the lack of clear effectiveness both short- or long-term and due to the increased risk of surgical injuries (low level of evidence).
Adhesions and Infertility: There are limited data in the literature regarding the potential benefit of performing systematic adhesiolysis when there is an incidental discovery of pelvic adhesions during laparoscopy to prevent infertility. For infertile women, in the event of fortuitous discovery of adhesions at laparoscopy, it is probably better not to perform complex adhesiolysis. Only adhesiolysis of tubo-ovarian adhesions that are minimal or slight in terms of their extension and/or their nature may be useful to improve the chances of spontaneous pregnancy. However, it remained to be decided on a case-by-case basis depending on other potential causes of infertility (low level of evidence). For women without known infertility issues, it is probably better not to perform systematic adhesiolysis in order to improve their pregnancy chances, considering the balance between the unknown benefit and the risks of complications inherent to surgery (low level of evidence).
The authors concluded that further investigations are needed to increase the quality of management regarding associated interventions such as the treatment of superficial endometriosis or adhesions carried out during a gynecologic surgical procedure and, thereby, bolster these recommendations.
Tehrani et al (2022) noted that various therapeutic modalities are available in the management of patients with ovarian endometrioma. In a randomized clinical trial, these researchers compared the effects of ethanol sclerotherapy (EST) and laparoscopic surgery on disease recurrence and ovarian factors of these patients. Patients with ovarian endometrioma and chronic pelvic pain were randomly divided into 2 groups. The 1st group underwent EST with a puncture needle (Cook) and the 2nd group underwent laparoscopic surgery. Both groups were followed up every 3 months to examine the recurrence rate. In this regard, US was carried out 3 months and 12 months after treatment, and serum anti-Mullerian hormone (AMH) levels were also re-assessed 12 weeks after the intervention. A total of 70 women with the mean age of 31.46 ± 4.71 years, and the mean body mass index (BMI) of 23.12 ± 1.01 were studied. The 2 groups were similar regarding age (p = 0.770), BMI (p = 0.371), history of gastro-intestinal (GI) signs (p = 0.794), history of urinary diseases (p = 0.324), dysmenorrhea (p = 0.403), pelvic pain (p = 0.454), dyspareunia (p = 0.448), location of cyst (p = 0.448), and diameter of cyst (p = 0.250). In the laparoscopic group, a significant decrease in AMH levels was observed after 12 weeks (p < 0.0001), while in the EST group, no significant changes were observed between pre-and post-operative AMH levels (p = 0.120). Cyst size decreased significantly in both groups 3 months (p < 0.001) and 12 months (p < 0.0001) following treatment. In the 3rd month, 8 patients in the EST group and 13 patients in the laparoscopic group had recurrences, and in the 12th month, 17 patients in the EST group and 15 patients in the laparoscopic group had recurrence of symptoms (p > 0.05). The authors concluded that although AMH level and mean cyst diameter were significantly lower 1 year after laparoscopy, recurrence rate of ovarian endometrioma was similar between EST and laparoscopy methods. These researchers stated that this trial was limited by a small sample size (n = 70) and possible selection bias because of the specificity of the study design; thus, further studies are needed to increase the generalizability of its findings. Furthermore, the result might be affected by the involvement of different surgeons and the different laboratory conditions.
In a retrospective study, Antonaci et al (2022) compared ovarian reserve, oocytes quality and pregnancy outcome of endometrioma treatment by laparoscopic stripping (LS) versus endometrioma EST in infertile women awaiting in-vitro fertilization (IVF). A total of 23 women underwent EST and 26 women LS; intra- and post-operative complications were recorded. The women were followed-up for 36 months for cyst recurrence, oocytes quality and pregnancy outcome. Serum MH levels after treatment were measured to observe the impact on the ovarian reserve. Women's satisfaction was investigated with patient global impression of improvement (PGI-I). During follow-up, there were 3 endometriomas recurrences following LS and none following EST. Six months after treatment AMH was 3.17 ± 2.15 in EST versus 2.22 ± 1.97 in LS (p = 0.045). Symptoms' improvement was comparable; no intra-operative complications occurred. In the LS group the post-operative complications were significantly higher. After IVF cycles, the quality of the retrieved oocytes was the same. In EST group, clinical pregnancy (48.1 % versus 19.6 %) and live-birth rates (36.5 % versus 14.3 %) were significantly increased compared to LS. Women's satisfaction was comparable at PGI-I. Both EST and the presence of an endometrioma sized 6 cm or less proved to be independent factors of a better live-birth rate in multi-variate analysis. The authors concluded that the effectiveness of EST was greater than LS for the treatment of endometrioma. Ovarian function was well-preserved. Hospital stay was shorter, fewer complications occurred, and pregnancy outcome was better following EST. This was a retrospective study with small sample size (n = 26 in the laparoscopic stripping group); its findings need to be validated by well-designed studies.
Marschall et al (2022) stated that placebo-controlled surgical designs are recommended to determine treatment effects for elective surgeries when there is genuine doubt regarding the effectiveness of the surgery. Some elective surgeries for pain have been unable to show an effect beyond sham surgery, suggesting contributions from contextual factors. However, the nature of contextual factors in elective surgery is largely unexamined. Furthermore, methodological difficulties in placebo-controlled surgical trials impact the ability to estimate the effectiveness of a surgical procedure. These include an overall lack of testing the success of blinding, absence of comparison to a no-surgery control group and dearth of test for neuropathic pain. For women with peritoneal endometriosis, there is uncertainty regarding the pain-relieving effect of surgery. Surgery may put patients at risk of complications such as post-surgical neuropathic pain, without guarantees of sufficient pelvic pain relief. The planned placebo-controlled trial aims to examine the effect of surgery on pelvic pain, widespread pain and neuropathic pain symptoms in women with peritoneal endometriosis, and to test the contribution of contextual factors to pain relief. A total of 100 women with peritoneal endometriosis will be randomized to either diagnostic laparoscopy with excision of endometrial tissue (active surgery), purely diagnostic laparoscopy (sham surgery) or delayed surgery (no-surgery control group). Outcomes include pelvic pain relief, widespread pain, neuropathic pain symptoms and QOL. Contextual factors are also assessed. Assessments will be obtained at baseline and 1-, 3- and 6-month post-randomization. Mixed linear models will be used to compare groups over time on all outcome variables.
Furthermore, an UpToDate review on “Endometriosis: Treatment of pelvic pain” (Schenken, 2022) does not mention peritoneal excision (stripping) as a management / therapeutic option.
References
The above policy is based on the following references:
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