1. Aetna considers transcatheter uterine artery embolization (UAE) medically necessary as an alternative to hysterectomy or myomectomy for the treatment of uterine fibroids when the member has persistence of one or more symptoms directly attributed to uterine fibroids, i.e., excessive menstrual bleeding (menorrhagia), bulk-related pelvic pain, pressure or discomfort, urinary symptoms referable to compression of the ureter or bladder, and/or dyspareunia.   Other uses of transcatheter UAE are considered experimental and investigational.

2. Aetna considers the following treatments for uterine fibroids experimental and investigational because their effectiveness and safety have not been established:

   • MRI-guided ultrasound ablation
   • Cryomyolysis

   • Laparoscopic uterine artery occlusion.

Uterine fibroids (leiomyomata) represent the most common gynecological tumor in women of reproductive age and are responsible for over 200,000 hysterectomies per year.  They can cause a variety of symptoms including menometrorrhagia, dysmenorrhea, pelvic pain, reproductive failure, and compression of adjacent pelvic viscera, or be totally asymptomatic.  A large array of treatment options exist for this disorder.  Surgical treatments include hysterectomy, abdominal myomectomy, laparoscopic myomectomy, myolysis, and more recently MRI-guided ultrasound ablation.  Non-surgical treatments include medical therapy (e.g., gonadotropin-releasing hormone agonist) and uterine artery embolization (UAE). 

For the last 20 years, therapeutic embolization has been successfully performed on various parts of the body.  In more recent years, this technology has been applied to uterine fibroids in an effort to eliminate the nagging symptoms associated with uterine fibroids and offer women an alternative to hysterectomy and myomectomy.  This outpatient procedure, which may require an overnight admission for pain control, uses angiographic techniques and fluoroscopic guidance to embolize the uterine arteries, similar to the methods used to control postoperative and post-partum hemorrhage.  The embolization, consisting of tiny particles of polyvinyl alcohol (500 to 700 micron size), occludes the blood supply to the fibroids, which results in their ischemic infarction and subsequent degeneration over a period of weeks and months.  Average fibroid volume reduction is approximately 50% in three months and 65% at one year. Uterine volume decreases by approximately 40% in three months.  The reduction in the fibroid's size leads to a decrease or resolution in the symptoms they cause.  The procedure takes approximately 1-2 hours and it is anticipated that most women can return to work 7 days after the procedure.

The initial studies that have been published to date suggest that both menorrhagia and symptoms caused by the bulk of these fibroids will be significantly improved or will resolve in 80-90% of patients on short-term follow-up.  The patients in these series have tolerated the procedure well and patient satisfaction is high, but they all require careful post-procedural pain management. While severe ischemic injury to the uterus has been feared, the literature suggests that this occurs in only 1-2 % of patients.  Unlike myomectomy, all fibroids can be treated simultaneously, regardless of their location or size in the uterus.  Unlike Lupron, the literature indicates that premature menopause is rarely induced.  It has been shown that if the procedure is not successful and surgery is needed, this surgery is rendered easier, with a likelihood of less bleeding.

However, long-term follow-up on a larger number of cases will be required before any definitive statement can be made about the ultimate role of embolization in the treatment of uterine fibroids as compared to the other available therapies.  The long-term outcome is not known, in that recanalization of the arteries could occur or collateral vessels could be recruited which might allow re-growth of the fibroids.  Post-procedure fertility and the ability to carry a pregnancy to term are not presently known since most patients in published series have not sought to become pregnant.  The effect on ovarian function has been a question, given the sporadic reports of amenorrhea after treatment.  It is not known whether ovarian infarction occasionally occurs to affect function or whether merely decreasing uterine flow is sufficient to affect ovarian function.  Further, it is not clear whether ovarian function is affected in only a few patients or whether it is more common and just not apparent clinically.

Despite the unknowns, it is clear that the initial experience with UAE suggests that this procedure is effective and safe in the short term and represents a promising new therapy for this very common medical condition.

A report by the American College of Obstetricians and Gynecologists (2004) stated that "UAE for the treatment of symptomatic fibroids, when performed by experienced physicians, appears to provide good short-term relief among appropriate candidates."  ACOG strongly recommends that women who wish to undergo UAE have a thorough evaluation with an obstetrician/gynecologist to help facilitate optimal collaboration with interventional radiologists and ensure that the procedure is appropriate.  There is insufficient data at this time to ensure that UAE is safe for women who may wish to become pregnant in the future, the report notes.  Moreover, few studies have assessed the effect of embolization on pregnancy-related outcomes.  For these reasons, ACOG considers the procedure investigational or relatively contraindicated in such women.  Also, the report warns that UAE is rarely, if ever, indicated in postmenopausal women.

UAE is contraindicated in women with any of the following conditions: 

• Women with a history of prior pelvic x-ray treatments, pelvic malignancy, chronic infections or severe endometriosis; or  
• Postmenopausal women with fibroid growth or rapid growth at any time (may indicate development of sarcoma); or 
• Women who may wish to become pregnant in the future; or
• Women who have evidence of current genito-urinary infection and/or malignancy.

A report on the management of uterine fibroids prepared for the Agency for Healthcare Research and Quality (Viswanathan, et al., 2007) stated that women who undergo UAE have shorter recoveries and spend less time in the hospital than women who have hysterectomies.

Currently, there is very little information regarding the effectiveness of MRI-guided ultrasound ablation for the treatment of uterine leiomyomata.  In a review on the surgical and non-surgical management of uterine leiomyomata, Myers et al (2002) concluded that available evidence on the management of uterine leiomyomata is of poor quality.  This is in agreement with the observation of Olive (2000) who stated that existing studies are generally small and of poor quality.  There is a strong need for appropriately designed and analyzed randomized clinical trials, and surgical trials should preferably be multi-center/multi-surgeon.

Recent studies by Tempany et al (2003) as well as Stewart et al (2003) suggested that MRI-guided focused ultrasound surgery appeared to be safe and effective for the treatment of uterine leiomyomas.  However, both studies were authored by the same group of investigators and addressed only the safety and feasibility of this approach in treating uterine fibroids.  These studies had small number of patients -- 9 in the study by Tempany et al (2003), and 55 in the study by Stewart et al (2003).  They only demonstrated the safety and feasibility of MRI-guided focused ultrasound ablation for the treatment of uterine fibroids; however, its clinical value has not been established.

The first FDA-approved MRI-guided focused ultrasound system for the treatment of women with symptomatic uterine fibroids is the ExAblate 2000 System (InSightec, Ltd.).  The U.S. pivotal trial included 192 women who had symptomatic uterine fibroids and were randomized to a hysterectomy (n = 83) or the ExAblate procedure (n = 109).  At 6 months, 70.6 % of the ExAblate patients experienced a greater than 10-point reduction in the Uterine Fibroid Symptoms and Quality of Life Questionnaire score.  The mean reduction in fibroid volume at 6 months was 13.5 %, but non-enhancing volume remained within the treated fibroid at 6 months.  The hysterectomy patients performed better at 6 months than the ExAblate patients on several quality-of-life measurements, including role physical, body pain, general health, vitality, and mental health.  The hysterectomy patients had a much higher rate of having at least 1 significant complication than the ExAblate patients (46 % versus 12 %).  The ExAblate patients missed less work than the hysterectomy patients (1.2 versus 19.2 working days) during the first 30 days post-surgery (FDA Summary of Safety and Effectiveness Results).

The FDA required InSightec to conduct a 3-year post-market study to better assess the long-term safety and effectiveness of the ExAblate 2000 System.  The study includes additional numbers of African-American women, because, as a group, these women have a greater incidence of uterine fibroids but were under-represented in the original study.

Further studies are needed to elucidate the exact role of MRI-guided focused ultrasound ablation in the management of uterine fibroids, especially studies that examine the correlation of treatment effect with changes in symptoms as well as comparisons of this new technology with other treatment methods such as UAE.

In a multi-center, clinical study, Stewart, et al. (2006) evaluated outcomes at 6 and 12 months after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for symptomatic uterine leiomyomas.  Pre-menopausal women with symptomatic uterine leiomyomas and no plans for future pregnancy (n = 109 at 6 months and n = 82 at 12 months) received a single treatment session of MRgFUS for uterine fibroids.  Main outcome measures were reduction in fibroid symptoms as measured by the symptom severity score (SSS) of the Uterine Fibroid Quality-of-Life Instrument (UFS-QOL), the only validated measure of leiomyoma symptomatology.  A 10-point reduction in the SSS was selected as the targeted improvement.  A total of 71 % of women undergoing MRgFUS reached the targeted symptom reduction at 6 months, and 51 % reached this at 12 months.  The magnitude of improvement in SSS was greater than predicted, with subjects having a mean decrease of 39 % and 36 % at 6 and 12 months, respectively.  This paralleled the improvement seen using the short form-36 instrument.  A modest volume reduction similar in magnitude to the treated volume was seen.  The incidence of adverse events was low.  These researchers concluded that MRgFUS treatment results in short-term symptom reduction for women with symptomatic uterine leiomyomas with an excellent safety profile.

In a review on percutaneous UAE for the treatment of symptomatic fibroids, Lupattelli et al (2005) stated that although randomized trials are still underway, UAE appears a good option for those patients who whish to conserve their fertility or when surgery is contra-indicated.  However, to assess the long-term effects of UAE longer follow-up is needed.  This is in agreement with the observation of Bachmann (2006) who noted that treatment options for women with symptomatic uterine leiomyomas have been expanded to include radiological interventions with UAE and focused ultrasound surgery despite the lack of long-term efficacy data.

An assessment by the Canadian Coordinating Office of Health Technology Assessment on MRI-guided focused ultrasound for the treatment of uterine fibroids (Chen, 2005) concluded that "[l]ong-term studies of larger patient groups are needed to provide further reliable evidence on the safety of this procedure, as well as its clinical and cost-effectiveness".  

An assessment by the BlueCross BlueShield Association Technology Evaluation Center (BCBSA, 2005) concluded that MRI-guided focused ultrasound for uterine fibroids did not meet the TEC criteria: "The evidence is insufficient to determine whether the use of MR-guided, focused ultrasound improves net health outcome or whether it is as beneficial as any established alternatives." The TEC assessment stated that limitations in quality of the existing evidence include significant loss to follow-up at longer follow-up intervals, lack of adequate well-controlled comparison studies, and lack of comparability between treatment groups in the available nonrandomized comparisons.

The TEC assessment considered both published evidence on MRI-guided focused ultrasound and unpublished evidence from the InSightec study that was submitted to the FDA to support a PMA.  The TEC assessment noted that the few available comparisons suggest that MRI-guided focused ultrasound may not be as effective as available alternatives.  The TEC assessment reported that patient satisfaction from the procedure is higher with hysterectomy, as is the degree of symptom relief.  The TEC assessment found no direct comparisons of MRI-guided ultrasound to either UAE or myomectomy available in the literature, but that this did not preclude TEC to reach some general and preliminary comparisons.  The TEC assessment noted that durability of MRI-guided ultrasound is a major concern; a substantially greater proportion of women undergo other (or repeat) procedures after MRI-guided ultrasound compared to either UAE or myomectomy.  The TEC assessment also found that available data suggest that fibroid volume reduction with MRI-guided ultrasound is much lower than with comparison procedures.  Uterine artery embolization appears to produce a more profound improvement in symptom severity scores than MRI-guided ultrasound.  For fertility preservation, myomectomy is the treatment of choice (TEC, 2005).  The TEC assessment stated that neither UAE nor MRI-guided ultrasound is recommended if the woman desires to preserve fertility.  The TEC assessment concluded that further study of the procedure and its durability, especially in light of other available treatments, is needed.

The National Institute for Health and Clinical Excellence (NICE, 2007) released  interventional procedures guidance that concluded that "[c]urrent evidence on the safety and efficacy of magnetic resonance image (MRI)-guided focused ultrasound for uterine fibroids does not appear adequate" and that "further research on the procedure and publication of long-term outcomes would be useful."  NICE reviewed the evidence on the safety and efficacy of the procedure, which comes from three uncontrolled case series.  Most of the papers excluded from the analysis were earlier reports on some of the same women.  The NICE assessment noted that a majority of published data have been reported by one study group. The NICE advisors observed that the primary endpoint in these case series was change in symptom severity rather than fibroid shrinkage, and that there is limited reduction in fibroid volume following the procedure (NICE, 2007).  The assessment stated that there is no evidence on the effects of this procedure on fertility.

A related NICE interventional procedure consultation document (NICE, 2006) stated that the maximum follow-up reported across all the studies was 19.5 months, and that most of the studies report on outcomes at 6 months.  A significant proportion of women included in these studies were lost to follow-up.  In addition, a significant proportion of women sought alternative treatments following the procedure, such as hysterectomy.

The NICE assessment listed skin burns as a potential complication from the procedure, occurring in 5% of subjects in one case series (NICE, 2007).  Another potential complication was reversible neural damage; two studies reported on cases of pain in the distribution of the sciatic nerve which resolved in both cases within one year of the procedure.  The NICE advisors also commented that thermal damage to adjoining structures was a theoretical concern.

The Agency for Healthcare Research and Quality's report on management of uterine fibroids (Viswanathan, et al., 2007) concluded that research is lacking for the long-term symptom relief of MRI-guided-ultrasound ablation.

An assessment of the evidence on treatment of uterine fibroids by BMJ Clinical Evidence concluded that the effectiveness of MRI-guided focused ultrasound is unknown (Lethaby & Vollenhoven, 2006).

Sharp (2006) stated that new technologies for the treatment of uterine leiomyomata include UAE, MRI-guided focused ultrasonography, laparoscopic uterine artery occlusion, and cryomyolysis. There is sound evidence for shorter hospital stay, quicker return to work, and a similar major complication rate compared with hysterectomy. Uterine artery embolization appears to be effective for up to 5 years in reducing bulk symptoms and menorrhagia associated with leiomyomata. The chance of reoperation for leiomyoma-related symptoms within 5 years is 20 to 29 %. Women who wish to become pregnant should be cautioned about potential complications during pregnancy. There is insufficient evidence to recommend UAE in post-menopausal women. With regard to MRI-guided focused ultrasonography, fibroid cryomyolysis (freezing), and laparoscopic uterine artery occlusion, Sharp (2006) commented that although the initial symptom reduction outcomes have been reported as favorable, more data are needed to better understand the durability of these results.

Hald et al (2007) compared clinical outcome 6 months after treatment with bilateral laparoscopic occlusion of the uterine artery versus uterine leiomyoma embolization.  A total of 66 pre-menopausal women with symptomatic uterine leiomyomata were randomized to treatment with either laparoscopic occlusion of uterine arteries or uterine leiomyoma embolization.  The primary outcome was reduction of blood loss from pre-treatment to 6 months post-operatively, measured by a Pictorial Bleeding Assessment Chart.  Secondary outcomes included patients' own assessment of symptom reduction, post-operative pain assessed using visual analog scales, ketobemidone used post-operatively, complications, secondary interventions, and failures.  Fifty-eight women were included; 6-month follow-up data were available for 28 participants in each group.  The percentage reduction in Pictorial Bleeding Assessment Chart scores did not differ between the treatment groups (52 % after uterine leiomyoma embolization and 53 % after laparoscopy, p = 0.96).  The study had 52 % power to detect a 20 % difference on the Pictorial Bleeding Assessment Chart.  Fewer participants in the group treated with uterine leiomyoma embolization complained of heavy bleeding after 6 months (4 % compared with 21 %, p = 0.044).  The post-operative use of ketobemidone was higher after uterine leiomyoma embolization (46 mg compared with 12 mg, p < 0.001).  The authors concluded that both laparoscopic occlusion of uterine vessels and embolization of uterine leiomyoma improved clinical symptoms in the majority of patients.  Participants with the laparoscopic procedure had less post-operative pain but heavier menstrual bleeding 6 months after treatment.  They noted that a larger study and longer follow-up is necessary before a definite conclusion can be made regarding the most effective treatment.