Uterine fibroids, also known as leiomyomas, are among the most common conditions affecting women in their reproductive years; symptoms include menorrhagia, pelvic pressure, or pain.

Treatment

Surgery, including hysterectomy and various myomectomy procedures, is considered the criterion standard for symptom resolution. However, there is the potential for surgical complications and, in the case of a hysterectomy, the uterus is not preserved. In addition, multiple myomectomies may be associated with longer operating time, postoperative febrile morbidity, and development of pelvic adhesions. There has been long-standing research interest in developing minimally invasive alternatives for treating uterine fibroids, including procedures that retain the uterus and permit future childbearing. Treatment options include uterine artery embolization and the transcutaneous magnetic resonance imaging-guided focused ultrasound therapy (see separate policy on 'Magnetic Resonance Imaging-Guided Focused Ultrasound' - Policy #054 in the Surgery Section). Various techniques to induce myolysis have also been studied including Nd:YAG lasers, bipolar electrodes, cryomyolysis, and radiofrequency ablation. With these techniques, an energy source is used to create areas of necrosis within uterine fibroids, reducing their volume and thus relieving symptoms. Early methods involved multiple insertions of probes into the fibroid, performed without imaging guidance. There were concerns about serosal injury and abdominopelvic adhesions with these techniques, possibly due to the multiple passes through the serosa needed to treat a single fibroid.^1, Newer systems using radiofrequency energy do not require repetitive insertions of needle electrodes. Ultrasonography is used laparoscopically or transcervically to determine the size and location of fibroids, to guide the probe, and to ensure the probe is in the correct location so that optimal energy is applied to the fibroid. Percutaneous approaches using magnetic resonance imaging guidance have also been reported.

Regulatory Status

In 2012, the Acessa™ System (Acessa Health, formerly Halt Medical) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process for percutaneous laparoscopic coagulation and ablation of soft tissue and treatment of symptomatic uterine fibroids under laparoscopic ultrasound guidance (K121858). The technology was previously approved in 2010, at which time it was called the Halt 2000GI™ Electrosurgical Radiofrequency Ablation System. In 2014, the ultrasound guidance system received marketing clearance from the FDA (K132744). FDA product code: GEI. In 2018, the third-generation Acessa™ ProVu System® was cleared for marketing by the FDA through the 510(k) process for use in percutaneous, laparoscopic coagulation and ablation of soft tissue, including treatment of symptomatic uterine fibroids under laparoscopic ultrasound guidance. (K181124). FDA product code: HFG.

In 2018, the Sonata® Sonography-Guided Transcervical Fibroid Ablation System (Gynsonics) was cleared for marketing by the FDA through the 510(k) process for diagnostic intrauterine imaging and transcervical treatment of symptomatic uterine fibroids (K173703). The Sonata system was previously known as Vizablate. FDA product codes: KNF, ITX, and IYO.

Cryoablation is a surgical procedure that uses previously approved and available cryoablation systems; and as a surgical procedure, it is not subject to regulation by the FDA. Other products addressed in this review (eg,Nd:YAG lasers, bipolar electrodes) have long-standing FDA approval, and there are no products specifically approved for the treatment of uterine fibroids.

Related Policies

• Magnetic Resonance Imaging-Guided Focused Ultrasound (Policy #054 in the Surgery Section)

WARNING: Uterine tissue may contain unsuspected cancer. The use of laparoscopic power morcellators during fibroid surgery may spread cancer, and decrease the long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.

CONTRAINDICATION: Laparoscopic power morcellators are contraindicated in gynecologic surgery in which the tissue to be morcellated is know or suspected to contain malignancy.

CONTRAINDICATION: Laparoscopic power morcellators are contraindicated for removal of uterine tissue containing suspected fibroids in patients who are:
• peri- or post-menopausal , or
• candidates for en bloc tissue removal, for example, through the vagina or via a mini-laparotomy incision.

Laparoscopic and percutaneous techniques of myolysis as a treatment of uterine fibroids are considered investigational.


Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage will follow the Horizon BCBSNJ Medical Policy.

Medicaid Coverage:
This service is not a covered benefit for members enrolled in Medicaid and NJ FamilyCare plans.

FIDE-SNP Coverage:
For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

[RATIONALE: This policy was created in 2009 and has been updated regularly with searches of the PubMed database until it was archived in December 2009. In July 2013, the review returned to active status. The most recent literature update was performed through June 26, 2020.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, 2 domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Radiofrequency Ablation

Clinical Context and Therapy Purpose

The purpose of radiofrequency ablation (RFA) in women who have uterine fibroids is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does the use of RFA improve the net health outcome in women with uterine fibroids?

The following PICO was used to select literature to inform this review.

Patients

The relevant population of interest is women with symptomatic uterine fibroids.

Interventions

The therapy being considered is laparoscopic or transcervical RFA of fibroids under ultrasonic guidance.

Comparators

The following therapies are currently being used to manage symptomatic uterine fibroids: medical management, uterine artery embolization (UAE), myomectomy, and hysterectomy. Surgery, including hysterectomy and myomectomy are considered the criterion standard for symptom resolution. However, there is the need to recover from surgery, and in the case of a hysterectomy, the uterus is not preserved. UAE is associated with poor pregnancy outcomes and is not advised in patients who desire to become pregnant.

A retrospective cohort from claims data of over 35,000 women found that of the less invasive procedures, myomectomy had the lowest 12-month reintervention rate (4.2%), followed by UAE (7.0%), and endometrial ablation (12.4%).^2,

Outcomes

The outcomes of interest are, complications, postoperative pain and recovery time, symptom resolution, fibroid recurrence and need for reintervention at 3 to 5 years, and health-related quality of life. The symptom severity score (SSS) is a 0 to 100 scale where higher SSSs indicate more severe symptoms. The EuroQol 5-Dimension (EQ-5D) is a 0 to 100 scale where lower scores indicate worse quality of life.

Review of Evidence

Systematic Reviews

A systematic review and meta-analysis by Sandberg et al (2018) evaluated the risk of reintervention for hysterectomy and quality of life after uterine-sparing interventions for fibroids (see Tables 1 and 2).^3, Risk of reintervention at 12 months was 0.3% for RFA compared with 3.6% for UAE and 1.1% for myomectomy. Symptom severity and quality of life scores were similar for the 3 treatments. Only 1 RFA study was identified on reintervention risk at 36 months; none was identified on reintervention risk at 60 months. A systematic review by Havryliuk et al (2017) that did not separate outcomes by the length of follow-up found a reintervention rate of 5.2% after RFA (4 studies, 12 to 36 mo follow-up) compared to 4.2% after myomectomy (6 studies, 12 to 52 mo follow-up).^4, There was no significant difference in complication rates between RFA (6.3%) and myomectomy (7.9%). The length of stay after myomectomy was 2 days (range 0.5 to 6.0). No data were provided on length of stay after RFA.

Lin et al (2018) conducted a meta-analysis of improvement in symptom severity, quality of life, and reintervention after RFA.^5, The review included 1 RCT and 7 non-comparative trials. The recurrence risk at a weighted mean follow-up of 24.65 months (range, 3 to 36 months) was 4.4%. Improvements in symptoms and quality of life were maintained out to 24 months in 3 studies and out to 36 months in 1 study. No studies were identified that had follow-up longer than 36 months.

Bradley et al (2019) conducted a systematic review of 32 prospective studies on laparoscopic, transvaginal, or transcervical RFA.^6, Most were conducted outside of the U.S. with devices that are not cleared or approved by the U.S. Food and Drug Administration.The overall reintervention risk was 4.2% at 12 months, 8.2% at 24 months, and 11.5% at 36 months. Reintervention rates at 12 months did not differ significantly for the laparoscopic, transvaginal, or transcervical RFA procedures. Because many of the devices are not available in the U.S., relevance for the current review is limited.

Table 1. Characteristics of Systematic Reviews on RFA

Study	Dates	Trials	Participants	N	Design	Duration, mo
Sandberg et al (2018)3,	2006-2016	45	Women with symptomatic uterine fibroids undergoing myomectomy, UAE, or RFA	17,789	Studies evaluating reintervention for hysterectomy and quality of life with consecutive enrollment and follow-up of ≥12 mo	11.2-34.7
Lin et al (2019)5,	2000-2018	8	Women with symptomatic uterine fibroids undergoing myomectomy, UAE, or RFA	581	Studies evaluating symptoms and quality of life	>12 mo
Bradley et al (2019)6,		32	Women with symptomatic uterine fibroids undergoing laparoscopic, transvaginal, or transcervical RFA	1283	Prospective studies for treatment of uterine fibroids with RFA (variety of devices)	12 - 36 mo

RFA: radiofrequency ablation; UAE: uterine artery embolization.

Table 2. Results of Systematic Reviews on RFA

Study	Reintervention Risk (95% CI), %			Symptom Severity Score (95% CI)			QOL (95% CI)
	At 12 Months	At 36 Months	At 60 Months	At 12 Months	At 24 Months	At 36 Months	At 12 Months	At 24 Months
Sandberg et al (2018)3,
Total studies	40	8	27	18			11
Myomectomy	1.1 (0.0 to 3.7)	1.2 (0.0 to 5.2)	12.2 (5.2 to 21.2)	-37.6 (-43.8 to -31.4)			39.9 (33.0 to 46.8)
UAE	3.6 (2.4 to 4.9)	7.4 (0.9 to 10.7)	14.4 (9.8 to 19.6)	-35.8 (-40.6 to -30.9)			38.9 (35.8 to 41.9)
RFA	0.3 (0.0 to 1.6)	10.4 (1 study)	Unknown	-37.0 (-44.6 to -29.4)			35.1 (28.7 to 41.6)
Lin et al (2019)5,		Range, 3 to 36 mo
Total Studies		7		6	3	1	3	1
RFA		4.39 (1.60−8.45)		-39.37 (-34.70 to -44.04)	-33.51 (-22.24 to -44.78)	-32.60 (-27.75 to -37.45)	29.21 (12.44 to 45.98)	38.60 (33.60 to 39.79)
P Value				<0.001	<0.001	<0.001	p<0.001	p<0.001
Bradley et al (2019)6,
Total Studies
RFA	4.2	11.5			-40		+39
					<0.001		<0.001

CI: confidence interval; QOL: quality of life; RFA: radiofrequency volumetric thermal ablation; UAE: uterine artery embolization.

Randomized Controlled Trials

One RCT evaluating RFA was included in the Sandberg et al (2018) systematic review, with Tables 3 and 4 describe trial characteristics and results.

Table 3. Summary of Key Randomized Controlled Trial Characteristics for RFA

					Interventions
Study	Countries	Sites	Dates	Participantsa	Active	Comparator
Brucker et al (2014)7,; Hahn et al (2015)8, Kramer et al (2016)9,	Germany	1	2012-2013	≥18 y Menstruating Symptomatic uterine fibroids <10 cm Uterine size ≤16 gestational wk Desire uterine conservation Not pregnant or lactating	RFA=26	LM=25

LM: laparoscopic myomectomy; RFA: radiofrequency volumetric thermal ablation.
^a Key eligibility criteria.

Table 4. Summary of Key Randomized Controlled Trial Outcomes for RFA

Study	Primary Outcome	Secondary Outcomes
	Hospital LOS (SD), ha	Mean SSS		Mean HRQOL
		12 mo	24 mo	12 mo	24 mo
Brucker et al (2014)7,; Hahn et al (2015)8, Kramer et al (2016)9,	50	43a	43	43	43
Laparoscopic RFA	10.0 (5.5)	24.7	16	87	89.4
Laparoscopic myomectomy	29.9 (14.2)	26	22.3	83	85.6
p	<0.001b	NSc	NS	NS	NS

HRQOL: health-related quality of life; LOS: length of stay; NS: not significant; RFA: radiofrequency volumetric thermal ablation; SSS: Symptom Severity Score.
^a Analyses at 12 and 24 months were per protocol and included 84% of randomized participants.
^b Met criteria for noninferiority: hospital LOS after RFA no more than 10% longer than after laparoscopic myomectomy.
^c Exact between-group p values were not reported.

In the Brucker et al (2014) trial, all patients in the myomectomy group were hospitalized overnight; although not explicitly stated, this appeared to be the standard procedure at the study hospital. In the RFA (Acessa) group, there was an unplanned hospitalization due to unexplained vertigo and 4 hospitalizations as a standard procedure because the patients also underwent adhesiolysis.

Secondary outcomes of the RCT were reported by Hahn et al (2015)^8, (12-month outcomes) and by Kramer et al (2016)^9, (12-month and 24-month outcomes). In addition to summary symptom and quality of life measures, the publications reported on 11 symptoms: heavy menstrual bleeding, increased abdominal girth, dyspareunia, pelvic discomfort/pain, dysmenorrhea, urinary frequency, urinary retention, sleep disturbance, backache, localized pain, and "other symptoms" (not specified).

Limitations of the 12- and 24-month analyses, shown in Tables 5 and 6, included lack of intention-to-treat analysis and failure to describe secondary study hypotheses and statistical analyses clearly. The RCT had a small sample size and thus might have been underpowered to detect clinically meaningful differences in secondary outcomes, so these results do not rule out potential differences between treatments.

Table 5. Study Relevance Limitations

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Brucker et al (2014)7,; Hahn et al (2015)8, Kramer et al (2016)9,					1. Insufficient to determine reintervention rates

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
^a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
^b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4.Not the intervention of interest.
^c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
^d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
^e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 6. Study Design and Conduct Limitations

Study	Allocationa	Blindingb	Selective Reportingc	Data Completenessd	Powere	Statisticalf
Brucker et al (2014)7,; Hahn et al (2015)8, Kramer et al (2016)9,				6. Not intent-to-treat	1. Power for secondary outcomes unclear

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
^a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
^b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
^c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
^d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
^e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
^f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4.Comparative treatment effects not calculated.

Prospective Single Arm Studies

Prospective single-arm studies are described in tables 7 and 8.

The pivotal study for the SONATA transcervical RFA system was a prospective single arm study with 147 premenopausal women who had symtomatic uterine fibroids with heavy menstrual bleeding.^10, Patients were excluded if they desired to become pregnant. There were 2 (1.4%) procedure-related adverse events during the first year of follow-up and no additional device-related adverse events between the 1- and 2- year follow-up. At the 24 month follow-up, patients reported significantly improved symptom severity scores, HRQL, and EQ-5D. The cumulative rate of surgical intervention for heavy menstrual bleeding was 5.2% (95% confidence interval [CI] 2.5% to 10.6%). Follow-up is continuing through 3 years.

The Fibroid Ablation Study EU (FAST-EU) was a prospective single-arm trial with the previously named VizAblate transcervical RFA. ^11, Fifty women who had heavy menstrual bleeding were included in the study. Patients were excluded if they desired to become pregnant. The primary outcome measure, that at least 50% of patients with >30% reduction in perfused fibroid volume, was achieved at the 3 month follow-up. Twelve-month follow-up was not in the original study design, and only 28 (58.3%) of participants agreed to return for an MRI at this time point. The Symptom Severity Score was obtained in all patients except for 1 patient due to pregnancy. A clinically significant minimum 10 point reduction in the Symptom Severity Score was obtained in 82% of patients at 3 months, 86% at 6 months, and 78% at 12 months. There were 34 adverse events deemed possibly, probably, or definitely related to the procedure. Four patients (8%) underwent surgical reintervention between 6 and 12 months post-ablation.

Table 7. Summary of Single Arm Study Characteristics

Study	Study Location	Participants	Treatment Delivery1	Follow-Up
Brolmann et al (2016) 11,FAST-EU	7 community or academic gynecologists in EU and Mexico	50 women > 28 years of age with heavy menstrual bleeding for at least 3 months and no desire to become pregnant	VizAblate(TM) transcervical RFA	12 mo
Miller et al (2020)10,	Community or academic gynecologists in the US and Mexico	147 premenopausal women 25-50 years of age with symptomatic uterine fibroids with heavy menstrual bleeding and no desire to become pregnant	Sonata transcervical RFA	2 years

RFA: radiofrequency ablation

Table 8. Case Series Results

Study	Baseline	3 mo	12 mo	24 mo
Brolmann et al (2016) 11,FAST-EU
n (%)	50	50	48
Percentage change in perfused fibroid volume (SD)	18.3 (20.6)	5.8 (9.6)	6.6 (11.3) n=28
Symptom Severity Score (SD)	61.7 (16.9)	31.7 (20.1)	26.6 (24.0)
HRQL	34.3 (19.0)	76.4 (22.2)	80.7 (24.7)
Surgical reintervention			4 (8%)
Miller et al (2020)10,
n (%)	147			125 (85%)
Symptom Severity Score (SD)	55 (19)			24 (18) P<.001
HRQL (SD)	40 (21)			83 (19) P<.001
EQ-5D (SD)	0.72 (0.21)			0.89 (0.14) P<0.001
Surgical reintervention				5.5%

EQ-5D Euroqol 5-dimension; HRQL: Health-related quality of life; SD: standard deviation

Pregnancy Outcomes After Radiofrequency Ablation

Keltz et al (2017) published a systematic review of published literature on pregnancy outcomes after thermal ablation of uterine fibroids.^12, For RFA, reviewers identified 20 pregnancies reported in 4 case series; the denominator (ie, the number of patients treated in these series) was not reported. Of the 20 pregnancies, 7 were undesired and were electively terminated. For the remaining 13 pregnancies, there was 1 spontaneous abortion and 12 full-term births. Nine of the 12 live births were delivered by cesarean section.

Section Summary: Radiofrequency Ablation

Prospecrtive case series, systematic reviews, and an RCT comparing RFA with laparoscopic myomectomy have been published. The meta-analyses found low rates of reintervention with RFA and quality of life outcomes that were similar to myomectomy and UAE at 12 months. Data on reintervention rates at 36 months was limited to a single study and no studies reported reintervention rates at 60 months. The RCT found that RFA was noninferior to laparoscopic myomectomy on the primary outcome (length of hospitalization). A number of secondary outcomes of the RCT were reported at 12 and 24 months, including symptoms and quality of life outcomes; none differed significantly between groups. The RCT only had 43 patients in subgroup analyses at 12 and 24 months, and may have had insufficient power for the secondary outcomes. The procedure is associated with a reduction in symptoms and improvement in quality of life in the short-term. The reintervention rate at longer follow-up is unknown. Because most trials excluded women who desired to become pregnant, the impact of RFA on pregnancy outcomes is also uncertain. Additional well-designed comparative trials with longer follow-up are needed to determine the effect of RFA on health outcomes compared with other treatment options, including myomectomy.

Laser or Bipolar Needles

Clinical Context and Therapy Purpose

The purpose of therapy with laser or bipolar needles in patients who have uterine fibroids is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does the use of laser or bipolar needles improve the net health outcome in women with uterine fibroids?

The following PICO was used to select literature to inform this review.

Patients

The relevant population of interest is women with symptomatic uterine fibroids.

Interventions

The therapy being considered is laser or bipolar needles.

Comparators

The following therapies are currently being used to manage symptomatic uterine fibroids: medical management, uterine artery embolization (UAE), myomectomy, and hysterectomy. Surgery, including hysterectomy and myomectomy are considered the criterion standard for symptom resolution. However, there is the need to recover from surgery, and in the case of a hysterectomy, the uterus is not preserved. UAE is associated with poor pregnancy outcomes and is not advised in patients who desire to become pregnant.

A retrospective cohort from claims data of over 35,000 women found that of the less invasive procedures, myomectomy had the lowest 12-month reintervention rate (4.2%), followed by UAE (7.0%), and endometrial ablation (12.4%).^2,

Outcomes

The outcomes of interest are, complications, postoperative pain and recovery time, symptom resolution, need for reintervention, and health-related quality of life. The immediate follow-up would be a week for postoperative pain and recovery, and 3 to 5 years of follow-up would be needed to monitor for fibroid recurrence and retreatment.

Review of Evidence

Case Series

Several case series were identified, most published in the 1990s. For example, Goldfarb (1995) reported on outcomes for 300 women with symptomatic fibroids no larger than 10 cm who underwent myolysis using either Nd:YAG or bipolar needles. ^13,The author reported that the coagulating effect of the bipolar needle devascularized the fibroids, and the resulting shrinkage was comparable to that produced by Nd:YAG laser. An earlier study by Goldfarb (1992), included 75 patients who presented with symptomatic fibroids 5 to 10 cm in diameter.^14, Symptoms included pelvic pain, pressure, dyspareunia, and recurrent menorrhagia. The Nd:YAG laser was inserted into the fibroid multiple times (eg, 75 to 100 punctures to coagulate a 5-cm fibroid). Based on an assessment by endovaginal ultrasound, the fibroids regressed in size and, after 6 to 14 months of follow-up, the size remained stable. No patient experienced significant complications. Nisolle et al (1993) reported on a case series of 48 women offered myolysis instead of myomectomy if they had completed childbearing.^15, The authors reported that maximal decrease in fibroid size had occurred by 6 months, however, as reported, it is unclear among the 28 of 48 patients with more than 2 fibroids whether all fibroids were treated in each patient, and, if not, how treated fibroids were selected. Additionally, no associated patient symptoms were reported.

Several authors have reported pelvic adhesions as a complication of the Nd:YAG laser procedure, presumably due to thermal damage to the serosal surface. In addition, the Nd:YAG laser produces a significant amount of smoke, which can obscure visibility.^16,17,

Section Summary: Laser or Bipolar Needles

The evidence base on the use of lasers or bipolar needles only includes case series, small in size, and published in the 1990s. RCTs comparing laser and bipolar needles with alternative treatments for uterine fibroids and reporting health outcomes are needed.

Cryomyolysis

Clinical Context and Therapy Purpose

The purpose of cryomyolysis in patients who have uterine fibroids is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does cryomyolysis improve the net health outcome in women with uterine fibroids?

The following PICO was used to select literature to inform this review.

Patients

The relevant population of interest is women with symptomatic uterine fibroids.

Interventions

The therapy being considered is cryomyolysis. Cryomyolysis entails inserting a -180°C cryoprobe into the center of a fibroid, which creates an "iceball" within the fibroid. Several freeze-thaw cycles are typically used, and the process may not be standardized.

Comparators

The following therapies are currently being used to manage symptomatic uterine fibroids: medical management, uterine artery embolization (UAE), myomectomy, and hysterectomy. Surgery, including hysterectomy and myomectomy are considered the criterion standard for symptom resolution. However, there is the need to recover from surgery, and in the case of a hysterectomy, the uterus is not preserved. UAE is associated with poor pregnancy outcomes and is not advised in patients who desire to become pregnant.

A retrospective cohort from claims data of over 35,000 women found that of the less invasive procedures, myomectomy had the lowest 12-month reintervention rate (4.2%), followed by UAE (7.0%), and endometrial ablation (12.4%).^2,

Outcomes

The outcomes of interest are, complications, postoperative pain and recovery time, symptom resolution, need for reintervention, and health-related quality of life. The immediate follow-up would be a week for postoperative pain and recovery, and 3 to 5 years of follow-up would be needed to monitor for fibroid recurrence and retreatment.

Review of Evidence

Case Series

No controlled studies evaluating cryomyolysis were identified.

Two case series have been identified. Zreik et al (1998)^18, published a prospective pilot study with 14 patients, and Zupi et al (2004)^19, presented their experience with 20 patients.^18,19, In both case series, the authors reported that patients had symptom resolution. In the Zreik et al (1998) series, cryomyolysis maintained or slightly reduced the myoma volume by 6%. In the Zupi et al (2004) study, cryomyolysis was associated with a 25% reduction in fibroid size. Zupi et al (2005) reported on the 1-year follow-up of these patients.^20, Mean shrinkage in fibroid size continued until 9 months after surgery, to a mean volume reduction of 60%. In the Sandberg et al (2018) systematic review (discussed above), the risk of reintervention was 15%.^3, Interpretation of these studies is limited due to their small sample sizes and lack of comparison groups.

Section Summary: Cryomyolysis

The literature on cryomyolysis includes small case series, with no literature identified in the last decade. Controlled studies comparing cryomyolysis with alternative treatments for uterine fibroids and differentiating between outcomes related to fibroid treatment and outcomes related to the treatment of abnormal bleeding are needed.

Magnetic Resonance Imaging-Guided Laser Ablation

Clinical Context and Therapy Purpose

The purpose of MRI-guided laser ablation in patients who have uterine fibroids is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does MRI-guided laser ablation improve the net health outcome in women with uterine fibroids?

The following PICO was used to select literature to inform this review.

Patients

The relevant population of interest is women with symptomatic uterine fibroids.

Interventions

The therapy being considered is MRI-guided laser ablation.

Comparators

The following therapies are currently being used to manage symptomatic uterine fibroids: medical management, uterine artery embolization (UAE), myomectomy, and hysterectomy. Surgery, including hysterectomy and myomectomy are considered the criterion standard for symptom resolution. However, there is the need to recover from surgery, and in the case of a hysterectomy, the uterus is not preserved. UAE is associated with poor pregnancy outcomes and is not advised in patients who desire to become pregnant.

A retrospective cohort from claims data of over 35,000 women found that of the less invasive procedures, myomectomy had the lowest 12-month reintervention rate (4.2%), followed by UAE (7.0%), and endometrial ablation (12.4%).^2,

Outcomes

The outcomes of interest are, complications, postoperative pain and recovery time, resolution of symptoms, need for reintervention, and health-related quality of life. The immediate follow-up would be a week for postoperative pain and recovery, and 3 to 5 years of follow-up would be needed to monitor for fibroid recurrence and retreatment

Review of Evidence

Nonrandomized Studies

No RCTs evaluating MRI-guided laser ablation were identified. A nonrandomized study by Hindley et al (2002) was identified (see Tables 9 and 10).^21, Results from the women treated with MRI-guided laser ablation were compared with a historical control group of 43 women who underwent a hysterectomy. Compared with the historical control group, the total score on the Menorrhagia Outcomes Questionnaire was significantly lower (ie, worse outcomes) in those undergoing percutaneous myolysis. The quality of life subscores did not differ statistically.

Table 9. Summary of Key Nonrandomized Trial Characteristics

Study	Type	Country	Participants	Treatment	Comparator	FU, y
Hindley et al (2002)21,	Cohort with historical controls	U.K.	109 women with symptomatic fibroids seeking to avoid surgery	66 to MRI-guided laser ablation	43 to hysterectomy	1

FU: follow-up; MRI: magnetic resonance imaging.

Table 10. Summary of Key Nonrandomized Trial Results

Study	Mean Fibroid Volume Reduction (Range), %		MOQ Total	MOQ QOL/Satisfaction
	At 3 Months	At 1 Year
Hindley et al (2002)21,
n/N (%)	47/66 (71)	24/66 (36)	34/66	33/66
MRI-guided laser ablation	-31 (21 to -76)	-41 (13 to -78)	51.5	51.5
Hysterectomy	NR	NR	48.7	49.0
p			0.02	0.06

MRI: magnetic resonance imaging; MOQ: Menorrhagia Outcomes Questionnaire; NR: not reported; QOL: Quality of Life.

The purpose of the limitations tables (see Tables 11 and 12) is to display notable limitations identified in each study. This information is synthesized as a summary of the body of evidence following each table and provides the conclusions on the sufficiency of the evidence supporting the position statement.

Table 11. Study Relevance Limitations

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Hindley et al (2002)21,	4. Self-selected population seeking to avoid open surgery				1. Not sufficient duration to assess reintervention

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
^a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
^b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4.Not the intervention of interest.
^c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
^d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
^e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 12. Study Design and Conduct Limitations

Study	Allocationa	Blindingb	Selective Reportingc	Data Completenessd	Powere	Statisticalf
Hindley et al (2002)21,	1-4. Not randomized	1-3. Not blinded		1.High loss to follow-up

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
^a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
^b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
^c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
^d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
^e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
^f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4.Comparative treatment effects not calculated.

Section Summary: MRI-Guided Laser Ablation

A single nonrandomized study with historical controls was identified. Data reporting was incomplete, and self-reported outcomes were worse compared with a historical control group of women undergoing a hysterectomy. RCTs comparing MRI-guided laser ablation with alternative treatments for uterine fibroids and reporting health outcomes are needed.

Summary of Evidence

For individuals who have symptomatic uterine fibroids who receive RFA, the evidence includes prospective cohorts, an RCT and systematic review. Relevant outcomes are symptoms, quality of life, and treatment-related morbidity. The meta-analysis found low rates of reintervention with RFA and quality of life outcomes that were similar to uterine artery embolization and myomectomy at 12 months. Data on reintervention rates at 36 months were limited to 1 study and no studies reported reintervention rates at 60 months. The single RCT with a follow-up longer than 3 months found that RFA was noninferior to laparoscopic myomectomy on the trial's primary outcome: length of hospitalization. A number of secondary outcomes were reported at 12 and 24 months, including symptoms and quality of life. None of the secondary outcomes demonstrated significant between-group differences in a subgroup analysis of 43 patients. The procedure has faster recovery than myomectomy, and provides a reduction in symptoms and improvement in quality of life in the short term. Recurrence and reintervention rates at longer follow-up are unknown. Well-designed comparative trials with longer follow-up are needed to determine the effect of RFA on health outcomes compared with other treatment options such as myomectomy. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have symptomatic uterine fibroids who receive laser or bipolar needles, the evidence includes case series. Relevant outcomes are symptoms, quality of life, and treatment-related morbidity. The case series were published in the 1990s, and the procedures used then may not reflect current practice. RCTs comparing laser or bipolar needles with alternative treatments for uterine fibroids are needed to evaluate the safety and efficacy of this technology adequately. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have symptomatic uterine fibroids who receive cryomyolysis, the evidence includes case series. Relevant outcomes are symptoms, quality of life, and treatment-related morbidity. Among the few case series, sample sizes were small (≤20 patients). RCTs comparing cryomyolysis with alternative treatments for uterine fibroids are needed to evaluate the safety and efficacy of this technology adequately. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have symptomatic uterine fibroids who receive magnetic resonance imaging-guided laser ablation, the evidence includes a study with historical controls. Relevant outcomes are symptoms, quality of life, and treatment-related morbidity. A single study with historical controls is not sufficiently robust to evaluate this technology. RCTs comparing magnetic resonance imaging-guided laser ablation with alternative treatments for uterine fibroids are needed to evaluate safety and efficacy adequately. The evidence is insufficient to determine the effects of the technology on health outcomes.

SUPPLEMENTAL INFORMATION

Practice Guidelines and Position Statements

American College of Obstetricians and Gynecologists

In 2019, the American College of Obstetricians and Gynecologists reaffirmed its 2008 position on alternatives to hysterectomy in the management of leiomyomas.^22,

Recommendations based on good and consistent scientific evidence were that abdominal myomectomy is a safe and effective treatment for women with symptomatic leiomyomas and that uterine artery embolization is a safe and effective option for appropriately selected women who want to retain their uteri. The bulletin contained no recommendations on myolysis using laparoscopic or percutaneous techniques.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Some currently ongoing and unpublished trials that might influence this policy are listed in Table 13.

Table 13. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT02260752	Patient-Centered Results for Uterine Fibroids (COMPARE-UF)	3,094	Sep 2020 published
NCT01563783a	The Trust (Treatment Results of Uterine Sparing Technologies) Study	260	Jun 2022
NCT03219385	Directed Ablation of Uterine Fibroids Using a Noninvasive Approach (DIANA)	180	Sep 2022
NCT03118037	Transcervical Radiofrequency Ablation of Uterine Fibroids Global Registry (SAGE)	100	Dec 2023
NCT02163525a	Post Market TRUST - U.S.A. Study	114	Jun 2024
NCT02100904	Uterine Leiomyoma Treatment With Radiofrequency Ablation (ULTRA) Registry (ULTRA Registry)	400	Jan 2025
Unpublished
NCT01750008a	The LUSTOR (Laparoscopic Uterine Sparing Techniques Outcomes and Reinterventions)Trial	51	Jun 2018

NCT: national clinical trial.
^a Denotes industry-sponsored or cosponsored trial.]
________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Laparoscopic and Percutaneous Techniques for the Myolysis of Uterine Fibroids
Myolysis of Uterine Fibroids
Laparoscopic Myolysis of Uterine Fibroids
Percutaneous Myolysis of Uterine Fibroids
Uterine Fibroids, Myolysis
Acessa System
Sonata Sonography-Guided Transcervical Fibroid Ablation System

References:
1. Jones S, O'Donovan P, Toub D. Radiofrequency ablation for treatment of symptomatic uterine fibroids. Obstet Gynecol Int. 2012; 2012: 194839. PMID 21961009

2. Davis MR, Soliman AM, Castelli-Haley J, et al. Reintervention Rates After Myomectomy, Endometrial Ablation, and Uterine Artery Embolization for Patients with Uterine Fibroids. J Womens Health (Larchmt). Oct 2018; 27(10): 1204-1214. PMID 30085898

3. Sandberg EM, Tummers FHMP, Cohen SL, et al. Reintervention risk and quality of life outcomes after uterine-sparing interventions for fibroids: a systematic review and meta-analysis. Fertil Steril. Apr 2018; 109(4): 698-707.e1. PMID 29653718

4. Havryliuk Y, Setton R, Carlow JJ, et al. Symptomatic Fibroid Management: Systematic Review of the Literature. JSLS. Jul-Sep 2017; 21(3). PMID 28951653

5. Lin L, Ma H, Wang J, et al. Quality of Life, Adverse Events, and Reintervention Outcomes after Laparoscopic Radiofrequency Ablation for Symptomatic Uterine Fibroids: A Meta-Analysis. J Minim Invasive Gynecol. Mar 2019; 26(3): 409-416. PMID 30253997

6. Bradley LD, Pasic RP, Miller LE. Clinical Performance of Radiofrequency Ablation for Treatment of Uterine Fibroids: Systematic Review and Meta-Analysis of Prospective Studies. J Laparoendosc Adv Surg Tech A. Dec 2019; 29(12): 1507-1517. PMID 31702440

7. Brucker SY, Hahn M, Kraemer D, et al. Laparoscopic radiofrequency volumetric thermal ablation of fibroids versus laparoscopic myomectomy. Int J Gynaecol Obstet. Jun 2014; 125(3): 261-5. PMID 24698202

8. Hahn M, Brucker S, Kraemer D, et al. Radiofrequency Volumetric Thermal Ablation of Fibroids and Laparoscopic Myomectomy: Long-Term Follow-up From a Randomized Trial. Geburtshilfe Frauenheilkd. May 2015; 75(5): 442-449. PMID 26097247

9. Kramer B, Hahn M, Taran FA, et al. Interim analysis of a randomized controlled trial comparing laparoscopic radiofrequency volumetric thermal ablation of uterine fibroids with laparoscopic myomectomy. Int J Gynaecol Obstet. May 2016; 133(2): 206-11. PMID 26892690

10. Miller CE, Osman KM. Transcervical Radiofrequency Ablation of Symptomatic Uterine Fibroids: 2-Year Results of the SONATA Pivotal Trial. J Gynecol Surg. Dec 01 2019; 35(6): 345-349. PMID 32226268

11. Brolmann H, Bongers M, Garza-Leal JG, et al. The FAST-EU trial: 12-month clinical outcomes of women after intrauterine sonography-guided transcervical radiofrequency ablation of uterine fibroids. Gynecol Surg. NA 2016; 13: 27-35. PMID 26918001

12. Keltz J, Levie M, Chudnoff S. Pregnancy Outcomes After Direct Uterine Myoma Thermal Ablation: Review of the Literature. J Minim Invasive Gynecol. May 2017; 24(4): 538-545. PMID 28109894

13. Goldfarb HA. Bipolar laparoscopic needles for myoma coagulation. J Am Assoc Gynecol Laparosc. Feb 1995; 2(2): 175-9. PMID 9050553

14. Goldfarb HA. Nd:YAG laser laparoscopic coagulation of symptomatic myomas. J Reprod Med. Jul 1992; 37(7): 636-8. PMID 1387912

15. Nisolle M, Smets M, Malvaux V, et al. Laparoscopic myolysis with the Nd:YAG laser. J Gynecol Surg. 1993; 9(2): 95-9. PMID 10171973

16. Donnez J, Squifflet J, Polet R, et al. Laparoscopic myolysis. Hum Reprod Update. Nov-Dec 2000; 6(6): 609-13. PMID 11129695

17. Phillips DR, Nathanson HG, Milim SJ, et al. Laparoscopic Leiomyoma Coagulation. J Am Assoc Gynecol Laparosc. Aug 1996; 3(4, Supplement): S39. PMID 9074213

18. Zreik TG, Rutherford TJ, Palter SF, et al. Cryomyolysis, a new procedure for the conservative treatment of uterine fibroids. J Am Assoc Gynecol Laparosc. Feb 1998; 5(1): 33-8. PMID 9454874

19. Zupi E, Piredda A, Marconi D, et al. Directed laparoscopic cryomyolysis: a possible alternative to myomectomy and/or hysterectomy for symptomatic leiomyomas. Am J Obstet Gynecol. Mar 2004; 190(3): 639-43. PMID 15041993

20. Zupi E, Marconi D, Sbracia M, et al. Directed laparoscopic cryomyolysis for symptomatic leiomyomata: one-year follow up. J Minim Invasive Gynecol. Jul-Aug 2005; 12(4): 343-6. PMID 16036195

21. Hindley JT, Law PA, Hickey M, et al. Clinical outcomes following percutaneous magnetic resonance image guided laser ablation of symptomatic uterine fibroids. Hum Reprod. Oct 2002; 17(10): 2737-41. PMID 12351555

22. American College of Obstetricians and Gynecologists. ACOG practice bulletin. Alternatives to hysterectomy in the management of leiomyomas. Obstet Gynecol. Aug 2008; 112(2 Pt 1): 387-400. PMID 18669742

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

58674
58578
58999