Pelvic Congestion Syndrome

Pelvic congestion syndrome is a chronic pelvic pain syndrome of variable location and intensity, which is associated with dyspareunia and postcoital pain and aggravated by standing. The syndrome occurs during the reproductive years, and pain is often greater before or during menses. The underlying etiology is thought to be related to varices of the ovarian veins, leading to pelvic vascular congestion. Because there are many etiologies of chronic pelvic pain, the pelvic congestion syndrome is often a diagnosis of exclusion, with the identification of varices using a variety of imaging methods, such as magnetic resonance imaging, computed tomography, or contrast venography. However, the syndrome is still not well-defined, and it is unclear whether pelvic congestion syndrome causes chronic pelvic pain.^1, Although venous reflux is common, not all women with this condition experience chronic pelvic pain and, conversely, chronic pelvic pain is reported by women without pelvic congestion syndrome.

Treatment

Initial treatment of pelvic congestion syndrome includes psychotherapy and medical therapy (eg, nonsteroidal anti-inflammatory drugs) and hormonal therapy. For patients who fail initial therapy, surgical ligation of the ovarian vein may be considered. Embolization therapy and/or sclerotherapy of the ovarian and internal iliac veins has been proposed as an alternative to surgical ovarian vein ligation. Endovascular occlusion can be performed using a variety of materials including coils, vascular plugs, glue, liquid embolic agents, and gelatin sponge or powder (Gelfoam).

Regulatory Status

Ovarian and internal iliac vein embolization are surgical procedures and, as such, are not subject to regulation by the U.S. Food and Drug Administration.

Various products (eg, coils, vascular plugs, glue, liquid embolic agents, Gelfoam) and/or delivery-assist devices would be used to embolize the vein(s), and they would be subject to Food and Drug Administration regulation. Several products have been cleared for marketing by the Food and Drug Administration through the 510(k) process for uterine fibroid embolization (eg, Embosphere® Microspheres, Cook Incorporated Polyvinyl Alcohol Foam Embolization Particles) and/or embolization of hypervascular tumors and arteriovenous malformations (eg, Contour® Emboli PVA). Several embolization delivery systems have also been cleared via the 510(k) process for arterial and venous embolization in the peripheral vasculature featuring vascular plugs (eg, ArtVentive Medical Group, Inc. Endoluminal Occlusion System [EOS^TM]) or coils (eg, Cook Incorporated MReye® Flipper®). FDA product code: KRD.

In November 2004, the sclerosant agent Sotradecol® (sodium tetradecyl sulfate injection) was approved by the U.S. Food and Drug Administration for use in the treatment of small uncomplicated varicose veins of the lower extremities that show simple dilation with competent valves (ANDA 040541).

Related Policies

• Treatment of Varicose Veins/Venous Insufficiency (Policy #033 in the Surgery Section)

Endovascular occlusion of the ovarian vein and internal iliac veins is considered investigational as a treatment of pelvic congestion syndrome.


Medicare Coverage:
Medicare Advantage coverage differs from the Horizon BCBSNJ Medical Policy.

For Medicare Advantage Products: Ovarian and Internal Iliac Vein Embolization as a Treatment of Pelvic Congestion Syndrome may be covered after medical treatment failures when reasonable and necessary. Individual consideration will be given.

NCD 20.28 states that therapeutic embolization is covered when done for hemorrhage, and for other conditions amenable to treatment by the procedure, when reasonable and necessary for the individual patient. Renal embolization for the treatment of renal adenocarcinoma continues to be covered as one type of therapeutic embolization, to:

· Reduce tumor vascularity preoperatively;
· Reduce tumor bulk in inoperable cases; or
· Palliate specific symptoms.

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.

Policy Guidelines: (Information to guide medical necessity determination based on the criteria contained within the policy statements above.)

Endovascular occlusion of the ovarian and internal iliac veins may require an overnight hospital stay. Endovascular occlusion of the internal iliac veins has been performed on an outpatient basis.


[RATIONALE: This policy was created in 2009 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through May 31, 2019.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are 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 to 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 a technology, two domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical uses 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 is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials 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.

Pelvic Congestion Syndrome

No randomized controlled trials have been published comparing endovascular occlusion for pelvic congestion syndrome with a relevant alternative comparator or sham/placebo treatment. A randomized, prospective trial comparing embolization with coils vs vascular plugs is discussed. The remaining published evidence consists of case series, most of which were retrospective and conducted outside of the United States. Complicating the literature on this indication is a lack of standardized diagnostic criteria.

Clinical Context and Therapy Purpose

The purpose of ovarian and/or internal iliac vein endovascular occlusion in patients who have pelvic congestion syndrome 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 ovarian and/or internal iliac vein endovascular occlusion improve the net health outcome in patients with pelvic congestion syndrome?

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

Patients

The relevant population of interest is patients with pelvic congestion syndrome.

Interventions

The therapies being considered are ovarian and internal iliac vein endovascular occlusion.

Comparators

The following therapies are currently being used to make decisions about pelvic congestion syndrome: medical therapy (eg, analgesics, hormonal therapy) and surgical ovarian vein ligation.

Outcomes

The general outcomes of interest are symptom reduction (eg, pain related to varicose veins) and adverse events. Procedural follow-up ranges from 1 to 3 months.

Systematic Reviews

Tu et al (2010) published a systematic review of literature on the diagnosis and management of pelvic congestion syndrome.^2, They observed that studies have rarely specified explicit diagnostic criteria for pelvic congestion syndrome and that definitions of pelvic pain have varied widely across studies. Moreover, most studies have not used objective outcome measures.

Two systematic reviews assessing endovascular occlusion for pelvic congestion syndrome were published between 2016 and 2018. Tables 1 and 2 summarize key characteristics and results.

Table 1. Systematic Review Characteristics

Study	Dates	Trials	Participants1	N (Range)	Design	Duration
Brown et al (2018)3,	1997-2014	14	Women with: pelvic congestion syndrome with signs of pelvic vein incompetence on catheter-based venography** Studies with: percutaneous intervention for pelvic congestion syndrome (eg, sclerosis or embolization) outcomes assessed pre- and post-treatment	828 (NR)	Quasi-randomized trial Prospective observational studies Case series*	1-288 months
Mahmoud et al (2016)4,	1997-2014	20	Women with: pelvic congestion syndrome** Studies with: endovascular treatment of pelvic venous reflux	1,081 (6-218)	Prospective observational studies Case series	1-72 months

¹Key eligibility criteria.

*Study design noted by author not consistent with design type.

**No specific diagnostic criteria specified for pelvic congestion syndrome.

Table 2. Systematic Review Results

Study	Patients with Symptomatic Improvement		Patients with Little to No Symptomatic Improvement		Procedural Complications	Reports of Worsening Symptoms
Brown et al (2018)3,	Overall relief		Overall relief
N (Total N)1	697 (762)		57 (697)		36 (944)2	6 (710)
% (Range)	91.5% (68.3 - 100%)		8.2% (0-31.7%)		3.8% (NR)	0.8% (0-4.1%)
Median	95.1		4.6		NR	0
IQRQ3-Q1	17.4		14.2		NR	0
Mahmoud et al (2016)4,	Short-term relief	Long-term relief	Short-term relief	Long-term relief
N (Total N)	571 (648)	624 (721)	77 (648)	97 (721)	120 (1041)	NR
% (Range)	88.1% (NR)	86.6% (NR)	11.9% (NR)	13.4% (NR)	11.5% (NR)	NR
Median	NR	NR	NR	NR	NR	NR
IQRQ3-Q1	NR	NR	NR	NR	NR	NR

IQR_Q3-Q1: interquartile range. NR: not reported.

¹Proportion of patients with outcome from population completing all relevant follow-up.

²Proportion of procedures with outcome from total number of procedures performed.

A systematic review by Mahmoud et al (2016) identified 20 case series (total N=1081 patients) assessing endovascular treatment for pelvic congestion syndrome.^4,Reviewers did not require any particular diagnostic criteria for pelvic congestion syndrome. Only a single study used a comparison group, but patients in it received conservative treatment because they were ineligible for vein embolization therapy; as a result, outcomes following the two interventions cannot be compared. The authors included a quality assessment for the included studies - which were deemed to be of poor quality.

Brown et al (2018) evaluated patient outcomes following percutaneous treatment of pelvic congestion syndrome (N=828).^3, Study inclusion criteria required symptom(s) of pelvic congestion syndrome and the presence of pelvic venous incompetence on catheter-based venography - criteria which were not specified or defined. This review also includes a randomized trial published by Chung and Huh (2003) that evaluated the efficacy of various treatments for pelvic congestion syndrome that had failed 4-6 months of treatment with medroxyprogesterone acetate (N=106).^5, However, this study compared ovarian vein coil embolization to hysterectomy with bilateral or unilateral oophorectomy and was therefore not assessed separately as evidence.

Randomized Studies

A randomized, prospective trial by Guirola et al (2018) in Spain compared the safety and efficacy of embolization with vascular plugs (VPs) or fibered platinum coils (FPCs) in women with pelvic congestion syndrome.^6, Patients were enrolled (N=100) and randomly assigned to each treatment group via block randomization (N=50). Diagnosis of pelvic congestion syndrome was accomplished through a symptom screening questionnaire followed by an ultrasound study. Patients with 3 or more positive symptom responses advanced to the ultrasound screening, and patients with pelvic veins >6 mm in diameter and/or venous reflux or dilated midline communicating veins were advanced to randomization. Follow-up screening occurred at 1, 3, 6, and 12 months. The primary outcome was clinical success assessed subjectively through patient responses regarding relief of symptoms and pain scores assessed with the visual analog scale. Clinical success was achieved in 89.7% of the FPC group and 90.6% of the VP group (p = 0.760). Improvement in visual analog scale pain scores at the end of 12 months was 90.2% overall and improvement was seen in 95.9% of the FPC group and 96% of the VP group (p>0.999). A total of 11 (22%) complications were seen in the FPC group and 5 (10%) in the VP group (p = 0.059). Minor adverse events included access site hematoma and ovarian vein extravasation. Device migrations were considered major complications. A major limitation in the study is the significant difference in age (p = 0.004) and pre-treatment visual analog scale pain score between groups (p = 0.004), both of which were higher in the VP group despite randomization.

Case Series

Tables 3 and 4 summarize the characteristics and results of select case series that have reported on symptom improvements in patients with pelvic congestion syndrome treated with endovascular occlusion.

Table 3. Summary of Key Case Series Characteristics for Pelvic Congestion Syndrome

Study	Country	Participants	Treatment Delivery	Follow-Up, mo
Hocquelet et al (2014)7,	France	33	Vein embolization (foam, coil)	26
Nasser et al (2014)8,	Brazil	113	Vein embolization (coil)	12
Laborda et al (2013)9,	Spain	202	Vein embolization (coil)	60
Gandini et al (2008)10,	Italy	38	Vein embolization (foam)	12
Kwon et al (2007)11,	Korea	67	Vein embolization (coil)	45
Kim et al (2006)12,	U.S.	127	Vein embolization (foam)	45

^a Denotes industry-sponsored or cosponsored trial.

Table 4. Summary of Key Case Series Results for Pelvic Congestion Syndrome

Study	Treatment	Clinical Outcome (at Least Substantial Improvement in Symptoms), %
Hocquelet et al (2014)7,	Vein embolization (foam, coil)	94 (61 complete, 33 partial)
Nasser et al (2014)8,	Vein embolization (coil)	100 (53 complete, 47 partial)
Laborda et al (2013)9,	Vein embolization (coil)	94 (34 complete)a
Gandini et al (2008)10,	Vein embolization (foam)	100
Kwon et al (2007)11,	Vein embolization (coil)	82
Kim et al (2006)12,	Vein embolization (foam)	83

^a Based on 179 patients who completed the 5-year follow-up.

Summary of Evidence

For individuals who have pelvic congestion syndrome who receive ovarian and/or internal iliac vein endovascular occlusion, the evidence includes randomized studies, case series and systematic reviews. Relevant outcomes are symptoms and treatment-related morbidity. According to systematic reviews of case series data, approximately 86.6%, 88.1%, and 91.5% of patients have reported some degree of symptom relief after ovarian and/or internal iliac vein endovascular occlusion at short-term, long-term, or overall follow-up. In a randomized trial of embolization with vascular plugs or coils in patients with pelvic congestion syndrome, adverse events were reported in 22% and 10% of patients, respectively. It is difficult to draw conclusions from these data because of a lack of a placebo control or comparative data from current alternative interventions. Moreover, definitions of pelvic congestion syndrome vary, making it challenging to define a patient population with symptoms arising from pelvic congestion. Randomized controlled trials using well-defined eligibility criteria and relevant comparators are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

SUPPLEMENTAL INFORMATION

Practice Guidelines and Position Statements

A fact sheet from the Society for Interventional Radiology on chronic pelvic pain in women endorsed ovarian vein embolization as an effective treatment option for pelvic congestion syndrome.^13,

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 5.

Table 5. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT03794466	Quantification of Pain Relief With Gonadal Vein Embolization for Pelvic Congestion Syndrome	30	Sep 2020 (recruiting)
NCT03165214	Effectiveness of Embolization of Pelvic Veins in Treatment of Pelvic Congestion Syndrome	52	Sep 2019 (recruiting)
NCT01909024a	Pelvic Embolisation to Reduce Recurrent Varicose Veins - Recurrent	270	Dec 2018 (unknown)

NCT: national clinical trial.
^a Denotes industry-sponsored or cosponsored trial.]
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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:
Ovarian and Internal Iliac Vein Endovascular Occlusion as a Treatment of Pelvic Congestion Syndrome
Internal Iliac Vein Endovascular Occlusion as a Treatment of Pelvic Congestion Syndrome
Endovascular Occlusion as a Treatment of Pelvic Congestion Syndrome, Ovarian and Internal Iliac Vein
Ovarian and Internal Iliac Vein Embolization as a Treatment of Pelvic Congestion Syndrome
Embolization Therapy, Ovarian Vein, for Pelvic Congestion Syndrome
Pelvic Congestion Syndrome, Embolization Therapy

References:
1. Ball E, Khan KS, Meads C. Does pelvic venous congestion syndrome exist and can it be treated? Acta Obstet Gynecol Scand. May 2012;91(5):525-528. PMID 22268663.

2. Tu FF, Hahn D, Steege JF. Pelvic congestion syndrome-associated pelvic pain: a systematic review of diagnosis and management. Obstet Gynecol Surv. May 2010;65(5):332-340. PMID 20591203.

3. Brown, CC, Rizer, MM, Alexander, RR, Sharpe, EE, Rochon, PP. Pelvic Congestion Syndrome: Systematic Review of Treatment Success. Semin Intervent Radiol, 2018 Apr 10;35(1). PMID 29628614.

4. Mahmoud O, Vikatmaa P, Aho P, et al. Efficacy of endovascular treatment for pelvic congestion syndrome. J Vasc Surg Venous Lymphat Disord. Jul 2016;4(3):355-370. PMID 27318059.

5. Chung, MM, Huh, CC. Comparison of treatments for pelvic congestion syndrome. Tohoku J. Exp. Med., 2003 Dec 3;201(3). PMID 14649734.

6. Guirola, JJ, Sánchez-Ballestin, MM, Sierre, SS. A Randomized Trial of Endovascular Embolization Treatment in Pelvic Congestion Syndrome: Fibered Platinum Coils versus Vascular Plugs with 1-Year Clinical Outcomes. J Vasc Interv Radiol, 2017 Nov 28;29(1). PMID 29174618.

7. Hocquelet A, Le Bras Y, Balian E, et al. Evaluation of the efficacy of endovascular treatment of pelvic congestion syndrome. Diagn Interv Imaging. Mar 2014;95(3):301-306. PMID 24183954.

8. Nasser F, Cavalcante RN, Affonso BB, et al. Safety, efficacy, and prognostic factors in endovascular treatment of pelvic congestion syndrome. Int J Gynaecol Obstet. Apr 2014;125(1):65-68. PMID 24486124.

9. Laborda A, Medrano J, de Blas I, et al. Endovascular treatment of pelvic congestion syndrome: visual analog scale (VAS) long-term follow-up clinical evaluation in 202 patients. Cardiovasc Intervent Radiol. Aug 2013;36(4):1006-1014. PMID 23456353.

10. Gandini R, Chiocchi M, Konda D, et al. Transcatheter foam sclerotherapy of symptomatic female varicocele with sodium-tetradecyl-sulfate foam. Cardiovasc Intervent Radiol. Jul-Aug 2008;31(4):778-784. PMID 18172712.

11. Kwon SH, Oh JH, Ko KR, et al. Transcatheter ovarian vein embolization using coils for the treatment of pelvic congestion syndrome. Cardiovasc Intervent Radiol. Jul-Aug 2007;30(4):655-661. PMID 17468903.

12. Kim HS, Malhotra AD, Rowe PC, et al. Embolotherapy for pelvic congestion syndrome: long-term results. J Vasc Interv Radiol. Feb 2006;17(2 Pt 1):289-297. PMID 16517774.

13. Society of Interventional Radiology (SIR). Diseases and conditions: Chronic pelvic pain (pelvic congestion syndrome) [Patient Center]. n.d.; https://www.sirweb.org/patients/pelvic-congestion-syndrome--chronic-pelvic- pain/. Accessed July 5, 2019.

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*

There are no specific CPT codes for this procedure.