Description:
Pelvic congestion syndrome is characterized by chronic pelvic pain that is often aggravated by standing; diagnostic criteria for this condition are not well-defined. Endovascular occlusion (e.g., embolization, sclerotherapy) of the ovarian and internal iliac veins has been proposed as a treatment for patients who fail medical therapy.

For individuals who have pelvic congestion syndrome who receive ovarian and/or internal iliac vein endovascular occlusion, the evidence includes case series and systematic reviews. Relevant outcomes are symptoms and treatment-related morbidity. According to a systematic review of case series data, approximately 80% of patients have reported some degree of symptom relief 12 months after ovarian and/or internal iliac vein endovascular occlusion. 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 are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

Background
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 (e.g., nonsteroidal anti-inflammatory drugs) and hormonal therapy. For patients who fail initial therapy, surgical ligation of the ovarian vein may be considered. Embolization therapy of the ovarian and internal iliac veins has been proposed as an alternative to surgical ovarian vein ligation. Vein embolization can be performed using a variety of materials including coils, glue and gel foam.

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 (e.g., 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 (e.g., Embosphere^® Microspheres, Cook Incorporated Polyvinyl Alcohol Foam Embolization Particles) and/or embolization of hypervascular tumors and arteriovenous malformations (e.g., 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 (e.g., ArtVentive Medical Group, Inc. Endoluminal Occlusion System (EOS^TM)) or coils (e.g., 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:
40111 Occlusion of Uterine Arteries Using Transcatheter Embolization

Policy:
Embolization of the ovarian vein and internal iliac veins is investigational and/or unproven therefore considered NOT MEDICALLY NECESSARY as a treatment of pelvic congestion syndrome.

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

Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all U.S. Food and Drug Administration (FDA)-approved devices, drugs, biologics, and imaging may not be considered investigational and thus, may be assessed only on the basis of their medical necessity.

Rationale
This evidence review was created in April 2004 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through June 12, 2022.

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, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent 1 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 (RCT) 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
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 evidence review 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.

Populations
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 (e.g., analgesics, hormonal therapy) and surgical ovarian vein ligation.

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

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
Tu et al. (2010) published a systematic review of literature on the diagnosis and management of pelvic congestion syndrome.² The authors 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

NR: Not reported.
*Study design noted by author not consistent with design type.
**No specific diagnostic criteria specified for pelvic congestion syndrome.

Table 2. Systematic Review Results

IQR: 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 (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 2 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 to 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 (VAS). Clinical success was achieved in 89.7% of the FPC group and 90.6% of the VP group (p = .760). Improvement in VAS 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 > .999). A total of 11 (22%) complications were seen in the FPC group and 5 (10%) in the VP group (p = .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 = .004) and pre-treatment VAS pain score between groups (p = .004), both of which were higher in the VP group despite randomization.

Comparative Studies
A single-center, retrospective cohort analysis by Gavrilov et al. (2020) in Russia compared the safety and efficacy of embolization with coils (N = 67) and endoscopic resection (N = 28) in women with pelvic congestion syndrome.⁷ Effects on pelvic venous pain, pelvic venous reflux, diameter of the pelvic veins, restoration of daily activity, and treatment safety were assessed. Clinical examinations were conducted at 1 day, 10 days, 30 days, and 36 months post-procedure. Pain reduction was observed at 3.6 ± 1.4 days after embolization and 2.5 ± 0.8 days after endoscopic resection (p = .49). At 1 month post-procedure, complete relief of pelvic pain was reported by 52 (77.6%) patients post-embolization and by 25 (89.3%) patients post-resection (p > .05). Rates of valvular incompetence decreased from 85% at baseline in both groups to 3% and 0% in the embolization and resection groups at 36 months, respectively. Postembolization syndrome was diagnosed in 13 (19.4%) patients. A 4-fold increased rate of venous thromboembolism was observed in the embolization group. The relative risk (RR) of this complication after embolization compared to resection was 1.4 (95% confidence interval [CI], 1.146 to 1.732). The time to post-embolization pain relief was statistically greater than the time calculated to postoperative pain relief (11.2 ± 1.7 day and 4.7 ± 0.5 days, p = .0002). Pelvic pain relief was achieved in 95.5% of patients in the embolization group and 100% of patients in the endoscopic resection group at 3 years. The authors note that endoscopic resection is associated with at least similar, and in some cases, superior outcomes, in terms of significantly shorter times to postprocedural pain relief and avoidance of postembolization syndrome. Evidence of selection bias through the use of differing eligibility criteria between groups limits the findings of this study.

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

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

^a Rate of successful pregnancy following previous infertility.
^b Based on 179 patients who completed the 5-year follow-up.

Section Summary: Pelvic Congestion Syndrome
In regard to the treatment of pelvic congestion syndrome, the evidence consists of systematic reviews, randomized studies, comparative studies, and case series. A retrospective analysis comparing coil embolization to endoscopic resection determined that resection is associated with significantly shorter times to postprocedural pain relief and avoidance of postembolization syndrome. Moreover, definitions of pelvic congestion syndrome vary, making it difficult to define a patient population with symptoms arising from pelvic congestion. Randomized controlled trials with well-defined eligibility criteria and relevant comparators are needed.

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, comparative 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. A retrospective analysis comparing coil embolization to endoscopic resection determined that resection is associated with significantly shorter times to postprocedural pain relief and avoidance of postembolization syndrome. 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 that the technology results in an improvement in the net health outcome.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in "Supplemental Information" if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings and include a description of management of conflict of interest.

Society for Interventional Radiology
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.¹⁵

U.S. Preventive Services Task Force Recommendations
Not applicable.

Ongoing and Unpublished Clinical Trials
Some currently unpublished and ongoing trials that might influence this review are listed in Table 5.

Table 5. Summary of Key Trials

NCT: national clinical trial.
a Denotes industry-sponsored or cosponsored trial.
* = NCT03165214 was withdrawn with no patients recruited and, therefore, deleted from the above table. 

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): 525-8. 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): 332-40. PMID 20591203
3. Brown CL, Rizer M, Alexander R, et al. Pelvic Congestion Syndrome: Systematic Review of Treatment Success. Semin Intervent Radiol. Mar 2018; 35(1): 35-40. 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): 355-70. PMID 27318059
5. Chung MH, Huh CY. Comparison of treatments for pelvic congestion syndrome. Tohoku J Exp Med. Nov 2003; 201(3): 131-8. PMID 14649734
6. Guirola JA, Sanchez-Ballestin M, Sierre S, et al. 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. Jan 2018; 29(1): 45-53. PMID 29174618
7. Gavrilov SG, Sazhin A, Krasavin G, et al. Comparative analysis of the efficacy and safety of endovascular and endoscopic interventions on the gonadal veins in the treatment of pelvic congestion syndrome. J Vasc Surg Venous Lymphat Disord. Jan 2021; 9(1): 178-186. PMID 32464289
8. Liu J, Han L, Han X. The Effect of a Subsequent Pregnancy After Ovarian Vein Embolization in Patients with Infertility Caused by Pelvic Congestion Syndrome. Acad Radiol. Oct 2019; 26(10): 1373-1377. PMID 30660471
9. 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): 301-6. PMID 24183954
10. 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): 65-8. PMID 24486124
11. 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): 1006-14. PMID 23456353
12. 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): 778-84. PMID 18172712
13. 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): 655-61. PMID 17468903
14. 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): 289-97. PMID 16517774
15. Society of Interventional Radiology (SIR). Diseases and conditions: Chronic pelvic pain (pelvic congestion syndrome) [Patient Center]. n.d.; https://www.sirweb.org/patient-center/pelvic-venous-disease/https://www.sirweb.org/patient-center/conditions-and-treatments/pelvic-venous-disease/. Accessed June 12, 2022.

Coding Section 

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This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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