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The Effect of a Subsequent Pregnancy After Ovarian Vein Embolization in Patients with Infertility Caused by Pelvic Congestion Syndrome

Open AccessPublished:January 16, 2019DOI:https://doi.org/10.1016/j.acra.2018.12.024

      Rationale and Objectives

      To report the effect of pregnancy on patients who have undergone pelvic vein embolization with pelvic congestion syndrome, which was suspected to be the only cause of infertility.

      Material and Methods

      Data from a total of 12 women (mean age: 36.5 ± 4.3 years, range: 29–45 years) were collected between May 2013 and June 2016. Transvenous embolization with fibre platinum coils combined with anhydrous alcohol was performed in unilateral or bilateral ovarian veins after the diagnosis of venous varices confirmed by transvaginal ultrasound or pelvic venography. The follow-up time was 2–3 years. The primary outcomes of this study were the technical procedure and clinical effect, especially the pregnancy rate and complications.

      Results

      The successful embolization rate was 100% with no significant complications during or after embolization. Ovarian vein embolization was performed unilaterally (7/12, 58.3%) or bilaterally (5/12, 41.7%). A total of 66.7% (8/12) of women had a subsequent pregnancy and complete pelvic pain relief, and 33.3% (4/12) of patients had partial pain relief. The numeric pain perception scores improved from 6.7 ± 1.1 to 2.7 ± 1.2 (p < 0.001).

      Conclusion

      Ovarian varices may be associated with infertility in some patients, and embolization of ovarian varices is a safe and effective method for those trying to become pregnant.

      Key Words

      INTRODUCTION

      Pelvic congestion syndrome (PCS) is characterized by chronic pelvic pain for at least 6 months as a result of varices or the insufficiency of pelvic veins. It usually manifests as chronic pelvic pain, dyspareunia, dysmenorrhea, or sterility, etc. (
      • Lopez A.J.
      Female pelvic vein embolization: indications, techniques, and outcomes.
      ). The aetiology of PCS is diverse, involving congenital or acquired nonobstructive causes and secondary obstructive factors as well as other factors contributing to venous dilatation (>5 mm) and insufficiency (
      • Rochon P.
      • Sharpe E.
      • Alexander R.
      • et al.
      Pelvic congestion syndrome: systematic review of treatment success.
      ,
      • Hamoodi I.
      • Hawthorn R.
      • Moss J.G.
      Can ovarian vein embolization cause more harm than good?.
      ). There is an abundant interconnecting plexus of veins in the bladder, vagina, uterus, and rectum in the pelvis. The fundus of the uterus drains to either the uterine or the ovarian plexus within the broad ligament (
      • Machan L.
      • Durham J.
      Pelvic congestion syndrome.
      ). Many pelvic veins are devoid of valves and have weak attachments between the adventitia and supporting connective tissue. All of these factors contribute to retrograde venous flow, progressive development of pelvic varicosities and dilatation. Secondary pelvic insufficiency is often caused by compression, such as nutcracker syndrome or May-Thurner syndrome (
      • Mahmoud O.
      • Vikatmaa P.
      • Aho P.
      • et al.
      Efficacy of endovascular treatment for pelvic congestion syndrome.
      ). Structural and hormonal changes with parity may have a role in the progression of PCS.
      A clear diagnosis should be made based on clinical manifestation, a physical examination, and an imaging examination. Currently, retrograde selective ovarian venography is regarded as the gold standard for the diagnosis of PCS (
      • Mahmoud O.
      • Vikatmaa P.
      • Aho P.
      • et al.
      Efficacy of endovascular treatment for pelvic congestion syndrome.
      ).
      Coil embolization of the ovarian vein has been the most favorable approach, with a clinical efficacy ranging from 70% to 100% (
      • Machan L.
      • Durham J.
      Pelvic congestion syndrome.
      ). The goal of this approach is to occlude the incompetent pelvic veins and eradicate reflux (
      • Bittles M.A.
      • Hoffer E.K.
      Gonadal vein embolization: treatment of varicocele and pelvic congestion syndrome.
      ). The left ovarian vein has been the most commonly occluded vein in most reported studies. The advantages of vascular intervention are increasingly recognized over treatment with drugs or surgery; therefore, it is gradually becoming a first-line treatment. Many authors have reported effective results with metallic coils and sclerotherapy on pain relief through a visual analogue score (VAS) (
      • Ganeshan A.
      • Upponi S.
      • Hon L.
      • et al.
      Chronic pelvic pain due to pelvic congestion syndrome: the role of diagnostic and interventional radiology.
      ,
      • Meissner M.
      • Gibson K.
      Clinical outcome after treatment of pelvic congestion syndrome: sense and nonsense.
      ). However, reports about pregnancy after embolization are rare. Thus, the purpose of this study is to examine pregnancy after ovarian vein embolization in patients with infertility due to PCS.

      MATERIAL AND METHODS

      Patients

      A search of the interventional radiology database was performed to identify patients with PCS who were treated using pelvic embolization between May 2013 and June 2016. For this type of study formal consent is not required. A total of 12 women were included in this study. The concrete flow chart for selection is shown in Figure 1. Women had a mean age of 36.5 ± 4.3 (29–45) years. The patients’ mean body mass index (BMI) was 22.0 ± 2.1 kg/m2. The BMI of 91.7% (11/12) of the patients was in the normal range. Chief complaints included abdominal pain (12/12; 100%), sterility (12/12; 100%), dyspareunia (5/12; 41.7%), dysmenorrhea (4/12; 33.3%), and mictional urgency (3/12; 25%). Characteristics of the 12 patients are listed in Table 1. The inclusion criteria were as follows: (1) the diameter of the ovarian veins was >6 mm, verified by transvaginal ultrasound or magnetic resonance imaging; (2) patients had a desire to become pregnant; (3) ovarian varices were suspected to be the only factor of infertility; and (4) no pathological changes were observed in the gynaecologic examination or endocrine evaluation. Exclusion criteria included (1) other factors that may have resulted in infertility; (2) patients with other obstructive diseases, such as nutcracker syndrome and May-Thurner syndrome; and (3) pelvic varicose veins that fed saphenous varicose veins. Before embolization was performed, all patients and their families were informed of the risks related to this procedure and radiation exposure to the pelvis; informed consent was obtained from all patients.
      Figure 1.
      Figure 1Flow chart showing the selection of study women. (Color version of figure is available online.)
      Table 1Characteristics of the 12 Women Who Underwent Pelvic Embolization for Pelvic Congestion Syndrome
      Data collectionValue
      Age (year)36.5 ± 4.3
      BMI22.0 ± 2.1
      Parity1 (0–2)
      Gravidity2 (0.25–2)
      Symptoms
       Chronic pelvic pain12 (100%)
       Sterility12 (100%)
       Dyspareunia5 (41.7%)
       Dysmenorrhea4 (33.3%)
       Mictional urgency3 (25%)
      Diameter of ovarian veins8.4 ± 1.9
      Ovarian vein reflux9 (75%)
      BMI, body mass index.

      Procedure

      The same team of interventional radiologists and assistant doctors, all with >10 years of experience in the field, performed all embolization procedures. Venography was performed under local anaesthesia through a jugular or femoral approach. A 5-French catheter and/or a microcatheter was advanced to the ovarian vein plexus. Prior to embolization, phlebography was necessary in order to investigate any ovarian vein varicocele or uterine venous engorgement. Through the sheath, a 5-F cobra (Cook) catheter was inserted to select the left renal vein. A 0.035-inch guidewire (Terumo, Tokyo, Japan) was then manipulated caudally into the left ovarian vein and a microcatheter (Direxion, Boston Scientific) was advanced down to the left ovarian vein plexus. If a more distal position was required, a microcatheter was used. For the embolization, anhydrous alcohol and platinum spiral coils (Cook) were used. 3–8 ml of anhydrous alcohol was injected into the veins for the purpose of damaging the endothelial cells of the vein before coil implantation. Then coil embolization was carried out from the distal end to the proximal until of the end of ovarian vein in order to complete occlusion. The embolization procedure was repeated on the right if necessary. Embolization of the internal iliac vein was also performed when necessary. At the end of the operation, angiography was done again to ensure the embolization was thorough (Fig 2).
      Figure 2.
      Figure 2(A) Renal venography demonstrating ovarian vein reflux into a dilated left ovarian vein. (B) Selective ovarian venography demonstrating large paraovarian veins and uterine veins crossing the midline. (C) Venograph of the left ovarian vein after embolization with coils combined with alcohol sclerotherapy of the paraovarian veins. (D) Right ovarian venography showing a large vein with reflux. (E) No reflux is seen in the right ovarian vein postembolization with coils and alcohol.
      After embolization, women were admitted to the inpatient department for 2 days to monitor pain and the femoral access site. Patients were instructed to avoid heavy lifting or any exertion more intense than walking for 3–7 days postdischarge. Nonsteroidal anti-inflammatory drugs were given orally for pain. Pelvic transvaginal duplex ultrasound scans were given 3 months after the procedure to assess ovarian vein or pelvic vein reflux. Levels of female hormones, including follicular stimulating hormone and luteinizing hormone, were obtained before and 3 months after embolization, respectively. All patients had follow-up appointments for a period of 24–36 months after surgery. The effects of a subsequent pregnancy and pain relief were obtained by follow-up telephone interviews.

      Statistical Analysis

      Statistical analysis was performed using SPSS 19.0 (SPSS Inc, Chicago, Illinois). Continuous data are described as the mean ± standard deviation or median (range). Paired sample t tests were used to evaluate differences before and after embolization. Categorical variables were expressed as percentages, using a chi-square test or Fisher's exact test to determine the differences. p < 0.05 was considered statistically significant.

      RESULTS

      According to the transvaginal duplex ultrasound scan 3 months after the procedure, 11 patients experienced good embolization results, with reflux either totally eliminated or significantly reduced. Only one patient showed moderate venous reflux as well as a 6 mm venous diameter, and she therefore underwent a re-embolization procedure 6 months after the first embolization. The patient achieved complete elimination of reflux after the second embolization. There was a notable reduction in the size of the ovarian vein after embolization (3.7 ± 0.8) compared to before embolization (8.4 ± 1.9), and the difference was statistically significant (p = 0.00).
      During the 24–36 monthes follow-up period, eight (66.7%) women were pregnant postoperatively. Among them, six had an intrauterine pregnancy leading to a live birth. However, one had an extrauterine pregnancy in the right fallopian tube, and a laparoscopic salpingectomy was then performed. Hereafter, the patient did not become pregnant by the end of the follow-up period. Another patient had embryo cessation during the early stage of pregnancy, and she was forced to undergo abortion. No news was received from this patient about a subsequent pregnancy. A total of four (33.3%) of the women never experienced any gravidity postembolization, and no positive diagnosis was made related to their infertility. We saw a significant difference in the pregnancy rate before and after embolization (p = 0.001). Meanwhile, there was obvious pelvic pain relief postembolization; the rate of pelvic pain declined to 16.7% from 100% (p = 0.00). A statistically significant improvement in overall pain level was achieved based on numeric pain perception scores; the mean pain level improved from 6.7 ± 1.1 before embolization to 2.7 ± 1.2 after embolization (p < 0.01). There were no significant differences in hormonal levels before and after this procedure with either the mean values of follicular stimulating hormone (6.3 ± 0.7 vs 6.5 ± 0.6 IU/l, p = 0.24) or the mean values of luteinizing hormone (7.0 ± 1.3 vs 6.9 ± 0.9 IU/l, p = 0.85) (Table 2).
      Table 2Comparison of the Characteristics of 12 Patients Before and After Embolization
      Pre-embolizationPostembolizationp
      Symptoms
       Successful pregnancy0 (0%)8 (66.7%)0.001
       Chronic pelvic pain12 (100%)1(8.3%)0.00
       Dyspareunia5 (41.7%)1 (8.3%)0.155
       Dysmenorrhea4 (33.3%)1 (8.3%)0.317
       Mictional urgency3 (25%)0 (0%)0.217
      Numeric pain perception scores6.7 ± 1.11.6 ± 1.30.00
      Diameter of ovarian veins (mm)8.4 ± 1.93.7 ± 0.80.00
      LH (IU/l)7.0 ± 1.36.9 ± 0.90.85
      FSH (IU/l)6.3 ± 0.76.5 ± 0.60.24
      FSH, follicular stimulating hormone; LH, luteinizing hormone.
      No serious complications occurred. A total of five women complained of mild to moderate pelvic or flank pain postembolization, which could be controlled by nonsteroidal anti-inflammatory medications.

      DISCUSSION

      Edwards first described the successful endovenous embolization of the refluxing veins in 1993. Since then, ovarian vein embolization, unilaterally or bilaterally, has been performed principally for PCS (
      • Lopez A.J.
      Female pelvic vein embolization: indications, techniques, and outcomes.
      ). Multiple reports demonstrate the success of this approach with favorable outcomes. Hocquelet et al. retrospectively analysed a total of 33 female patients undergoing pelvic venous embolization, and the clinical efficacy reached 94% during the 26 month follow-up period, with VAS reduced from 7.37 to 1.36 (
      • Hocquelet A.
      • Le Bras Y.
      • Balian E.
      • et al.
      Evaluation of the efficacy of endovascular treatment of pelvic congestion syndrome.
      ). Kwon et al. reported a series of 67 patients treated with coil embolization alone, and symptom improvement occurred in 82% of patients postembolization (
      • Gandini Roberto
      • Chiocchi Marcello
      • Konda Daniel
      • et al.
      Transcatheter foam sclerotherapy of symptomatic female varicocele with sodium-tetradecyl-sulfate foam.
      ). Labourda et al. treated 202 patients with pelvic pain with coils, and clinical benefit was achieved in 94% of the patients as measured by a visual analogue scale (VAS) pain questionnaire. In most cases, the left ovarian or iliac vein is responsible for symptoms and is therefore often treated first, but the right side may also be treated if indicated (
      • Mahmoud O.
      • Vikatmaa P.
      • Aho P.
      • et al.
      Efficacy of endovascular treatment for pelvic congestion syndrome.
      ,
      • Ganeshan A.
      • Upponi S.
      • Hon L.
      • et al.
      Chronic pelvic pain due to pelvic congestion syndrome: the role of diagnostic and interventional radiology.
      ). In the present study, the clinical efficacy was 91.7%, and the numeric pain perception scores declined from 6.7 ± 1.1 to 1.6 ± 1.3. The recurrence rate was reported as 5–12.5% in the literature (
      • Kim H.S.
      • Malhotra A.D.
      • Rowe P.C.
      • et al.
      Embolotherapy for pelvic congestion syndrome: long-term results.
      ,
      • 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.
      ). In the present study, the recurrence rate was 8.3%. Until now, multiple sclerosants had been utilized in combination with ovarian vein mechanical occlusion, including foam, glue, and liquid sclerosants. These agents may be used in isolation or together. Gandini et al. reported the use of 3% sodium tetradecyl sulfate foam combined with coils to treat 38 patients with PCS, with improvement being as high as 100% (
      • Gandini Roberto
      • Chiocchi Marcello
      • Konda Daniel
      • et al.
      Transcatheter foam sclerotherapy of symptomatic female varicocele with sodium-tetradecyl-sulfate foam.
      ). Marcelin C et al. performed embolization in 17 women, who suffered from PCS, with ethylene vinyl alcohol copolymer (Onyx glue) together with coils, attaining a good result of 76.4–94.1% clinical efficacy for primary and second treatment, respectively (
      • Marcelin C.
      • Izaaryene J.
      • Castelli M.
      • et al.
      Embolization of ovarian vein for pelvic congestion syndrome with ethylene vinyl alcohol copolymer (Onyx ®).
      ). Currently, transcatheter embolization of the pelvic veins is the least invasive and most efficacious management option for pelvic varices (
      • Meissner M.
      • Gibson K.
      Clinical outcome after treatment of pelvic congestion syndrome: sense and nonsense.
      ).
      In this study, of the 12 patients, eight became pregnant and six had successful deliveries. Meanwhile, this procedure appeared to do no harm to ovaries, as no significant differences in hormonal levels were observed before and after this procedure (p > 0.05). Reports about pregnancy and ovary hormone levels after embolization are rare. Kim et al. found no significant change in hormone levels after embolotherapy in 127 women with ovarian varices treated with ovarian and pelvic vein embolotherapy, and two successful pregnancies were noted (
      • Kim H.S.
      • Malhotra A.D.
      • Rowe P.C.
      • et al.
      Embolotherapy for pelvic congestion syndrome: long-term results.
      ). Pavel et al. reported that two women with infertility were able to conceive (one intrauterine; one extrauterine pregnancy) after the embolization of the dilated left ovarian vein with steel coils. No pathological changes were observed in their gynaecological examinations or endocrine evaluations, thus ovarian varices seemed to be the sole suspected factor of their infertility (
      • Pavel Tarazov
      • Prozorovskij K.
      • Rumiantseva Svetlana
      Pregnancy after embolization of an ovarian varicocele associated with infertility—report of two cases.
      ). Dos Santos et al. reported good safety outcomes for coil embolization of pelvic veins in 8 patients (
      • Dos Santos S.J.
      • Holdstock J.M.
      • Harrison C.C.
      • et al.
      The effect of a subsequent pregnancy after transjugular coil embolisation for pelvic vein reflux.
      ). In our cohort, embolization of ovarian veins enhanced the chance of becoming pregnant, and no changes were observed in female hormone levels. We also found that in 91.7% (11/12) of cases in our study, the women were in the normal range of BMI, this could be proved by Nanavati et al. PCS is more likely to happen in women with normal a BMI compared to obese women (
      • Nanavati R.
      • Jasinski P.
      • Adrahtas D.
      Correlation between pelvic congestion syndrome and body mass index.
      ).
      No major complications were noted in the study. No more than half of the women complained of mild to moderate pelvic or flank pain postembolization, which could be controlled by nonsteroidal anti-inflammatory medications. The absence of severe complications also showed that embolization did not seem to pose any immediate life-threatening risks to patients.
      Our study has a few limitations. First, this was a small study with a limited number of patients, which may limit the application of this data to broad population. Second, this was a retrospective study. These drawbacks can be overcome by prospective, randomized, and controlled trials with a larger number of participants.
      In conclusion, venous embolization for the treatment of PCS is safe and effective with coils and anhydrous alcohol. Pertinent pain symptoms as well as sterility will be improved obviously postembolization, without any significant change in ovarian function. In the future, more in-depth research is needed to fully identify potential complication and to properly determine the application of this procedure to discussions of fertility.

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