RETRACTED ARTICLE: Monopolar versus bipolar laparoscopic ovarian drilling in clomiphene-resistant polycystic ovaries (PCO): a preliminary study

Abstract

The objective of this study is to compare the safety and efficacy of laparoscopic ovarian drilling (LOD) utilizing monopolar versus bipolar needle in clomiphene-resistant polycystic ovaries (PCO) in infertile women. This study is a prospective randomized comparative diagnostic trial. The procedures were performed in an endoscopic unit of a tertiary care referral facility and university hospital. Eighty clomiphene-resistant PCO patients were randomly assigned by using a computerized random table into group A and group B for monopolar and bipolar LOD of 40 patients in each group, respectively. The intervention was LOD using monopolar or bipolar needle in groups A and B, respectively. The main outcome measures are resumption of regular menstruation, spontaneous ovulation, and pregnancy. Both groups showed a significant postoperative improvement of menstrual patterns and hormonal profiles if compared to preoperative levels without significant difference between both groups. Spontaneous ovulation resumed in 13 (32.5 %) and 25 (62 %), p = 0.007, while spontaneous pregnancy within 1 year after LOD occurred in 9 (22.5 %) and 18 (45 %) cases (p = 0.033) in both groups, respectively. Both monopolar and bipolar needles are effective tools for LOD in clomiphene citrate (CC)-resistant PCO infertile patients as a second-line therapy. Utilizing bipolar LOD is superior to monopolar LOD due to a significantly higher postoperative incidence of resumption of spontaneous ovulation and spontaneous pregnancy. Theoretical less adhesion formation following bipolar LOD requires a second-look laparoscopy study. In the meantime, spread of bipolar LOD should be encouraged.

Introduction

Polycystic ovarian syndrome (PCOS) is the commonest hyperandrogenic disorder in women and represents one of the most common causes of anovulatory infertility, with an estimated prevalence of 4–7 % worldwide [1]. It may be associated with menstrual irregularities, hirsutism, infertility, or a combination of any of them. For fertility enhancement, weight reduction, life style modification, metformin, and clomiphene citrate (CC) are the first-line therapy of most cases. Since a long time, it has been suggested that unilateral or bilateral laparoscopic ovarian drilling (LOD) is advised only when first-line therapy failed (clomiphene citrate (CC)-resistant) or if the patient is at a high risk of hyperstimulation or multiple pregnancy [2, 3]. The main benefits of LOD are shorter time to pregnancy, less need to ovulation induction drugs, more comfort, cost-effective, and possibility to be performed ambulatory. However, the results of LOD are not better than those of CC as a first-line treatment in PCOS [4].

Many LOD techniques like electrocauterization and laser vaporization using carbon dioxide (CO2), argon, or Nd:YAG (neodymium-doped yttrium aluminum garnet; Nd:Y3Al5O) crystal lasers have been used to create multiple perforations in the ovarian surface to have an access for limited destruction of the androgen-producing ovarian stroma. Nevertheless, there is insufficient evidence to support any one surgical technique over another relating to achievement of pregnancy [5]. To minimize the possibility of short-term and long-term complications of LOD, refinements of surgical techniques and instrumentation were described. Bipolar energy probe as a potentially safe method was tested. Microlaparoscopic ovarian drilling technique (MLOD) under local anesthesia would allow outpatient management without general anesthesia. Fertiloscopy (transvaginal hydrolaparoscopy) can be utilized for LOD as an office procedure [6]. This study aims to compare safety and efficacy of LOD utilizing monopolar versus bipolar needle in CC-resistant PCO patients.

Patient and methods

Recruitment of patients

This prospective, cross-sectional, single-center, open randomized clinical study took place at the Women’s Health University Hospital, Assiut University, from June 2013 to November 2014. The institutional review board approved the study. It comprised 80 CC-resistant PCO patients diagnosed clinically, endocrinologically, and sonographically as PCO attending gynecologic and infertility clinics that were selected for the study.

Clinical work-up

During the study period, all PCO patients who received CC at a maximal dose of 200 mg daily from day 2 for 5 days for 6 successive cycles with proved anovulation using day 21 serum progesterone were evaluated. PCO women with other factors of infertility like male, tubal, peritoneal factors, as well as endometriosis were excluded from this study. The diagnosis of PCO patients was based on the Rotterdam European Society of Human Reproduction/American Society for Reproductive Medicine Sponsored PCOS Consensus Workshop Group [7] with the existence of two of the following three criteria to make the diagnosis of PCOS: oligo-ovulation/anovulation, clinical or biochemical signs of hyperandrogenism, and polycystic ovaries by ultrasound. All patients were assessed clinically (to determine menstrual pattern and body mass index), sonographically (to measure ovarian volume and antral follicle count at time of ovarian quiescence), and at the laboratory (to measure day 3 to 5 serum LH, FSH, LH/FSH ratio, total testosterone, and estradiol).

Hormonal assay

Blood samples were collected in a dry plastic disposable syringe on heparinized tubes and then centrifuged. Serum concentration of E2, FSH, and LH were measured by immunoassay, and interpretation of assays was performed according to manufacturer recommendations. Pregnancy was ruled out by pregnancy test in serum in all cases with oligo or amenorrhea. In this study, anti-Mullerian hormone (AMH) estimation was not requested as it is an expensive test and is not done at our institution for free department.

Randomization and exclusion criteria

The patients were randomly assigned by using a computerized random table (Fig. 1) into group A and group B for monopolar and bipolar diathermy LOD of 40 patients in each group, respectively. In both groups, tubal patency and mobility were confirmed by flushing of the tubes with methylene blue. Women with one or both tubes blocked were excluded from this study. Occurrence of associated pelvic pathology-like pelvic adhesions, tubal block, or typical pelvic endometriosis was considered as exclusion criteria of this study.

Fig. 1

Randomization chart

Surgical techniques

LOD was performed in the follicular phase of natural cycle via three ports of entry after insufflation of the peritoneal cavity by electronic high-flow pneumoperitoneum insufflator with CO₂ gas. In group A, LOD was performed using an insulated monopolar needle (Fig. 2). The uninsulated tip of the needle was 8 mm long and its caliber was 1 mm. The needle was inserted into the antimesentric ovarian surface as close to perpendicularly as possible after proper grasping of the ovarian ligament. A short duration of a cutting current of 100 W was used to aid the entry of the needle aiming at minimization of capsular thermal damage with subsequent adhesion formation. The whole length of the needle was inserted into the ovary and was activated for 4 s with 40 W of coagulating mode. In this study, we were restricted to the rule of 4 (4 punctures of each ovary, for 4 s utilizing 40 W setting) regardless of the ovarian size. The amount of energy used is computed as (Joules) = power (watt) × duration (second) × number of punctures. By this way, the estimated energy for each ovary in this study would be 640 J.

Fig. 2

Monopolar LOD

In group B (Fig. 3), LOD was performed with a reusable 3-mm bipolar needle with two adjacent terminal needles at the tip of each 1 mm caliber, loaded inside a 3–5-mm adaptor. The needle has two fine needles at the tip each of less than 1 mm caliber. LOD was performed in the same way like group A. After drilling, the ovary was allowed to cool in a pole of saline to prevent excessive heat trauma. After exploration of the upper abdomen, the peritoneal cavity was rinsed with 500 cm³ lactated Ringer’s solution.

Fig. 3

Bipolar LOD

Follow-up schedule

All women were subjected to strict postoperative follow-up for evidence of any complications or complaints. They were discharged 4–6 h postoperatively on prophylactic antibiotics. They were asked to come to the office for the next 6 cycles for reassessment of regularity of the menstrual cycles, ovulation rate (as evaluated by TVS folliculometry and serum progesterone on day 21), and pregnancy rate. Postdrilling anovulation was treated with 100 mg CC/day for 5 days with meticulous observation of any evidence of OHSS. Due to financial restrictions, serum levels of FSH and LH (day 2 of the cycle), E2, and testosterone were requested once for each patient during the follow-up period usually on the first follow-up visit.

Statistical analysis

It was done using SPSS 17.0 statistical software packages (SPSS, Inc., Chicago, IL). Data were presented using descriptive statistics in the form of frequencies and percentages for qualitative variables, and ranges, means and SDs, medians and quartiles for quantitative variables in box plots. The comparability of baseline characteristics according to outcome was ascertained by Student t test (unpaired t test) for continuous variables and Mann-Whitney U test when appropriate and W2 test for categorical variables. To evaluate the univariate relation between variables, Pearson correlation coefficient was calculated. Values were considered significant if p ≤ 05.

Results

We assessed 234 patients for eligibility to participate in the study. A total of 154 women were excluded from the study due to association with other factors of infertility (Fig. 1). Table 1 shows the demographic data and the main complaint of the women. Subjects in both groups were similar in mean age, parity, duration of infertility, and body mass index (BMI). After LOD, there was a significant reduction in the mean levels of LH, LH/FSH ratio, and testosterone in both groups (p < 0.05). On the other hand, there were no significant changes of the mean levels of FSH and E2 in any group (p > 0.05). There was a statistically significant difference between both groups regarding the postoperative fall in LH level as it declined in 4 (10 %) and 11 (27 %) women in groups A and B, respectively. However, there was no significant post-LOD increase in the FSH level (an ovarian reserve test) in both groups.

Table 1 Sociodemographic data of studied groups

There was an insignificant difference between both groups regarding sonographic appearance of PCOS. In both groups, menstrual pattern improved significantly if compared to the preoperative pattern. However, none of both groups was superior to the other in this regard. Table 2 shows a comparison between both groups regarding ovulation rate (after LOD) with a statistically significant difference (p < 0. 05). Moreover, bipolar LOD achieved a significantly higher pregnancy rate if compared to monopolar LOD as shown in Table 3. Likewise, Table 4 shows a comparison between the two groups regarding pregnancy rate after LOD with or without standard CC induction of ovulation 100 mg/day with a statistically significant difference (p < 0.05).

Table 2 Ovulation rate in both groups within 6 months follow-up

Discussion

Treatment of PCOS should be targeted toward the patient’s primary complaint, whether infertility, hirsutism, or menstrual irregularities. This study focuses only on CC-resistant infertility. Clomiphene citrate (CC) in a standard or maximal dose is well recognized as a first-line therapy for infertile women with PCOS. Gonadotropin therapy (GT) has traditionally been the preferred therapy for CC-resistant cases. However, the ability to achieve monofollicular ovulation is challenging, and there is a considerable risk for ovarian hyperstimulation syndrome (OHSS) with GT use. On the other hand, LOD is not associated with an increased risk of multiple pregnancy or OHSS [2, 3]. As reported by our team, LOD was found to cause a decline of already increased serum levels of serum vascular endothelial growth factor and insulin-like growth factor-1 which may explain increased vascularity demonstrated by Doppler blood flow measurements in PCOS [8]. In this study, there is no case of postoperative OHSS even with the use of antiestrogens following LOD. The basic concept behind LOD is destruction of a part of the ovarian stroma and, hence, decreasing functional ovarian mass which may diminish intraovarian androgen production and possibly encourage increased FSH levels.

An extra advantage of LOD is the low cost if compared to GTs [9]. In this study, the cost of LOD using either monopolar or bipolar diathermy was cheaper than a single course of GTs (around 800 EP Vs 1200 EP/case) putting in mind that, at our country, the Ministry of Health and the National Medical System do not cover GT therapy for infertility but may cover LOD.

Utilizing different energy modalities, LOD results in a limited destruction of androgen-producing ovarian tissue and reduction of the peripheral conversion of androgens to estrogens. Previously, we used CO₂ laser LOD, but nowadays, we completely prohibited for this purpose. As CO₂ laser beam penetrates just a few millimeters, its efficacy for destruction of ovarian stroma is doubtful. Moreover, its superficial burn of the capsule may invite adhesions. LOD objective is hardly achieved utilizing laser simply because of the limited depth of penetration. Nevertheless, a small sample-sized study found comparable results between diathermy and CO₂ laser LOD [10] but without a second-look laparoscopy to evaluate postoperative adhesion.

Since a long time [6], fertiloscopic LOD utilizing a fine bipolar electrode was described. Despite being an interesting office transvaginal approach first described by Gordts [11], with minimal possibility of postoperative adhesion formation, yet this study was pilot without comparison of fertiloscopic LOD to conventional laparoscopic LOD.

In a previous study, our team could prove the occurrence of post-LOD adhesions despite following microsurgical principles and even in women who got pregnant after monopolar LOD [12]. Following this study, our institution seriously searched for an alternative approach. We tried unilateral LOD and single-puncture LOD without published studies. Utilizing bipolar electrocoagulation seems an attractive option for LOD as the energy goes from one electrode to the other electrode of the used needle. By this way, theoretically, there would be no or trivial damage of tissues away from the two electrodes. On the other hand, using monopolar electrode is associated with primary and secondary coagulation of a wide area surrounding the desired area. That is why vital organ injuries following monopolar electrode use were reported [13]. Moreover, bipolar energy is devoid of common monopolar disadvantages like fire and explosion, neuromuscular stimulation, affection of pacemakers, diathermy burns from the electrode or the neutral plate, and conduction problems such as direct coupling, insulation failure, and capacitive coupling. In this study, we reported neither monopolar nor bipolar diathermy complications which may be attributed to the short duration of the procedure, proper following of the safety guidelines for energy modality use, and good quality instrumentation.

In this study, we utilized a reusable 3-mm bipolar needle with two adjacent terminal needles at the tip each of 1 mm caliber (Fig. 3) which is assumed to be more or less effective in a similar manner like Versapoint disposable electrode. However, it is cheaper and has a sharper tip. Fining the electrode while the sharp tip of the needle already perforated the capsule is one of the success arguments to minimize capsular diathermy damage and hence theoretically less postoperative adhesions. An additional point that shared in better pregnancy rate among the bipolar LOD is concise stromal destruction between the two electrodes (Table 3). By this way, less stromal damage and more preservation of the ovarian reserve than monopolar LOD is achieved. It should be mentioned that over-destruction of the stroma by electrode is not an advantage as the main purpose of the procedure is not to burn as much as we can but just decrease ovarian androgens to increase FSH. Highlighting this concept among gynecologists would save many women from overdrilling with subsequent premature ovarian failure.

Table 3 Pregnancy rate (after the drilling) in both groups

The idea of bipolar LOD is not new. Previously, Fernandez proposed bipolar LOD (using a 5-French bipolar energy probe) as a potentially safer method compared to monopolar energy in terms of the risk of postoperative adhesions and the risk of overtreatment that could lead to ovarian failure. This novel technique was performed in six cases with restoration of ovulation in five cases [14]. However, this was a pilot non-comparative study.

Regarding the efficacy of LOD in CC-resistant PCO patients, our study found that 55 women (68.8 %) resumed regular menstruation and 47.5 % started to ovulate spontaneously after the drilling. These results coincided with a previous study [15] which reported postoperative spontaneous ovulation and pregnancy in 64 and 27 % of cases. Likewise, others [16] reported resumption of regular menstruation and normal ovulation in 67 and 58.8 % of cases, respectively, while pregnancy occurred in 33.8 % of cases.

Relatively, a lower pregnancy rate in this study can be explained by higher BMI with a mean of 28.9 versus 22.5 kg/m² in one study [17]. BMI correlates in both increased rate of cycle disturbance and infertility; even moderate obesity (BMI >27 kg/m²) is associated with reduced chances of ovulation and pregnancy secondary to disturbance in insulin metabolism. Another explanation is the short period of following our study (4–6 months after LOD). High pregnancy rate of 46.9 % was reported after 1 year of follow-up [16].

This study is characterized by being a comparative one. Previously, a small sample-sized study compared monopolar versus bipolar LOD [18]. Table 4 summarizes the main difference between this study and their study which may be attributed to a large sample size reported by our study.

Table 4 Comparison between our study and Sharma et al. study [18]

After surgical treatment of PCOS by electrocauterization, most authors have reported a fall in LH levels responsible for resumption of ovulation and conception [19]. In our study, LH level decline was achieved in both groups after LOD.

Regarding adhesions after LOD, it is established that monopolar energy is associated with a high incidence of periovarian adhesions [12]. A small pilot study [20] had reported on the efficacy of laparoscopic low-watt bipolar electrocoagulation of the ovaries in women with PCOS. At second-look laparoscopy or caesarean section in 20 women, fine string-like adhesions on the ovaries were found in two (10 %) women. Thus, it is hypothesized that bipolar energy is safer than unipolar (monopolar) energy in terms of the risk of postoperative adhesions and the risk of overtreatment that can lead to ovarian failure.

Limitations of the current study included relatively small sample size, short period of follow-up, lack of second-look laparoscopy of both groups, and lack of evaluation of postoperative adhesions in women who failed to get pregnant within 6 months despite good ovulation.

From this study, it is concluded that both monopolar and bipolar are effective tools for LOD in CC-resistant PCO infertile patients as a second-line therapy. Utilizing bipolar LOD is superior to monopolar LOD due to significantly higher postoperative incidence of resumption of spontaneous ovulation and spontaneous pregnancy. Theoretical less adhesion formation following bipolar LOD requires a second-look laparoscopy study in future studies even with minilaparoscopy. At the meantime, spread of bipolar LOD should be encouraged.