Comparison of laparoscopic drilling by diathermy and laser for ovulation induction in clomiphene citrate-resistant women with polycystic ovary syndrome

Objective: The aim of the present study was to compare the effectiveness of laparoscopic ovarian drilling (LOD) with monopolar diathermy and CO2 laser on the serum levels of hormone and pregnancy outcome in clomiphene citrate (CC) resistant infertile women with polycystic ovarian syndrome (PCOS). Materials and Methods: Thirty women underwent laparoscopic ovarian diathermy (group A) and thirty women underwent laparoscopic ovarian laser (group B). Serum levels of LH, FSH, Testosterone and Progesterone, menstrual cycles' regularity, ovulation and Pregnancy rates were compared between the two groups. Results: In this study, there was no significant difference in the main demographic, clinical and endocrinological characteristics between two groups. The percentage of women with PCOS resumed regular menstrual cycle in group A and B was 73% and 76% respectively (P-value=0.5). There was no significant difference in hormonal profiles (LH, FSH, Testosterone and Progesterone) between two groups. Similarly, there was no statistically difference in the total ovulation rate between two groups (40% vs.43.3% in group A and B respectively). Finally, there was no significant difference in the pregnancy and miscarriage rate in women with CC resistant PCOS undergoing diathermy compared with laser therapy. Conclusions: Both laparoscopic ovarian diathermy and laparoscopic ovarian laser have good effects on ovulation induction in PCOS women but none of these two methods had any obvious advantages over another method. Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. The prevalence of this syndrome is approximately 6% of women in their reproductive years. Infertility due to ovulatory dysfunction is a common problem for women with PCOS (1). Clinical signs of this syndrome are Professor of obstetric & gynecology, Clinical and Research Center for Infertility, Shahid Sadoughi University, Yazd, Iran. Infertility flowship, Clinical and Research Center for Infertility, Shahid Sadoughi University, Yazd, Iran. Medical Doctor, Clinical and Research Center for Infertility, Shahid Sadoughi University. Yazd, Iran. Correspondence: Bouali Ave, Safaeyeh, Yazd, Iran Email: { HYPERLINK "mailto:[email protected]" } menstrual disorder, oligo-ovulation or anovulation, hirsutism, acne, and in severe cases alopecia. Obesity is common in this syndrome but it is not universal (2). Although the primary defect in PCOS remains unclear, a genetic factor is suspected to play a role in the etiology of the disease (3). The optimal management of PCOS is uncertain, but treatment focuses on amelioration of the chemical features. For the most part, treatment aims to restore ovulatory cycles so that pregnancy can be achieved. The first line treatment for PCOS related anovulatory infertility is clomiphene citrate (CC) (4). The ovulation rate with this drug is more than 80 % (5). However, 15% to 20% of women Middle East Fertility Society Journal Vol. 12, No. 2, 2007 Copyright © Middle East Fertility Society Vol. 12, No. 2, 2007 Aflatoonian et al. Laparoscopic ovarian drilling in PCO 97 remain anovulatory despite treatment with incremental doses of CC, and pregnancy rates are disappointing (33% to 40%). In addition, the miscarriage rate is high (30% to 40%) (6). Because of its anti-estrogenic effects, an increasing dosage of CC will lead to thickening of the cervical mucus and failure of endometrial development. Therefore, women resistant to CC medication will usually be treated with exogenous gonadotrophins. As a result, another treatment for PCOS is gonadotropins or pulsatile Gonadotrophinreleasing hormone (GnRH). In fact, Gonadotrophins are more effective than GnRH (7), but they have a higher risk of serious side effects, such as multiple pregnancy and the ovarian hyperstimulation syndrome (OHSS); while GnRH therapy is effective with lower risk of these side effects (8, 9). It has now been recognized that laparoscopic ovarian drilling (LOD) is an effective second-line treatment for CC-resistant anovulatory infertility associated with PCOS (10). Grzechocinska et al (2000) assessed the results of CC ovarian stimulation vs. Laparoscopic diathermy of the ovaries in infertile women with PCOS. Results showed that the ovulation rate was 68% vs. 90.9% and the pregnancy rate was 28% vs. 63.3% respectively. Therefore, it seems that much more successful results could be achieved by LOD in comparison with stimulation of the ovaries with CC in PCOS women (11). Kriplani et al (2001) applied LOD using monopolar diathermy on seventy women with CC resistant PCOS and followed up them for 4.5 years. Their results showed that ovulation and pregnancy rates were 81.8% and 54.5% respectively, which means that LOD is an effective surgical procedure in women with CC resistant PCOS (12). With laparoscopic surgery, the possibility of inducing ovulation by LOD was raised. The other advantages of LOD are decreasing the risk of OHSS and multiple pregnancies and occurrence of consecutive ovulations without the need for further treatment; while the disadvantages are the need for a surgical procedure and creation of tubo-ovarian adhesions (13). The aim of this study was to compare resumption of menstrual regularity, biochemical changes, ovulation, pregnancy and miscarriage rates in women who had CC-resistant PCOS and were treated by laparoscopic drilling by diathermy or laser for ovulation induction. MATERIALS AND METHODS A randomized controlled trial was conducted to compare the success rate of two different surgery methods, namely laparoscopic ovarian diathermy and laparoscopic ovarian CO2 laser vaporization in the treatment of PCOS. Written informed consent was obtained from all patients and has been written in paper. Also, Ethical committee of Yazd Shahid Sadughi University of Medical Science approved this study (figure 1). In total, 60 women who attended at Yazd Clinical and Research Center for Infertility were diagnosed with PCOS between August 2004 and September 2005. The inclusion criteria for this study were as follows: 20 to 38 years of age, CC resistance (no ovulation after three cycles of up to 150 mg of CC from day 5 to day 9 of menstrual each month), infertility of more than 12 months duration, a body mass index(BMI) of less than 35kg/m2, and typical findings on sonography, such as ovarian stromal hypertrophy and multiple (≥10), small (6-8mm) follicles arranged in the periphery of the ovary (14). All the women’ husbands had normal semen analysis (>20 million per milliliter, >30% normal forms, and >50% motility) (15). The other inclusion criteria were early follicular phase (defined as days 2-5 of the menstrual cycle) serum LH/FSH ratio more than 2 and /or raised serum androgen levels (testosterone≥2.5nmol/l) and oligo or amenorrhea. The exclusion criteria were included other endocrinological abnormalities such as hyperprolactinaemia, and thyroid dysfunction, Women with tubal disease diagnosed by laparoscopy and partners with male factor. Randomization was performed using computergenerated sequences that were sealed in number opaque envelopes. Ovarian diathermy or laser surgery was performed by one expert surgeon as follows; the procedure was undertaken in the operating theater under general anesthesia. Routine pneumoperitoneum was achieved using a Verres needle (Karl Storz, 30675ND, Germany), and the laparoscope (Olympus, JAPAN) was introduced at 96 Aflatoonian et al. Laparoscopic ovarian drilling in PCO MEFSJ Table1. The characteristics of 60 women who underwent laparoscopic ovarian diathermy (groupA=diathermy, groupB=laser) for anovulatory infertility due to polycystic ovarian syndrome. Values are given as mean ±SD and number of observations as n (%). The results of hormonal levels shown are those obtained before the operation. T test and Chi-Square was used for statistical analysis. Characteristics Group A N=30 Group B N=30 P-value Age (years) 25.2±3.9 24.77±3.1 0.64 Duration of infertility (years) 5.2±2.9 5.1±3.3 0.92 Body mass index (Kg/m2) 24.95±4.4 26.19±5.06 0.31 Menstrual cycle pattern Oligomenorrhea 25(83.4%) 26(86.7) Amenorrhea (≥3periods/y) 5(16.6) 4(13.3) 0.22 Hirsutism Yes 22(73.3) 25(83.3) 0.32 No 8(26.7) 5(16.7) Acne present Yes 20(66.7) 22(73.3) 0.19 No 10(33.3) 8(26.7) Infertility Primary 24(80) 25(83.3) 0.56 Secondary 6(20) 5(16.7) Serum LH(mIu/ml) 14.6±4.7 14.8±4.6 0.59 Serum FSH(mIu/ml) 6.39±5.5 6.27±3.5 0.92 Serum LH/FSH ratio 2.28±1.08 2.36±4.05 0.48 Serum Testosterone (nmol/l) 2.85±2.4 2.73±0.6 0.53 the umbilicus. Two ports were used; one at the suprapubic level and one in the left iliac fossa, both 5 mm. Under laparoscopic control, each ovarian pedicle was grasped using an atraumatic forceps. The pelvic organs were inspected and tubal assessment was confirmed by transcervical injection of methylene-blue dye. The ovary was lifted up and sited to the anterior wall of the uterus away from bowel. In group A, a monopolar electrocautry needle of 0.5 cm in length was used to drill 6 holes with the depth of 5 mm in each ovary. The diathermy was done with cutting power at 30 watt and was continued for 6 seconds; while in group B, Laser therapy was performed with CO2 laser, with the power setting at 30 Watt and 15 punctures with superficial penetration were made in each ovary and this power was continued for 6 seconds. At the end of the procedure, to avoid adhesion formation, extensive pelvic lavage was performed with 250ml of Ringer Lactate’s solution. At hospital discharge, the women in both groups were not treated with any drugs for 1 year. Following ovarian laparoscopic diathermy or laser, women were asked to keep a record of their menstrual cycle. A blood sample was taken on day 21 after the first spontaneous menstruation for measurement of serum concentration of LH (mIu/ml), FSH (mIu/ml), Progesterone (ng/ml) and Testosterone (nmol/l) level. The following outcome measures were collected and reported for 1 year. Ovulation rates were determined by progesterone levels of more than 10 ng/ml in the luteal phase (timed 21 days after the first spontaneous menstruation) for both groups. Pregnancy outcomes included serum BHCG of more than 50 IU/L, and fetal heart activity on abdominal ultrasound scan, after 8 weeks of gestation. SSPS version 13 was used to do the appropriate statistical tests including Student's T Test, Chisquare and Fisher exact test. The results are expressed as means and standard deviation. Differences were considered to be statistically significant if p-value was <0.05.