AL-AZHAR ASSIUT MEDICAL JOURNAL AAMJ, VOL 13 , NO 1 , JANUREY 2015 SUPPL-2

LAPAROSCOPIC OVARIAN DRILLING BEFORE ICSI CYCLE; DOSE IT IMPROVES THE CLINICAL OUTCOMES IN WOMEN WITH POLYCYSTIC OVARY SYNDROME? Ahmed Roshdy Aziz Assisted reproduction technology (ART) unit, International Islamic Center for Population Studies and Research (IICPSR), Al-Azhar University, Cairo, Egypt. ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ ABSTRACT Background: 5-10% of the women in reproductive-age have polycystic ovary syndrome (PCOS) that leads to ovulation dysfunction, and infertility. Treatment of PCOS graduated from Lifestyle modifications to Laparoscopic ovarian drilling (LOD) as a surgical method for ovulation; which prevents the risks of multiple pregnancy and OHSS. Also, several studies have reported the impact of LOD prior to assisted reproduction technology (ART) is improving the pregnancy rate. Objectives: The effect of LOD on ICSI outcomes in PCOS patients is still unknown. This study was carried on to evaluate the effect of LOD done to the women with PCOS before intracytoplasmic sperm injection (ICSI) cycle on the ICSI outcome. Methodology: This is a retrospective study, which analyze the clinical outcome of 180 patients with ovarian factor infertility diagnosed as PCOS, which underwent ICSI cycles. The studied population are divided into two equal groups based on if the patients underwent LOD within 6 months before ICSI cycles or not. Results: shows a significant decrease in incidence of OHSS among LOD patients, and the number of chemical and clinical pregnancy was higher but statistically the difference was not significant. Conclusion: LOD treatment can be considered as a useful technique for PCOS patients before ICSI cycle specially for patient how have history of OHSS, as it may increase the pregnancy rate, and significantly reduce OHSS. Keywords: LOD, Polycystic Ovary Syndrome, ICSI.

INTRODUCTION risk of OHSS in previous treatment cycle 5-10% of the women in reproductive-age (Flyckt RL, et al.,2011, Tozer AJ, et al., have polycystic ovary syndrome (PCOS) 2001, Amer SA, et al 2002). that leads to ovulation dysfunction, and Serum luteinizing hormone (LH) and infertility. Treatment of PCOS graduated testosterone levels were normalized from Lifestyle modifications to following LOD, while their levels Laparoscopic ovarian drilling (LOD) as a remained unchanged over long-term surgical method for ovulation (Kawwass. follow-up. Other study also showed that et al.,2010, Boomsma. etal.,2006, LOD can reduce the risk of cancellation of Rebecca. et al., 2011). the ART treatment cycle, but there are no Although the mechanism of LOD is not significant differences in pregnancy, clear, this method prevents the risks of miscarriage, or live birth rate (Rimington multiple pregnancy and OHSS. Also MR, et al 1997, Flyckt RL, et al., 2011). several studies have reported the impact of The effect of LOD on ICSI outcomes in LOD prior to assisted reproduction PCOS patients is still unknown. This study technology (ART) in decreasing the OHSS was carried on to evaluate the effect of risk and improving the pregnancy rate in LOD done to the women with PCOS women with a history of cancellation of before intracytoplasmic sperm injection ICSI cycle due to risk of OHSS or even (ICSI) cycle on the ICSI outcome. 220 | P a g e Ahmed Roshdy Aziz AAMJ, VOL 13 , NO 1 , JANUREY 2015 SUPPL-2

MATERIALS AND METHODS ultrasonography guidance, 34-36 hours A retrospective cohort study was designed after HCG injection, and ICSI was to examine the effect of LOD treatment for performed. At least 2 embryos were PCOS patients before ICSI cycles, the transferred at day 2. The luteal phase study extract the data from the files of 180 support with (Crinone 0.8 vaginal cream, patients (in assisted reproduction unit in Merk serono., United Kingdom) were Misr center) with ovarian factor infertility performed. The serum beta human diagnosed as PCOS if the patient have at chorionic subunit was measured at day 14 least 2 signs of Rotterdam criteria: of ET to document the chemical pregnancy anovulation or oligomenorrhoea, clinical if serum beta-hCG (β-hCG) >50 IU/L, and or biochemical signs of hyperandrogenism clinical pregnancy diagnosed by observing and the typical ultrasound (US) patterns fetal pole with fetal heart beats during (polycystic ovaries) (Boomsma CM, et al., transvaginal ultrasonography 2 weeks 2006); All the patients received antagonist after positive β-hCG.The patients were protocol for controlled ovarian stimulation considered at risk of OHSS if serum for ICSI cycle. estradiol (E2) levels more than 3500 pg/ml The study protocol was approved by the on the day of hCG administration. ethics committee of Misr Center hospital The clinical outcome compared between and patients gave their informed consent to the two studied groups regarding; number use their data retrospectively in this study. of collected MII oocytes, number of grade All patient included in this study aged 25 - A embryos, chemical and clinical 35 years, duration of infertility > or = 2 pregnancy rate, and the risk of OHSS. year, and body mass index (BMI) < or =30. Data was analyzed using Statistical The studied population are divided into Package for the Social Sciences 16.0 two equal groups which include 90 patient (SPSS, SPSS Inc., USA). Quantitative each, based on if the patients underwent variables described in mean ± SD and 95% LOD within 6 months before ICSI cycles confidence interval (CI), qualitative data or not. LOD was performed by unipolar presented in frequency, while categorical needle electrode with a coagulating current variables expressed in percentage. 40 W power. In each ovary, four drilling Student’s t test and Mann-Whitney U test points were made and duration of each were used to ascertain the significance of diathermy application was about 4 differences between mean values of the seconds. variables such as demographic The patients received 300 IU/daily of characteristics, number of oocytes and highly purified follicle stimulating embryo obtained. Chi-squares analysis (χ² hormone (Hp-FSH, Fostimone, IBSA., tests) was performed to measure the Switzerland) from second day of proportions of categorical variables menstrual cycle till the mean follicular between two groups. P value<0.05 is diameter of at least 4 follicle > 18mm, a statically significant. dose of 0.25 mg/day of GnRH antagonist (Cetrotide, Sereno, Switzerland) was RESULTS started at cycle day 7 of and continued A total of 180 women were enrolled in this until the day of human chorionic study retrospectively and divided to two gonadotropin (Choriomone 5000IU, groups (n = 90 /each). The age, BMI, and IBSA., Switzerland) two injections. serum day 3 FSH levels of the patients Oocyte retrieval was done under vaginal showed in Table 1. There is no statistically

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significant difference in mean age, BMI, experience a higher cycle cancellation rate day 3 FSH levels showed a statistically due to an exaggerated response to significant difference P=0.019. gonadotropin therapy that leading to the Table1: The Age, BMI, and day 3 FSH increased risk of OHSS (Kawwass JF, et level in the two groups: al., 2010, Ferraretti AP, et al., 2001, Group I (n = Group II P value (Student Patient data 90) (n = 90) t test) Rahmani E, et al., 2012). 27.21 ± Age (years) 27.96 ± 3.82 0.106 We evaluated the ICSI cycle outcome in 4.13 24.86 ± BMI (kg/m2) 25.02 ± 2.71 0.569 90 women with PCOS who were treated by 2.55 Day 3 FSH ovarian electrosurgical drilling and then 6.64 ± 1.83 5.93 ± 1.89 0.019 level (IU/L) compared with 90 patients without history Table 2 show that among 90 patients who of ovarian drilling. Our results, shows a were treated by electro-cauterization, 6 significant decrease in incidence of OHSS women (6.7%) were diagnosed with among LOD patients, and the number of OHSS as compared with 13 (7.14%) chemical and clinical pregnancy was patients in group II, indicating that there is higher but statistically the difference was a significant difference P=0.025. not significant. Table 2: distribution of patient how had Tozer et al., 2001 retrospectively OHSS among both groups. compared IVF outcomes between PCOS Without P value (Chi- With LOD LOD squqre test) patients undergoing LOD and PCOS 13 OHSS 6 (6.7%) 0.025 (14.7%) patients who did not undergo LOD. They Table 3 show the mean number of MII found a trend toward increased ongoing oocytes and Grade A embryos obtained pregnancy rates and decreased risk of were more in group II (P = 0.001); developing severe OHSS despite the fact however, this difference was not clinically that all LOD treated patients remained significant. anovulatory after the procedure. Table 3: The embryology lab outcomes In another study by Greenblatt and Casper in the ICSI cycle in two groups: (Greenblatt E, Casper RF., 1987), they With LOD Without LOD P value (Mann-Whitney test)have showed that ovarian trauma disrupts Number of MII oocytes 12.44 ± 3.25 13.48 ± 3.02 <0.001 Number of grade A embryos 9.84 ± 2.65 10.50 ± 2.67 0.033 local androgen synthesis that leads to a

Table 4 show the number of patients how reduction in intraovarian androgen had chemical and clinical pregnancy in concentration that is followed by negative group I was higher than group II, but effects of androgen on follicular statistically the difference was not maturation. Subsequently it results in significant. decreased peripheral conversion of androgen to estrogen that causes positive Table 4: distribution of the patient feedback on LH secretion (Sumioki H, among two group regarding there Utsunomiya T., 1998). Although, other clinical outcome. Without P value (Mann- factors such as inhibin and other local With LOD LOD Whitney test) Chemical ovarian substances may be involved 42 (47%) 39 (43%) 0.033** pregnancy (Tropeano G, et al., 1997). Clinical 40 (44%) 36 (40%) 0.013** pregnancy Breborowicz et al., 2012 in their study showed that prior to IVF, transvaginal DISCUSSION ovarian drilling in patients with severe PCOS patients respond differently to PCOS on metformin therapy leads to an controlled ovarian hyperstimulation increase in E2 level, meaning an increase compared with normal ovaries, they

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in number of mature oocytes and embryos This study has several limitations such as as well as available blastocyst. lack of access to early pregnancy outcomes In our study, the pregnancy rate in group I and life birth rate information. was higher, but the number of MII oocytes and Grade A embryos was less in patients CONCLUSION with history of LOD, although these There was a difference in the pregnancy differences were not clinically significant. rate in women with PCOS undergoing Weerakiet et al., 2007 in a cross-sectional LOD as compared to patients without study evaluated the effect of LOD on history of LOD. Due to significant ovarian reserve. Anti-mullerian hormone reduction in OHSS in women undergoing (AMH), inhibin B, basal FSH, antral LOD, this surgical treatment may be follicle count (AFC) and ovarian volume considered as a useful technique in the were measured and compared with related management of patients who have values in PCOS women underwent LOD, previously developed OHSS. Though PCOS women who did not undergo LOD there are ongoing concerns about long- and normal women with regular menstrual term effects of LOD on ovarian function. cycles. Their findings revealed that AMH level was lower in LODPCOS group (4.6 REFERENCES ± 3.16 ng/mL) as compared to the non- Amer SA, Li TC, Cooke ID. Laparoscopic LOD-PCOS group (5.99 ± 3.36 ng/mL), ovarian diathermy in women with but the difference was not statistically polycystic ovarian syndrome: a significant. retrospective study on the influence Furthermore, AMH level was significantly of the amount of energy used on the lower in normal women with regular outcome. Hum menstrual cycles, indicating the reduced Reprod. 2002;17(4):1046–1051. risk factors for developing OHSS and good Api M. Is ovarian reserve diminished after ovarian reserve. The serum FSH mean laparoscopic ovarian levels were significantly higher in LOD- drilling? Gynocol PCOS group. There were no significant Endocrinol. 2009;25(3):159–165. differences in inhibin B mean levels Breborowicz AK, Keltz MD, Chau P, between groups. Therefore, they Stein D, Lederman M, Gonzales E. concluded that the ovarian reserve was Transvaginal ovarian drilling diminished in LOD-PCOS women as (TVOD) for severe polycystic ovary compared to non-LOD-PCOS women. syndrome (PCOS) prior to in vitro Mural in his literature review fertilization (IVF) improves demonstrated that although the available outcomes. Fertil data in the literature is limited, there was Steril. 2012;98(3):S212–S212. no concrete evidence of a diminished Boomsma CM, Eijkemans MJ, Hughes ovarian reserve or premature ovarian EG, Visser GH, Fauser BC, Macklon failure associated with LOD in women NS. A meta-analysis of pregnancy with PCOS. He indicated that LOD is outcomes in women with polycystic considered as an effective method to ovary syndrome. Hum Reprod enhance the ovarian function and Update. 2006;12(6):673–683. normalize ovarian morphologic and Ferraretti AP, Gianaroli L, Magli MC, endocrinologic properties if it is performed Lammarrone E, Feliciani E, Fortini properly (Api M. 2009). D. Transvaginal ovarian drilling: a

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