Gonadotrophins for ovulation induction in women with polycystic ovarian syndrome

Nienke S Weiss, Marleen Nahuis, Neriman Bayram, Ben Willem J Mol, Fulco Van der Veen, Madelon van Wely

Ovulation induction with follicle stimulating hormone (FSH) is the second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on clomiphene citrate (CC). To compare the effectiveness and safety of gonadotrophins as a second-line treatment for ovulation induction in women with CC-resistant PCOS. We searched the Menstrual Disorders & Subfertility Group's Specialist Register of controlled trials, the Cochrane Central Register of Controlled Trials, MEDLINE (1966 to October 2014), EMBASE (1980 to October 2014), CINAHL (1982 to October 2014), National Research Register and web-based trials databases such as Current Controlled Trials. There was no language restriction. All randomised controlled trials reporting data on comparing clinical outcomes in women with PCOS who did not ovulate or conceive on CC, and undergoing ovulation induction with urinary FSH (uFSH: FSH-P or FSH-HP), HMG/HP-HMG or recombinant FSH. We included trials reporting on ovulation induction followed by intercourse or intrauterine insemination. We excluded studies that used co-treatment with CC, metformin, LH or letrozole. Three review authors (NW, MN and MvW) independently selected studies for inclusion, assessed study quality and extracted study data. Primary outcomes were live birth rate per woman (effectiveness outcome) and incidence of ovarian hyperstimulation syndrome (OHSS) per woman (safety outcome). Secondary outcomes were clinical pregnancy, miscarriage, multiple pregnancy, total gonadotrophin dose and total duration of stimulation per woman. We combined data using a fixed-effect model to calculate the odds ratio (OR). We summarised the overall quality of evidence for the main outcomes using GRADE criteria. The review includes 14 trials with 1726 women. Ten trials compared rFSH versus urinary-derived gonadotrophins (three rFSH versus HMG and seven rFSH versus FSH-HP), four trials compared FSH-P with HMG. We found no trials that compared FSH-HP with FSH-P.We found no evidence of a difference in live birth for rFSH versus urinary-derived gonadotrophins (OR 1.26, 95% CI 0.80 to 1.99, 5 trials, 505 women, I² = 0%, low-quality evidence) or clinical pregnancy rate (OR 1.08, 95% CI 0.83 to 1.39, 8 trials, 1330 women, I² = 0, low-quality evidence). This suggests that for the observed average live birth per woman with urinary-derived FSH of 16%, the chance of live birth following rFSH is between 13% and 26%.For the comparison HMG or HP-HMG versus FSH-P there was also no difference in the evidence on live birth rate (OR 1.36, 95% CI 0.58 to 3.18, 3 trials, 138 women, I² = 0%, low-quality evidence). This suggests that for a woman with a live birth rate of 18% with HMG or HP-HMG, the chance of live birth following uFSH is between 9% and 37%.Trial authors used various definitions for OHSS. Pooling the data, we found no evidence of a difference for rFSH versus urinary-derived gonadotrophins (OR 1.52, 95% CI 0.81 to 2.84, 10 trials, 1565 women, I(2) = 0%, very low-quality evidence) and for HMG or HP-HMG versus FSH-P (OR 9.95, 95% CI 0.47 to 210.19, 2 trials, 53 women, I² = 0%, very low-quality evidence). In women with PCOS and CC resistance or CC failure, we found no evidence of a difference in live birth and OHSS rates between urinary-derived gonadotrophins and rFSH or HMG/HP-HMG. Evidence for all outcomes was of low or very low quality. We suggest weighing costs and convenience in the decision to use one or the other.