Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: a network meta-analysis

The comparative efficacies of ovulation-induction treatments in patients with clomiphene citrate-resistant (CCR) polycystic ovary syndrome (PCOS) are not well known. Therefore, we conducted a network meta-analysis to rank the reproductive efficacies of these treatments. We ultimately included 26 randomized clinical trials with 2722 participants and 9 types of therapies: clomiphene citrate (CC), metformin, letrozole, follicle stimulating hormone (FSH), human menopausal gonadotropin (hMG), unilateral laparoscopic ovarian drilling (ULOD), bilateral laparoscopic ovarian drilling (BLOD), the combination of metformin with letrozole (metformin+letrozole), and the combination of metformin with CC (metformin+CC). The network meta-analysis demonstrates that hMG therapy result in higher pregnancy rates than BLOD, ULOD and CC therapies. Pregnancy, live birth and ovulation rates are significantly higher in metformin+letrozole and FSH groups than CC group. The abortion rate in the metformin+letrozole group is significantly lower than that in the metformin+CC group. Ranking probabilities show that, apart from gonadotropin (FSH and hMG), metformin+letrozole is also potentially more effective in improving reproductive outcomes than other therapies. In conclusion, owing to the low quality of evidence and the wide confidence intervals, no recommendation could be made for the treatment of ovulation-induction in patients with CCR PCOS.