Is a GnRH Antagonist Protocol Better in PCOS Patients? A Meta-Analysis of RCTs

Objective: To review published randomized controlled trials (RCTs) evaluating the outcomes of in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) utilization of gonadotropin-releasing hormone (GnRH) antagonists for ovarian stimulation in polycystic ovarian syndrome (PCOS) patients compared with classic luteal long agonist protocols. Design: A meta-analysis of prospective randomized trials published in English between 2002 and 2013. Patient(s) and Interventions: Nine RCTs examining PCOS patients undergoing IVF/ICSI including 588 women who underwent long agonist protocols and 554 women who underwent GnRH antagonist protocols. Main Outcome Measure(s): Clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and ovarian hyperstimulation syndrome (OHSS) rate. Result(s): Nine RCTs were included in this analysis. The CPR-per-embryo transferred was similar in the two groups (relative risk (RR): 0.97, 95% confidence interval (CI): 0.85–1.10). Non-significant estimates comparing the two protocols were found for age, BMI, total dose of gonadotropin administered, number of days of stimulation and number of oocytes retrieved. After meta-analysis of 4 of the RCTs, it was concluded that a GnRH antagonist protocol is better than an agonist long protocol to reduce the rate of severe OHSS (odds ratio (OR): 1.56, 95% CI: 0.29–8.51). Conclusion(s): With respect to CPR, a GnRH antagonist protocol is similar to a GnRH agonist long protocol. However, for severe OHSS, a GnRH antagonist protocol is significantly better in PCOS patients.