Abstract
ObjectiveTo 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.DesignA meta-analysis of prospective randomized trials published in English between 2002 and 2013.Patient(s) and InterventionsNine 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.
Highlights
The first reports of gonadotropin-releasing hormone (GnRH) agonists for in vitro fertilization (IVF) were published in the 1980s
Pooling the results of these nine randomized controlled trials (RCTs) showed no significant difference between patients treated with the long agonist protocol compared with the antagonist protocol in age (weighted mean difference (WMD): 0.18, 95% confidence interval (CI): 20.47–0.83) and BMI (WMD: 20.31, 95% CI: 20.90–0.27)
A significant difference was observed in the amount of gonadotropin administered in Polycystic ovarian syndrome (PCOS) patients between the two protocols (WMD: 367.90, 95% CI: 87.62–648.18) in the random-effect model
Summary
The first reports of gonadotropin-releasing hormone (GnRH) agonists for in vitro fertilization (IVF) were published in the 1980s. The function of GnRH agonists to suppress luteinizing hormone (LH) and prevent premature LH surges allowed optimal timing of human chorionic gonadotropin (hCG) administration and ovum collection, which improved IVF outcomes with respect to pregnancy rates [1]. Blockade of endogenous LH secretion by antagonists combined with ovulation induction could result in improved follicular development. Women with PCOS undergoing IVF are at risk for a higher rate of ovarian hyperstimulation syndrome (OHSS). Triggering ovum final maturation with hCG is an important mechanism in OHSS. To overcome this barrier, GnRH antagonist protocols that use GnRH agonist triggering emerged. Since the publication of Hesham’s [2] meta-analysis of 5 randomized controlled trials (RCTs), another series of RCTs [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19] has been published
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