Melatonin supplementation during controlled ovarian stimulation for women undergoing assisted reproductive technology: systematic review and meta-analysis of randomized controlled trials

Objective: To examine the best evidence available regarding the effect of melatonin supplementation during controlled ovarian stimulation (COS) on the main assisted reproductive technology (ART) outcomes. Design: Systematic review and meta-analysis of randomized clinical trials (RCT). Setting: Not applicable. Patient(s): Women undergoing COS for ART. Intervention(s): Melatonin supplementation during COS for women undergoing ART. Main Outcome Measure(s): Live birth rate, and number of congenital abnormalities. Comparisons were performed using risk ratio (RR) or mean difference (MD). Result(s): Five RCTs were considered eligible, and their data were extracted and included in a meta-analysis. No studies reported live-birth or congenital abnormalities. Our estimates were imprecise for distinguishing between no effect and benefit considering clinical pregnancy (RR, 1.21; 95% confidence interval [CI], 0.98-1.50, five studies, 680 women, low quality-evidence) and the number of oocytes retrieved (MD, 0.6; 95% CI, -0.2-2.2, five studies, 680 women, low quality-evidence). Our estimates were imprecise for distinguishing among harm, no effect, and benefit considering miscarriage (RR, 1.07; 95% CI, 0.43-2.68, two studies, 143 clinical pregnancies, low quality-evidence) and interventions to reduce the risk of OHSS (RR, 1.01; 95% CI, 0.33-3.08, one study, 358 women, low quality-evidence). Conclusion(s): More studies investigating the role of melatonin supplementation are still needed before recommending its use in clinical practice. (Fertil Steril (R) 2014; 101: 154- 61. (c) 2014 by American Society for Reproductive Medicine.)