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

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. Systematic review and meta-analysis of randomized clinical trials (RCT). Not applicable. Women undergoing COS for ART. Melatonin supplementation during COS for women undergoing ART. Live birth rate, clinical pregnancy rate, number of retrieved oocytes, miscarriage rate, ovarian hyperstimulation syndrome (OHSS) rate, and number of congenital abnormalities. Comparisons were performed using risk ratio (RR) or mean difference (MD). 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). More studies investigating the role of melatonin supplementation are still needed before recommending its use in clinical practice.