Oral melatonin supplementation during in vitro fertilization treatment: a systematic PRISMA review and meta-analysis of randomized controlled trials

High levels of reactive oxygen species (ROS) have been suspected of reducing the success rate of assisted reproductive technology (ART). Melatonin has anti-oxidative properties and could therefore be of interest as a supplement in in vitro-fertilization (IVF) protocols. The objective of this study was to evaluate if a melatonin supplementation given in vivo to women undergoing IVF-treatment can improve the outcome.A systematic literature search was performed on PubMed, Embase and Cochrane. The methodological quality of the included studies was assessed using the version 2 of the Cochrane risk-of-bias tool (RoB2). Primary outcome was clinical pregnancy rate (CPR). Secondary outcomes were total number of oocytes, number of mature oocytes, embryo quality, biochemical pregnancy rate, miscarriage rate and live birth rate (LBR).Seven randomized controlled trials (RCT) were included. The meta-analysis demonstrated a significantly higher mature oocyte count when melatonin was used (Mean Diff. = 1,82; 95% CI 0.37-3.27; p = .01). All seven studies showed a trend for increase in CPR, although not significant. No other measured outcomes showed a significant improvement. Two studies had 'low risk', three 'some concerns' and two studies had 'high risk' of bias.This meta-analysis including RCT indicates that an oral melatonin supplement during IVF-treatment can increase the number of mature oocytes, and a trend for increase CPR, albeit not significant. Most of the included studies were small. The methodological quality in three of the seven studies was moderate and two were low. Further investigations are needed to support the positive findings.