Melatonin improved the outcomes of women with ART: a systematic review and meta-analysis of randomized trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 41064014 · doi:10.3389/frph.2025.1680984
What was done
A systematic review and meta-analysis (PRISMA-compliant, PROSPERO CRD420251003042) evaluated randomized controlled trials published before March 5, 2025, identified via PubMed/MEDLINE, Embase, and Cochrane Library. Eligible studies assessed the efficacy of melatonin supplementation in infertile women undergoing assisted reproductive technologies (ART) on at least one embryo development or pregnancy outcome. The primary outcome was clinical pregnancy rate; secondary outcomes included oocyte yield, fertilization rate, MII oocyte number, and high-quality embryo formation. Eleven RCTs with 1,481 participants were included.
What was found
Melatonin significantly improved clinical pregnancy rate (OR = 1.59, 95% CI: 1.22 to 2.07), high-quality embryo count (MD = 0.43, 95% CI: 0.07 to 0.79), MII oocyte count (SMD = 0.99, 95% CI: 0.29 to 1.69), and fertilization rate (OR = 1.32, 95% CI: 1.01 to 1.73). Oocyte yield was not significantly different (SMD = 0.45, 95% CI: -0.04 to 0.94). Subgroup analysis indicated enhanced pregnancy outcomes with <= 3 mg/day melatonin and under GnRH-a long protocols.
Why it matters
This review suggests that low-cost oral melatonin supplementation may serve as a beneficial adjunct to improve laboratory parameters and clinical pregnancy rates in ART cycles.
Limits
The total sample across 11 trials is relatively modest (1,481 participants). Moderate to high heterogeneity was present in secondary outcomes, publication bias was noted for MII oocyte count, and the abstract does not report critical endpoints such as live birth rate or long-term outcomes.