Melatonin supplementation and outcomes of assisted reproductive technology: a systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of clinical trials
PubMed 41286761 · doi:10.1186/s12884-025-08503-1
What was done
A systematic review and meta-analysis of clinical trials evaluating melatonin supplementation during assisted reproductive technology (ART). Four databases (PubMed, Embase, Web of Science, Google Scholar) were searched from inception to April 2020. Risk of bias was evaluated by one author using the Cochrane Collaboration checklist. Pooled risk ratios (RR) and mean differences (MD) were calculated for clinical pregnancy rate (CPR), live birth rate (LBR), miscarriage rate, fertilization rate, oocyte counts, and embryo quality, with subgroup analyses by comparator type and patient indication.
What was found
Across 11 included trials (published 2008–2019): - Melatonin significantly increased CPR (RR 1.24, 95% CI 1.04 to 1.47; 10 studies), mature MII oocytes (MD 1.39, 95% CI 0.74 to 2.04; 8 studies), top-quality embryos (MD 0.56, 95% CI 0.24 to 0.88; 6 studies), and fertilization rate (RR 1.10, 95% CI 1.03 to 1.17 in 4 studies; MD 0.13, 95% CI 0.01 to 0.24 in 3 studies). - Melatonin did not significantly alter live birth rate (RR 1.23, 95% CI 0.85 to 1.80; 3 studies), total oocytes retrieved (MD 0.58, 95% CI -0.12 to 1.27; 9 studies), or miscarriage rate (RR 0.96, 95% CI 0.50 to 1.82; 6 studies). - In subgroup analyses by control type or patient characteristics (PCOS, normal ovarian reserve, prior low fertilization), CPR improvements lost statistical significance. MII oocyte count was increased in PCOS (MD 0.97, 95% CI 0.22 to 1.73) but not in women with normal ovarian function (MD 1.49, 95% CI -0.33 to 3.31).
Why it matters
Melatonin may modestly improve laboratory endpoints like oocyte maturity and embryo quality during ART, but current evidence does not demonstrate an improvement in live birth rate.
Limits
The literature search ended in April 2020. Only 3 of 11 studies reported live birth rates. Risk of bias was assessed by a single author rather than in duplicate. Total participant sample size was not reported in the abstract.