Melatonin and Female Fertility: A Systematic Review and Meta-Analysis of Clinical Supplementation, In Vitro Experiments, and Observational Evidence

Background/Objectives: Melatonin has been proposed as a potential strategy to improve female fertility, but existing evidence is dispersed across assisted reproduction, reproductive disorders, and in vitro studies. This study aimed to comprehensively evaluate the relationships of melatonin supplementation, in vitro melatonin treatment, and endogenous melatonin levels with female fertility. Methods: PubMed, Web of Science, and EMBASE were searched from inception through February 2026. Randomized and non-randomized intervention studies, observational studies, and in vitro studies involving human oocytes or embryos were included. Random-effects meta-analyses were performed, and certainty of evidence was assessed using GRADE. Results: Thirty-six publications were included. Among women undergoing ART, melatonin supplementation increased the clinical pregnancy rate (RR = 1.55, 95% CI: 1.23–1.94) and live birth (RR = 1.59, 95% CI: 1.01–2.51). Melatonin supplementation also improved selected ovarian and embryological outcomes. In vitro treatment increased fertilization (OR = 1.97, 95% CI: 1.40–2.76) and blastocyst formation (OR = 2.00, 95% CI: 1.33–3.03). Observational studies showed higher morning serum melatonin levels in women with PCOS (MD = 7.83 pg/mL, 95% CI: 3.56–12.11). The certainty of evidence ranged from very low to moderate. Conclusions: Melatonin supplementation may improve selected reproductive outcomes, including clinical pregnancy and live birth, although evidence for live birth remains limited. In vitro and observational findings further support a potential role of melatonin in female reproductive function, but its clinical value requires confirmation in high-quality studies.