The Effect of Dietary Supplements on Female Infertility in Terms of Endometrial Thickness, Pregnancy, Live Birth and Miscarriage: A Systematic Review and Meta-Analysis

Background/Objectives: Although current research suggests beneficial effects of dietary supplements on female infertility, existing evidence is often inconsistent and of limited certainty. This systematic review and meta-analysis aimed to investigate the effect of dietary supplements on female infertility in terms of endometrial thickness, pregnancy, live birth, and miscarriage compared to placebo (primary objective) and compared to placebo or a no-treatment comparator (secondary objective). Methods: PubMed, Embase, and CENTRAL were searched up to March 2025. Randomized controlled trials assessing the effect of dietary supplements compared to placebo or a no-treatment comparator among infertile women were included. Screening, data extraction, risk of bias, and certainty of evidence assessments were conducted by two independent reviewers. Data was synthesized quantitatively using random effects restricted maximum likelihood models. Results: Twenty placebo-controlled and 20 no-treatment comparator studies were included. Most studies had some concerns in risk of bias. Primary analyses showed an improvement in endometrial thickness following N-acetyl-cysteine supplementation compared to placebo, while no effect was found for supplements on pregnancy-related outcomes. Certainty of evidence of primary analyses was low. Secondary analyses indicated positive differences in endometrial thickness and pregnancy-related outcomes following supplementation with different supplements compared to placebo and no treatment. Conclusions: This review found no high-certainty evidence that dietary supplements improve female infertility outcomes when compared with placebo. Secondary analyses combining placebo and no-treatment comparator studies generated hypotheses for myo-inositol, N-acetyl-cysteine, vitamin D, vitamin E, and ≥3 substance dietary supplements, but these are at higher risk of bias and require confirmation in adequately powered placebo-controlled trials with live birth as the primary outcome.