The effects of oral antioxidants on outcomes of assisted reproductive technology: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND

The clinical efficacy of antioxidants in assisted reproductive technology (ART) remains inconsistent. This systematic review and meta-analysis aimed to evaluate the impact of oral antioxidant supplementation on reproductive outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET).

METHODS

We systematically searched PubMed, Scopus, Embase, and Web of Science databases from inception to February 2026 for randomized controlled trials (RCTs) investigating oral antioxidants in patients undergoing ART. We performed meta-analyses by pooling effect sizes, conducting subgroup analyses, and exploring heterogeneity. Methodological quality was assessed using the Risk of Bias (RoB) tool, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Sensitivity analyses and publication bias assessments were also conducted.

RESULTS

This meta-analysis suggests that oral antioxidant supplementation may provide potential clinical benefits for women undergoing IVF/ICSI-ET. The pooled estimates indicated a significant improvement in the clinical pregnancy rate (RR = 1.29, 95% CI: 1.070-1.554), the number of morphologically mature oocytes (MII oocytes) (MD = 2.99, 95% CI: 1.82-4.16), the number of high-quality embryos (MD = 1.08, 95%CI: 0.69-1.47), and the live birth rate (RR = 1.407, 95% CI: 1.052-1.881). Due to the limited number of included studies, further large-scale RCTs are required to confirm these findings regarding high-quality embryos, live birth rates, and miscarriage rates, thereby strengthening the overall level of evidence.

CONCLUSION

Oral antioxidant supplementation as an adjuvant therapy shows potential clinical benefits in improving clinical pregnancy rates, MII oocyte yields, the number of high-quality embryos, and live birth rates in women undergoing IVF/ICSI-ET. Notably, antioxidants appear to offer broader clinical utility in patients undergoing the antagonist protocol. Given the current limitations in study volume and methodological heterogeneity, future well-designed RCTs-stratified by patient characteristics and employing standardized antioxidant regimens-are warranted. In particular, studies prioritizing live birth as the primary endpoint are essential to establish definitive clinical recommendations.

SYSTEMATIC REVIEW REGISTRATION: identifier CRD420251238213.