Persisting challenges for antioxidants use in treatment of male infertility

Oxidative stress {OS} has emerged as a major etiological factor to male infertility and is present in significant proportion of subfertile patients classified as Male Oxidative Stress Infertility. This review aimed to critically evaluate the current challenges associated with the use of antioxidants in the management of male infertility.

This manuscript was conducted using review of literature addressing oxidative stress, antioxidant therapy, diagnostic biomarkers, sperm DNA damage, assisted reproductive technologies {ART}, and clinical outcomes in male infertility. Review was conducted using PubMed, Scopus, and Web of Science to identify relevant studies published from January 2000 to March 2026, with emphasis on systematic reviews, randomized controlled trials and clinical guidelines. The evidence was critically evaluated across several major challenges that were identified and analyzed, including oxidative stress assessment, antioxidant mechanisms, diagnostic standardization, patient selection, treatment protocols, reductive stress, bioavailability, outcome measures, long-term safety, ART interactions, and publication bias. Major barriers that contribute to the inconsistency in the outcome of antioxidants use include the absence of standardized diagnostic criteria for oxidative stress, lack of consensus regarding antioxidant formulations and dosages, heterogeneity among clinical trials, and the risk of reductive stress resulting from excessive supplementation.

Despite the biological rationale supporting antioxidant therapy in male infertility, substantial challenges continue to limit its evidence-based clinical application. Future research should prioritize standardized diagnostic approaches, biomarker-guided patient selection, optimization of dosage and treatment duration, and assessment of clinically relevant reproductive outcomes.