Global Andrology Forum Clinical Guidelines on Antioxidant Use in the Treatment of Male Infertility

Antioxidant (AOX) therapy has long been investigated for the management of male infertility. It has potential benefits, but persistent controversy affects its broad acceptance and clinical utility. This study aimed to develop standardized, evidence-based guidelines for AOX use by synthesizing the best available evidence and achieving global expert consensus.

A comprehensive literature review was conducted by senior experts of the Global Andrology Forum (GAF). Additionally, data on the real-life use of oxidative stress (OS) testing and AOX use obtained from the largest global survey of practicing physicians conducted by GAF, which served as a reference point for this study. In phase one, 151 international specialists (>5 years' experience) participated in a modified Delphi process to evaluate AOX therapy in male infertility. Experts reviewed draft statements and rated agreement on a 10-point Likert scale. Statements achieving >80% consensus (with score >7/10) were accepted. The original eight statements were expanded to 19 and finalized into 18. In phase two, 84 senior physicians (>10 years' experience) graded the Delphi-approved statements using the GRADE approach.

Four out of the 18 statements failed to reach consensus and were excluded. Of the final 14 statements, seven (50%) were graded as "Strong" and seven (50%) as "Weak." Current evidence indicates that AOX therapy can reduce OS, improve sperm quality, and potentially enhance reproductive outcomes. However, benefits vary by agent, regimen, and patient population. The guidelines emphasize the need to document OS and to consider underlying factors before initiating AOX therapy, and caution against indiscriminate or prolonged use.

Developed through a dual-validation process and endorsed by a globally diverse expert panel, these GAF guidelines represent the first standardized, evidence-based guidelines for AOX use in male infertility. By addressing heterogeneity in research and practice, they provide clinicians with practical, safe, and patient-centered recommendations for rational AOX therapy worldwide.