Antioxidants for male subfertility.

This was a systematic review and meta-analysis of randomized trials in subfertile men. Participants were men attending fertility clinics with impaired semen parameters or sperm DNA damage, and some couples were undergoing assisted reproduction such as IVF, ICSI, or IUI. Trials were conducted in multiple countries and compared oral antioxidants with placebo, no treatment, or other antioxidant regimens.

The review evaluated oral antioxidant supplements for male subfertility, but the included trials used many different regimens rather than one standardized product. Active interventions included vitamin E, zinc, coenzyme Q10 or ubiquinol, N-acetylcysteine, carnitines, docosahexaenoic acid, magnesium, pentoxifylline, and mixed antioxidant formulations, typically given orally for about 3 weeks to 24 months. Comparators were placebo or no treatment, and some studies also used head-to-head antioxidant comparisons.

Overall, oral antioxidants may improve live birth and clinical pregnancy in subfertile men, but the evidence is low to very low quality. Across pooled analyses, antioxidants increased live birth (OR 4.21, 95% CI 2.08 to 8.51, 4 RCTs, 277 men) and clinical pregnancy (OR 3.43, 95% CI 1.92 to 6.11, 7 RCTs, 522 men). They were also associated with lower sperm DNA fragmentation (MD -13.85, 95% CI -17.28 to -10.41, 2 RCTs, 100 men) and improved sperm motility in several analyses, but heterogeneity was often high. Benefits were not consistently shown for miscarriage, gastrointestinal adverse events, or IVF/ICSI subgroups, and the review cautioned that routine use is not yet supported by robust evidence.

The evidence base was small and methodologically limited, with many trials contributing only single outcomes. Certainty was low to very low because of imprecision, heterogeneity, and incomplete reporting of adverse events. The interventions, doses, and durations varied widely across studies, limiting direct comparability and generalizability, and benefits were not consistent in assisted reproduction subgroups.