Effect of Antioxidants on Sperm Quality Parameters in Subfertile Men: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Antioxidant supplementation has been identified as an important intervention for subfertile men. However, the effectiveness of different antioxidants in improving sperm quality remains unclear. In this study, a network meta-analysis (NMA) was designed to evaluate the effects of different antioxidants on sperm quality parameters in subfertile men. Published randomized controlled trials (RCTs) of antioxidants in subfertile men were searched in the PubMed, Embase, and Cochrane Library databases from inception to January 31, 2021. Eight antioxidants (folic acid, zinc, vitamin E, carnitine, selenium, coenzyme q10 [CoQ10], N-acetylcysteine, and vitamin C) and a placebo (control) were included in our study. A Bayesian NMA with random effects was performed for each outcome (sperm concentration, sperm motility, and sperm morphology); the surface under the cumulative ranking curves (SUCRAs) for the effectiveness of each intervention was applied to identify the optimal intervention. Eighteen studies with 1,790 subfertile men were included in the study. CoQ10 elicited a significant increase in sperm concentration (mean difference [MD] = 5.95; 95% confidence interval [CI] 0.05, 10.79) compared with the placebo; it achieved the highest rank in efficacy among all the antioxidants (SUCRA: 79.4%). With regard to sperm motility, carnitine (MD = 12.43; 95% CI 4.07, 20.26) and CoQ10 (MD = 7.33; 95% CI 0.35, 14.17) showed significant beneficial effects compared with the placebo; the efficacy of carnitine was the highest among all the antioxidants (SUCRA: 88.7%). With regard to sperm morphology, the efficacy of vitamin C tended to be the highest (SUCRA: 93.6%), although it did not show significant beneficial effect (MD = 7.73; 95% CI -0.94, 16.33) compared with the placebo. Overall, for subfertile men, CoQ10 and carnitine interventions showed better effectiveness in increasing sperm concentration and sperm motility, respectively. SIGNIFICANCE: The effectiveness of different antioxidants in improving sperm quality in subfertile men remains unclear. To the best of our knowledge, this is the first study to compare the effectiveness of different antioxidants on sperm quality parameters in subfertile men.