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

Abstract

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.

Effect of antioxidants on semen parameters in men with oligo‐astheno‐teratozoospermia: a network meta‐analysis

“…This approach is obviously not comparable with that used in our NMA, where the analysis was restricted to antioxidant treatments in men with idiopathic OAT. In the NMA by Su et al, 89 more comparable in design with our NMA, CoQ10 and carnitine showed better efficacy in increasing sperm concentration and sperm motility, respectively. The lack of effect of CoQ10 on sperm concentration in our analysis may partly depend on the exclusion of the Safarinejad trials, 65,68 which were instead included in the NMA by Su et al 89 In addition, while in the NMA of Su et al 89 oligozoospermia, asthenozoospermia, or teratozoospermia were considered as a single condition, in our NMA, as a major strength, improvement of each seminal parameter was quantified only in the series that exhibited an alteration of that particular parameter at baseline.…”

“…This approach is obviously not comparable with that used in our NMA, where the analysis was restricted to antioxidant treatments in men with idiopathic OAT. In the NMA by Su et al., 89 more comparable in design with our NMA, CoQ10 and carnitine showed better efficacy in increasing sperm concentration and sperm motility, respectively. The lack of effect of CoQ10 on sperm concentration in our analysis may partly depend on the exclusion of the Safarinejad trials, 65,68 which were instead included in the NMA by Su et al 89 .…”

“…In the NMA by Su et al., 89 more comparable in design with our NMA, CoQ10 and carnitine showed better efficacy in increasing sperm concentration and sperm motility, respectively. The lack of effect of CoQ10 on sperm concentration in our analysis may partly depend on the exclusion of the Safarinejad trials, 65,68 which were instead included in the NMA by Su et al 89 . In addition, while in the NMA of Su et al 89 .…”

“…The lack of effect of CoQ10 on sperm concentration in our analysis may partly depend on the exclusion of the Safarinejad trials, 65,68 which were instead included in the NMA by Su et al 89 . In addition, while in the NMA of Su et al 89 . oligozoospermia, asthenozoospermia, or teratozoospermia were considered as a single condition, in our NMA, as a major strength, improvement of each seminal parameter was quantified only in the series that exhibited an alteration of that particular parameter at baseline.…”

Research progress of glutathione peroxidase family (GPX) in redoxidation

“…Frontiers in Pharmacology frontiersin.org improve sperm motility (Su et al, 2021). Nevertheless, SNGPX4 KO mice have normal survival and fertility.…”