The effect of antioxidant supplementation on operated or non-operated varicocele-associated infertility: A systematic review and meta-analysis

Abstract

ABSTRACT Introduction In patients with varicocele-associated infertility, the effect of antioxidant supplementation on fertility is unknown. Objectives To perform a systematic review and meta-analysis exploring the role of antioxidant supplementation in patients with operated or non-operated varicocele. Methods We searched PubMed, Cochrane Library, Web of Science and Scopus databases, as well as sources of grey literature until May 2021 (PROSPERO: CRD42021248195). We produced a qualitative synthesis of the main results extracted from the included studies. Based on data availability, we undertook an inverse variance, random effects meta-analysis of odds ratios (ORs) to determine the pregnancy rate after antioxidant supplementation versus no treatment in patients undergoing surgical repair of varicocele at three and six months of treatment. In these patients, we determined the effect of antioxidant supplementation versus no treatment or placebo on semen parameters (concentration, motility, morphology, and DNA fragmentation). Results We included 14 studies (980 individuals) in the systematic review. Of the 14 studies, 2 explored the effect of antioxidant supplementation in patients with non-operated varicocele, 1 compared antioxidants versus surgical repair of varicocele, while 11 explored antioxidants after surgical repair of varicocele and were also included in the meta-analysis. Regarding pregnancy rates, no significant differences were demonstrated after treatment with antioxidants versus no treatment at three (OR: 2.28, 95% CI: 0.7–7.48) and six months (OR: 1.88, 95% CI: 0.62–5.72). Accordingly, contradictory findings were reported in sperm concentration, morphology, and motility, as well as DNA fragmentation. Conclusions Our findings indicate that antioxidant supplementation does not improve pregnancy rates and semen parameters in patients with varicocele-associated infertility, in the absence of previous screening for oxidative stress. Based on the previous notion, most included studies also raised methodological concerns. Therefore, definitive conclusions about the efficacy of antioxidant supplementation in this setting cannot be drawn and further research on the field is mandatory. Disclosure Work supported by industry: no.