The Effect of Antioxidant Supplementation on Operated or Non-Operated Varicocele-Associated Infertility: A Systematic Review and Meta-Analysis

Nikolaos Pyrgidis,Nikolaos Sofikitis,Vasileios Palapelas,Aris Kaltsas,Ioannis Mykoniatis,Athanasios Zachariou,Maksim Tishukov,Fotios Dimitriadis,Evangelos N Symeonidis,Georgios Hatzichristodoulou,Ioannis Sokolakis,Chara Tsiampali

doi:10.3390/antiox10071067

Abstract

In patients with varicocele-associated infertility, the effect of antioxidant supplementation on fertility is unknown. We performed a systematic review and meta-analysis to explore their role in patients with operated or non-operated varicocele. We searched major databases and sources of grey literature until May 2021 (PROSPERO: CRD42021248195). 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. 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.

Highlights

IntroductionVaricocele is defined as the abnormal dilation of the pampiniform plexus caused by blood reflux from the testicular vein in patients with congenital insufficient or absent venous valves [1]
2 randomized controlled trials (RCTs) explored the effect of antioxidant treatment in patients with non-operated varicocele versus placebo [23,24], 1 non-RCT
RCTs explored the effect of antioxidant treatment versus placebo or no further postoperative treatment in patients undergoing surgical repair of varicocele and were included in the meta-analysis [26,27,28,29,30,31,32,33,34,35,36]

Summary

Introduction

Varicocele is defined as the abnormal dilation of the pampiniform plexus caused by blood reflux from the testicular vein in patients with congenital insufficient or absent venous valves [1]. Most men with varicocele present normal semen parameters and can father children [2]. Varicocele is considered the most common correctable cause of male infertility with an overall prevalence of 25% in men with abnormal semen parameters and 35–40% in infertile men [3]. The exact mechanism of varicocele-associated infertility is multifactorial and not fully understood [4]. It has been postulated that scrotal hyperthermia, hypoxia, reflux of toxic metabolites, and increased intravenous pressure induce oxidative stress and, in turn, lead to testicular dysfunction and infertility [5,6]

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Discussion

Conclusion