The Effect of Varicocele Treatment on Fertility in Adults: A Systematic Review and Meta-analysis of Published Prospective Trials

Context: The benefits and harms of varicocele treatment versus observation in adult infertile males are still controversial. Objective: To systematically pool the evidence on outcomes of varicocele treatment (any surgical or radiological) versus observation in adult infertile men. Evidence acquisition: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Only prospective randomized and nonrandomized studies were included until November 2021. The primary outcome was pregnancy rate; the secondary outcomes were improvements in sperm concentration, normal morphology, and progressive sperm motility after treatment compared to baseline. Men ≥18 yr of age with any-grade varicoceles were included. Evidence synthesis: Of 557 articles identified, 12 were eligible for inclusion, involving 1357 patients. Varicoceles were treated surgically in ten and radiologically in four studies. Varicocele treatment improved pregnancy rates (odds ratio 1.29; 95% confidence interval [CI] 1.00–1.65; p = 0.048) and sperm concentration (mean difference 12.34 million/ml, 95% CI 3.49–21.18; p = 0.006) compared with observation. Proportions of spermatozoa with normal morphology and progressive motility were not statistically different from those with observation. However, considering treatment arm only, sperm concentration, progressive motility, and normal sperm morphology were improved compared with baseline. A subgroup analysis showed that the benefit of varicocele treatment is evident in men with an abnormal semen analysis. The main limitation is represented by the heterogeneity of the included studies, mostly in terms of study population, fertility of the partner, outcome evaluation, lack of long-term outcomes, and intermediate/high risk of bias. Conclusions: Treatment of any-grade varicoceles may improve pregnancy rates and sperm concentration in adult infertile men, while benefits in sperm motility and normal morphology are less clear. Patient summary: In this systematic review and meta-analysis of all published prospective trials on varicocele treatment, significant evidence emerged on its benefit in terms of improved pregnancy rates and sperm concentration, while benefits in sperm motility and morphology are less clear.