Pharmacologic and Nutritional Therapies in Idiopathic Male Infertility: A Systematic Review and Meta-Analysis
Abstract
Background: Pharmacologic and nutritional therapies are prescribed for men with idiopathic infertility, but their effectiveness by intervention class remains uncertain.
Objectives: To evaluate these interventions on semen parameters and clinical pregnancy in men with idiopathic infertility, stratified by mechanism of action.
Materials and methods: We searched PubMed, Embase, Scopus, Cochrane CENTRAL, ClinicalTrials.gov, and Google Scholar (January 2010 to January 2026) for randomized controlled trials comparing pharmacologic or nutritional interventions with placebo or no treatment in men with idiopathic infertility. Semen parameters were the primary outcomes, analyzed by mechanism of action using three-level random-effects models with Knapp-Hartung adjustment. Certainty of evidence was assessed using GRADE.
Prospero: CRD420261289976.
Results: Forty-one RCTs (3615 men) were included. Antioxidants were associated with higher sperm concentration (SMD: 1.09, 95% CI: 0.10 to 2.08), progressive motility (SMD: 1.11, 95% CI: 0.32 to 1.90), total motility (SMD: 0.69, 95% CI: 0.26 to 1.13), and normal morphology (SMD: 0.43, 95% CI: 0.05 to 0.82); prediction intervals crossed the null for all. PDE inhibitors showed numerically higher point estimates for concentration (SMD: 1.96, 95% CI: -2.25 to 6.17) and morphology (SMD: 1.28, 95% CI: -0.47 to 3.02); methyl donors reduced DNA fragmentation (SMD: -1.17, 95% CI: -2.82 to 0.47). Confidence intervals for these included the null.…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 3,615 participants or records.
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