A Systematic Review and Meta-analysis on the Impact of Infertility on Men's General Health

Context: Male infertility has been associated with increased morbidity and mortality. Objective: To perform a systematic review and meta-analysis to provide the most critical evidence on the association between infertility and the risk of incident comorbidities in males. Evidence acquisition: A systematic review and meta-analysis was performed according to the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and registered on PROSPERO. All published studies on infertile versus fertile men regarding overall mortality and risks of cancer, diabetes, and cardiovascular events were selected from a database search on PubMed, EMBASE, Google Scholar, and Cochrane. Forest plot and quasi-individual patient data meta-analysis were used for pooled analyses. A risk of bias was assessed using the ROBINS-E tool. Evidence synthesis: Overall, an increased risk of death from any cause was found for infertile men (hazard risk [HR] 1.37, [95% confidence interval {CI} 1.04–1.81], p = 0.027), and a 30-yr survival probability of 91.0% (95% CI 89.6–92.4%) was found for infertile versus 95.9% (95% CI 95.3–96.4%) for fertile men (p < 0.001). An increased risk emerged of being diagnosed with testis cancer (relative risk [RR] 1.86 [95% CI 1.41–2.45], p < 0.001), melanoma (RR 1.30 [95% CI 1.08–1.56], p = 0.006), and prostate cancer (RR 1.66 [95% CI 1.06–2.61], p < 0.001). As well, an increased risk of diabetes (HR 1.39 [95% CI 1.09–1.71], p = 0.008), with a 30-yr probability of diabetes of 25.0% (95% CI 21.1–26.9%) for infertile versus 17.1% (95% CI 16.1–18.1%) for fertile men (p < 0.001), and an increased risk of cardiovascular events (HR 1.20 [95% CI 1.00–1.44], p = 0.049), with a probability of major cardiovascular events of 13.9% (95% CI 13.3–14.6%) for fertile versus 15.7% (95% CI 14.3–16.9%) for infertile men (p = 0.008), emerged. Conclusions: There is statistical evidence that a diagnosis of male infertility is associated with increased risks of death and incident comorbidities. Owing to the overall high risk of bias, results should be interpreted carefully. Patient summary: Male fertility is a proxy of general men's health and as such should be seen as an opportunity to improve preventive strategies for overall men's health beyond the immediate reproductive goals.