The association between mortality and male infertility: systematic review and meta-analysis

Objective: To summarize the current body of evidence on the relationship between impaired male fertility and the risk of early death through a systematic review and meta-analysis of population-based retrospective cohort studies. Methods: PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases were searched from inception to August 2020 according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Pooled Risk Ratio (RR), Risk Difference (Δr), Hazard Ratio (HR) and Standardized Mortality Ratio (SMR) differences among male factor infertility cohorts were compared to fertile/normospermic control populations or to national mortality data. Results: Six studies from 2006 to 2020 met inclusion criteria. Three studies examined male infertility and mortality (ntot = 202,456; ndeaths = 1396), while four studies examined survival in relation to semen parameters (ntot = 59,291; ndeaths = 643). Comparing infertile to fertile men, pooled HR for the risk of death was 1.26 (95%CI:1.01-1.59). Pooled RR and Δr of death for combined oligo- and azoospermic men vs normospermic men was 1.67 (95%CI:1.26-2.21) and 0.37% (95%CI:0.18-0.55%) respectively. When comparing oligo- and normospermic men to azoospermic men, the cumulative HR was 1.31 (95%CI:1.11-1.54) and 2.17 (95%CI:1.55-3.04) respectively. Infertile men had a lower overall risk of death compared to the overall population (SMR, 0.38, 95%CI:0.31-0.45). Conclusion: Compared to fertile men, infertile men had a higher risk of death. Moreover, the risk of death increased with increasing severity of semen quality impairment. However, compared to men from the general population, infertile men have a lower risk of death suggesting that social determinants of health are also important.