Association between male infertility and male-specific malignancies: systematic review and meta-analysis of population-based retrospective cohort studies

Objective: To investigate the current evidence that correlates impaired male fertility with the risk of developing male-related malignancies. Design: Systematic review and meta-analysis of population-based retrospective cohort studies. Setting: Not applicable. Patient(s): Men diagnosed with impaired fertility status and subsequently observed to determine incidence risk in developing testicular cancer (TCa) or prostate cancer (PCa). Intervention(s): Not applicable. Main Outcome Measure(s): Pooled risk ratio (RR) differences among male factor infertility subjects compared with a fertile control population, and meta-regression analysis according to age at baseline, mean follow-up, range of study time, and year of publication. Result(s): Six studies met the inclusion criteria and were critically examined. Four studies examined male infertility and TCa (n = 161,634; 174 TCa cases), and four examined infertility in relation to PCa (n = 183,950 men; 377 PCa cases) from 1963 to 2014. The pooled RR was 2.033 (95% confidence interval [CI], 1.66–2.48); heterogeneity: Q = 3.04 (degree of freedom [df] = 3); I² = 1.55% for TCa and 1.68 (95% CI, 1.17–2.4); Q = 23.3(df = 3); I² = 87.1% for PCa. Conclusion(s): Male infertility was associated with a subsequent risk of both TCa and PCa. Although the clinical significance of these findings remains uncertain, future studies should evaluate the underlying mechanisms to determine whether testis and prostate screening practices should be altered in men with male infertility. Clinical Trial Registration Number: PROSPERO 167277