The link between male infertility and other diseases/ risk of future morbidities has been explored in a number of studies using administrative databases to date. Each of these is limited by the retrospective nature and the vagaries of coding and detection of disease. The detection of prostate cancer is further challenged by the variable rate of PSA testing that occurs in different practice settings or countries. In this study, the authors used the need for IVF to conceive and the use of ICSI (intracytoplasmic sperm injection during IVF) as surrogates for infertility and male factor infertility, as ICSI is most commonly used for sperm abnormalities.1 Detection of prostate cancer was based on Swedish national registries, limiting detection bias to some degree. They report a hazard ratio of 1.64 for men who conceived with the assistance of IVF and a hazard ratio of 2.15 for men who required ICSI for conception (1.0 = natural conception). Furthermore, they identified that men who were diagnosed with prostate cancer after treatment with assisted conception were diagnosed at an early age (HR, 1.9 for diagnosis before age 55) and were at least as likely to have androgen-deprivation therapy (HR, 1.9; P=.07), a marker for clinically significant/ advanced disease.
At least one common causal link may exist between male infertility and prostate cancer. Both conditions are associated with defects in DNA mismatch repair genes, and increased genetic screening may be helpful to identify the infertile men with these gene mutations, and, therefore, who are at risk for subsequent prostate cancer development. At present, it is increasingly popular to counsel men with severe infertility about their potential risk of other associated medical problems in later life, but no testing to identify those at greatest risk exists; so, the medical recommendations have limited practical value. With these data and with widespread adoption of cancer-predisposing gene testing panels, it is likely that we will soon be able to perform specific testing of infertile men to identify those at risk and allow evidence-based testing of those men.
Of course, any study that relies on administrative database analysis has limitations. ICSI or IVF may be done for female, rather than male infertility. Androgen-deprivation therapy may be applied for localized prostate cancer (eg, prior to radiation) and advanced cancer. Early diagnosis is a surrogate for genetically based and more aggressive disease, but it is not an absolute indicator. And detection of prostate cancer is highly dependent on screening, which may be more common in men from couples who have had prior exposure to medical therapy (eg, infertility treatment.) However, these data are strong, and the potential causal link is compelling that men with infertility are prone to develop clinically significant prostate cancer. Therefore, these infertile men should be considered for and counseled regarding prostate cancer screening.