A Systematic Review and Meta-Analysis of Male Infertility and the Subsequent Risk of Cancer

Abstract

ObjectivesThe primary objective of this systemic review and meta-analysis was to investigate the risk of developing composite outcome of all cancers, regardless of the type of cancer among men with infertility diagnosis compared to fertile counterparts. The secondary objective was to compare the pooled risk of developing individual specific cancers between two groups.MethodsA systematic literature search was performed on the databases of PubMed (including Medline), Scopus, and Web of Science to retrieve observational studies published in English language from 01.01.1990 to 28. 02. 2021. They assessed cancer events in males with an infertility diagnosis compared to controls without infertility. The outcomes of interest were a composite outcome of cancers including all known cancer types, and also specific individual cancers. The fixed/random effects model was used to analyze heterogeneous and non-heterogeneous results. Publication bias was assessed using the Harbord test, Egger test, Begg test, and funnel plot. The pooled odds ratio of cancers was calculated using the DerSimonian and Laird, and inverse variance methods. Studies’ quality and risk of bias were assessed using structured standard tools.ResultsWe included eight cohort studies involving 168,327 men with the diagnosis of infertility and 2,252,806 men without it. The total number of composite outcome of cancers as well as individual cancers including prostate, testicular and melanoma were 1551, 324, 183 and 121 in the infertile men and 12164, 3875, 849, and 450 in the fertile men, respectively. The pooled OR of the composite outcome of cancers, regardless of the type of cancer, in men with infertility was 1.4 folds higher than those without infertility (pooled OR = 1.43, 95% confidence interval [CI]: 1.25-1.64). Meta-analysis of individual cancers including prostate, testicular and melanoma between two groups was carried out. The pooled ORs of testicular and prostate cancers in men with the diagnosis of infertility were significantly higher than controls without infertility (pooled OR = 1.91, 95% CI: 1.52-2.42 and pooled OR = 1.48, 95% CI: 1.05-2.08, respectively). Additionally, the pooled OR of melanoma in men with infertility was 1.3 folds higher than those without infertility (pooled OR = 1.31, 95% CI: 1.06-1.62).ConclusionA greater risk of cancers in men with male infertility was found suggesting that the history of male infertility might be an important risk factor for developing cancers in later life. Further well-designed long-term population-based prospective studies, considering all known cancers and their accompanying risk factors should be conducted to support our findings.

Male infertility: what on earth is going on? Pilot international questionnaire study regarding clinical evaluation and fertility treatment for men

“…Although honest, this is hugely disappointing and something that must be urgently addressed by our speciality, not least because clinical history and examination are key tools for diagnosis, appropriate investigation and management. Recent work has also identified associations between male infertility and various malignancies ( Hanson et al 2018 , Behboudi-Gandevani et al 2021 ). For example, infertile men are reported to be at least three times more likely to develop testicular cancer ( Walsh et al 2009 , Del Giudice et al 2020 ).…”

Counseling for the man with severe male infertility

“…In a recent meta-analysis, including eight studies involving 168 327 infertile men and 2 252 806 controls, the diagnosis of infertility was associated with a 40% higher risk of developing cancer in the years following an infertility evaluation. Specifically, men with an infertility diagnosis had a higher risk of testicular cancer, prostate cancer, and melanoma [47]. Infertile men were also found to have a higher PSA suggesting future studies examining early screening of infertile men should be considered [48].…”

Current global status of male reproductive health

“…Male infertility may provide a window into later health and, as such, may be a harbinger of significant future medical problems. Indeed, current health and reproductive fitness are closely associated but reproductive health also seems to be a biomarker of future health; severe cardiometabolic conditions, genetic syndromes, or cancers appear to be increased in men with semen abnormalities ( Eisenberg et al , 2015a , b ; Behboudi-Gandevani et al , 2021 ; Hansen et al , 2023 ). There are, however, several important knowledge gaps with this emerging literature.…”