{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:04:07Z","timestamp":1792123447941,"version":"4.4.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 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\u2019 quality and risk of bias were assessed using structured standard tools.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We 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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.696702","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T06:30:39Z","timestamp":1634193039000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["A Systematic Review and Meta-Analysis of Male Infertility and the Subsequent Risk of Cancer"],"prefix":"10.3389","volume":"11","author":[{"given":"Samira","family":"Behboudi-Gandevani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razieh","family":"Bidhendi-Yarandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Hossein","family":"Panahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojtaba","family":"Vaismoradi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2009.09.009","article-title":"International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) Revised Glossary of ART Terminology, 2009","volume":"92","author":"Zegers-Hochschild","year":"2009","journal-title":"Fertil Steril"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.5539\/gjhs.v7n6p226","article-title":"The Prevalence and Causes of Primary Infertility in Iran: A Population-Based Study","volume":"7","author":"Kazemijaliseh","year":"2015","journal-title":"Glob J Health Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dem046","article-title":"International Estimates of Infertility Prevalence and Treatment-Seeking: Potential Need and Demand for Infertility Medical Care","volume":"22","author":"Boivin","year":"2007","journal-title":"Hum Reprod"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu106","article-title":"Semen Quality, Infertility and Mortality in the USA","volume":"29","author":"Eisenberg","year":"2014","journal-title":"Hum Reprod (Oxford England)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1603568","article-title":"Male Infertility and Risk of Nonmalignant Chronic Diseases: A Systematic Review of the Epidemiological Evidence","volume":"35","author":"Glazer","year":"2017","journal-title":"Semin Reprod Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1055\/s-0037-1603583","article-title":"Male Infertility and Risk of Cancer","volume":"35","author":"Rogers","year":"2017","journal-title":"Semin Reprod Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.5534\/wjmh.180055","article-title":"Metabolic Syndrome and Male Fertility","volume":"37","author":"Martins","year":"2019","journal-title":"World J Mens Health"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-020293","article-title":"Risk of Metabolic Disorders in Childless Men: A Population-Based Cohort Study","volume":"8","author":"Bungum","year":"2018","journal-title":"BMJ Open"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.01.002","article-title":"New Insights to Guide Patient Care: The Bidirectional Relationship Between Male Infertility and Male Health","volume":"113","author":"Kasman","year":"2020","journal-title":"Fertil Steril"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.5812\/ijem.107418","article-title":"The Association Between Male Infertility and Cardiometabolic Disturbances: A Population-Based Study","volume":"19","author":"Behboudi-Gandevani","year":"2021","journal-title":"Int J Endocrinol Metab"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1080\/21681805.2021.1889027","article-title":"Increased Risk for Prostate Cancer Related Mortality Among Childless Men in a Population-Based Cohort Followed for Up to 40 Years","volume":"55","author":"Elenkov","year":"2021","journal-title":"Scand J Urol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.04.042","article-title":"Association Between Male Infertility and Male-Specific Malignancies: Systematic Review and Meta-Analysis of Population-Based Retrospective Cohort Studies","volume":"114","author":"Del Giudice","year":"2020","journal-title":"Fertil Steril"},{"key":"B13","doi-asserted-by":"publisher","first-page":"19210","DOI":"10.1038\/srep19210","article-title":"Reduced Risk of Prostate Cancer in Childless Men as Compared to Fathers: A Systematic Review and Meta-Analysis","volume":"6","author":"Mao","year":"2016","journal-title":"Sci Rep"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2021.02.003","article-title":"Updating Guidance for Reporting Systematic Reviews: Development of the PRISMA 2020 Statement","volume":"134","author":"Page","year":"2021","journal-title":"J Clin Epidemiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmx021","article-title":"The Diagnosis of Male Infertility: An Analysis of the Evidence to Support the Development of Global WHO Guidance-Challenges and Future Research Opportunities","volume":"23","author":"Barratt","year":"2017","journal-title":"Hum Reprod Update"},{"key":"B16","unstructured":"WellsGA\n            SheaB\n            O\u2019ConnellD\n            PetersonJ\n            WelchV\n            LososM\n          Ottawa, ON, CanadaOttawa Hospital Research InstituteThe Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomized Studies in Meta-Analyses"},{"key":"B17","doi-asserted-by":"publisher","first-page":"i4919","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: A Tool for Assessing Risk of Bias in Non-Randomised Studies of Interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"key":"B18","year":"2011"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.05.022","article-title":"Increased Risk of Cancer Among Azoospermic Men","volume":"100","author":"Eisenberg","year":"2013","journal-title":"Fertil Steril"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2014.11.080","article-title":"Increased Risk of Cancer in Infertile Men: Analysis of U.S. Claims Data","volume":"193","author":"Eisenberg","year":"2015","journal-title":"J Urol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2015.10.027","article-title":"Subfertility Increases Risk of Testicular Cancer: Evidence From Population-Based Semen Samples","volume":"105","author":"Hanson","year":"2016","journal-title":"Fertil Steril"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2008.562","article-title":"Increased Risk of Testicular Germ Cell Cancer Among Infertile Men","volume":"169","author":"Walsh","year":"2009","journal-title":"Arch Intern Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25075","article-title":"Increased Risk of High-Grade Prostate Cancer Among Infertile Men","volume":"116","author":"Walsh","year":"2010","journal-title":"Cancer"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.321.7264.789","article-title":"Risk of Testicular Cancer in Men With Abnormal Semen Characteristics: Cohort Study","volume":"321","author":"Jacobsen","year":"2000","journal-title":"BMJ"},{"key":"B25","doi-asserted-by":"publisher","first-page":"l5214","DOI":"10.1136\/bmj.l5214","article-title":"Risk of Prostate Cancer for Men Fathering Through Assisted Reproduction: Nationwide Population Based Register Study","volume":"366","author":"Al-Jebari","year":"2019","journal-title":"BMJ"},{"key":"B26","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.fertnstert.2017.11.005","article-title":"Male Infertility: A Biomarker of Individual and Familial Cancer Risk","volume":"109","author":"Hanson","year":"2018","journal-title":"Fertil Steril"},{"key":"B27","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/978-1-62703-038-0_34","article-title":"A Review of Genome-Wide Approaches to Study the Genetic Basis for Spermatogenic Defects","volume":"927","author":"Aston","year":"2013","journal-title":"Methods Mol Biol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.10.028","article-title":"Genetic Intersection of Male Infertility and Cancer","volume":"109","author":"Nagirnaja","year":"2018","journal-title":"Fertil Steril"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2020.518961","article-title":"Psychosocial Consequences of Female Infertility in Iran: A Meta-Analysis","volume":"11","author":"Zarif Golbar Yazdi","year":"2020","journal-title":"Front Psychiatry"},{"key":"B30","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s12978-020-00973-0","article-title":"A Rapid Scoping Review of Fear of Infertility in Africa","volume":"17","author":"Boivin","year":"2020","journal-title":"Reprod Health"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew123","article-title":"Prevalence of Infertility and Help Seeking Among 15 000 Women and Men","volume":"31","author":"Datta","year":"2016","journal-title":"Hum Reprod (Oxford England)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s13187-017-1282-8","article-title":"The Effect of Educational Program Based on PRECEDE Model in Promoting Prostate Cancer Screening in a Sample of Iranian Men","volume":"34","author":"Jeihooni","year":"2019","journal-title":"J Cancer Educ"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000101","article-title":"Lifestyle and Cancer Risk","volume":"21","author":"Katzke","year":"2015","journal-title":"Cancer J"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.696702\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T06:31:13Z","timestamp":1634193073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.696702\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,14]]},"references-count":33,"alternative-id":["10.3389\/fonc.2021.696702"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.696702","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,14]]},"article-number":"696702"}}