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Semin Reprod Med 2017; 35(03): 298-303
DOI: 10.1055/s-0037-1603583
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Male Infertility and Risk of Cancer

Marc J. Rogers
1   Department of Urology, University of Washington School of Medicine, Seattle, Washington
,
Thomas J. Walsh
1   Department of Urology, University of Washington School of Medicine, Seattle, Washington
› Author Affiliations
Further Information

Publication History

Publication Date:
28 June 2017 (online)

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Abstract

Male infertility is a complex and incompletely understood process that is thought to affect around 10% of the male population. Infertility is a complex interaction between genetics and environmental factors, which is increasingly being recognized as a potential marker of contemporary or future medical disease, including cancer. The best characterized association between infertility and cancer risk is that of testicular germ cell tumor, but increased risk for prostate cancer, melanoma, non-Hodgkin's lymphoma, and others have also been described. Much like infertility, the mechanism behind these associations is not completely understood. Several hypotheses have been put forth including testicular dysgenesis syndrome, chromosomal abnormalities, damaged DNA repair mechanisms, or Y chromosome abnormalities. With the use of advance reproductive techniques, more men are bypassing a male fertility specialist who may be positioned to diagnose or counsel patients regarding these risks.

Keywords

male infertility - cancer risk - testicular cancer - abnormal semen analysis
 

  • References

  • 1 Zegers-Hochschild F, Adamson GD, de Mouzon J. , et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril 2009; 92 (5): 1520-1524
    CrossrefPubMedGoogle Scholar
  • 2 Male Infertility Best Practice Policy Committee of the American Urological Association; Practice Committee of the American Society for Reproductive Medicine. Report on optimal evaluation of the infertile male. Fertil Steril 2006; 86 (05) (Suppl. 01) S202-S209
    PubMedGoogle Scholar
  • 3 Thonneau P, Marchand S, Tallec A. , et al. Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989). Hum Reprod 1991; 6 (06) 811-816
    CrossrefPubMedGoogle Scholar
  • 4 Honig SC, Lipshultz LI, Jarow J. Significant medical pathology uncovered by a comprehensive male infertility evaluation. Fertil Steril 1994; 62 (05) 1028-1034
    CrossrefPubMedGoogle Scholar
  • 5 Anderson JE, Farr SL, Jamieson DJ, Warner L, Macaluso M. Infertility services reported by men in the United States: national survey data. Fertil Steril 2009; 91 (06) 2466-2470
    CrossrefPubMedGoogle Scholar
  • 6 Louis JF, Thoma ME, Sørensen DN. , et al. The prevalence of couple infertility in the United States from a male perspective: evidence from a nationally representative sample. Andrology 2013; 1 (05) 741-748
    CrossrefPubMedGoogle Scholar
  • 7 Skakkebaek NE, Jørgensen N, Main KM. , et al. Is human fecundity declining?. Int J Androl 2006; 29 (01) 2-11
    CrossrefPubMedGoogle Scholar
  • 8 Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med 2012; 9 (12) e1001356
    CrossrefPubMedGoogle Scholar
  • 9 Gunnell DJ, Ewings P. Infertility prevalence, needs assessment and purchasing. J Public Health Med 1994; 16 (01) 29-35
    CrossrefPubMedGoogle Scholar
  • 10 Dyer S, Chambers GM, de Mouzon J. , et al. International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology 2008, 2009 and 2010. Hum Reprod 2016; 31 (07) 1588-1609
    CrossrefPubMedGoogle Scholar
  • 11 Sherins RJ, Thorsell LP, Dorfmann A. , et al. Intracytoplasmic sperm injection facilitates fertilization even in the most severe forms of male infertility: pregnancy outcome correlates with maternal age and number of eggs available. Fertil Steril 1995; 64 (02) 369-375
    CrossrefPubMedGoogle Scholar
  • 12 Ziebe S, Devroey P. ; State of ART 2007 Workshop Group. Assisted reproductive technologies are an integrated part of national strategies addressing demographic and reproductive challenges. Hum Reprod Update 2008; 14 (06) 583-592
    CrossrefPubMedGoogle Scholar
  • 13 Kolettis PN, Sabanegh ES. Significant medical pathology discovered during a male infertility evaluation. J Urol 2001; 166 (01) 178-180
    CrossrefPubMedGoogle Scholar
  • 14 Eisenberg ML, Li S, Behr B, Pera RR, Cullen MR. Relationship between semen production and medical comorbidity. Fertil Steril 2015; 103 (01) 66-71
    CrossrefPubMedGoogle Scholar
  • 15 Huyghe E, Matsuda T, Thonneau P. Increasing incidence of testicular cancer worldwide: a review. J Urol 2003; 170 (01) 5-11
    CrossrefPubMedGoogle Scholar
  • 16 Holmes Jr L, Escalante C, Garrison O. , et al. Testicular cancer incidence trends in the USA (1975-2004): plateau or shifting racial paradigm?. Public Health 2008; 122 (09) 862-872
    CrossrefPubMedGoogle Scholar
  • 17 Richiardi L, Bellocco R, Adami HO. , et al. Testicular cancer incidence in eight northern European countries: secular and recent trends. Cancer Epidemiol Biomarkers Prev 2004; 13 (12) 2157-2166
    PubMedGoogle Scholar
  • 18 Znaor A, Lortet-Tieulent J, Jemal A, Bray F. International variations and trends in testicular cancer incidence and mortality. Eur Urol 2014; 65 (06) 1095-1106
    CrossrefPubMedGoogle Scholar
  • 19 Nieman CL, Kazer R, Brannigan RE. , et al. Cancer survivors and infertility: a review of a new problem and novel answers. J Support Oncol 2006; 4 (04) 171-178
    PubMedGoogle Scholar
  • 20 Polland A, Berookhim BM. Fertility concerns in men with genitourinary malignancies: Treatment dilemmas, fertility options, and medicolegal considerations. Urol Oncol 2016; 34 (09) 399-406
    CrossrefPubMedGoogle Scholar
  • 21 Ostrowski KA, Walsh TJ. Infertility with testicular cancer. Urol Clin North Am 2015; 42 (03) 409-420
    CrossrefPubMedGoogle Scholar
  • 22 Tournaye H, Dohle GR, Barratt CL. Fertility preservation in men with cancer. Lancet 2014; 384 (9950): 1295-1301
    CrossrefPubMedGoogle Scholar
  • 23 Ginsberg JP. New advances in fertility preservation for pediatric cancer patients. Curr Opin Pediatr 2011; 23 (01) 9-13
    CrossrefPubMedGoogle Scholar
  • 24 Skakkebaek NE. Possible carcinoma-in-situ of the testis. Lancet 1972; 2 (7776): 516-517
    PubMedGoogle Scholar
  • 25 Pryor JP, Cameron KM, Chilton CP. , et al. Carcinoma in situ in testicular biopsies from men presenting with infertility. Br J Urol 1983; 55 (06) 780-784
    CrossrefPubMedGoogle Scholar
  • 26 Carroll PR, Whitmore Jr WF, Richardson M. , et al. Testicular failure in patients with extragonadal germ cell tumors. Cancer 1987; 60 (01) 108-113
    CrossrefPubMedGoogle Scholar
  • 27 Swerdlow AJ, Huttly SR, Smith PG. Testis cancer: post-natal hormonal factors, sexual behaviour and fertility. Int J Cancer 1989; 43 (04) 549-553
    CrossrefPubMedGoogle Scholar
  • 28 Forman D, Møller H. Testicular cancer. Cancer Surv 1994; 19-20: 323-341
    PubMedGoogle Scholar
  • 29 Møller H, Skakkebaek NE. Risk of testicular cancer in subfertile men: case-control study. BMJ 1999; 318 (7183): 559-562
    CrossrefPubMedGoogle Scholar
  • 30 Dieckmann KP, Pichlmeier U. Clinical epidemiology of testicular germ cell tumors. World J Urol 2004; 22 (01) 2-14
    CrossrefPubMedGoogle Scholar
  • 31 Richiardi L, Akre O, Montgomery SM, Lambe M, Kvist U, Ekbom A. Fecundity and twinning rates as measures of fertility before diagnosis of germ-cell testicular cancer. J Natl Cancer Inst 2004; 96 (02) 145-147
    CrossrefPubMedGoogle Scholar
  • 32 Brown LM, Pottern LM, Hoover RN. Testicular cancer in young men: the search for causes of the epidemic increase in the United States. J Epidemiol Community Health 1987; 41 (04) 349-354
    CrossrefPubMedGoogle Scholar
  • 33 Haughey BP, Graham S, Brasure J, Zielezny M, Sufrin G, Burnett WS. The epidemiology of testicular cancer in upstate New York. Am J Epidemiol 1989; 130 (01) 25-36
    CrossrefPubMedGoogle Scholar
  • 34 Baker JA, Buck GM, Vena JE, Moysich KB. Fertility patterns prior to testicular cancer diagnosis. Cancer Causes Control 2005; 16 (03) 295-299
    CrossrefPubMedGoogle Scholar
  • 35 Doria-Rose VP, Biggs ML, Weiss NS. Subfertility and the risk of testicular germ cell tumors (United States). Cancer Causes Control 2005; 16 (06) 651-656
    CrossrefPubMedGoogle Scholar
  • 36 Raman JD, Nobert CF, Goldstein M. Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol 2005; 174 (05) 1819-1822 , discussion 1822
    CrossrefPubMedGoogle Scholar
  • 37 Jacobsen R, Bostofte E, Engholm G. , et al. Risk of testicular cancer in men with abnormal semen characteristics: cohort study. BMJ 2000; 321 (7264): 789-792
    CrossrefPubMedGoogle Scholar
  • 38 Walsh TJ, Croughan MS, Schembri M, Chan JM, Turek PJ. Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med 2009; 169 (04) 351-356
    CrossrefPubMedGoogle Scholar
  • 39 Hanson HA, Anderson RE, Aston KI, Carrell DT, Smith KR, Hotaling JM. Subfertility increases risk of testicular cancer: evidence from population-based semen samples. Fertil Steril 2016; 105 (02) 322-328.e1
    CrossrefPubMedGoogle Scholar
  • 40 Eisenberg ML, Li S, Brooks JD, Cullen MR, Baker LC. Increased risk of cancer in infertile men: analysis of U.S. claims data. J Urol 2015; 193 (05) 1596-1601
    CrossrefPubMedGoogle Scholar
  • 41 Eisenberg ML, Betts P, Herder D, Lamb DJ, Lipshultz LI. Increased risk of cancer among azoospermic men. Fertil Steril 2013; 100 (03) 681-685
    CrossrefPubMedGoogle Scholar
  • 42 Centers for Disease Control. Cancer Among Men. 2016; Available at: https://www.cdc.gov/cancer/dcpc/data/men.htm . Accessed December 2016
    PubMedGoogle Scholar
  • 43 Walsh TJ, Schembri M, Turek PJ. , et al. Increased risk of high-grade prostate cancer among infertile men. Cancer 2010; 116 (09) 2140-2147
    PubMedGoogle Scholar
  • 44 Jørgensen KT, Pedersen BV, Johansen C, Frisch M. Fatherhood status and prostate cancer risk. Cancer 2008; 112 (04) 919-923
    CrossrefPubMedGoogle Scholar
  • 45 Wirén SM, Drevin LI, Carlsson SV. , et al. Fatherhood status and risk of prostate cancer: nationwide, population-based case-control study. Int J Cancer 2013; 133 (04) 937-943
    CrossrefPubMedGoogle Scholar
  • 46 Eisenberg ML, Park Y, Brinton LA, Hollenbeck AR, Schatzkin A. Fatherhood and incident prostate cancer in a prospective US cohort. Int J Epidemiol 2011; 40 (02) 480-487
    CrossrefPubMedGoogle Scholar
  • 47 Mao Y, Xu X, Zheng X, Xie L. Reduced risk of prostate cancer in childless men as compared to fathers: a systematic review and meta-analysis. Sci Rep 2016; 6: 19210
    CrossrefPubMedGoogle Scholar
  • 48 Richiardi L, Akre O. Fertility among brothers of patients with testicular cancer. Cancer Epidemiol Biomarkers Prev 2005; 14 (11, Pt 1): 2557-2562
    CrossrefPubMedGoogle Scholar
  • 49 Anderson RE, Hanson HA, Patel DP. , et al. Cancer risk in first- and second-degree relatives of men with poor semen quality. Fertil Steril 2016; 106 (03) 731-738
    CrossrefPubMedGoogle Scholar
  • 50 Skakkebaek NE, Rajpert-De Meyts E, Buck Louis GM. , et al. Male reproductive disorders and fertility trends: influences of environment and genetic susceptibility. Physiol Rev 2016; 96 (01) 55-97
    CrossrefPubMedGoogle Scholar
  • 51 Tvrda E, Agarwal A, Alkuhaimi N. Male reproductive cancers and infertility: a mutual relationship. Int J Mol Sci 2015; 16 (04) 7230-7260
    CrossrefPubMedGoogle Scholar
  • 52 Burns WR, Sabanegh E, Dada R, Rein B, Agarwal A. Is male infertility a forerunner to cancer?. Int Braz J Urol 2010; 36 (05) 527-536
    CrossrefPubMedGoogle Scholar
  • 53 Matzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nat Med 2008; 14 (11) 1197-1213
    CrossrefPubMedGoogle Scholar
  • 54 Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 2001; 16 (05) 972-978
    CrossrefPubMedGoogle Scholar
  • 55 Juul A, Almstrup K, Andersson AM. , et al. Possible fetal determinants of male infertility. Nat Rev Endocrinol 2014; 10 (09) 553-562
    CrossrefPubMedGoogle Scholar
  • 56 Nordkap L, Joensen UN, Blomberg Jensen M, Jørgensen N. Regional differences and temporal trends in male reproductive health disorders: semen quality may be a sensitive marker of environmental exposures. Mol Cell Endocrinol 2012; 355 (02) 221-230
    CrossrefPubMedGoogle Scholar
  • 57 Kido T, Lau YF. Roles of the Y chromosome genes in human cancers. Asian J Androl 2015; 17 (03) 373-380
    PubMedGoogle Scholar
  • 58 Dolci S, Campolo F, De Felici M. Gonadal development and germ cell tumors in mouse and humans. Semin Cell Dev Biol 2015; 45: 114-123
    CrossrefPubMedGoogle Scholar
  • 59 Baker SM, Bronner CE, Zhang L. , et al. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 1995; 82 (02) 309-319
    CrossrefPubMedGoogle Scholar
  • 60 Terribas E, Bonache S, García-Arévalo M. , et al. Changes in the expression profile of the meiosis-involved mismatch repair genes in impaired human spermatogenesis. J Androl 2010; 31 (04) 346-357
    CrossrefPubMedGoogle Scholar
  • 61 Hu MH, Liu SY, Wang N, Wu Y, Jin F. Impact of DNA mismatch repair system alterations on human fertility and related treatments. J Zhejiang Univ Sci B 2016; 17 (01) 10-20
    CrossrefPubMedGoogle Scholar
  • 62 Winters BR, Walsh TJ. The epidemiology of male infertility. Urol Clin North Am 2014; 41 (01) 195-204
    CrossrefPubMedGoogle Scholar
  • 63 Hotaling JM, Davenport MT, Eisenberg ML, VanDenEeden SK, Walsh TJ. Men who seek infertility care may not represent the general U.S. population: data from the National Survey of Family Growth. Urology 2012; 79 (01) 123-127
    PubMedGoogle Scholar