Preservation of fertility in men with cancer
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20253568Keywords:
Male fertility preservation, Cancer therapy, Sperm cryopreservation, Onco-fertility, CounsellingAbstract
Fertility preservation in males is acknowledging a developing recognition as essential in treatment planning for cancer. Many currently available cancer therapies including chemotherapy, radiation and novel immunotherapy can affect sperm production, testicular function and reproductive potential. Although sperm cryopreservation is the gold standard for patients, considering post pubertal patients, experimental approaches to preserve fertility including cryopreservation of testicular tissue as an option for prepubertal boys, are in development. Whilst we do not currently lack options, several barriers prevent patients from timely access to fertility counselling, primarily a lack of awareness at their diagnosis or timely education of specific services. Early access to fertility preservation services as part of oncology health care can improve reproductive outcome and enhance long-term quality of life for survivors. Changes in our current practices will require better communication, collaboration, and a focus on improving patient access to fertility preservation options.
Metrics
References
Liu X, Liu B, Liu S, Xian Y, Zhao W, Zhou B, et al. Male cancer patient sperm cryopreservation for fertility preservation: 10-year monocentric experience. J Assist Reprod Genet. 2023;40(12):2755-67.
Albamonte MI, Vitullo AD. Preservation of fertility in female and male prepubertal patients diagnosed with cancer. J Assist Reprod Genet. 2023;40(12):2755-67. DOI: https://doi.org/10.1007/s10815-023-02945-2
International Agency for Research on Cancer. India Fact Sheet. GLOBOCAN 2022. Lyon: IARC. 2024.
National Cancer Institute. Cancer Diagnosis. Bethesda (MD): NCI. 2022.
Cancer Control: Knowledge into Action: WHO Guide for Effective Programmes: Module 3: Early Detection. Geneva: World Health Organization; 2007. PMID: 24716262.
Barak S. Fertility preservation in male patients with cancer. Best Pract Res Clin Obstet Gynaecol. 2019;55:59-66. DOI: https://doi.org/10.1016/j.bpobgyn.2018.12.004
Katz DJ, Kolon TF, Feldman DR, Mulhall JP. Fertility preservation strategies for male patients with cancer. Nat Rev Urol. 2013;10(7):1-8. DOI: https://doi.org/10.1038/nrurol.2013.145
Wyns C, Kanbar M, Giudice MG, Poels J. Fertility preservation for prepubertal boys. Hum Reprod Update. 2021;27(3):433-59. DOI: https://doi.org/10.1093/humupd/dmaa050
Goossens E, Jahnukainen K, Mitchell RT, Pelt AV, Pennings G, Rives N, et al. Fertility preservation in boys: recent developments and new insights. Hum Reprod Open. 2020;2020(3):hoaa016. DOI: https://doi.org/10.1093/hropen/hoaa016
Yang EH, Strohl HB, Su HI. Fertility preservation before and after cancer treatment in children, adolescents, and young adults. Cancer. 2024;130(3):344-55. DOI: https://doi.org/10.1002/cncr.35108
Kawai K, Nishiyama H. Preservation of fertility of adult male cancer patients treated with chemotherapy. Int J Clin Oncol. 2018;24(1):1-6. DOI: https://doi.org/10.1007/s10147-018-1333-0
Holoch P, Wald M. Current options for preservation of fertility in the male. Fertil Steril. 2011;96(6):286-90. DOI: https://doi.org/10.1016/j.fertnstert.2011.06.028
Klosky JL, Wang F, Russell KM, Zhang H, Flynn JS, Huang L, et al. Prevalence and predictors of sperm banking in adolescents newly diagnosed with cancer: examination of adolescent, parent, and provider factors influencing fertility preservation outcomes. J Clin Oncol. 2017;35(34):3830-6. DOI: https://doi.org/10.1200/JCO.2016.70.4767
Quinn GP, Vadaparampil ST, King L, Miree CA, Wilson C, Raj O, et al. Impact of physicians’ personal discomfort and attitudes on discussion of fertility preservation with cancer patients. Patient Educ Couns. 2009;77(3):338-43. DOI: https://doi.org/10.1016/j.pec.2009.09.007
Nahata L, Cohen LE, Yu RN, Kroon L, Sanders JE, Ginsberg JP. Fertility counseling and preservation practices in pediatric oncology: results of a survey of pediatric oncologists. J Clin Oncol. 2016;34(35):4324-9.
Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(19):2500-10. DOI: https://doi.org/10.1200/JCO.2013.49.2678
Schover LR, Brey K, Lichtin A, Lipshultz LI, Jeha S. Knowledge and experience regarding cancer, infertility, and sperm banking in younger male survivors. J Clin Oncol. 2002;20(7):1880-9. DOI: https://doi.org/10.1200/JCO.2002.07.175
Kelvin JF, Quinn GP, Vadaparampil ST, Sehovic I, King L, Meade C, et al. Fertility preservation knowledge, counseling, and actions among adolescent and young adult cancer patients: a review. J Adolesc Young Adult Oncol. 2016;5(1):30-44.
Bleyer A. The clinical pharmacology of anticancer agents in adolescents. J Clin Oncol. 1990;8(10):1751-65.
Lowe SW, Ruley HE, Jacks T, Housman DE. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 1993;74(6):957-67. DOI: https://doi.org/10.1016/0092-8674(93)90719-7
Korsmeyer SJ. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Cancer Res. 1992;52(19):5659s-62s. DOI: https://doi.org/10.1182/blood.V80.4.879.bloodjournal804879
Hamano I, Hatakeyama S, Ohyama C. Fertility preservation of patients with testicular cancer. Reprod Med Biol. 2017;16(3):240-51. DOI: https://doi.org/10.1002/rmb2.12037
Delbes G, Chan D, Robaire B. The effects of chemotherapeutic agents on male reproduction. Fertil Steril. 2010;93(1):1-12.
Petersen PM, Skakkebaek NE, Vistisen K, Rørth M, Giwercman A. Semen quality and reproductive hormones before and after orchiectomy in men with testicular cancer. J Urol. 1999;161(3):822-6. DOI: https://doi.org/10.1016/S0022-5347(01)61781-6
Brydøy M, Fossa SD, Klepp O, Bremnes RM, Wist EA, Wentzel-Larsen T, et al. Paternity following treatment for testicular cancer. J Natl Cancer Inst. 2005;97(21):1580-8. DOI: https://doi.org/10.1093/jnci/dji339
Lampe H, Horwich A, Norman A, Nicholls J, Dearnaley DP, Fisher C, et al. Fertility after chemotherapy for testicular germ cell cancers. J Clin Oncol. 1997;15(1):239-45. DOI: https://doi.org/10.1200/JCO.1997.15.1.239
van Casteren NJ, van Santbrink EJ, van Inzen W, Romijn JC, Dohle GR. Sperm DNA integrity in men treated for testicular cancer. Hum Reprod. 2009;24(5):1025-31.
Huyghe E, Matsuda T, Daudin M, Chevreau C, Bachaud JM, Plante P, et al. Fertility after testicular cancer treatments. Cancer. 2004;100(4):732-7. DOI: https://doi.org/10.1002/cncr.11950
Huddart RA, Norman A, Moynihan C, Horwich A, Parker C, Nicholls E, et al. Fertility, gonadal and sexual function in survivors of testicular cancer. Br J Cancer. 2005;93(2):200-7. DOI: https://doi.org/10.1038/sj.bjc.6602677
Petersen PM, Giwercman A, Daugaard G, Rørth M, Skakkebaek NE. Effect of graded testicular doses of radiotherapy in patients with testicular cancer. Eur J Cancer. 2002;38(10):1362-9.
van Casteren NJ, Boellaard WP, Romijn JC, Dohle GR. Successful fatherhood using cryopreserved semen in testicular cancer survivors. Fertil Steril. 2008;89(3):731-6.
Kenney LB, Cohen LE, Shnorhavorian M, Metzger ML, Lockart B, Hijiya N, et al. Male reproductive health after childhood, adolescent, and young adult cancers: a report from the Children’s Oncology Group. J Clin Oncol. 2012;30(30):3722-8. DOI: https://doi.org/10.1200/JCO.2011.38.6938
Meseguer M, Molina N, Garcia-Velasco JA, Remohi J, Pellicer A, Garrido N. Sperm cryopreservation in oncological patients: a 14-year follow-up study. Fertil Steril. 2006;85(3):640-5. DOI: https://doi.org/10.1016/j.fertnstert.2005.08.022
Ramasamy R, Ricci JA, Palermo GD, Gosden LV, Rosenwaks Z, Schlegel PN. Successful fertility treatment for azoospermic men after cancer therapy. J Clin Oncol. 2006;24(31):4864-9.
Castro S, Ng Yin K, d’Aniello F, Ghezzi M, De Filippo G, Mirabelli M, et al. Pubertal induction with gonadotropin therapy in males. Hum Reprod Open. 2025;(2):hoad026. DOI: https://doi.org/10.1093/hropen/hoaf026
Meistrich ML. The effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertil Steril. 2013;100(5):1180-6. DOI: https://doi.org/10.1016/j.fertnstert.2013.08.010
Schrader M, Müller M, Straub B, Miller K. The impact of chemotherapy on male fertility: a survey of the biologic basis and clinical aspects. Reprod Toxicol. 2001;15(6):611-7. DOI: https://doi.org/10.1016/S0890-6238(01)00182-4
Shalet SM. Effects of cancer chemotherapy on gonadal function of patients. Cancer Treat Rev. 1980;7(3):141-52. DOI: https://doi.org/10.1016/S0305-7372(80)80028-4
Tempest HG, Ko E, Chan P, Robaire B, Rademaker A, Martin RH. Sperm aneuploidy frequencies analysed before and after chemotherapy in testicular cancer and Hodgkin’s lymphoma patients. Hum Reprod. 2008;23(2):251-8. DOI: https://doi.org/10.1093/humrep/dem389
De Kretser DM, Burger HG, Hudson B. The relationship between germinal cell function and levels of LH, FSH, and testosterone in oligospermic and azoospermic men. J Clin Endocrinol Metab. 1974;38(5):787-93. DOI: https://doi.org/10.1210/jcem-38-5-787
Chapman RM, Sutcliffe SB, Malpas JS. Cytotoxic-induced testicular damage in man: clinical, pathological and endocrine features. Br J Cancer. 1981;43(4):445-51.
Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2010;28(2):332-9. DOI: https://doi.org/10.1200/JCO.2009.24.9037
Mehta SR, Suhag V, Semwal M, Sharma N. Radiotherapy: Basic Concepts and Recent Advances. Med J Armed Forces India. 2010;66(2):158-62. DOI: https://doi.org/10.1016/S0377-1237(10)80132-7
Amols HI. New technologies in radiation therapy: ensuring patient safety, radiation safety and regulatory issues in radiation oncology. Health Phys. 2008;95(5):658-65. DOI: https://doi.org/10.1097/01.HP.0000326334.64242.46
Ding M, Newman F, Chen C, Stuhr K, Gaspar LE. Dosimetric comparison between 3DCRT and IMRT using different multileaf collimators in the treatment of brain tumours. Med Dosim. 2009;34(1):1-8. DOI: https://doi.org/10.1016/j.meddos.2007.04.001
Georgakopoulos I, Kouloulias V, Ntoumas G-N, Desse D, Koukourakis I, Kougioumtzopoulou A, et al. Radiotherapy and testicular function: a comprehensive review of the radiation-induced effects with an emphasis on spermatogenesis. Biomedicines. 2024;12(7):1492. DOI: https://doi.org/10.3390/biomedicines12071492
Petersen PM, Giwercman A, Daugaard G, Rørth M, Petersen JH, Skakkeaek NE, et al. Effect of graded testicular doses of radiotherapy in patients treated for carcinoma-in-situ in the testis. J Clin Oncol. 2002;20(6):1537-43. DOI: https://doi.org/10.1200/JCO.2002.20.6.1537
Farhood B, Mortezaee K, Haghi-Aminjan H, Khanlarkhani N, Salehi E, Nashtaei MS, et al. A systematic review of radiation-induced testicular toxicities following radiotherapy for prostate cancer. J Cell Physiol. 2019;234(9):14828-37. DOI: https://doi.org/10.1002/jcp.28283
Berthelsen JG. Sperm counts and serum follicle-stimulating hormone levels before and after radiotherapy and chemotherapy in men with testicular germ cell cancer. Fertil Steril. 1984;41(2):281-6. DOI: https://doi.org/10.1016/S0015-0282(16)47605-3
Martin RH, Hildebrand K, Yamamoto J, Rademaker A, Barnes M, Douglas G, et al. An increased frequency of human sperm chromosomal abnormalities after radiotherapy. Mutat Res. 1986;174(3):219-25. DOI: https://doi.org/10.1016/0165-7992(86)90155-7
Gandini L, Sgrò P, Lombardo F, Paoli D, Culasso F, Toselli L, et al. Effect of chemo- or radiotherapy on sperm parameters of testicular cancer patients. Hum Reprod. 2006;21(11):2882-9. DOI: https://doi.org/10.1093/humrep/del167
Meirow D, Schenker JG. Cancer and male infertility. Hum Reprod. 1995;10(8):2017-22. DOI: https://doi.org/10.1093/oxfordjournals.humrep.a136228
Giwercman A, Petersen PM. Cancer and male infertility. Baillieres Clin Endocrinol Metab. 2000;14(3):453-71. DOI: https://doi.org/10.1053/beem.2000.0091
Brannigan RE, Fantus RJ, Halpern JA. Fertility preservation in men: a contemporary overview and a look toward emerging technologies. Fertil Steril. 2021;115(5):1126-39. DOI: https://doi.org/10.1016/j.fertnstert.2021.03.026
Duma N, Lambertini M. It is time to talk about fertility and immunotherapy. Oncologist. 2020;25(4):277-8. DOI: https://doi.org/10.1634/theoncologist.2019-0837
Arecco L, de Moura Leite L, Gentile G, Jankovic K, Stana M, Ottonello S, et al. Gonadotoxicity of immunotherapy and targeted agents in patients with cancer and impact on subsequent pregnancies. Hum Reprod. 2025;40(8):1452-66. DOI: https://doi.org/10.1093/humrep/deaf096
Caturegli P, Di Dalmazi G, Lombardi M, Grosso F, Larman HB, Larman T, et al. Hypophysitis secondary to cytotoxic T-lymphocyte-associated protein 4 blockade: insights into pathogenesis from an autopsy series. Am J Pathol. 2016;186(12):3225-35. DOI: https://doi.org/10.1016/j.ajpath.2016.08.020
Poulet FM, Wolf JJ, Herzyk DJ, DeGeorge JJ. An evaluation of the impact of PD-1 pathway blockade on reproductive safety of therapeutic PD-1 inhibitors. Birth Defects Res B Dev Reprod Toxicol. 2016;107(2):108-19. DOI: https://doi.org/10.1002/bdrb.21176
Duma N, Abdel-Ghani A, Yadav S, Hoversten KP, Reed CT, Sitek AN, et al. Sex differences in tolerability to anti-programmed cell death protein 1 therapy in patients with metastatic melanoma and non-small cell lung cancer: are we all equal? Oncologist. 2019;24(11):e1148-55. DOI: https://doi.org/10.1634/theoncologist.2019-0094
Salzmann M, Tosev G, Heck M, Schadendorf D, Maatouk I, Enk AH, et al. Male fertility during and after immune checkpoint inhibitor therapy: a cross-sectional pilot study. Eur J Cancer. 2021;152:41-8. DOI: https://doi.org/10.1016/j.ejca.2021.04.031
Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J, Taylor HS, et al. Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(19):1994-2001. DOI: https://doi.org/10.1200/JCO.2018.78.1914
Su HI, Lacchetti C, Letourneau J, Partridge AH, Qamar R, Quinn GP, et al. Fertility preservation in people with cancer: ASCO guideline update. J Clin Oncol. 2025;43(12):1488-515. DOI: https://doi.org/10.1200/JCO-24-02782
Tran KTD, Valli-Pulaski H, Colvin A, Orwig KE. Male fertility preservation and restoration strategies for patients undergoing gonadotoxic therapies. Biol Reprod. 2022;107(2):382-405. DOI: https://doi.org/10.1093/biolre/ioac072
Schulz M, Risopatrón J, Uribe P, Isachenko E, Isachenko V, Sánchez R. Human sperm vitrification: A scientific report. Andrology. 2020;8(6):1642-50. DOI: https://doi.org/10.1111/andr.12847
Stigliani S, Massarotti C, De Leo C, Maccarini E, Sozzi F, Cagnacci A, et al. Fifteen Year Regional Center Experience in Sperm Banking for Cancer Patients: Use and Reproductive Outcomes in Survivors. Cancers (Basel). 2021;13(1):116. DOI: https://doi.org/10.3390/cancers13010116
Hovatta O. Cryopreservation of testicular tissue. Mol Cell Endocrinol. 2000;169(1-2):113-5. DOI: https://doi.org/10.1016/S0303-7207(00)00363-4
Bahadur G, Chatterjee R, Ralph D. Testicular tissue cryopreservation in boys: ethical and legal issues. Hum Reprod. 2000;15(6):1416-20. DOI: https://doi.org/10.1093/humrep/15.6.1416