Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Fertility preservation strategies for male patients with cancer

Nature Reviews Urology volume 10, pages 463–472 (2013)Cite this article

Subjects

Abstract

With the increasing number of patients surviving cancer, there is increasing interest in long-term quality of life, especially with respect to cancer-related infertility. Although infertility most commonly occurs as the result of treatment with gonadotoxic agents, it can also manifest before treatment has commenced. Current fertility preservation strategies for the postpubertal male patient with cancer focus on sperm cryopreservation before therapy. Sperm acquisition techniques should be discussed with the patient as early as possible, by either an oncologist or a specialist in male reproduction. For patients rendered infertile by cancer treatment who did not cryopreserve sperm beforehand, there are no techniques currently available to restore fertility. For the prepubertal male patient, cryopreservation of sperm is impossible. However, emerging research—primarily in animal models—into promising fertility preservation and restoration strategies might provide a clinical solution in the future. Advances in the protection and cryopreservation of spermatogonial stem cells (SSCs) might translate into clinical options for fertility preservation before treatment. Restoring fertility after treatment might also be possible via SSC autotransplantation or in vitro maturation of SSCs. Before any of these techniques become clinically viable, a number of scientific, logistical and ethical issues will need to be resolved.

Key Points

  • Infertility related to cancer is a major issue for many cancer survivors and should be discussed as early as possible during treatment planning

  • Impairment of fertility related to cancer can manifest before, during or after treatment

  • Existing fertility preservation strategies for men focus on acquiring sperm for cryopreservation before therapy; patients rendered infertile by cancer treatments who did not cryopreserve sperm beforehand are unable to father a biological child

  • Promising advances in spermatogonial stem cell research might lead to future fertility preservation and restoration options for male patients with cancer

  • A number of scientific, logistical and ethical barriers might need to be overcome before investigational fertility preservation strategies can be used clinically, especially for prepubertal patients

  • Development of, and adherence to, clinical care pathways, education of oncological health-care providers and involvement of male reproductive specialists should be included in the management of infertility in male patients with cancer

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Potential options for fertility preservation in the future.

Similar content being viewed by others

References

  1. Living beyond cancer: finding a new balance. President's Cancer Panel 2003–2004 Annual Report 17 [online], (2013).

  2. Lee, S. J. et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J. Clin. Oncol. 24, 2917–2931 (2006).

    Article  PubMed  Google Scholar 

  3. Jemal, A. et al. Global cancer statistics. CA Cancer J. Clin. 61, 69–90 (2011).

    Article  PubMed  Google Scholar 

  4. Siegel, R., Naishadham, D. & Jemal, A. Cancer statistics, 2013. CA Cancer J. Clin. 63, 11–30 (2013).

    Article  PubMed  Google Scholar 

  5. Bleyer, A. Young adult oncology: the patients and their survival challenges. CA Cancer J. Clin. 57, 242–255 (2007).

    Article  PubMed  Google Scholar 

  6. American Cancer Society. Cancer Facts and Figures 2012 [online], (2013).

  7. Tschudin, S. & Bitzer, J. Psychological aspects of fertility preservation in men and women affected by cancer and other life-threatening diseases. Hum. Reprod. Update 15, 587–597 (2009).

    Article  PubMed  Google Scholar 

  8. Schover, L. R., Brey, K., Lichtin, A., Lipshultz, L. I. & Jeha, S. Knowledge and experience regarding cancer, infertility, and sperm banking in younger male survivors. J. Clin. Oncol. 20, 1880–1889 (2002).

    Article  PubMed  Google Scholar 

  9. Rieker, P. P., Fitzgerald, E. M. & Kalish, L. A. Adaptive behavioral responses to potential infertility among survivors of testis cancer. J. Clin. Oncol. 8, 347–355 (1990).

    Article  CAS  PubMed  Google Scholar 

  10. Saito, K., Suzuki, K., Iwasaki, A., Yumura, Y. & Kubota, Y. Sperm cryopreservation before cancer chemotherapy helps in the emotional battle against cancer. Cancer 104, 521–524 (2005).

    Article  PubMed  Google Scholar 

  11. Wallace, W. H. & Thomson, A. B. Preservation of fertility in children treated for cancer. Arch. Dis. Child. 88, 493–496 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nieman, C. L. et al. Fertility preservation and adolescent cancer patients: lessons from adult survivors of childhood cancer and their parents. Cancer Treat. Res. 138, 201–217 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Peate, M. et al. It's now or never: fertility-related knowledge, decision-making preferences, and treatment intentions in young women with breast cancer--an Australian fertility decision aid collaborative group study. J. Clin. Oncol. 29, 1670–1677 (2011).

    Article  PubMed  Google Scholar 

  14. Anderson, R. A. et al. Do doctors discuss fertility issues before they treat young patients with cancer? Hum. Reprod. 23, 2246–2251 (2008).

    Article  PubMed  Google Scholar 

  15. Green, D. M. et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J. Clin. Oncol. 28, 332–339 (2010).

    Article  PubMed  Google Scholar 

  16. Thomson, A. B. et al. Semen quality and spermatozoal DNA integrity in survivors of childhood cancer: a case-control study. Lancet 360, 361–367 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Lass, A. et al. A programme of semen cryopreservation for patients with malignant disease in a tertiary infertility centre: lessons from 8 years' experience. Hum. Reprod. 13, 3256–3261 (1998).

    Article  CAS  PubMed  Google Scholar 

  18. Chung, K. et al. Sperm cryopreservation for male patients with cancer: an epidemiological analysis at the University of Pennsylvania. Eur. J. Obstet. Gynecol. Reprod. Biol. 113 (Suppl. 1), S7–S11 (2004).

    Article  PubMed  Google Scholar 

  19. Pietzak, E. J. et al. Histology of testicular biopsy specimens obtained for cryopreservation and future re-implantation as a fertility-preserving technique. Presented at the 2012 American Academy of Pediatrics National Conference in New Orleans.

  20. Agarwal, A. & Allamaneni, S. S. Disruption of spermatogenesis by the cancer disease process. J. Natl Cancer Inst. Monogr. 2005, 9–12 (2005).

    Article  Google Scholar 

  21. Paduch, D. A. Testicular cancer and male infertility. Curr. Opin. Urol. 16, 419–427 (2006).

    Article  PubMed  Google Scholar 

  22. Hall, E. & Burt, V. K. Male fertility: psychiatric considerations. Fertil. Steril. 97, 434–439 (2012).

    Article  PubMed  Google Scholar 

  23. Pereira, M. L. & Garcia e Costa, F. The blood-testis barrier as a target of some chemotherapeutic agents. Chemotherapy 53, 446–448 (2007).

    Article  CAS  PubMed  Google Scholar 

  24. Bucci, L. R. & Meistrich, M. L. Effects of busulfan on murine spermatogenesis: cytotoxicity, sterility, sperm abnormalities, and dominant lethal mutations. Mutat. Res. 176, 259–268 (1987).

    Article  CAS  PubMed  Google Scholar 

  25. Ginsberg, J. P. New advances in fertility preservation for pediatric cancer patients. Curr. Opin. Pediatr. 23, 9–13 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. van der Kaaij, M. A., van Echten-Arends, J., Simons, A. H. & Kluin-Nelemans, H. C. Fertility preservation after chemotherapy for Hodgkin lymphoma. Hematol. Oncol. 28, 168–179 (2010).

    Article  PubMed  Google Scholar 

  27. Mackie, E. J., Radford, M. & Shalet, S. M. Gonadal function following chemotherapy for childhood Hodgkin's disease. Med. Pediatr. Oncol. 27, 74–78 (1996).

    Article  CAS  PubMed  Google Scholar 

  28. DeSantis, M., Albrecht, W., Holtl, W. & Pont, J. Impact of cytotoxic treatment on long-term fertility in patients with germ-cell cancer. Int. J. Cancer 83, 864–865 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Colpi, G. M., Contalbi, G. F., Nerva, F., Sagone, P. & Piediferro, G. Testicular function following chemo-radiotherapy. Eur. J. Obstet. Gynecol. Reprod. Biol. 113 (Suppl. 1), S2–S6 (2004).

    Article  CAS  PubMed  Google Scholar 

  30. Rowley, M. J., Leach, D. R., Warner, G. A. & Heller, C. G. Effect of graded doses of ionizing radiation on the human testis. Radiat. Res. 59, 665–678 (1974).

    Article  CAS  PubMed  Google Scholar 

  31. Centola, G. M., Keller, J. W., Henzler, M. & Rubin, P. Effect of low-dose testicular irradiation on sperm count and fertility in patients with testicular seminoma. J. Androl. 15, 608–613 (1994).

    CAS  PubMed  Google Scholar 

  32. Speiser, B., Rubin, P. & Casarett, G. Aspermia following lower truncal irradiation in Hodgkin's disease. Cancer 32, 692–698 (1973).

    Article  CAS  PubMed  Google Scholar 

  33. Budgell, G. J., Cowan, R. A. & Hounsell, A. R. Prediction of scattered dose to the testes in abdominopelvic radiotherapy. Clin. Oncol. (R. Coll. Radiol.) 13, 120–125 (2001).

    CAS  Google Scholar 

  34. Brenner, D. J. & Hall, E. J. Computed tomography—an increasing source of radiation exposure. N. Engl. J. Med. 357, 2277–2284 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Feldschuh, J., Brassel, J., Durso, N. & Levine, A. Successful sperm storage for 28 years. Fertil. Steril. 84, 1017 (2005).

    Article  PubMed  Google Scholar 

  36. Hourvitz, A. et al. Intracytoplasmic sperm injection (ICSI) using cryopreserved sperm from men with malignant neoplasm yields high pregnancy rates. Fertil. Steril. 90, 557–563 (2008).

    Article  PubMed  Google Scholar 

  37. Fossa, S. D. & Magelssen, H. Fertility and reproduction after chemotherapy of adult cancer patients: malignant lymphoma and testicular cancer. Ann. Oncol. 15 (Suppl. 4), iv259–iv265 (2004).

    PubMed  Google Scholar 

  38. Sunkara, S. K. et al. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum. Reprod. 26, 1768–1774 (2011).

    Article  PubMed  Google Scholar 

  39. O'Connell, M., McClure, N. & Lewis, S. E. The effects of cryopreservation on sperm morphology, motility and mitochondrial function. Hum. Reprod. 17, 704–709 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Pacey, A. A. Fertility issues in survivors from adolescent cancers. Cancer Treat. Rev. 33, 646–655 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Schmiegelow, M. L. et al. Penile vibratory stimulation and electroejaculation before anticancer therapy in two pubertal boys. J. Pediatr. Hematol. Oncol. 20, 429–430 (1998).

    Article  CAS  PubMed  Google Scholar 

  42. Sabanegh, E. Male Infertility—Problems and Solutions (ed. Klein, E. A.) (Humana Press, New York, 2011).

    Book  Google Scholar 

  43. Schlegel, P. N. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum. Reprod. 14, 131–135 (1999).

    Article  CAS  PubMed  Google Scholar 

  44. Hsiao, W. et al. Successful treatment of postchemotherapy azoospermia with microsurgical testicular sperm extraction: the Weill Cornell experience. J. Clin. Oncol. 29, 1607–1611 (2011).

    Article  PubMed  Google Scholar 

  45. Schrader, M. et al. “Onco-tese”: testicular sperm extraction in azoospermic cancer patients before chemotherapy-new guidelines? Urology 61, 421–425 (2003).

    Article  CAS  PubMed  Google Scholar 

  46. Katz, D. J., Matsushita, K., Bennett, N. & Mulhall, J. P. Outcomes of fertility preservation strategies in male teenagers with cancer [abstract 1985]. J. Urol. 187 (Suppl.), e801 (2012).

    Google Scholar 

  47. Binsaleh, S., Sircar, K. & Chan, P. T. Feasibility of simultaneous testicular microdissection for sperm retrieval and ipsilateral testicular tumor resection in azoospermic men. J. Androl. 25, 867–871 (2004).

    Article  PubMed  Google Scholar 

  48. Kalsi, J. et al. Analysis of the outcome of intracytoplasmic sperm injection using fresh or frozen sperm. BJU Int. 107, 1124–1128 (2011).

    Article  PubMed  Google Scholar 

  49. Nicopoullos, J. D. et al. Use of surgical sperm retrieval in azoospermic men: a meta-analysis. Fertil. Steril. 82, 691–701 (2004).

    Article  PubMed  Google Scholar 

  50. Ulug, U., Bener, F., Karagenc, L., Ciray, N. & Bahceci, M. Outcomes in couples undergoing ICSI: comparison between fresh and frozen-thawed surgically retrieved spermatozoa. Int. J. Androl. 28, 343–349 (2005).

    Article  PubMed  Google Scholar 

  51. Bieri, S., Rouzaud, M. & Miralbell, R. Seminoma of the testis: is scrotal shielding necessary when radiotherapy is limited to the para-aortic nodes? Radiother. Oncol. 50, 349–353 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Harris, S. J. & Buchanan, R. B. Irradiation of the scrotum: what some men need MOST: the Manual Orchid Shielding Technique. Clin. Oncol. (R. Coll. Radiol.) 8, 254–256 (1996).

    Article  CAS  Google Scholar 

  53. Fraass, B. A., Kinsella, T. J., Harrington, F. S. & Glatstein, E. Peripheral dose to the testes: the design and clinical use of a practical and effective gonadal shield. Int. J. Radiat. Oncol. Biol. Phys. 11, 609–615 (1985).

    Article  CAS  PubMed  Google Scholar 

  54. Ishiguro, H. et al. Gonadal shielding to irradiation is effective in protecting testicular growth and function in long-term survivors of bone marrow transplantation during childhood or adolescence. Bone Marrow Transplant. 39, 483–490 (2007).

    Article  CAS  PubMed  Google Scholar 

  55. Bazzi, W. M. et al. Partial orchiectomy and testis intratubular germ cell neoplasia: world literature review. Urol. Ann. 3, 115–118 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Lawrentschuk, N., Zuniga, A., Grabowksi, A. C., Rendon, R. A. & Jewett, M. A. Partial orchiectomy for presumed malignancy in patients with a solitary testis due to a prior germ cell tumor: a large North American experience. J. Urol. 185, 508–513 (2011).

    Article  PubMed  Google Scholar 

  57. Toren, P. J. et al. Small incidentally discovered testicular masses in infertile men—is active surveillance the new standard of care? J. Urol. 183, 1373–1377 (2010).

    Article  PubMed  Google Scholar 

  58. Wyns, C., Curaba, M., Vanabelle, B., Van Langendonckt, A. & Donnez, J. Options for fertility preservation in prepubertal boys. Hum. Reprod. Update 16, 312–328 (2010).

    Article  PubMed  Google Scholar 

  59. Shetty, G. & Meistrich, M. L. Hormonal approaches to preservation and restoration of male fertility after cancer treatment. J. Natl Cancer Inst. Monogr. 2005, 36–39 (2005).

    Article  CAS  Google Scholar 

  60. Meistrich, M. L. & Shetty, G. Inhibition of spermatogonial differentiation by testosterone. J. Androl. 24, 135–148 (2003).

    Article  CAS  PubMed  Google Scholar 

  61. Morris, I. D. Protection against cytotoxic-induced testis damage—experimental approaches. Eur. Urol. 23, 143–147 (1993).

    Article  CAS  PubMed  Google Scholar 

  62. Manabe, F., Takeshima, H. & Akaza, H. Protecting spermatogenesis from damage induced by doxorubicin using the luteinizing hormone-releasing hormone agonist leuprorelin: an image analysis study of a rat experimental model. Cancer 79, 1014–1021 (1997).

    Article  CAS  PubMed  Google Scholar 

  63. Kangasniemi, M., Wilson, G., Parchuri, N., Huhtaniemi, I. & Meistrich, M. L. Rapid protection of rat spermatogenic stem cells against procarbazine by treatment with a gonadotropin-releasing hormone antagonist (Nal-Glu) and an antiandrogen (flutamide). Endocrinology 136, 2881–2888 (1995).

    Article  CAS  PubMed  Google Scholar 

  64. Brennemann, W., Brensing, K. A., Leipner, N., Boldt, I. & Klingmuller, D. Attempted protection of spermatogenesis from irradiation in patients with seminoma by D-Tryptophan-6 luteinizing hormone releasing hormone. Clin. Investig. 72, 838–842 (1994).

    Article  CAS  PubMed  Google Scholar 

  65. Fossa, S. D., Klepp, O. & Norman, N. Lack of gonadal protection by medroxyprogesterone acetate-induced transient medical castration during chemotherapy for testicular cancer. Br. J. Urol. 62, 449–453 (1988).

    Article  CAS  PubMed  Google Scholar 

  66. Johnson, D. H. et al. Effect of a luteinizing hormone releasing hormone agonist given during combination chemotherapy on posttherapy fertility in male patients with lymphoma: preliminary observations. Blood 65, 832–836 (1985).

    CAS  PubMed  Google Scholar 

  67. Redman, J. & Bajorunas, D. in Workshop on Psychosexual and Reproductive Issues Affecting Patients with Cancer 90–94 (American Cancer Society, New York, 1987).

    Google Scholar 

  68. Waxman, J. Preserving fertility in Hodgkin's disease. Baillieres Clin. Haematol. 1, 185–190 (1987).

    Article  CAS  PubMed  Google Scholar 

  69. Kelnar, C. J. et al. Testicular changes during infantile 'quiescence' in the marmoset and their gonadotrophin dependence: a model for investigating susceptibility of the prepubertal human testis to cancer therapy? Hum. Reprod. 17, 1367–1378 (2002).

    Article  CAS  PubMed  Google Scholar 

  70. Ogawa, T., Dobrinski, I., Avarbock, M. R. & Brinster, R. L. Leuprolide, a gonadotropin-releasing hormone agonist, enhances colonization after spermatogonial transplantation into mouse testes. Tissue Cell 30, 583–588 (1998).

    Article  CAS  PubMed  Google Scholar 

  71. Kanter, M., Topcu-Tarladacalisir, Y. & Parlar, S. Antiapoptotic effect of L-carnitine on testicular irradiation in rats. J. Mol. Histol. 41, 121–128 (2010).

    Article  CAS  PubMed  Google Scholar 

  72. Okada, F. K., Stumpp, T. & Miraglia, S. M. Carnitine reduces testicular damage in rats treated with etoposide in the prepubertal phase. Cell Tissue Res. 337, 269–280 (2009).

    Article  CAS  PubMed  Google Scholar 

  73. Carmely, A. et al. Protective effect of the immunomodulator AS101 against cyclophosphamide-induced testicular damage in mice. Hum. Reprod. 24, 1322–1329 (2009).

    Article  CAS  PubMed  Google Scholar 

  74. Lirdi, L. C., Stumpp, T., Sasso-Cerri, E. & Miraglia, S. M. Amifostine protective effect on cisplatin-treated rat testis. Anat. Rec. (Hoboken) 291, 797–808 (2008).

    Article  CAS  Google Scholar 

  75. Brook, P. F., Radford, J. A., Shalet, S. M., Joyce, A. D. & Gosden, R. G. Isolation of germ cells from human testicular tissue for low temperature storage and autotransplantation. Fertil. Steril. 75, 269–274 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Wyns, C., Van Langendonckt, A., Wese, F. X., Donnez, J. & Curaba, M. Long-term spermatogonial survival in cryopreserved and xenografted immature human testicular tissue. Hum. Reprod. 23, 2402–2414 (2008).

    Article  PubMed  Google Scholar 

  77. Ginsberg, J. P. et al. An experimental protocol for fertility preservation in prepubertal boys recently diagnosed with cancer: a report of acceptability and safety. Hum. Reprod. 25, 37–41 (2010).

    Article  CAS  PubMed  Google Scholar 

  78. Sato, T. et al. In vitro production of functional sperm in cultured neonatal mouse testes. Nature 471, 504–507 (2011).

    Article  CAS  PubMed  Google Scholar 

  79. Keros, V. et al. Methods of cryopreservation of testicular tissue with viable spermatogonia in pre-pubertal boys undergoing gonadotoxic cancer treatment. Hum. Reprod. 22, 1384–1395 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. de Rooij, D. G. The spermatogonial stem cell niche. Microsc. Res. Tech. 72, 580–585 (2009).

    Article  CAS  PubMed  Google Scholar 

  81. Curaba, M., Poels, J., van Langendonckt, A., Donnez, J. & Wyns, C. Can prepubertal human testicular tissue be cryopreserved by vitrification? Fertil. Steril. 95, 2123.e9–2123.e12 (2011).

    Google Scholar 

  82. Poels, J., Van Langendonckt, A., Dehoux, J. P., Donnez, J. & Wyns, C. Vitrification of non-human primate immature testicular tissue allows maintenance of proliferating spermatogonial cells after xenografting to recipient mice. Theriogenology 77, 1008–1013 (2012).

    Article  CAS  PubMed  Google Scholar 

  83. Brinster, R. L. Male germline stem cells: from mice to men. Science 316, 404–405 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Trefil, P. et al. Restoration of spermatogenesis after transplantation of c-Kit positive testicular cells in the fowl. Theriogenology 74, 1670–1676 (2010).

    Article  CAS  PubMed  Google Scholar 

  85. Brinster, R. L. & Zimmermann, J. W. Spermatogenesis following male germ-cell transplantation. Proc. Natl Acad. Sci. USA 91, 11298–11302 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Honaramooz, A. et al. Fertility and germline transmission of donor haplotype following germ cell transplantation in immunocompetent goats. Biol. Reprod. 69, 1260–1264 (2003).

    Article  CAS  PubMed  Google Scholar 

  87. Schlatt, S., Foppiani, L., Rolf, C., Weinbauer, G. F. & Nieschlag, E. Germ cell transplantation into X-irradiated monkey testes. Hum. Reprod. 17, 55–62 (2002).

    Article  CAS  PubMed  Google Scholar 

  88. Schlatt, S. et al. Germ cell transfer into rat, bovine, monkey and human testes. Hum. Reprod. 14, 144–150 (1999).

    Article  CAS  PubMed  Google Scholar 

  89. Radford, J., Shalet, S. & Lieberman, B. Fertility after treatment for cancer. Questions remain over ways of preserving ovarian and testicular tissue. BMJ 319, 935–936 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Chuma, S. et al. Spermatogenesis from epiblast and primordial germ cells following transplantation into postnatal mouse testis. Development 132, 117–122 (2005).

    Article  CAS  PubMed  Google Scholar 

  91. Jahnukainen, K. et al. Testicular recovery after irradiation differs in prepubertal and pubertal non-human primates, and can be enhanced by autologous germ cell transplantation. Hum. Reprod. 26, 1945–1954 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Ogawa, T., Arechaga, J. M., Avarbock, M. R. & Brinster, R. L. Transplantation of testis germinal cells into mouse seminiferous tubules. Int. J. Dev. Biol. 41, 111–122 (1997).

    CAS  PubMed  Google Scholar 

  93. Schlatt, S., von Schonfeldt, V. & Nieschlag, E. Germ cell transplantation in the male: animal studies with a human perspective. Hum. Fertil. (Camb.) 2, 143–148 (1999).

    Article  Google Scholar 

  94. Ohta, H. & Wakayama, T. Generation of normal progeny by intracytoplasmic sperm injection following grafting of testicular tissue from cloned mice that died postnatally. Biol. Reprod. 73, 390–395 (2005).

    Article  CAS  PubMed  Google Scholar 

  95. Shinohara, T. et al. Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination. Hum. Reprod. 17, 3039–3045 (2002).

    Article  CAS  PubMed  Google Scholar 

  96. Honaramooz, A. et al. Sperm from neonatal mammalian testes grafted in mice. Nature 418, 778–781 (2002).

    Article  CAS  PubMed  Google Scholar 

  97. Wu, X. et al. Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules. Proc. Natl Acad. Sci. USA 106, 21672–21677 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Goossens, E., Geens, M., De Block, G. & Tournaye, H. Spermatogonial survival in long-term human prepubertal xenografts. Fertil. Steril. 90, 2019–2022 (2008).

    Article  PubMed  Google Scholar 

  99. Nagano, M., Patrizio, P. & Brinster, R. L. Long-term survival of human spermatogonial stem cells in mouse testes. Fertil. Steril. 78, 1225–1233 (2002).

    Article  PubMed  Google Scholar 

  100. Kanatsu-Shinohara, M. et al. Long-term culture of male germline stem cells from hamster testes. Biol. Reprod. 78, 611–617 (2008).

    Article  CAS  PubMed  Google Scholar 

  101. Aponte, P. M. et al. Propagation of bovine spermatogonial stem cells in vitro. Reproduction 136, 543–557 (2008).

    Article  CAS  PubMed  Google Scholar 

  102. Cremades, N., Sousa, M., Bernabeu, R. & Barros, A. Developmental potential of elongating and elongated spermatids obtained after in-vitro maturation of isolated round spermatids. Hum. Reprod. 16, 1938–1944 (2001).

    Article  CAS  PubMed  Google Scholar 

  103. Sousa, M., Cremades, N., Alves, C., Silva, J. & Barros, A. Developmental potential of human spermatogenic cells co-cultured with Sertoli cells. Hum. Reprod. 17, 161–172 (2002).

    Article  PubMed  Google Scholar 

  104. Sa, R. et al. Cytological and expression studies and quantitative analysis of the temporal and stage-specific effects of follicle-stimulating hormone and testosterone during cocultures of the normal human seminiferous epithelium. Biol. Reprod. 79, 962–975 (2008).

    Article  CAS  PubMed  Google Scholar 

  105. Tesarik, J., Guido, M., Mendoza, C. & Greco, E. Human spermatogenesis in vitro: respective effects of follicle-stimulating hormone and testosterone on meiosis, spermiogenesis, and Sertoli cell apoptosis. J. Clin. Endocrinol. Metab. 83, 4467–4473 (1998).

    Article  CAS  PubMed  Google Scholar 

  106. Aslam, I. & Fishel, S. Short-term in-vitro culture and cryopreservation of spermatogenic cells used for human in-vitro conception. Hum. Reprod. 13, 634–638 (1998).

    Article  CAS  PubMed  Google Scholar 

  107. Sadri-Ardekani, H. et al. Propagation of human spermatogonial stem cells in vitro. JAMA 302, 2127–2134 (2009).

    Article  CAS  PubMed  Google Scholar 

  108. Sadri-Ardekani, H., Akhondi, M. A., van der Veen, F., Repping, S. & van Pelt, A. M. In vitro propagation of human prepubertal spermatogonial stem cells. JAMA 305, 2416–2418 (2011).

    Article  CAS  PubMed  Google Scholar 

  109. Zhu, Y. et al. Generation of male germ cells from induced pluripotent stem cells (iPS cells): an in vitro and in vivo study. Asian J. Androl. 14, 574–579 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Yang, S. et al. Derivation of male germ cells from induced pluripotent stem cells in vitro and in reconstituted seminiferous tubules. Cell Prolif. 45, 91–100 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Knoepfler, P. S. Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine. Stem Cells 27, 1050–1056 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Marion, R. M. et al. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460, 1149–1153 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Okita, K., Ichisaka, T. & Yamanaka, S. Generation of germline-competent induced pluripotent stem cells. Nature 448, 313–317 (2007).

    Article  CAS  PubMed  Google Scholar 

  114. Zhou, H. et al. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4, 381–384 (2009).

    Article  CAS  PubMed  Google Scholar 

  115. Shi, Y. et al. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3, 568–574 (2008).

    Article  CAS  PubMed  Google Scholar 

  116. Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T. & Yamanaka, S. Generation of mouse induced pluripotent stem cells without viral vectors. Science 322, 949–953 (2008).

    Article  CAS  PubMed  Google Scholar 

  117. Patel, R. P. et al. Testicular microlithiasis and antisperm antibodies following testicular biopsy in boys with cryptorchidism. J. Urol. 174, 2008–2010 (2005).

    Article  PubMed  Google Scholar 

  118. Wyns, C. et al. Management of fertility preservation in prepubertal patients: 5 years' experience at the Catholic University of Louvain. Hum. Reprod. 26, 737–747 (2011).

    Article  CAS  PubMed  Google Scholar 

  119. Franck, P. et al. Testicular relapse after 13 years of complete remission of acute lymphoblastic leukemia. Urol. Int. 60, 239–241 (1998).

    Article  CAS  PubMed  Google Scholar 

  120. Quaranta, B. P., Halperin, E. C., Kurtzberg, J., Clough, R. & Martin, P. L. The incidence of testicular recurrence in boys with acute leukemia treated with total body and testicular irradiation and stem cell transplantation. Cancer 101, 845–850 (2004).

    Article  PubMed  Google Scholar 

  121. Fujita, K. et al. Isolation of germ cells from leukemia and lymphoma cells in a human in vitro model: potential clinical application for restoring human fertility after anticancer therapy. Cancer Res. 66, 11166–11171 (2006).

    Article  CAS  PubMed  Google Scholar 

  122. Geens, M. et al. The efficiency of magnetic-activated cell sorting and fluorescence-activated cell sorting in the decontamination of testicular cell suspensions in cancer patients. Hum. Reprod. 22, 733–742 (2007).

    Article  CAS  PubMed  Google Scholar 

  123. Hou, M. et al. Decontamination of leukemic cells and enrichment of germ cells from testicular samples from rats with Roser's T-cell leukemia by flow cytometric sorting. Reproduction 134, 767–779 (2007).

    Article  CAS  PubMed  Google Scholar 

  124. Sato, T. et al. In vitro production of fertile sperm from murine spermatogonial stem cell lines. Nat. Commun. 2, 472 (2011).

    Article  CAS  PubMed  Google Scholar 

  125. Boneva, R. S. & Folks, T. M. Xenotransplantation and risks of zoonotic infections. Ann. Med. 36, 504–517 (2004).

    Article  PubMed  Google Scholar 

  126. Fortunato, A. & Tosti, E. The impact of in vitro fertilization on health of the children: an update. Eur. J. Obstet. Gynecol. Reprod. Biol. 154, 125–129 (2011).

    Article  PubMed  Google Scholar 

  127. Goossens, E., Frederickx, V., de Block, G., van Steirteghem, A. & Tournaye, H. Evaluation of in vivo conception after testicular stem cell transplantation in a mouse model shows altered post-implantation development. Hum. Reprod. 21, 2057–2060 (2006).

    Article  PubMed  Google Scholar 

  128. Barton, S. E. et al. Population-based study of attitudes toward posthumous reproduction. Fertil. Steril. 98, 735.e5–740.e5 (2012).

    Article  Google Scholar 

  129. Ethics Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in cancer patients. Fertil. Steril. 83, 1622–1628 (2005).

  130. Schover, L. R., Brey, K., Lichtin, A., Lipshultz, L. I. & Jeha, S. Oncologists' attitudes and practices regarding banking sperm before cancer treatment. J. Clin. Oncol. 20, 1890–1897 (2002).

    Article  PubMed  Google Scholar 

  131. Schaefer, F., Marr, J., Seidel, C., Tilgen, W. & Scharer, K. Assessment of gonadal maturation by evaluation of spermaturia. Arch. Dis. Child. 65, 1205–1207 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Rutter, M. Normal psychosexual development. J. Child. Psychol. Psychiatry 11, 259–283 (1971).

    Article  Google Scholar 

  133. Kinsey, A. C., Pomeroy, W. R. & Martin, C. E. Sexual behavior in the human male. 1948. Am. J. Public Health. 93, 894–898 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Hagenas, I. et al. Clinical and biochemical correlates of successful semen collection for cryopreservation from 12-18-year-old patients: a single-center study of 86 adolescents. Hum. Reprod. 25, 2031–2038 (2010).

    Article  PubMed  Google Scholar 

  135. Bahadur, G. et al. Semen quality and cryopreservation in adolescent cancer patients. Hum. Reprod. 17, 3157–3161 (2002).

    Article  CAS  PubMed  Google Scholar 

  136. Kreuser, E. D., Hetzel, W. D., Hautmann, R. & Pfeiffer, E. F. Reproductive toxicity with and without LHRHA administration during adjuvant chemotherapy in patients with germ cell tumors. Horm. Metab. Res. 22, 494–498 (1990).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Supported by The Sidney Kimmel Center for Prostate and Urologic Cancers.

Author information

Authors and Affiliations

  1. Department of Surgery, Male Sexual and Reproductive Medicine Program, Memorial Sloan-Kettering Cancer Center, Urology Service, 1275 York Avenue, New York, 10065, NY, USA

    Darren J. Katz & John P. Mulhall

  2. Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10065, NY, USA

    Darren R. Feldman

  3. The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street and Civic Center Boulevard, Philadelphia, 19104-4399, PA, USA

    Thomas F. Kolon

Authors
  1. Darren J. Katz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas F. Kolon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Darren R. Feldman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John P. Mulhall
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors researched data for the article and contributed to the discussion of content. D. J. Katz, T. F. Kolon and J. P. Mulhall wrote the article and reviewed the manuscript before submission.

Corresponding author

Correspondence to John P. Mulhall.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Katz, D., Kolon, T., Feldman, D. et al. Fertility preservation strategies for male patients with cancer. Nat Rev Urol 10, 463–472 (2013). https://doi.org/10.1038/nrurol.2013.145

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2013.145

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer