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Oncofertility and the Male Cancer Patient

  • Oncofertility (JS Jeruss, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Oncofertility as a discipline plays an important, adjunctive role in the treatment of male patients with cancer. Despite recommendations by the American Society of Clinical Oncology, many clinicians managing malignancies in males fail to consistently incorporate fertility preservation as a routine aspect of health care. Providers involved in the treatment of oncologic patients should have an awareness of the impact of their prescribed treatments on reproductive potential, just as they would be knowledgeable of the potential deleterious effects of cancer therapies on vital organs such as the kidneys, lungs, and liver. Providers should then have a discussion with their patients regarding these potential adverse therapeutic effects or consult a fertility preservation specialist to discuss these matters and fertility preservation options with the patient. Cryopreservation of sperm remains an excellent option for male fertility preservation as it is readily available and results in storage of viable gametes for future use in the event of post treatment infertility. With the use of assisted reproductive techniques (ART), cryopreserved sperm may ultimately result in successful paternity, even in the setting of very low numbers of stored sperm. While sperm cryopreservation is usually an option for adolescent and adult males, fertility preservation in pre-pubertal males presents a more challenging problem. To date, no clinically proven methods are available to preserve fertility in these males. However, some centers do offer experimental protocols under the oversight of an IRB, such as testicular tissue cryopreservation in these males. The hope is that one day science will provide a mechanism for immature germ cells from the testicular tissue of these patients to be used in vivo or in vitro to facilitate reproduction. In closing, studies have shown that the patient’s regard for his provider is enhanced when the issue fertility preservation is raised. While oncologic care is often fraught with time constraints and acute medical concerns, fertility preservation care in the male can typically be administered quickly and without disruption of the overall plan of care.

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Abbreviations

ART:

Assisted reproductive techniques

ASCO:

American Society of Clinical Oncology

ASRM:

American Society for Reproductive Medicine

FSH:

Follicle stimulating hormone

GnRH:

Gonadotropic releasing hormone

Gy:

Gray

HCG:

Human chorionic gonadotropin

IVF:

In-vitro fertilization

ICSI:

Intracytoplasmic sperm injection

LH:

Luteinizing hormone

RPLND:

Retroperitoneal lymph node dissection

References and Recommended Readings

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, et al. SEER Cancer Statistics Review. National Cancer Institute, 1975–2008

  2. Bleyer A. Young adult oncology: the patients and their survival challenges. CA Cancer J Clin. 2007;57:242.

    Article  PubMed  Google Scholar 

  3. Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355:1572.

    Article  PubMed  CAS  Google Scholar 

  4. Schover LR. Motivation for parenthood after cancer: a review. Journal of the National Cancer Institute. Monographs, 2, 2005

  5. Ginsberg JP, Carlson CA, Lin K et al. An experimental protocol for fertility preservation in prepubertal boys recently diagnosed with cancer: a report of acceptability and safety. Human Reproduction. 2010;25:37. Outlines a current protocol for experimental testicular cryopreservation in prepubertal boys. It is noteworthy that current ASRM / ASCO recommendations stipulate that testicular tissue cryopreservation in prepubertal boys should only be performed in the setting of an IRB-approved experimental protocol such as this.

    Article  PubMed  CAS  Google Scholar 

  6. Mertens AC, Yasui Y, Neglia JP, et al. Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2001;19:3163.

    CAS  Google Scholar 

  7. Fertility preservation and reproduction in cancer patients. Fertility and Sterility. 2005;83:1622

    Google Scholar 

  8. Lee SJ, Schover LR, Partridge AH, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2006;24:2917.

    Article  Google Scholar 

  9. Green DM, Kawashima T, Stovall M, et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2010;28:332.

    Article  Google Scholar 

  10. Muller J, Skakkebaek NE. Quantification of germ cells and seminiferous tubules by stereological examination of testicles from 50 boys who suffered from sudden death. Int J Androl. 1983;6:143.

    Article  PubMed  CAS  Google Scholar 

  11. Clermont Y. The cycle of the seminiferous epithelium in man. Am J Anat. 1963;112:35.

    Article  PubMed  CAS  Google Scholar 

  12. Clermont Y. Spermatogenesis in man. A study of the spermatogonial population. Fertility and Sterility. 1966;17:705

    Google Scholar 

  13. Clermont Y. Renewal of spermatogonia in man. Am J Anat. 1966;118:509.

    Article  PubMed  CAS  Google Scholar 

  14. Jahnukainen K, Ehmcke J, Hou M et al. Testicular function and fertility preservation in male cancer patients. Best practice & research. Clinical Endocrinology & Metabolism. 2011;25:287. Review of the anatomy and physiology of pre-pubertal and pubertal males in relation to oncofertility.

    Article  Google Scholar 

  15. Ehmcke J, Hubner K, Scholer HR, et al. Spermatogonia: origin, physiology and prospects for conservation and manipulation of the male germ line. Reprod Fertil Dev. 2006;18:7.

    Article  PubMed  Google Scholar 

  16. Ehmcke J, Wistuba J, Schlatt S. Spermatogonial stem cells: questions, models and perspectives. Hum Reprod Updat. 2006;12:275.

    Article  CAS  Google Scholar 

  17. Meachem S, von Schonfeldt V, Schlatt S. Spermatogonia: stem cells with a great perspective. Reproduction. 2001;121:825.

    Article  PubMed  CAS  Google Scholar 

  18. Clermont Y, Leblond CP. Differentiation and renewal of spermatogonia in the monkey, Macacus rhesus. Am J Anat. 1959;104:237.

    Article  PubMed  CAS  Google Scholar 

  19. Clermont Y. Two classes of spermatogonial stem cells in the monkey (Cercopithecus aethiops). Am J Anat. 1969;126:57.

    Article  PubMed  CAS  Google Scholar 

  20. Simorangkir DR, Marshall GR, Ehmcke J, et al. Prepubertal expansion of dark and pale type A spermatogonia in the rhesus monkey (Macaca mulatta) results from proliferation during infantile and juvenile development in a relatively gonadotropin independent manner. Biol Reprod. 2005;73:1109.

    Article  PubMed  CAS  Google Scholar 

  21. van Alphen MM, van de Kant HJ, Davids JA, et al. Dose-response studies on the spermatogonial stem cells of the rhesus monkey (Macaca mulatta) after X irradiation. Radiat Res. 1989;119:443.

    Article  PubMed  Google Scholar 

  22. van Alphen MM, van de Kant HJ, de Rooij DG. Repopulation of the seminiferous epithelium of the rhesus monkey after X irradiation. Radiat Res. 1988;113:487.

    Article  PubMed  Google Scholar 

  23. Kanatsu-Shinohara M, Toyokuni S, Morimoto T, et al. Functional assessment of self-renewal activity of male germline stem cells following cytotoxic damage and serial transplantation. Biol Reprod. 2003;68:1801.

    Article  PubMed  CAS  Google Scholar 

  24. Ogawa T, Ohmura M, Yumura Y, et al. Expansion of murine spermatogonial stem cells through serial transplantation. Biol Reprod. 2003;68:316.

    Article  PubMed  CAS  Google Scholar 

  25. Dohle GR. Male infertility in cancer patients: Review of the literature. International journal of urology: official journal of the Japanese Urological Association. 2010;17:327. Provides a concise review of infertility in the male cancer patient.

    Article  Google Scholar 

  26. Sabanegh Jr ES, Ragheb AM. Male fertility after cancer. Urology. 2009;73:225.

    Article  PubMed  Google Scholar 

  27. Hallak J, Kolettis PN, Sekhon VS, et al. Cryopreservation of sperm from patients with leukemia: is it worth the effort? Cancer. 1999;85:1973.

    PubMed  CAS  Google Scholar 

  28. Berthelsen JG, Skakkebaek NE. Gonadal function in men with testis cancer. Fertil Steril. 1983;39:68.

    PubMed  CAS  Google Scholar 

  29. Rueffer U, Breuer K, Josting A, et al. Male gonadal dysfunction in patients with Hodgkin's disease prior to treatment. Annals of Oncology: Official Journal of the European Society for Medical Oncology / ESMO. 2001;12:1307.

    Article  CAS  Google Scholar 

  30. Schover LR, Brey K, Lichtin A, et al. Knowledge and experience regarding cancer, infertility, and sperm banking in younger male survivors. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2002;20:1880.

    Article  Google Scholar 

  31. Tempest HG, Ko E, Chan P, et al. Sperm aneuploidy frequencies analysed before and after chemotherapy in testicular cancer and Hodgkin's lymphoma patients. Hum Reprod. 2008;23:251.

    Article  PubMed  CAS  Google Scholar 

  32. Vigersky RA, Chapman RM, Berenberg J, et al. Testicular dysfunction in untreated Hodgkin's disease. Am J Med. 1982;73:482.

    Article  PubMed  CAS  Google Scholar 

  33. Petersen PM, Skakkebaek NE, Vistisen K, et al. Semen quality and reproductive hormones before orchiectomy in men with testicular cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 1999;17:941.

    CAS  Google Scholar 

  34. Foster RS, McNulty A, Rubin LR, et al. The fertility of patients with clinical stage I testis cancer managed by nerve sparing retroperitoneal lymph node dissection. J Urol. 1994;152:1139.

    PubMed  CAS  Google Scholar 

  35. Liguori G, Trombetta C, Bucci S et al. Semen quality before and after orchiectomy in men with testicular cancer. Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica / Associazione ricerche in urologia. 2008;80:99

  36. Herr HW, Bar-Chama N, O'Sullivan M, et al. Paternity in men with stage I testis tumors on surveillance. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 1998;16:733.

    CAS  Google Scholar 

  37. Sklar C. Reproductive physiology and treatment-related loss of sex hormone production. Medical and Pediatric Oncology. 1999;33:2.

    Article  PubMed  CAS  Google Scholar 

  38. van Alphen MM, van de Kant HJ, de Rooij DG. Depletion of the spermatogonia from the seminiferous epithelium of the rhesus monkey after X irradiation. Radiat Res. 1988;113:473.

    Article  PubMed  Google Scholar 

  39. de Rooij DG, van de Kant HJ, Dol R, et al. Long-term effects of irradiation before adulthood on reproductive function in the male rhesus monkey. Biol Reprod. 2002;66:486.

    Article  PubMed  Google Scholar 

  40. Meseguer M, Garrido N, Remohi J, et al. Testicular sperm extraction (TESE) and ICSI in patients with permanent azoospermia after chemotherapy. Hum Reprod. 2003;18:1281.

    Article  PubMed  CAS  Google Scholar 

  41. Kenney LB, Laufer MR, Grant FD, et al. High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer. 2001;91:613.

    Article  PubMed  CAS  Google Scholar 

  42. van Casteren NJ, van der Linden GH, Hakvoort-Cammel FG, et al. Effect of childhood cancer treatment on fertility markers in adult male long-term survivors. Pediatric Blood & Cancer. 2009;52:108.

    Article  Google Scholar 

  43. Centola GM, Keller JW, Henzler M, et al. Effect of low-dose testicular irradiation on sperm count and fertility in patients with testicular seminoma. J Androl. 1994;15:608.

    PubMed  CAS  Google Scholar 

  44. Ash P. The influence of radiation on fertility in man. Br J Radiol. 1980;53:271.

    Article  PubMed  CAS  Google Scholar 

  45. Pryant RM, Meistrich ML, Wilson G, et al. Long-term reduction in sperm count after chemotherapy with and without radiation for Non-Hodgkin's lymphomas. J Clin Oncol. 1993;11:239.

    Google Scholar 

  46. Howell S, Shalet S. Gonadal damage from chemotherapy and radiotherapy. Endocrinol Metab Clin N Am. 1998;27:927.

    Article  CAS  Google Scholar 

  47. Hart R. Preservation of fertility in adults and children diagnosed with cancer. BMJ. 2008;337:a2045.

    Article  PubMed  Google Scholar 

  48. Sandeman TF. The effects of x irradiation on male human fertility. Br J Radiol. 1966;39:901.

    Article  PubMed  CAS  Google Scholar 

  49. Hahn EW, Feingold SM, Simpson L, et al. Recovery from aspermia induced by low-dose radiation in seminoma patients. Cancer. 1982;50:337.

    Article  PubMed  CAS  Google Scholar 

  50. Anserini P, Chiodi S, Spinelli S et al. Semen analysis following allogeneic bone marrow transplantation. Additional data for evidence-based counselling. Bone Marrow Transplantation. 2002;30:447

    Google Scholar 

  51. Shalet SM, Tsatsoulis A, Whitehead E, et al. Vulnerability of the human Leydig cell to radiation damage is dependent upon age. J Endocrinol. 1989;120:161.

    Article  PubMed  CAS  Google Scholar 

  52. Brauner R, Czernichow P, Cramer P, et al. Leydig-cell function in children after direct testicular irradiation for acute lymphoblastic leukemia. N Engl J Med. 1983;309:25.

    Article  PubMed  CAS  Google Scholar 

  53. Sklar CA, Robison LL, Nesbit ME, et al. Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Children Cancer Study Group. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 1990;8:1981.

    CAS  Google Scholar 

  54. Sarafoglou K, Boulad F, Gillio A, et al. Gonadal function after bone marrow transplantation for acute leukemia during childhood. J Pediatr. 1997;130:210.

    Article  PubMed  CAS  Google Scholar 

  55. Waxman J. Chemotherapy and the adult gonad: a review. Journal of the Royal Society of Medicine. 1983;76:144.

    PubMed  CAS  Google Scholar 

  56. Waxman J, Terry Y, Rees LH, et al. Gonadal function in men treated for acute leukaemia. British Medical Journal. 1983;287:1093.

    Article  PubMed  CAS  Google Scholar 

  57. Waxman JH, Terry YA, Wrigley PF, et al. Gonadal function in Hodgkin's disease: long-term follow-up of chemotherapy. British Medical Journal. 1982;285:1612.

    Article  PubMed  CAS  Google Scholar 

  58. Nurmio M, Keros V, Lahteenmaki P, et al. Effect of childhood acute lymphoblastic leukemia therapy on spermatogonia populations and future fertility. J Clin Endocrinol Metab. 2009;94:2119.

    Article  PubMed  CAS  Google Scholar 

  59. Kreuser ED, Xiros N, Hetzel WD, et al. Reproductive and endocrine gonadal capacity in patients treated with COPP chemotherapy for Hodgkin's disease. J Cancer Res Clin Oncol. 1987;113:260.

    Article  PubMed  CAS  Google Scholar 

  60. Meistrich ML, Wilson G, Brown BW, et al. Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer. 1992;70:2703.

    Article  PubMed  CAS  Google Scholar 

  61. Bokemeyer C, Schmoll HJ, van Rhee J, et al. Long-term gonadal toxicity after therapy for Hodgkin's and non-Hodgkin's lymphoma. Ann Hematol. 1994;68:105.

    Article  PubMed  CAS  Google Scholar 

  62. Ridola V, Fawaz O, Aubier F, et al. Testicular function of survivors of childhood cancer: a comparative study between ifosfamide- and cyclophosphamide-based regimens. Eur J Cancer. 2009;45:814.

    Article  PubMed  CAS  Google Scholar 

  63. Lampe H, Horwich A, Norman A, et al. Fertility after chemotherapy for testicular germ cell cancers. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 1997;15:239.

    CAS  Google Scholar 

  64. Pectasides D, Pectasides M, Farmakis D, et al. Testicular function in patients with testicular cancer treated with bleomycin-etoposide-carboplatin (BEC(90)) combination chemotherapy. Eur Urol. 2004;45:187.

    Article  PubMed  CAS  Google Scholar 

  65. Nalesnik JG, Sabanegh Jr ES, Eng TY, et al. Fertility in men after treatment for stage 1 and 2A seminoma. Am J Clin Oncol. 2004;27:584.

    Article  PubMed  Google Scholar 

  66. Fossa SD, Horwich A, Russell JM et al. Optimal planning target volume for stage I testicular seminoma: A Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 1999;17:1146

  67. Jacobsen KD, Olsen DR, Fossa K, et al. External beam abdominal radiotherapy in patients with seminoma stage I: field type, testicular dose, and spermatogenesis. Int J Radiat Oncol Biol Phys. 1997;38:95.

    Article  PubMed  CAS  Google Scholar 

  68. Littley MD, Shalet SM, Beardwell CG, et al. Radiation-induced hypopituitarism is dose-dependent. Clin Endocrinol. 1989;31:363.

    Article  CAS  Google Scholar 

  69. Muller J, Sonksen J, Sommer P, et al. Cryopreservation of semen from pubertal boys with cancer. Medical and Pediatric Oncology. 2000;34:191.

    Article  PubMed  CAS  Google Scholar 

  70. Hovav Y, Dan-Goor M, Yaffe H, et al. Electroejaculation before chemotherapy in adolescents and young men with cancer. Fertil Steril. 2001;75:811.

    Article  PubMed  CAS  Google Scholar 

  71. Hourvitz A, Goldschlag DE, Davis OK, et al. Intracytoplasmic sperm injection (ICSI) using cryopreserved sperm from men with malignant neoplasm yields high pregnancy rates. Fertil Steril. 2008;90:557.

    Article  PubMed  Google Scholar 

  72. Hallak J, Hendin BN, Thomas Jr AJ, et al. Investigation of fertilizing capacity of cryopreserved spermatozoa from patients with cancer. J Urol. 1998;159:1217.

    Article  PubMed  CAS  Google Scholar 

  73. Li FP, Fine W, Jaffe N, et al. Offspring of patients treated for cancer in childhood. Journal of the National Cancer Institute. 1979;62:1193.

    PubMed  CAS  Google Scholar 

  74. Byrne J, Rasmussen SA, Steinhorn SC, et al. Genetic disease in offspring of long-term survivors of childhood and adolescent cancer. Am J Hum Genet. 1998;62:45.

    Article  PubMed  CAS  Google Scholar 

  75. van Casteren NJ, van Santbrink EJ, van Inzen W, et al. Use rate and assisted reproduction technologies outcome of cryopreserved semen from 629 cancer patients. Fertil Steril. 2008;90:2245.

    Article  PubMed  Google Scholar 

  76. Meseguer M, Molina N, Garcia-Velasco JA, et al. Sperm cryopreservation in oncological patients: a 14-year follow-up study. Fertil Steril. 2006;85:640.

    Article  PubMed  Google Scholar 

  77. Zorn B, Virant-Klun I, Stanovnik M, et al. Intracytoplasmic sperm injection by testicular sperm in patients with aspermia or azoospermia after cancer treatment. Int J Androl. 2006;29:521.

    Article  PubMed  CAS  Google Scholar 

  78. Schover LR, Brey K, Lichtin A, et al. Oncologists' attitudes and practices regarding banking sperm before cancer treatment. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2002;20:1890.

    Article  Google Scholar 

  79. Goodwin T, Elizabeth Oosterhuis B, Kiernan M, et al. Attitudes and practices of pediatric oncology providers regarding fertility issues. Pediatric Blood & Cancer. 2007;48:80.

    Article  Google Scholar 

  80. Quinn GP, Vadaparampil ST, Gwede CK, et al. Discussion of fertility preservation with newly diagnosed patients: oncologists' views. Journal of Cancer Survivorship: Research and Practice. 2007;1:146.

    Article  Google Scholar 

  81. Quinn GP, Vadaparampil ST, Lee JH et al. Physician referral for fertility preservation in oncology patients: a national study of practice behaviors. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2009;27:5952. Recent reviews of referral patterns among oncologists to reproductive specialists. These articles highlight the ongoing impediments to routine implementation of fertility preservation in oncology practices.

    Article  Google Scholar 

  82. Forman EJ, Anders CK, Behera MA. A nationwide survey of oncologists regarding treatment-related infertility and fertility preservation in female cancer patients. Fertility and Sterility. 2010;94:1652. Recent reviews of referral patterns among oncologists to reproductive specialists. These articles highlight the ongoing impediments to routine implementation of fertility preservation in oncology practices.

    Article  PubMed  Google Scholar 

  83. Sheth KR, Sharma V, Helfand BT, Cashy J, Smith K, Hedges JC, Kohler TS, Woodruff TK, Brannigan RE. Improved fertility preservation care for male patients with cancer after establishment of a formalized oncofertility program. J Urol. 2012;187:979.

    Article  PubMed  Google Scholar 

  84. Rieker PP, Fitzgerald EM, Kalish LA. Adaptive behavioral responses to potential infertility among survivors of testis cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 1990;8:347.

    CAS  Google Scholar 

  85. Green D, Galvin H, Horne B. The psycho-social impact of infertility on young male cancer survivors: a qualitative investigation. Psycho-Oncology. 2003;12:141.

    Article  PubMed  Google Scholar 

  86. Gurevich M, Bishop S, Bower J, et al. (Dis)embodying gender and sexuality in testicular cancer. Social Science & Medicine. 2004;58:1597.

    Article  Google Scholar 

  87. Saito K, Suzuki K, Iwasaki A, et al. Sperm cryopreservation before cancer chemotherapy helps in the emotional battle against cancer. Cancer. 2005;104:521.

    Article  PubMed  Google Scholar 

  88. The Ethics Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in cancer patients. Fertility and Sterility. 2005;83:1622.

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Authors and Affiliations

  1. Department of Urology, Mayo Clinic, Rochester, MN, USA

    Landon W. Trost MD

  2. Department of Urology, Northwestern University, Feinberg School of Medicine, 303 E Chicago Ave, Tarry 16-703, Chicago, IL, 60611, USA

    Robert E. Brannigan MD

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Correspondence to Robert E. Brannigan MD.

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Trost, L.W., Brannigan, R.E. Oncofertility and the Male Cancer Patient. Curr. Treat. Options in Oncol. 13, 146–160 (2012). https://doi.org/10.1007/s11864-012-0191-7

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