European Journal of Pediatrics

, Volume 170, Issue 6, pp 703–708

Educational paper

The effect of cancer therapy on fertility, the assessment of fertility and fertility preservation options for pediatric patients


Over the past several decades, pediatric oncologists have seen the growth in the number of patients surviving their cancer. This is in large part due to the use of multimodal therapy including chemotherapy, surgery, and radiotherapy. As the number of survivors of pediatric cancer continues to grow, however, we need to begin to focus on improving the quality of the lives that are being saved. Unfortunately, many regimens used today to cure pediatric cancer patients are gonadotoxic. Therefore, many of our survivors must contend with infertility. It is critical that pediatric oncologists consider the likelihood of gonadotoxicity prior to beginning therapy in this patient population in order to counsel patients and their families properly in order to potentially offer fertility preservation options. Conclusion: Infertility is a critical quality of life issue for pediatric cancer survivors and their families. Fertility preservation techniques need to continue to be studied and developed in order to lessen the likelihood that future cancer survivors will be infertile. This review outlines the risk for infertility, provides an assessment of the survivors reproductive functioning, and summarizes the currently available methods of preserving fertility in pediatric cancer survivors.


Fertility preservation Gonadotoxicity Infertility Pediatric cancer survivor Pediatric oncology 


  1. 1.
    Ahmed SR, Shalet SM, Campbell RH, Deakin DP (1983) Primary gonadal damage following treatment of brain tumors in childhood. J Pediatr 103:562–565PubMedCrossRefGoogle Scholar
  2. 2.
    Ash P (1980) The influence of radiation on fertility in man. Br J Radiol 53(628):271–278PubMedCrossRefGoogle Scholar
  3. 3.
    Bahadur G, Chatterjee R, Ralph D (2000) Testicular tissue cryopreservation in boys. Ethical and legal issues: case report. Hum Reprod 15(6):1416–1420PubMedCrossRefGoogle Scholar
  4. 4.
    Bath LE, Critchley HO, Chambers SE et al (1999) Ovarian and uterine characteristics after total body irradiation in childhood and adolescence: response to sex steroid replacement. Br J Obstet Gynaecol 106(12):1265–1272PubMedCrossRefGoogle Scholar
  5. 5.
    Brinster RL (2007) Male germline stem cells: from mice to men. Science 316(5823):404–405PubMedCrossRefGoogle Scholar
  6. 6.
    Brinster RL, Avarbock MR (1994) Germline transmission of donor haplotype following spermatogonial transplantation. Proc Natl Acad Sci USA 91(24):11303–11307PubMedCrossRefGoogle Scholar
  7. 7.
    Brinster RL, Nagano M (1998) Spermatogonial stem cell transplantation, cryopreservation and culture. Semin Cell Dev Biol 9(4):401–409PubMedCrossRefGoogle Scholar
  8. 8.
    Brinster RL, Zimmermann JW (1994) Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci USA 91(24):11298–11302PubMedCrossRefGoogle Scholar
  9. 9.
    Chiarelli AM, Marrett LD, Darlington G (1999) Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964–1988 in Ontario, Canada. Am J Epidemiol 150(3):245–254PubMedGoogle Scholar
  10. 10.
    Chung K, Irani J, Knee G et al (2004) Sperm cryopreservation for male patients with cancer: an epidemiological analysis at the University of Pennsylvania. Eur J Obstet Gynecol Reprod Biol 113(Suppl 1):S7–11PubMedCrossRefGoogle Scholar
  11. 11.
    da Cunha MF, Meistrich ML, Fuller LM (1984) Recovery of spermatogenesis after treatment for Hodgkin’s disease: limiting dose of MOPP chemotherapy. J Clin Oncol 2:571–577PubMedGoogle Scholar
  12. 12.
    Dolmans MM, Marinescu C, Saussoy P et al (2010) Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood 116(16):2908–2914. doi:10.1182/01-265751 PubMedCrossRefGoogle Scholar
  13. 13.
    Feldschuh J, Brassel J, Durso N, Levine A (2005) Successful sperm storage for 28 years. Fertil Steril 84(4):1017PubMedCrossRefGoogle Scholar
  14. 14.
    Ginsberg JP, Ogle SK, Tuchman LK et al (2008) Sperm banking for adolescent and young adult cancer patients: sperm quality, patient, and parent perspectives. Pediatr Blood Cancer 50(3):594–598PubMedCrossRefGoogle Scholar
  15. 15.
    Ginsberg JP, Carlson CA, Lin K et al (2009) An experimental protocol for fertility preservation in prepubertal boys recently diagnosed with cancer: a report of acceptability and safety. Hum Reprod 25(1):37–41PubMedCrossRefGoogle Scholar
  16. 16.
    Green DM, Kawashima T, Stovall M et al (2009) Fertility of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 27(16):2677–2685PubMedCrossRefGoogle Scholar
  17. 17.
    Green DM, Sklar CA, Boice JD Jr et al (2009) Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol 27(14):2374–2381PubMedCrossRefGoogle Scholar
  18. 18.
    Green DM, Kawashima T, Stovall M et al (2010) Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 28(2):332–339PubMedCrossRefGoogle Scholar
  19. 19.
    Hewitt M, Weiner SL, Simone JV (eds) (2003) Childhood cancer survivorship: improving care and quality of life. National Academy Press, Washington, DCGoogle Scholar
  20. 20.
    Hobbie WL, Ginsberg JP, Ogle SK et al (2005) Fertility in males treated for Hodgkins disease with copp/abv hybrid. Pediatr Blood Cancer 44(2):193–196PubMedCrossRefGoogle Scholar
  21. 21.
    Howell S, Shalet S (1998) Gonadal damage from chemotherapy and radiotherapy. Endocrinol Metab Clin North Am 27(4):927–943PubMedCrossRefGoogle Scholar
  22. 22.
    Jeruss JS, Woodruff TK (2009) Preservation of fertility in patients with cancer. N Engl J Med 360(9):902–911PubMedCrossRefGoogle Scholar
  23. 23.
    Johnston RJ, Wallace WH (2009) Normal ovarian function and assessment of ovarian reserve in the survivor of childhood cancer. Pediatr Blood Cancer 53(2):296–302PubMedCrossRefGoogle Scholar
  24. 24.
    Lass A, Akagbosu F, Abusheikha N et al (1998) A programme of semen cryopreservation for patients with malignant disease in a tertiary infertility centre: lessons from 8 years’ experience. Hum Reprod 13(11):3256–3261PubMedCrossRefGoogle Scholar
  25. 25.
    Levine J, Canada A, Stern CJ (2010) Fertility preservation in adolescents and young adults with cancer. J Clin Oncol 28(32):4831–4841. doi:10.1200/JCO.2009.22.8312 PubMedCrossRefGoogle Scholar
  26. 26.
    Longhi A, Macchiagodena M, Vitali G, Bacci G (2003) Fertility in male patients treated with neoadjuvant chemotherapy for osteosarcoma. J Pediatr Hematol Oncol 25(4):292–296PubMedCrossRefGoogle Scholar
  27. 27.
    Lushbaugh CC, Casarett GW (1976) The effects of gonadal irradiation in clinical radiation therapy: a review. Cancer 37(2 Suppl):1111–1125PubMedCrossRefGoogle Scholar
  28. 28.
    Mackie EJ, Radford M, Shalet SM (1996) Gonadal function following chemotherapy for childhood Hodgkin’s disease. Med Pediatr Oncol 27(2):74–78PubMedCrossRefGoogle Scholar
  29. 29.
    Meirow D (1999) Ovarian injury and modern options to preserve fertility in female cancer patients treated with high dose radio-chemotherapy for hemato-oncological neoplasias and other cancers. Leuk Lymphoma 33(1–2):65–76PubMedGoogle Scholar
  30. 30.
    Meirow D, Nugent D (2001) The effects of radiotherapy and chemotherapy on female reproduction. Hum Reprod Update 7(6):535–543PubMedCrossRefGoogle Scholar
  31. 31.
    Meistrich ML (2009) Male gonadal toxicity. Pediatr Blood Cancer 53(2):261–266PubMedCrossRefGoogle Scholar
  32. 32.
    Menon S, Rives N, Mousset-Simeon N et al (2009) Fertility preservation in adolescent males: experience over 22 years at Rouen University Hospital. Hum Reprod 24(1):37–44PubMedCrossRefGoogle Scholar
  33. 33.
    Ogilvy-Stuart AL, Clark DJ, Wallace WH et al (1992) Endocrine deficit after fractionated total body irradiation. Arch Dis Child 67(9):1107–1110PubMedCrossRefGoogle Scholar
  34. 34.
    Oktay K, Cil AP, Bang H (2006) Efficiency of oocyte cryopreservation: a meta-analysis. Fertil Steril 86(1):70–80PubMedCrossRefGoogle Scholar
  35. 35.
    Papadakis V, Vlachopapadopoulou E, Van Syckle K et al (1999) Gonadal function in young patients successfully treated for Hodgkin disease. Med Pediatr Oncol 32(5):366–372PubMedCrossRefGoogle Scholar
  36. 36.
    Poirot C, Vacher-Lavenu MC, Helardot P et al (2002) Human ovarian tissue cryopreservation: indications and feasibility. Hum Reprod 17(6):1447–1452PubMedCrossRefGoogle Scholar
  37. 37.
    Revel A, Revel-Vilk S (2010) Fertility preservation in young cancer patients. J Hum Reprod Sci 3(1):2–7PubMedCrossRefGoogle Scholar
  38. 38.
    Sanchez-Serrano M, Crespo J, Mirabet V et al (2010) Twins born after transplantation of ovarian cortical tissue and oocyte vitrification. Fertil Steril 93(1):268 e11–e13Google Scholar
  39. 39.
    Shalet SM, Tsatsoulis A, Whitehead E, Read G (1989) Vulnerability of the human leydig cell to radiation damage is dependent upon age. J Endocrinol 120(1):161–165PubMedCrossRefGoogle Scholar
  40. 40.
    Sherins RJ, Olweny CL, Ziegler JL (1978) Gynaecomastia and gonadal dysfunction in adolescent boys treated with combination chemotherapy for Hodgkins disease. N Engl J Med 299:12–16PubMedCrossRefGoogle Scholar
  41. 41.
    Sklar CA, Robison LL, Nesbit ME et al (1990) Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the children cancer study group. J Clin Oncol 8(12):1981–1987PubMedGoogle Scholar
  42. 42.
    Smitz J, Dolmans MM, Donnez J et al (2010) Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: implications for fertility preservation. Hum Reprod Update 16(4):395–414PubMedCrossRefGoogle Scholar
  43. 43.
    Steiner AZ (2009) Clinical implications of ovarian reserve testing. Obstet Gynecol Surv 64(2):120–128PubMedCrossRefGoogle Scholar
  44. 44.
    van Beek RD, Smit M, van den Heuvel-Eibrink MM et al (2007) Inhibin b is superior to FSH as a serum marker for spermatogenesis in men treated for Hodgkin’s lymphoma with chemotherapy during childhood. Hum Reprod 22(12):3215–3222PubMedCrossRefGoogle Scholar
  45. 45.
    van Casteren NJ, van der Linden GH, Hakvoort-Cammel FG et al (2009) Effect of childhood cancer treatment on fertility markers in adult male long-term survivors. Pediatr Blood Cancer 52(1):108–112PubMedCrossRefGoogle Scholar
  46. 46.
    van Rooij IA, Broekmans FJ, Scheffer GJ et al (2005) Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study. Fertil Steril 83(4):979–987PubMedCrossRefGoogle Scholar
  47. 47.
    Wallace WH, Shalet SM, Hendry JH et al (1989) Ovarian failure following abdominal irradiation in childhood: the radiosensitivity of the human oocyte. Br J Radiol 62(743):995–998PubMedCrossRefGoogle Scholar
  48. 48.
    Wallace WH, Anderson RA, Irvine DS (2005) Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol 6(4):209–218PubMedCrossRefGoogle Scholar
  49. 49.
    Wennerholm UB, Soderstrom-Anttila V, Bergh C et al (2009) Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data. Hum Reprod 24(9):2158–2172PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Division of Oncology, Center for Childhood Cancer ResearchDepartment of Pediatrics, University of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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