Evaluation of ovarian and testicular tissue cryopreservation in children undergoing gonadotoxic therapies

  • Samir N. Babayev
  • Erol Arslan
  • Stanley Kogan
  • Fred Moy
  • Kutluk OktayEmail author
Fertility Preservation



Ovarian and testicular tissue cryopreservation are the only fertility preservation options for sexually immature individuals. Because of their experimental nature, it is important to determine safety and possible bundling with other medicallyindicated procedures.

Study design

Prospective observational.


Cryopreservation indications included cancer in 75 % of females and 50 % of males, while non-cancer indications included various hematological conditions. Similar numbers of females (12/28) and males (3/9) underwent prior chemotherapy. Females underwent laparoscopic (27/28) or robotic (1/28) approaches while incisional biopsy was used in males. Bundling of ovarian and testicular harvesting with other medicallyindicated procedures was performed in 42 % and 22 %, respectively. The operative time inclusive of bundled procedures was similar (1.6 ± 0.1 vs. 0.9 ± 0.3 h) but the discharge time was significantly longer for females than males (10.4 ± 0.6 vs. 4.6 ± 0.6 h, p < 0.05) due to frequent bundling of medically-indicated procedures in females. All procedures were successfully completed without complications or significant blood loss.


Pediatric gonadal tissue cryopreservation can be combined with other medically-indicated procedures to minimize the potential inconvenience, additional anesthetic risks, and costs.


Hematology/oncology Children Cryopreservation Fertility preservation 



This study was supported by the National Institute of Child Health and Development as well as National Cancer Institute, National Institute of Health (HD 053112 and R21HD061259) to KO.


  1. 1.
    Akar M, Oktay K. Restoration of ovarian endocrine function by ovarian transplantation. Trends in endocrinology and metabolism: TEM 2005;16(8):374–80. doi: 10.1016/j.tem.2005.06.011
  2. 2.
    AmericanCancerSociety. Cancer Facts & Figures 2010. American Cancer Society; 2010.Google Scholar
  3. 3.
    Andersen CY, Rosendahl M, Byskov AG, Loft A, Ottosen C, Dueholm M, et al. Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue. Hum Reprod. 2008;23(10):2266–72. doi: 10.1093/humrep/den244.PubMedCrossRefGoogle Scholar
  4. 4.
    Behringer K, Thielen I, Mueller H, Goergen H, Eibl AD, Rosenbrock J, Halbsguth T, Eichenauer DA, Fuchs M, Reiners KS, Renno JH, van der Ven K, Kuehr M, von Wolff M, Diehl V, Engert A, Borchmann P. Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial. Annals of oncology : official journal of the European Society for Medical Oncology/ESMO 2012;23(7):1818–25. doi: 10.1093/annonc/mdr575
  5. 5.
    Byrne J, Fears TR, Mills JL, Zeltzer LK, Sklar C, Meadows AT, et al. Fertility of long-term male survivors of acute lymphoblastic leukemia diagnosed during childhood. Pediatr Blood Canc. 2004;42(4):364–72. doi: 10.1002/pbc.10449.CrossRefGoogle Scholar
  6. 6.
    Byrne J, Fears TR, Mills JL, Zeltzer LK, Sklar C, Nicholson HS, et al. Fertility in women treated with cranial radiotherapy for childhood acute lymphoblastic leukemia. Pediatr Blood Canc. 2004;42(7):589–97. doi: 10.1002/pbc.20033.CrossRefGoogle Scholar
  7. 7.
    Chow EJ, Friedman DL, Yasui Y, Whitton JA, Stovall M, Robison LL, et al. Timing of menarche among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Pediatr Blood Canc. 2008;50(4):854–8. doi: 10.1002/pbc.21316.CrossRefGoogle Scholar
  8. 8.
    Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354(17):1813–26. doi: 10.1056/NEJMra052638.PubMedCrossRefGoogle Scholar
  9. 9.
    Couto-Silva AC, Trivin C, Thibaud E, Esperou H, Michon J, Brauner R. Factors affecting gonadal function after bone marrow transplantation during childhood. Bone marrow transplant. 2001;28(1):67–75. doi: 10.1038/sj.bmt.1703089.PubMedCrossRefGoogle Scholar
  10. 10.
    Demeestere I, Simon P, Emiliani S, Delbaere A, Englert Y. Fertility preservation: successful transplantation of cryopreserved ovarian tissue in a young patient previously treated for Hodgkin’s disease. Oncologist. 2007;12(12):1437–42. doi: 10.1634/theoncologist.12-12-1437.PubMedCrossRefGoogle Scholar
  11. 11.
    Demeestere I, Simon P, Englert Y, Delbaere A. Preliminary experience of ovarian tissue cryopreservation procedure: alternatives, perspectives and feasibility. Reproductive Biomedicine Online. 2003;7(5):572–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Demirtas E, Elizur SE, Holzer H, Gidoni Y, Son WY, Chian RC, et al. Immature oocyte retrieval in the luteal phase to preserve fertility in cancer patients. Reproductive Biomedicine Online. 2008;17(4):520–3.PubMedCrossRefGoogle Scholar
  13. 13.
    Dobrinski I. De novo morphogenesis of functional testis tissue after ectopic transplantation of isolated cells. Organogenesis. 2007;3(2):79–82.PubMedCrossRefGoogle Scholar
  14. 14.
    Dolmans MM, Marinescu C, Saussoy P, Van Langendonckt A, Amorim C, Donnez J. Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood. 2010;116(16):2908–14. doi: 10.1182/blood-2010-01-265751.PubMedCrossRefGoogle Scholar
  15. 15.
    Fain-Kahn V, Poirot C, Uzan C, Prades M, Gouy S, Genestie C, et al. Feasibility of ovarian cryopreservation in borderline ovarian tumours. Hum Reprod. 2009;24(4):850–5. doi: 10.1093/humrep/den459.PubMedCrossRefGoogle Scholar
  16. 16.
    Feigin E, Abir R, Fisch B, Kravarusic D, Steinberg R, Nitke S, et al. Laparoscopic ovarian tissue preservation in young patients at risk for ovarian failure as a result of chemotherapy/irradiation for primary malignancy. J Pediatr Surg. 2007;42(5):862–4. doi: 10.1016/j.jpedsurg.2006.12.041.PubMedCrossRefGoogle Scholar
  17. 17.
    Ginsberg JP, Carlson CA, Lin K, Hobbie WL, Wigo E, Wu X, et al. An experimental protocol for fertility preservation in prepubertal boys recently diagnosed with cancer: a report of acceptability and safety. Hum Reprod. 2010;25(1):37–41. doi: 10.1093/humrep/dep371.PubMedCrossRefGoogle Scholar
  18. 18.
    Goossens E, Frederickx V, De Block G, Van Steirteghem AC, Tournaye H. Reproductive capacity of sperm obtained after germ cell transplantation in a mouse model. Hum Reprod. 2003;18(9):1874–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Green DM, Sklar CA, Boice Jr JD, Mulvihill JJ, Whitton JA, Stovall M, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2009;27(14):2374–81. doi: 10.1200/JCO.2008.21.1839.CrossRefGoogle Scholar
  20. 20.
    Lawrenz B, Rothmund R, Neunhoeffer E, Huebner S, Henes M. Fertility preservation in prepubertal girls prior to chemotherapy and radiotherapy-review of the literature. J Pediatr Adolesc Gynecol. 2012;25(5):284–8. doi: 10.1016/j.jpag.2011.05.009.PubMedCrossRefGoogle Scholar
  21. 21.
    Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, Beck LN, Brennan LV, Oktay K, American Society of Clinical O. 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(18):2917–31. doi: 10.1200/JCO.2006.06.5888 Google Scholar
  22. 22.
    Locatelli F, Giorgiani G, Pession A, Bozzola M. Late effects in children after bone marrow transplantation: a review. Haematologica. 1993;78(5):319–28.PubMedGoogle Scholar
  23. 23.
    Madanat LM, Malila N, Dyba T, Hakulinen T, Sankila R, Boice Jr JD, et al. Probability of parenthood after early onset cancer: a population-based study. Int J Canc J Int Canc. 2008;123(12):2891–8. doi: 10.1002/ijc.23842.CrossRefGoogle Scholar
  24. 24.
    Meirow D. Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol. 2000;169(1–2):123–31.PubMedCrossRefGoogle Scholar
  25. 25.
    Meirow D, Levron J, Eldar-Geva T, Hardan I, Fridman E, Zalel Y, et al. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med. 2005;353(3):318–21. doi: 10.1056/NEJMc055237.PubMedCrossRefGoogle Scholar
  26. 26.
    Oktay K, Buyuk E, Veeck L, Zaninovic N, Xu K, Takeuchi T, et al. Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;363(9412):837–40. doi: 10.1016/S0140-6736(04)15728-0.PubMedCrossRefGoogle Scholar
  27. 27.
    Oktay K, Economos K, Kan M, Rucinski J, Veeck L, Rosenwaks Z. Endocrine function and oocyte retrieval after autologous transplantation of ovarian cortical strips to the forearm. JAMA. 2001;286(12):1490–3.PubMedCrossRefGoogle Scholar
  28. 28.
    Oktay K, Karlikaya G. Ovarian function after transplantation of frozen, banked autologous ovarian tissue. N Engl J Med. 2000;342(25):1919. doi: 10.1056/NEJM200006223422516.PubMedCrossRefGoogle Scholar
  29. 29.
    Oktay K, Karlikaya GG, Aydin BA. Ovarian cryopreservation and transplantation: basic aspects. Mol Cell Endocrinol. 2000;169(1–2):105–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Oktay K, Nugent D, Newton H, Salha O, Chatterjee P, Gosden RG. Isolation and characterization of primordial follicles from fresh and cryopreserved human ovarian tissue. Fertil Steril. 1997;67(3):481–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Oktay K, Oktem O. Ovarian cryopreservation and transplantation for fertility preservation for medical indications: report of an ongoing experience. Fertil Steril. 2010;93(3):762–8. doi: 10.1016/j.fertnstert.2008.10.006.PubMedCrossRefGoogle Scholar
  32. 32.
    Oktay K, Rodriguez-Wallberg KA, Sahin G. Fertility preservation by ovarian stimulation and oocyte cryopreservation in a 14-year-old adolescent with Turner syndrome mosaicism and impending premature ovarian failure. Fertility and sterility. 2010;94(2):753.e715–759. doi: 10.1016/j.fertnstert.2010.01.044.CrossRefGoogle Scholar
  33. 33.
    Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer. 2007;110(10):2222–9. doi: 10.1002/cncr.23071.PubMedCrossRefGoogle Scholar
  34. 34.
    Poirot C, Vacher-Lavenu MC, Helardot P, Guibert J, Brugieres L, Jouannet P. Human ovarian tissue cryopreservation: indications and feasibility. Hum Reprod. 2002;17(6):1447–52.PubMedCrossRefGoogle Scholar
  35. 35.
    Quinn GP, Murphy D, Knapp C, Stearsman DK, Bradley-Klug KL, Sawczyn K, Clayman ML. Who decides? Decision making and fertility preservation in teens with cancer: a review of the literature. The Journal of adolescent health: official publication of the Society for Adolescent Medicine 2011;49(4):337–46. doi: 10.1016/j.jadohealth.2011.01.005
  36. 36.
    Rodriguez-Wallberg KA, Oktay K. Fertility preservation medicine: options for young adults and children with cancer. J Pediatr Hematol Oncol. 2010;32(5):390–6. doi: 10.1097/MPH.0b013e3181dce339.PubMedGoogle Scholar
  37. 37.
    Rodriguez-Wallberg KA, Oktay K. Options on fertility preservation in female cancer patients. Canc Treat Rev. 2012;38(5):354–61. doi: 10.1016/j.ctrv.2011.10.002.CrossRefGoogle Scholar
  38. 38.
    Sato T, Katagiri K, Yokonishi T, Kubota Y, Inoue K, Ogonuki N, et al. In vitro production of fertile sperm from murine spermatogonial stem cell lines. Nat Comm. 2011;2:472. doi: 10.1038/ncomms1478.CrossRefGoogle Scholar
  39. 39.
    Schmidt KT, Larsen EC, Andersen CY, Andersen AN. Risk of ovarian failure and fertility preserving methods in girls and adolescents with a malignant disease. BJOG: Int J Obstet Gynecol. 2010;117(2):163–74. doi: 10.1111/j.1471-0528.2009.02408.x.CrossRefGoogle Scholar
  40. 40.
    Shinohara T, Inoue K, Ogonuki N, Kanatsu-Shinohara M, Miki H, Nakata K, et al. Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination. Hum Reprod. 2002;17(12):3039–45.PubMedCrossRefGoogle Scholar
  41. 41.
    Sklar CA, Mertens AC, Mitby P, Whitton J, Stovall M, Kasper C, et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Canc Inst. 2006;98(13):890–6. doi: 10.1093/jnci/djj243.CrossRefGoogle Scholar
  42. 42.
    Soleimani R, Heytens E, Darzynkiewicz Z, Oktay K. Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise. Aging. 2011;3(8):782–93.PubMedGoogle Scholar
  43. 43.
    Song Y, Silversides FG. Production of offspring from cryopreserved chicken testicular tissue. Poult Sci. 2007;86(7):1390–6.PubMedGoogle Scholar
  44. 44.
    Sonmezer M, Oktay K. Fertility preservation in female patients. Hum Reprod Updat. 2004;10(3):251–66. doi: 10.1093/humupd/dmh021.CrossRefGoogle Scholar
  45. 45.
    Telfer EE, McLaughlin M. In vitro development of ovarian follicles. Semin Reprod Med. 2011;29(1):15–23. doi: 10.1055/s-0030-1268700.PubMedCrossRefGoogle Scholar
  46. 46.
    van den Berg H, Repping S, van der Veen F. Parental desire and acceptability of spermatogonial stem cell cryopreservation in boys with cancer. Hum Reprod. 2007;22(2):594–7. doi: 10.1093/humrep/del375.PubMedCrossRefGoogle Scholar
  47. 47.
    Van Saen D, Goossens E, De Block G, Tournaye H. Regeneration of spermatogenesis by grafting testicular tissue or injecting testicular cells into the testes of sterile mice: a comparative study. Fertil Steril. 2009;91(5 Suppl):2264–72. doi: 10.1016/j.fertnstert.2008.02.100.PubMedCrossRefGoogle Scholar
  48. 48.
    Wallace WH, Shalet SM, Crowne EC, Morris-Jones PH, Gattamaneni HR. Ovarian failure following abdominal irradiation in childhood: natural history and prognosis. Clin Oncol. 1989;1(2):75–9.CrossRefGoogle Scholar
  49. 49.
    Wenzel L, Dogan-Ates A, Habbal R, Berkowitz R, Goldstein DP, Bernstein M, et al. Defining and measuring reproductive concerns of female cancer survivors. J Natl Canc Inst Monogr. 2005;34:94–8. doi: 10.1093/jncimonographs/lgi017.CrossRefGoogle Scholar
  50. 50.
    Wyns C, Curaba M, Petit S, Vanabelle B, Laurent P, Wese JF, et al. Management of fertility preservation in prepubertal patients: 5 years’ experience at the Catholic University of Louvain. Hum Reprod. 2011;26(4):737–47. doi: 10.1093/humrep/deq387.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Samir N. Babayev
    • 1
  • Erol Arslan
    • 1
    • 2
  • Stanley Kogan
    • 5
  • Fred Moy
    • 1
    • 2
    • 3
    • 6
  • Kutluk Oktay
    • 1
    • 2
    • 3
    • 4
    • 7
    • 8
    Email author
  1. 1.Department of Obstetrics and GynecologyNew York Medical CollegeValhallaUSA
  2. 2.Department of Cell Biology and AnatomyNew York Medical CollegeValhallaUSA
  3. 3.Department of PathologyNew York Medical CollegeValhallaUSA
  4. 4.Department of MedicineNew York Medical CollegeValhallaUSA
  5. 5.Department of UrologyNew York Medical CollegeValhallaUSA
  6. 6.Biometric, Data Management and PK/PD Unit, Graduate School of Basic Medical Sciences, Department of PathologyNew York Medical CollegeValhallaUSA
  7. 7.Division of Reproductive Medicine & Infertility, and Institute for Fertility PreservationNew York Medical CollegeRye and ValhallaUSA
  8. 8.Laboratory of Molecular Reproduction and Fertility PreservationNew York Medical CollegeValhallaUSA

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