Ovarian Tissue Cryopreservation and Transplantation: Banking Reproductive Potential for the Future

  • David Lee
Part of the Cancer Treatment and Research book series (CTAR, volume 138)

Transplantation of cryopreserved ovarian tissue is a technology that holds promise for preserving reproductive potential for the future. It may be apropos for cancer survivors who will undergo treatment with sterility-inducing chemotherapy or radiation. Although there is some evidence suggesting cellular and molecular injury with the freezing and thawing process, there are examples in both animals and humans that transplantation of cryopreserved ovarian tissue can lead to successful restoration of fertility. Currently, cryopreservation of ovarian tissue is the only option available to preserve fertility in prepubertal girls or women who cannot delay their cancer treatment. For this patient population, ovarian tissue banking and subsequent transplantation is the only fertility-preserving method that has resulted in live-born pregnancies. The technology of ovarian tissue banking is currently at the forefront of the emerging field of oncofertilty.


Ovarian Tissue Ovarian Failure Primordial Follicle Premature Ovarian Failure Immature Oocyte 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Blatt J. Pregnancy outcome in long-term survivors of childhood cancer. Med Pediatr Oncol 1999;33:29–33.CrossRefPubMedGoogle Scholar
  2. 2.
    Meirow D, Nugent D. The effects of radiotherapy and chemotherapy on female reproduction. Hum Reprod Update 2001;7:535–543.CrossRefPubMedGoogle Scholar
  3. 3.
    Greenlee RT, Murray T, Bolden S, et al. Cancer statistics, 2000. CA Cancer J Clin 2000;50:7–33.CrossRefPubMedGoogle Scholar
  4. 4.
    Meirow D. Ovarian injury and modern options to preserve fertility in female cancer patients treated with high dose radio-chemotherapy for hemato-oncological neoplasias and other cancer. Leuk Lymphoma 1999:33:65–76.PubMedGoogle Scholar
  5. 5.
    Meirow D. Epidemiology and infertility in cancer patients. In: Gosden R, Tulandi T, editors. Preservation of fertility. London: Taylor and Francis, 2004:21–38.Google Scholar
  6. 6.
    Koyama H, Wada T, Nishizawa Y, et al. Cyclophosphamide-induced ovarian failure and its therapeutic significance in patients with breast cancer. Cancer 1977;39:1403–1409.CrossRefPubMedGoogle Scholar
  7. 7.
    Goldhirsch A, Gelber RD, Castiglione M. The magnitude of endocrine effects of adjuvant chemotherapy for premenopausal breast cancer patients. The International Breast Cancer Study Group. Ann Oncol 1990;1:183–188.PubMedGoogle Scholar
  8. 8.
    Chiarelli AM, Marrett LD, Darlington G. Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964–1988 in Ontario, Canada. Am J Epidemiol 1999;150:245–254.PubMedGoogle Scholar
  9. 9.
    Falcone T, Attaran M, Bedaiwy M, et al. Ovarian function preservation in the cancer patient. Fertil Steril 2004;81:243–257.CrossRefPubMedGoogle Scholar
  10. 10.
    Wallace WH, Shalet SM, Hendry JH, et al. Ovarian failure following ovarian irradiation in childhood: the radiosensitivity of the human oocyte. Br J Radiol 1989;62:995–998.CrossRefPubMedGoogle Scholar
  11. 11.
    Wallace WH, Thomson AB, Saran F, Kelsey TW. Predicting age of ovarian failure after radiation to a field that includes the ovaries. Int J Radiat Oncol Biol Phys 2005;62:738–744.PubMedGoogle Scholar
  12. 12.
    Critchley HOD, Wallace WHB, Shalet SM, et al. Abdominal irradiation in childhood: potential for pregnancy. Br J Obstet Gynaecol 1992:99:392–394.PubMedGoogle Scholar
  13. 13.
    Bath LE, Critchley HO, Chambers SE, et al. Ovarian and uterine characteristics after total body irradiation in childhood and adolescence: response to sex steroid replacement. Br J Obstet Gynaecol 1999;106:1265–1272.PubMedGoogle Scholar
  14. 14.
    Rappaport R, Brauner R, Czernichow P, et al. Effect of hypothalamic and pituitary irradiation on pubertal development in children with cranial tumors. J Clin Endocrinol Metab 1982; 154:1164–1168.CrossRefGoogle Scholar
  15. 15.
    Davies HA, Didcock E, Didi M, et al. Growth, puberty and obesity after treatment for leukemia. Acta Paediatr Suppl 1995;411:45–51.CrossRefPubMedGoogle Scholar
  16. 16.
    Ogilvy-Stuart AL, Clayton PE, Shalet SM. Cranial irradiation and early puberty. J Clin Endocrinol Metab 1994;78:1282–1286.CrossRefPubMedGoogle Scholar
  17. 17.
    Kwon JS, Case AM. Preserving reproductive function in women with cancer. Sexuality, Reproduction & Menopause 2004;2(2):222–229. (A Publication of the American Society for Reproductive Medicine) http://www.srmjournal.org/home.
  18. 18.
    Blumenfeld Z. Preservation of fertility and ovarian function and minimalization of chemotherapy associated gonadotoxicity and premature ovarian failure: the role of inhibin-A and–B as markers. Mol Cell Endocrinol 2002;187:93–105.CrossRefPubMedGoogle Scholar
  19. 19.
    Revel A, Laufer N. Protecting female fertility from cancer therapy. Mol Cell Endocrinol 2002;187:83–91.CrossRefPubMedGoogle Scholar
  20. 20.
    Ataya K, Pydyn E, Ramahi-Ataya A, et al. Is radiation-induced ovarian failure in rhesus monkeys preventable by luteinizing hormone-releasing hormone agonists: preliminary observations. J Clin Endocrinol Metab 1995;80:790–795.CrossRefPubMedGoogle Scholar
  21. 21.
    Ataya K, Rao LV, Lawrence E, et al. Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide-induced ovarian follicular depletion in rhesus monkeys. Biol Reprod 1995;52:365–372.CrossRefPubMedGoogle Scholar
  22. 22.
    Blumenfeld Z, Avivi I, Linn S, et al. Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy. Hum Reprod 1996;11:1620–1626.PubMedGoogle Scholar
  23. 23.
    Waxman JH, Ahmed R, Smith D, et al. Failure to preserve fertility in patients with Hodgkin’s disease. Cancer Chemother Pharmacol 1987;19:159–162.CrossRefPubMedGoogle Scholar
  24. 24.
    Oktay K, Cil AP, Bang H. Efficiency of oocyte cryopreservation: a meta-analysis. Fertil Steril 2006;86:70–80.CrossRefPubMedGoogle Scholar
  25. 25.
    Porcu E, Fabbri R, Damiano G, et al. Clinical experience and applications of oocyte cryopreservation. Mol Cell Endocrinol 2000;169:33–37.CrossRefPubMedGoogle Scholar
  26. 26.
    Fabbri R, Porcu E, Marsella T, et al. Human oocyte cryopreservation: new perspectives regarding oocyte survival. Hum Reprod 2001;16:411–416.CrossRefPubMedGoogle Scholar
  27. 27.
    Borini A, Bonu MA, Coticchio G, et al. Pregnancies and births after oocyte cryopreservation. Fert Steril 2004;82:601–605.CrossRefGoogle Scholar
  28. 28.
    Eppig J, O’Brien M. Development in vitro of mouse oocytes from primordial follicles. Biol Reprod 1996;54:197–207.CrossRefPubMedGoogle Scholar
  29. 29.
    Cha KY, Chung HM, Lim JM, et al. Freezing immature oocytes. Mol Cell Endocrinol 2000;169:43–47.CrossRefPubMedGoogle Scholar
  30. 30.
    Parrott JA, Skinner MK. Direct actions of kit-ligand on theca cell growth and differentiation during follicle development. Endocrinology 1997;138:3819–3827.CrossRefPubMedGoogle Scholar
  31. 31.
    Elvin JA, Yan C, Wang P, et al. Molecular characterization of the follicle defects in growth differentiation factor 9-deficient ovary. Mol Endocrinol 1999;13:1018–1034.CrossRefPubMedGoogle Scholar
  32. 32.
    Nilsson E, Parrott JA, Skinner MK. Basic fibroblast growth factor induces primordial follicle development and initiates folliculogenesis. Mol Cell Endocrinol 2001;175:123–123.CrossRefPubMedGoogle Scholar
  33. 33.
    Otsuka F, Moore RK, Shimasaki S. Biological function and cellular mechanism of bone morphogenetic protein-6 in the ovary. J Biol Chem 2001;276:32889–32895.CrossRefPubMedGoogle Scholar
  34. 34.
    Nilsson EE, Kezele P, Skinner MK. Leukemia inhibitory factor promotes the primordial to primary follicle transition in rat ovaries. Mol Cell Endocrinol 2002;188:65–73.CrossRefPubMedGoogle Scholar
  35. 35.
    Yoon S, Kim K, Chung H, et al. Gene expression profiling of early follicular development in primordial, primary and secondary follicles. Fert Steril 2006;85:193–203.CrossRefGoogle Scholar
  36. 36.
    Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endo Rev 1996;17:121–155.Google Scholar
  37. 37.
    Zeleznik AJ. The physiology of follicle selection. Reprod Biol Endocrinol 2004;2:31.CrossRefPubMedGoogle Scholar
  38. 38.
    Kreeger PK, Fernandes NN, Woodruff TK, et al. Regulation of mouse follicle development by follicle-stimulating hormone in a three-dimensional in vitro culture system is dependent on follicle stage and dose. Biol Reprod 2005;73:942–950.CrossRefPubMedGoogle Scholar
  39. 39.
    Kreeger PK, Deck JW, Woodruff TK, et al. The in vitro regulation of ovarian follicle development using alginate-extracellular matrix gels. Biomaterials 2006;27:714–723.CrossRefPubMedGoogle Scholar
  40. 40.
    Pangas SA, Saudye H, Shea LD, et al. Novel approach for the three-dimensional culture of granulosa cell-oocyte complexes. Tissue Eng. 2003;9:1013–1021.CrossRefPubMedGoogle Scholar
  41. 41.
    Xu M, West E, Shea LD, et al. Identification of a stage-specific permissive in vitro culture environment for follicle growth and oocyte development. Biol Reprod 2006;75:916–923.CrossRefPubMedGoogle Scholar
  42. 42.
    Xu M, Kreeger PK, Shea LD, et al. Tissue-engineered follicles produce live, fertile offspring. Tissue Eng 2006;12:2739–2746.CrossRefPubMedGoogle Scholar
  43. 43.
    Oktay K, Nugent D, Newton H, et al. Isolation and characterization of primordial follicles from fresh and cryopreserved human ovarian tissue. Fert Steril 1997;67:481–486.CrossRefGoogle Scholar
  44. 44.
    Gosden RG, Baird DT, Wade JC, et al. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at–196 degrees C. Hum Reprod 1994;9:597–603.PubMedGoogle Scholar
  45. 45.
    Yeoman RR, Wolf DP, Lee DM. Co-culture of monkey ovarian tissue increases survival after vitrification and slow-rate freezing. Fert Steril 2005;83:1248–1254.CrossRefGoogle Scholar
  46. 46.
    Deanesly R. Immature rat ovaries grafted after freezing and thawing. J Endocrinol 1954;11:197–200.CrossRefPubMedGoogle Scholar
  47. 47.
    Parkes A, Smith, AU. Preservation of ovarian tissue at–79 Degrees C for transplantation. Acta Endocrinol 1954;17:313–320.PubMedGoogle Scholar
  48. 48.
    Parrot D. The fertility of mice with orthotopic ovarian grafts derived from frozen tissue. J Reprod Fertil 1960;1:230–241.CrossRefGoogle Scholar
  49. 49.
    Oktay K, Aydin B, Karlikaya G. A technique for laparoscopic transplantation of frozen-banked ovarian tissue. Fertil Steril 2001;75:1212–1216.CrossRefPubMedGoogle Scholar
  50. 50.
    Donnez J, Dolmans MM, Demylle D, et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet 2004;364:1405–1410.CrossRefPubMedGoogle Scholar
  51. 51.
    Silber SJ, Lenahan KM, Levine DJ, et al. Ovarian transplantation between monozygotic twins discordant for premature ovarian failure. New Engl J Med 2005;353:58–63.CrossRefPubMedGoogle Scholar
  52. 52.
    Oktay K, Economos K, Kan M, et al. Endocrine function and oocyte retrieval after autologous transplantation of ovarian cortical strips to the forearm. J Am Med Assoc 2001;286:1490–1493.CrossRefGoogle Scholar
  53. 53.
    Lee DM, Yeoman R, Battaglia DE, et al. Birth of a monkey after heterotopic transplantation of fresh ovarian tissue and assisted reproduction. Nature 2004;428:137–138.CrossRefPubMedGoogle Scholar
  54. 54.
    Harp R, Leibach J, Black J, et al. Cryopreservation of murine ovarian tissue. Cryobiology 1994;31:336–343.CrossRefPubMedGoogle Scholar
  55. 55.
    Sztein J, Sweet H, Farley J, et al. Cryopreservation and orthotopic transplantation of mouse ovaries: New approach in gamete banking. Biol Reprod 1998;58:1071–1074.CrossRefPubMedGoogle Scholar
  56. 56.
    Schnorr JA OS, Toner JP, Hsiu JG, Willams RF, Hodgen GD. Fresh and cryopreserved extrapelvic ovarian transplantation in non-human primates: folliculogenesis, ovulation, corpus luteum function, endometrial development, and menstrual patterns. Abstract presented at: the American Society of Reproductive Medicine 2000 Annual Meeting; October 21–26, 2000; San Diego, California.Google Scholar
  57. 57.
    Gougeon A, Ecochard R, Thalabard JC. Age-related changes of the population of human ovarian follicles: increase in the disappearance rate of non-growing and early-growing follicles in aging women. Biol Reprod 1994;50:653–663.CrossRefPubMedGoogle Scholar
  58. 58.
    Gougeon A. Ovarian follicular growth in humans: ovarian ageing and population of growing follicles. Maturitas 1998;30:137–142.CrossRefPubMedGoogle Scholar
  59. 59.
    Oktay K, Karlikaya G. Ovarian function after transplantation of frozen, banked autologous ovarian tissue. N Engl J Med 2000;342:1919.CrossRefPubMedGoogle Scholar
  60. 60.
    Radford JA, Lieberman BA, Brison DR, et al. Orthotopic reimplantation of cryopreserved ovarian cortical strips after high-dose chemotherapy for Hodgkin’s lymphoma. Lancet 2001;357:1172–1175.CrossRefPubMedGoogle Scholar
  61. 61.
    Oktay K, Buyuk E, Veeck L, et al. Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet 2004;363:837–840.CrossRefPubMedGoogle Scholar
  62. 62.
    Meirow D, Levron J, Eldar-Geva T, et al. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. New Eng J Med 2005;355:318–321.CrossRefGoogle Scholar
  63. 63.
    Demeestere I, Simon P, Buxant F, et al. Ovarian function and spontaneous pregnancy after combined heterotopic and orthotopic cryopreserved ovarian tissue transplantation in a patient previously treated with bone marrow transplantation: case report. Hum Reprod 2006;21:2010–2014.CrossRefPubMedGoogle Scholar
  64. 64.
    Leporrier M, von Theobald P, Roffe JL, et al. A new technique to protect ovarian function before pelvic irradiation. Heterotopic ovarian autotransplantation. Cancer 1987;60:2201–2204.CrossRefPubMedGoogle Scholar
  65. 65.
    Wang X, Chen H, Yin HK, et al. Fertility after intact ovary transplantation. Nature 2002; 415:385.CrossRefPubMedGoogle Scholar
  66. 66.
    Bedaiwy MA, Jeremias E, Gurunluogly R, et al. Restoration of ovarian function after autotransplantation of intact frozen-thawed sheep ovaries with microvascular anastomosis. Fertil Steril 2003;79:594–602.CrossRefPubMedGoogle Scholar
  67. 67.
    Imhof M, Bergmeister H, Lipovac M, et al. Orthotopic microvascular re-anastomosis of whole cryopreserved ovine ovaries resulting in pregnancy and life birth. Fertil Steril 2006; 85(Suppl 1):1208–1215.CrossRefPubMedGoogle Scholar
  68. 68.
    Shaw JM, Bowles J, Koopman P, et al. Fresh and cryopreserved ovarian tissue from donors with lymphoma, transmit the cancer to graft recipients. Hum Reprod 1996;11:1668–1673.PubMedGoogle Scholar
  69. 69.
    Kim SS, Hwang IT, Lee HC. Heterotopic autotransplantation of cryobanked human ovarian tissue as a strategy to restore ovarian function. Fertil Steril 2004;82:930–932.CrossRefPubMedGoogle Scholar
  70. 70.
    Sonmezer M, Shamonki MI, Oktay K. Ovarian tissue cryopreservation: benefits and risks. Cell Tissue Res 2005;322:125–132.CrossRefPubMedGoogle Scholar
  71. 71.
    Lee DM, Yeoman RR, Yu T, et al. Sphingosine-1-phosphate inhibits apoptosis in rhesus monkey ovarian tissue in vitro and may improve reproductive function in xenografts. 2005 Joint American Society for Reproductive Medicine/Canadian Fertility & Andrology Society Meeting, Oct. 15–19, Montreal, Quebec, CANADA. Fertil Steril 2005;84(Suppl 1):S2.CrossRefGoogle Scholar
  72. 72.
    Gunasena KT, Lakey JR, Villines PM, et al. Allogeneic and xenogeneic transplantation of cryopreserved ovarian tissue to athymic mice. Biol Reprod 1997;57:226–231.CrossRefPubMedGoogle Scholar
  73. 73.
    Snow M. Cox SL, Jenkin G, et al. Generation of live young from xenografted mouse ovaries. Science 2002;297:2227.CrossRefPubMedGoogle Scholar
  74. 74.
    Weissman A, Gotlieb L, Colgan T, et al. Preliminary experience with subcutaneous human ovarian cortex transplantation in the NOD-SCID mouse. Biol Reprod 1999;60:1462–1467.CrossRefPubMedGoogle Scholar
  75. 75.
    Kim SS, Soules M, Gosden RG, et al. The evidence of follicle maturation and subsequent ovulation in human ovarian tissue xenografted into severe combined immunodeficient (SCID) mice. Fertil Steril 2000;74:S34.CrossRefGoogle Scholar
  76. 76.
    Nisolle M, Casanas-Roux F, Qu J, et al. Histologic and ultrastructural evaluation of fresh and frozen-thawed human ovarian xenografts in nude mice. Fert Steril 2000;74:122–129.CrossRefGoogle Scholar
  77. 77.
    Oktay K, Newton H, Gosden RG. Transplantation of cryopreserved human ovarian tissue results in follicle growth initiation in SCID mice. Fertil Steril 2000;73:599–603.CrossRefPubMedGoogle Scholar
  78. 78.
    Lee K, Lee S, SJ Y, et al. Resumption of the human primordial follicle growth in xenografts after vitrification of the ovarian tissues. Fertil Steril 2000;74(3 Suppl 1):S214.CrossRefGoogle Scholar
  79. 79.
    Kim SS, Kang HG, Kim NH, et al. Assessment of the integrity of human oocytes retrieved from cryopreserved ovarian tissue after xenotransplantation. Hum Reprod 2005;20:2502–2508.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • David Lee

There are no affiliations available

Personalised recommendations