Skip to main content
SpringerLink
Log in

Ovarian Tissue Cryopreservation: Where Are We Now?

  • Chapter
Book cover Biennial Review of Infertility

  • 823 Accesses

Abstract

Early detection and advanced treatment strategies in cancer have improved survival outcomes, leading to an increased interest for fertility preservation. Following the first description of the successful restoration of ovarian function after transplantation of the previously cryopreserved ovarian cortical pieces, the field of fertility preservation entered into an accelerated phase. Once the cancer community and the patients took notice of the possibility of successfully and safely preserving fertility, fertility preservation became an increasingly important part of cancer care with attention to the improvement of the post-survival quality of life.

While embryo or oocyte cryopreservation can be offered to those individuals who have sufficient time for ovarian stimulation before chemotherapy, a sufficient time period is not available to all cancer patients. Moreover, especially in pre-pubertal children, ovarian stimulation is not feasible. When such limitations exist and when there is also the desire for the preservation of endocrine function, ovarian cryopreservation and transplantation stands out among the other techniques.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mussett MV, Parrott DM. Factors affecting the fertility of mice with orthotopic ovarian grafts. J Reprod Fertil. 1961;2:80–97.

    Article  CAS  PubMed  Google Scholar 

  2. Newton H, Aubard Y, Rutherford A, Sharma V, Gosden R. Low temperature storage and grafting of human ovarian tissue. Hum Reprod. 1996;11(7):1487–91.

    Article  CAS  PubMed  Google Scholar 

  3. Gosden RG, Baird DT, Wade JC, Webb R. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at −196 degrees C. Hum Reprod. 1994;9(4):597–603.

    CAS  PubMed  Google Scholar 

  4. Baird DT, Campbell B, de Souza C, Telfer E. Long-term ovarian function in sheep after ovariectomy and autotransplantation of cryopreserved cortical strips. Eur J Obstet Gynecol Reprod Biol. 2004;113 Suppl 1:S55–9.

    Article  PubMed  Google Scholar 

  5. Hovatta O, Silye R, Krausz T, Abir R, Margara R, Trew G, Lass A, Winston RM. Cryopreservation of human ovarian tissue using dimethylsulphoxide and propanediol-sucrose as cryoprotectants. Hum Reprod. 1996;11(6):1268–72.

    Article  CAS  PubMed  Google Scholar 

  6. Gook DA, Edgar DH, Stern C. Effect of cooling rate and dehydration regimen on the histological appearance of human ovarian cortex following cryopreservation in 1, 2-propanediol. Hum Reprod. 1999;14(8):2061–8.

    Article  CAS  PubMed  Google Scholar 

  7. Rosendahl M, Andersen CY, Ernst E, Westergaard LG, Rasmussen PE, Loft A, Andersen AN. Ovarian function after removal of an entire ovary for cryopreservation of pieces of cortex prior to gonadotoxic treatment: a follow-up study. Hum Reprod. 2008;23(11):2475–83.

    Article  PubMed  Google Scholar 

  8. Harel S, Ferme C, Poirot C. Management of fertility in patients treated for Hodgkin’s lymphoma. Haematologica. 2011;96(11):1692–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Hreinsson J, Zhang P, Swahn ML, Hultenby K, Hovatta O. Cryopreservation of follicles in human ovarian cortical tissue. Comparison of serum and human serum albumin in the cryoprotectant solutions. Hum Reprod. 2003;18(11):2420–8.

    Article  CAS  PubMed  Google Scholar 

  10. Keros V, Xella S, Hultenby K, Pettersson K, Sheikhi M, Volpe A, Hreinsson J, Hovatta O. Vitrification versus controlled-rate freezing in cryopreservation of human ovarian tissue. Hum Reprod. 2009;24(7):1670–83.

    Article  CAS  PubMed  Google Scholar 

  11. Sugimoto M, Maeda S, Manabe N, Miyamoto H. Development of infantile rat ovaries autotransplanted after cryopreservation by vitrification. Theriogenology. 2000;53(5):1093–103.

    Article  CAS  PubMed  Google Scholar 

  12. Bordes A, Lornage J, Demirci B, Franck M, Courbiere B, Guerin JF, Salle B. Normal gestations and live births after orthotopic autograft of vitrified-warmed hemi-ovaries into ewes. Hum Reprod. 2005;20(10):2745–8.

    Article  PubMed  Google Scholar 

  13. Isachenko V, Isachenko E, Weiss JM. Human ovarian tissue: vitrification versus conventional freezing. Hum Reprod. 2009;24(7):1767–8. author reply 8–9.

    Article  CAS  PubMed  Google Scholar 

  14. Isachenko V, Isachenko E, Kreienberg R, Woriedh M, Weiss J. Human ovarian tissue cryopreservation: quality of follicles as a criteria of effectiveness. Reprod Biomed Online. 2010;20(4):441–2.

    Article  CAS  PubMed  Google Scholar 

  15. Oktay K, Karlikaya G. Ovarian function after transplantation of frozen, banked autologous ovarian tissue. N Engl J Med. 2000;342(25):1919.

    Article  CAS  PubMed  Google Scholar 

  16. Oktay K, Aydin BA, Karlikaya G. A technique for laparoscopic transplantation of frozen-banked ovarian tissue. Fertil Steril. 2001;75(6):1212–6.

    Article  CAS  PubMed  Google Scholar 

  17. Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, Martinez-Madrid B, van Langendonckt A. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;364(9443):1405–10.

    Article  CAS  PubMed  Google Scholar 

  18. Meirow D, Levron J, Eldar-Geva T, Hardan I, Fridman E, Zalel Y, Schiff E, Dor J. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med. 2005;353(3):318–21.

    Article  CAS  PubMed  Google Scholar 

  19. Demeestere I, Simon P, Buxant F, Robin V, Fernandez SA, Centner J, Delbaere A, Englert Y. 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(8):2010–4.

    Article  PubMed  Google Scholar 

  20. Andersen CY, Rosendahl M, Byskov AG, Loft A, Ottosen C, Dueholm M, Schmidt KL, Andersen AN, Ernst E. Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue. Hum Reprod. 2008;23(10):2266–72.

    Article  PubMed  Google Scholar 

  21. Donnez J, Silber S, Andersen CY, Demeestere I, Piver P, Meirow D, Pellicer A, Dolmans MM. Children born after autotransplantation of cryopreserved ovarian tissue. A review of 13 live births. Ann Med. 2011;43(6):437–50.

    Article  PubMed  Google Scholar 

  22. Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, Quinn G, Wallace WH, Oktay K. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31:2500–10.

    Article  PubMed  Google Scholar 

  23. Revel A, Laufer N, Ben Meir A, Lebovich M, Mitrani E. Micro-organ ovarian transplantation enables pregnancy: a case report. Hum Reprod. 2011;26(5):1097–103.

    Article  PubMed  Google Scholar 

  24. Donnez J, Dolmans MM, Pellicer A, Diaz-Garcia C, Sanchez Serrano M, Schmidt KT, Ernst E, Luyckx V, Andersen CY. Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: a review of 60 cases of reimplantation. Fertil Steril. 2013;99(6):1503–13.

    Article  PubMed  Google Scholar 

  25. 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.

    Article  CAS  PubMed  Google Scholar 

  26. Oktay K, Buyuk E, Veeck L, Zaninovic N, Xu K, Takeuchi T, Opsahl M, Rosenwaks Z. Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;363(9412):837–40.

    Article  PubMed  Google Scholar 

  27. Rosendahl M, Loft A, Byskov AG, Ziebe S, Schmidt KT, Andersen AN, Ottosen C, Andersen CY. Biochemical pregnancy after fertilization of an oocyte aspirated from a heterotopic autotransplant of cryopreserved ovarian tissue: case report. Hum Reprod. 2006;21(8):2006–9.

    Article  CAS  PubMed  Google Scholar 

  28. Stern CJ, Gook D, Hale LG, Agresta F, Oldham J, Rozen G, Jobling T. First reported clinical pregnancy following heterotopic grafting of cryopreserved ovarian tissue in a woman after a bilateral oophorectomy. Hum Reprod. 2013;28(11):2996–9.

    Article  CAS  PubMed  Google Scholar 

  29. Oktay K. Spontaneous conceptions and live birth after heterotopic ovarian transplantation: is there a germline stem cell connection? Hum Reprod. 2006;21(6):1345–8.

    Article  PubMed  Google Scholar 

  30. Oktay K, Turkcuoglu I, Rodriguez-Wallberg KA. Four spontaneous pregnancies and three live births following subcutaneous transplantation of frozen banked ovarian tissue: what is the explanation? Fertil Steril. 2011;95(2):804.e7–10.

    Article  Google Scholar 

  31. 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.

    Article  PubMed  Google Scholar 

  32. Demeestere I, Simon P, Moffa F, Delbaere A, Englert Y. Birth of a second healthy girl more than 3 years after cryopreserved ovarian graft. Hum Reprod. 2010;25(6):1590–1.

    Article  CAS  PubMed  Google Scholar 

  33. Ernst E, Bergholdt S, Jorgensen JS, Andersen CY. The first woman to give birth to two children following transplantation of frozen/thawed ovarian tissue. Hum Reprod. 2010;25(5):1280–1.

    Article  PubMed  Google Scholar 

  34. Oktay K, Goswami S, Darzynkiewicz Z. Manipulating ovarian aging: a new frontier in fertility preservation. Aging (Albany NY). 2011;3(1):19–21.

    Google Scholar 

  35. Diaz-Garcia C, Milenkovic M, Groth K, Dahm-Kahler P, Olausson M, Brannstrom M. Ovarian cortex transplantation in the baboon: comparison of four different intra-abdominal transplantation sites. Hum Reprod. 2011;26(12):3303–11.

    Article  CAS  PubMed  Google Scholar 

  36. Yin H, Wang X, Kim SS, Chen H, Tan SL, Gosden RG. Transplantation of intact rat gonads using vascular anastomosis: effects of cryopreservation, ischaemia and genotype. Hum Reprod. 2003;18(6):1165–72.

    Article  PubMed  Google Scholar 

  37. Courbiere B, Caquant L, Mazoyer C, Franck M, Lornage J, Salle B. Difficulties improving ovarian functional recovery by microvascular transplantation and whole ovary vitrification. Fertil Steril. 2009;91(6):2697–706.

    Article  PubMed  Google Scholar 

  38. Arav A, Gavish Z, Elami A, Natan Y, Revel A, Silber S, Gosden RG, Patrizio P. Ovarian function 6 years after cryopreservation and transplantation of whole sheep ovaries. Reprod Biomed Online. 2010;20(1):48–52.

    Article  CAS  PubMed  Google Scholar 

  39. Shaw JM, Bowles J, Koopman P, Wood EC, Trounson AO. Fresh and cryopreserved ovarian tissue samples from donors with lymphoma transmit the cancer to graft recipients. Hum Reprod. 1996;11(8):1668–73.

    Article  CAS  PubMed  Google Scholar 

  40. Kim SS, Radford J, Harris M, Varley J, Rutherford AJ, Lieberman B, Shalet S, Gosden R. Ovarian tissue harvested from lymphoma patients to preserve fertility may be safe for autotransplantation. Hum Reprod. 2001;16(10):2056–60.

    Article  CAS  PubMed  Google Scholar 

  41. Meirow D, Hardan I, Dor J, Fridman E, Elizur S, Ra’anani H, Slyusarevsky E, Amariglio N, Schiff E, Rechavi G, Nagler A, Ben YD. Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients. Hum Reprod. 2008;23(5):1007–13.

    Article  PubMed  Google Scholar 

  42. Ajala T, Rafi J, Larsen-Disney P, Howell R. Fertility preservation for cancer patients: a review. Obstet Gynecol Int. 2010;2010:160386.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Telfer EE, McLaughlin M, Ding C, Thong KJ. A two-step serum-free culture system supports development of human oocytes from primordial follicles in the presence of activin. Hum Reprod. 2008;23(5):1151–8.

    Article  CAS  PubMed  Google Scholar 

  44. Smitz J, Dolmans MM, Donnez J, Fortune JE, Hovatta O, Jewgenow K, Picton HM, Plancha C, Shea LD, Stouffer RL, Telfer EE, Woodruff TK, Zelinski MB. Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: implications for fertility preservation. Hum Reprod Update. 2010;16(4):395–414.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Telfer EE, McLaughlin M. In vitro development of ovarian follicles. Semin Reprod Med. 2011;29(1):15–23.

    Article  CAS  PubMed  Google Scholar 

  46. Sauvat F, Capito C, Sarnacki S, Poirot C, Bachelot A, Meduri G, Dandolo L, Binart N. Immature cryopreserved ovary restores puberty and fertility in mice without alteration of epigenetic marks. PLoS One. 2008;3(4):e1972.

    Article  PubMed Central  PubMed  Google Scholar 

  47. Gosden RG, Boulton MI, Grant K, Webb R. Follicular development from ovarian xenografts in SCID mice. J Reprod Fertil. 1994;101(3):619–23.

    Article  CAS  PubMed  Google Scholar 

  48. Bosma GC, Custer RP, Bosma MJ. A severe combined immunodeficiency mutation in the mouse. Nature. 1983;301(5900):527–30.

    Article  CAS  PubMed  Google Scholar 

  49. Oktay K, Newton H, Mullan J, Gosden RG. Development of human primordial follicles to antral stages in SCID/hpg mice stimulated with follicle stimulating hormone. Hum Reprod. 1998;13(5):1133–8.

    Article  CAS  PubMed  Google Scholar 

  50. Weissman A, Gotlieb L, Colgan T, Jurisicova A, Greenblatt EM, Casper RF. Preliminary experience with subcutaneous human ovarian cortex transplantation in the NOD-SCID mouse. Biol Reprod. 1999;60(6):1462–7.

    Article  CAS  PubMed  Google Scholar 

  51. Oktay K, Newton H, Gosden RG. Transplantation of cryopreserved human ovarian tissue results in follicle growth initiation in SCID mice. Fertil Steril. 2000;73(3):599–603.

    Article  CAS  PubMed  Google Scholar 

  52. Nisolle M, Casanas-Roux F, Qu J, Motta P, Donnez J. Histologic and ultrastructural evaluation of fresh and frozen-thawed human ovarian xenografts in nude mice. Fertil Steril. 2000;74(1):122–9.

    Article  CAS  PubMed  Google Scholar 

  53. Oktem O, Oktay K. A novel ovarian xenografting model to characterize the impact of chemotherapy agents on human primordial follicle reserve. Cancer Res. 2007;67(21):10159–62.

    Article  CAS  PubMed  Google Scholar 

  54. Baird DT, Webb R, Campbell BK, Harkness LM, Gosden RG. Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at −196 C. Endocrinology. 1999;140(1):462–71.

    CAS  PubMed  Google Scholar 

  55. Liu J, Van der Elst J, Van den Broecke R, Dhont M. Early massive follicle loss and apoptosis in heterotopically grafted newborn mouse ovaries. Hum Reprod. 2002;17(3):605–11.

    Article  PubMed  Google Scholar 

  56. Morita Y, Perez GI, Paris F, Miranda SR, Ehleiter D, Haimovitz-Friedman A, Fuks Z, Xie Z, Reed JC, Schuchman EH, Kolesnick RN, Tilly JL. Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med. 2000;6(10):1109–14.

    Article  CAS  PubMed  Google Scholar 

  57. Titus S, Li F, Stobezki R, Akula K, Unsal E, Jeong K, Dickler M, Robson M, Moy F, Goswami S, Oktay K. Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans. Sci Transl Med. 2013;5(172):172ra21.

    Article  PubMed  Google Scholar 

  58. Soleimani R, Heytens E, Oktay K. Enhancement of neoangiogenesis and follicle survival by sphingosine-1-phosphate in human ovarian tissue xenotransplants. PLoS One. 2011;6(4):e19475.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Oktay K, Bedoschi G, Pacheco F, Stobezki R, Turan V. Robotically assisted ovarian tissue transplantation with human extracellular matrix: ovarian stimulation and in vitro fertilization outcomes. Fertil Steril. 2014;102(3):e37.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Molecular Reproduction and Fertility Preservation, Department of Obstetrics and Gynecology, New York Medical College, Valhalla, NY, USA

    Giuliano Bedoschi MD & Kutluk Oktay MD

  2. Innovation Institute for Fertility Preservation and IVF, New York, NY, USA

    Giuliano Bedoschi MD & Kutluk Oktay MD

Authors
  1. Giuliano Bedoschi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kutluk Oktay MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kutluk Oktay MD .

Editor information

Editors and Affiliations

  1. Professor, Departments of Surgery (Urology), Obstetrics and Gynecology, and Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA

    Douglas T. Carrell

  2. James J. Colt Professor of Urology, Chairman, Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York, USA

    Peter N. Schlegel

  3. Professor, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Catherine Racowsky

  4. Scientific Director, Reproductive Medicine Unit, S.I.S.M.E.R. s.r.l., Day Surgery Clinic della Riproduzione (SISMeR), Bologna, Bologna, Italy

    Luca Gianaroli

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bedoschi, G., Oktay, K. (2015). Ovarian Tissue Cryopreservation: Where Are We Now?. In: Carrell, D., Schlegel, P., Racowsky, C., Gianaroli, L. (eds) Biennial Review of Infertility. Springer, Cham. https://doi.org/10.1007/978-3-319-17849-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-17849-3_6

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-17848-6

  • Online ISBN: 978-3-319-17849-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation