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History, Evolution and Current State of Ovarian Tissue Auto-Transplantation with Cryopreserved Tissue: a Successful Translational Research Journey from 1999 to 2020

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Abstract

The loss of fertility and early menopause are common after gonadotoxic therapies and radical pelvic surgery. The strategy of ovarian tissue cryopreservation and auto-transplantation was introduced to prevent this significant quality of health issue. Ovarian transplantation with cryopreserved tissue has gone through remarkable evolution in the last 20 years. In this review, we detail the history and evolution of ovarian transplantation with cryopreserved tissue from its origins to the present. Ovarian cryopreservation and transplantation approach was first tested with animal models. The approach was then validated in human ovarian xenografting models before being applied to patients in pioneering clinical studies. The first orthotopic and heterotopic approaches to ovarian transplantation was developed by Oktay et al. who reported the first successful restoration of ovarian function with these approaches beginning in 2000 with first embryo development in 2004. Controversy remains on when the first live birth occurred after orthotopic ovarian transplantation with cryopreserved tissue as the patient was ovulating with elevated progesterone levels in the case reported in 2004; first live birth is likely to be the one reported by Meirow et al. in 2005. Nevertheless, the technique has evolved to reach a level where most recent live birth rates are exceeding 35% and the procedure is no longer considered experimental by many.

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References

  1. Oktay K, Karlikaya G. Ovarian function after transplantation of frozen, banked autologous ovarian tissue. NJEM. 1999;342(25):1919.

    Google Scholar 

  2. Morris RT. A case of heteroplastic ovarian grafting, followed by pregnancy, and the delivery of a living child. Med Rec. 1906;69:697–8.

    Google Scholar 

  3. Morris RT. Lectures on appendicitis and notes on other subjects. New York: GR Putnam’s sons; 1985. (156–9)

    Google Scholar 

  4. Parkes AS, Smith AU. Regeneration of rat ovarian tissue grafted after exposure to low temperature. Proc R Soc Lond B Biol Sci. 1953;140:455–67.

    CAS  PubMed  Google Scholar 

  5. Green SH, Smith AU, Zuckerman S. The number of oocytes in ovarian autografts after freezing and thawing. J Endocrinol. 1956;13:330–4.

    CAS  PubMed  Google Scholar 

  6. Deanesly R. Egg survival in immature rat ovaries grafted after freezing and thawing. Proc R Soc Lond B Biol Sci. 1957;147(928):412–21.

    CAS  PubMed  Google Scholar 

  7. Parrot DM. The fertility of mice with orthotopic grafts derived from frozen tissue. J Reprod Fertil. 1960;1:230–41.

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  9. Oktay K. Ovarian tissue cryopreservation and transplantation: preliminary findings and implications for cancer patients. Hum Reprod Update. 2001;7(6):526–34.

    CAS  PubMed  Google Scholar 

  10. Danjean R, Boeckx W, Gordt S, Brosens I. Ovarian transplantation by selective microvascular-anastomoses in the rabbit. Br J Obstet Gynaecol. 1982;89:652–6.

    Google Scholar 

  11. Betteridge KJ. Homotransplantation of ovaries with vascular anastomoses in rabbits: response to transplants to HCG. J Endocrinol. 1970;47:451–61.

    CAS  PubMed  Google Scholar 

  12. Harrison FA, Chambers SG, Green EA. Auto-transplantation of the ovary to the neck of the sow. J Endocrinol. 1979;83:46.

    Google Scholar 

  13. Revel A, Elami A, Bor A, Yavin S, Natan Y, Arav A. Whole sheep ovary cryopreservation and transplantation. Fertil Steril. 2004;82(6):1714–5.

    PubMed  Google Scholar 

  14. Harp R, Leibach J, Black J, Keldahl C, Karow A. Cryopreservation of murine ovarian tissue. Cryobiology. 1994;31:336–43.

    CAS  PubMed  Google Scholar 

  15. Cox SL, Shaw JM, Jenkin G. Transplantation of cryopreserved fetal ovarian tissue to adult recipients in mice. J Reprod Fertil. 1996;107:315–22.

    CAS  PubMed  Google Scholar 

  16. Sztein JM, Sweet H, Farley J, Mobraaten L. Cryopreservation and orthotopic transplantation of mouse ovaries: new approach in gamete banking. Biol Reprod. 1998;58:1071–4.

    CAS  PubMed  Google Scholar 

  17. 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 

  18. Dissen GA, Lara HE, Fahrenbach WH, Costa ME, Ojeda SR. Immature rat ovaries revascularized rapidly after auto-transplantation and show a gonadotropin-dependent increase in angiogenic factor gene expression. Endocrinology. 1994;134:1146–54.

    CAS  PubMed  Google Scholar 

  19. 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;140:462–71.

    CAS  PubMed  Google Scholar 

  20. Hovatta O, Silye R, Krausz T. Cryopreservation of human ovarian tissue using dimethylsulphoxide and propanediol-sucrose as cryoprotectants. Hum Reprod. 1996;11:1268–172.

    CAS  PubMed  Google Scholar 

  21. 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.

    CAS  PubMed  Google Scholar 

  22. 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;13:1133–8.

    CAS  PubMed  Google Scholar 

  23. 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.

    CAS  PubMed  Google Scholar 

  24. 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.

    CAS  PubMed  Google Scholar 

  25. Wells SAJ, Ellis GJ, Gunnells JC, Schneider AB, Sherwood LM. Parathyroid autotransplantation in primary parathyroid hyperplasia. NJEM. 1976;295:57–62.

    Google Scholar 

  26. Wagner PK, Seesko HG, Rothmund M. Replantation of cryopreserved human parathyroid tissue. World J Surg. 1991;15:751–5.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  28. Oktay K, Buyuk E, Rosenwaks Z, Rucinski J. A technique for transplantation of ovarian cortical strips to the forearm. Fertil Steril. 2003;80:193–8.

    PubMed  Google Scholar 

  29. Oktay K, Buyuk E, Veeck L. Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet (London, England). 2004;363:837–40.

    Google Scholar 

  30. Stern CJ, Gook D, Hale LG. Delivery of twins following heterotopic grafting of frozen-thawed ovarian tissue. Hum Reprod. 2014;29(8):1828.

    CAS  PubMed  Google Scholar 

  31. Stern K RG, Gook D, Agresta F, Braat D, Hale L. Are there factors which predict the success of ovarian tissue grafting in onco- fertility patients? Abstract presented at: 32nd annual meeting of the European Society of Human Reproduction and Embryology. 2016:2016. Helsinki, Finland.

  32. 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.

    PubMed  Google Scholar 

  33. 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-e10.

    PubMed  Google Scholar 

  34. Sanders JE, Hawley J, Levy W, Gooley T, Buckner CD, Deeg HJ, et al. Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood. 1996;87(7):3045–52.

    CAS  PubMed  Google Scholar 

  35. Salooja N, Szydlo RM, Socie G, Rio B, Chatterjee R, Ljungman P, et al. Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey. Lancet. 2001;358(9278):271–6.

    CAS  PubMed  Google Scholar 

  36. Donnez J, Dolmans MM, Demylle D. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;364:1405–10.

    CAS  PubMed  Google Scholar 

  37. Oktay K, Tilly J. Livebirth after cryopreserved ovarian tissue autotransplantation. Lancet. 2004;364:2091–2.

    PubMed  Google Scholar 

  38. Wallace WH, Pritchard J. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;364:2093–4.

    PubMed  Google Scholar 

  39. Hubinont C, Debieve F, Biard JM, Bernard P. Livebirth after cryopreserved ovarian tissue transplantation. Lancet. 2012;380(9837):106.

    CAS  PubMed  Google Scholar 

  40. 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.

    CAS  PubMed  Google Scholar 

  41. Donnez J, Jadoul P, Pirard C, Hutchings G, Demylle D, Squifflet J, et al. Live birth after transplantation of frozen-thawed ovarian tissue after bilateral oophorectomy for benign disease. Fertil Steril. 2012;98(3):720–5.

    PubMed  Google Scholar 

  42. Stern CJ, Gook D, Hale LG, et al. First reported clinical pregnancy following heterotopic grafting of cryopreserved ovarian tissue in a woman after a bilateral oophorectomy. Hum Reprod (Oxford, England). 2013;28(11):2996–9.

    CAS  Google Scholar 

  43. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Andersen CY, Rosendahl M, Byskov AG, et al. Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue. Human reproduction (Oxford, England). 2008;23(10):2266–72.

    Google Scholar 

  45. Donnez J, Dolmans MM. Transplantation of ovarian tissue. Best Pract Res Clin Obstet Gynaecol. 2014;28(8):1188–97.

    PubMed  Google Scholar 

  46. Paris F, Perez GI, Fuks Z, Haimovitz-Friedman A, Nguyen H, Bose M, et al. Sphingosine 1-phosphate preserves fertility in irradiated female mice without propagating genomic damage in offspring. Nat Med. 2002;8(9):901–2.

    CAS  PubMed  Google Scholar 

  47. Li F, Turan V, Lierman S, Cuvelier C, De Sutter P, Oktay K. Sphingosine-1-phosphate prevents chemotherapy-induced human primordial follicle death. Hum Reprod. 2014;29(1):107–13.

    CAS  PubMed  Google Scholar 

  48. Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387–401.

    CAS  PubMed  Google Scholar 

  49. Jayakumaran J, Patel SD, Gangrade BK, Narasimhulu DM, Pandian SR, Silva C. Robotic-assisted laparoscopy in reproductive surgery: a contemporary review. J Robot Surg. 2017;11(2):97–109.

    PubMed  Google Scholar 

  50. Oktay K, Taylan E, Sugishita Y, Goldberg GM. Robot-assisted laparoscopic transplantation of frozen-thawed ovarian tissue. J Minim Invasive Gynecol. 2017;24(6):897–8.

    PubMed  Google Scholar 

  51. Leal Ghezzi T, Campos CO. 30 years of robotic surgery. World J Surg. 2016;40(10):2550–7.

    PubMed  Google Scholar 

  52. Silber SJ, Lenahan KM, Levine DJ, Pineda JA, Gorman KS, Friez MJ, et al. Ovarian transplantation between monozygotic twins discordant for premature ovarian failure. N Engl J Med. 2005;353(1):58–63.

    CAS  PubMed  Google Scholar 

  53. Oktay K, Bedoschi G, Pacheco F, Turan V, Emirdar V. First pregnancies, live birth, and in vitro fertilization outcomes after transplantation of frozen-banked ovarian tissue with a human extracellular matrix scaffold using robot-assisted minimally invasive surgery. Am J Obstet Gynecol. 2016;214(1):94 e1-e9.

    PubMed  Google Scholar 

  54. Jansen LA, De Caigny P, Guay NA, Lineaweaver WC, Shokrollahi K. The evidence base for the acellular dermal matrix AlloDerm: a systematic review. Ann Plast Surg. 2013;70(5):587–94.

    CAS  PubMed  Google Scholar 

  55. Pacheco F, Oktay K. Current success and efficiency of autologous ovarian transplantation: a meta-analysis. Reprod Sci. 2017;24(8):1111–20.

    PubMed  Google Scholar 

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Funding

This report was partially supported by RO1 HD053112 from the Eunice Kennedy Shriver,

National Institute of Child Health and Human Development (NICHD), and National Cancer Institute (KO).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA

    Loris Marin, Giuliano Bedoschi, Tai Kawahara & Kutluk H Oktay

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  1. Loris Marin
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  2. Giuliano Bedoschi
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  4. Kutluk H Oktay
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Correspondence to Kutluk H Oktay.

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Marin, L., Bedoschi, G., Kawahara, T. et al. History, Evolution and Current State of Ovarian Tissue Auto-Transplantation with Cryopreserved Tissue: a Successful Translational Research Journey from 1999 to 2020. Reprod. Sci. 27, 955–962 (2020). https://doi.org/10.1007/s43032-019-00066-9

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