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Chapter 13 Human Ovarian Tissue Vitrification

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Cryopreservation of Mammalian Gametes and Embryos

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1568))

Abstract

Ovarian freezing and transplantation has garnered increasing interest as a potential way of preserving fertility in cancer patients as well as for women who just wish to delay childbearing. This chapter spells out our techniques of ovarian cortex vitrification and results for frozen compared to fresh ovarian cortex transplantation (in one single series from one center for the sake of consistency), as well as potentially provides insight into the mechanism behind ovarian follicle recruitment. This represents an effort to simplify and popularize an approach that has yielded favorable results (all cases recovered ovulation and 75% had successful spontaneous pregnancy) in one single, disciplined study. It should be clear that this is a review for the more general reader of our original scientific papers published in Reproductive BioMedicine Online, New England Journal of Medicine, Fertility and Sterility, Human Reproduction, Molecular Human Reproduction, and Journal of Assisted Reproduction and Genetics (JARG).

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References

  1. Silber S, Pineda J, Lenahan K, DeRosa M, Melnick J (2015) Fresh and cryopreserved ovary transplantation and resting follicle recruitment. Reprod Biomed Online 30(6):643–650

    Article  PubMed  Google Scholar 

  2. Silber S (2015) Unifying theory of adult resting follicle recruitment and fetal oocyte arrest. Reprod Biomed Online 31(4):472–475

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Silber SJ (2012) Ovary cryopreservation and transplantation for fertility preservation. Mol Hum Reprod 18(2):59–67

    Article  CAS  PubMed  Google Scholar 

  5. Demeestere I, Simon P, Englert Y, Delbaere A (2003) Preliminary experience of ovarian tissue cryopreservation procedure: alternatives, perspectives and feasibility. Reprod Biomed Online 7(5):572–579

    Article  PubMed  Google Scholar 

  6. Demeestere I, Simon P, Moffa F, Delbaere A, Englert Y (2010) Birth of a second healthy girl more than 3 years after cryopreserved ovarian graft. Hum Reprod 25(6):1590–1591

    Article  CAS  PubMed  Google Scholar 

  7. Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, Martinez-Madrid B, van Langendonckt A (2004) Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet 364(9443):1405–1410

    Article  CAS  PubMed  Google Scholar 

  8. Donnez J, Dolmans MM, Pellicer A, Diaz-Garcia C, Sanchez Serrano M, Schmidt KT, Ernst E, Luyckx V, Andersen CY (2013) Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: a review of 60 cases of reimplantation. Fertil Steril 99(6):1503–1513

    Article  PubMed  Google Scholar 

  9. Donnez J, Silber S, Andersen CY, Demeestere I, Piver P, Meirow D, Pellicer A, Dolmans MM (2011) Children born after autotransplantation of cryopreserved ovarian tissue. a review of 13 live births. Ann Med 43(6):437–450

    Article  PubMed  Google Scholar 

  10. Meirow D, Levron J, Eldar-Geva T, Hardan I, Fridman E, Zalel Y, Schiff E, Dor J (2005) Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med 353(3):318–321

    Article  CAS  PubMed  Google Scholar 

  11. Poirot C, Abirached F, Prades M, Coussieu C, Bernaudin F, Piver P (2012) Induction of puberty by autograft of cryopreserved ovarian tissue. Lancet 379(9815):588

    Article  PubMed  Google Scholar 

  12. Sanchez M, Alama P, Gadea B, Soares SR, Simon C, Pellicer A (2007) Fresh human orthotopic ovarian cortex transplantation: long-term results. Hum Reprod 22(3):786–791

    Article  CAS  PubMed  Google Scholar 

  13. Silber SJ, DeRosa M, Pineda J, Lenahan K, Grenia D, Gorman K, Gosden RG (2008) A series of monozygotic twins discordant for ovarian failure: ovary transplantation (cortical versus microvascular) and cryopreservation. Hum Reprod 23(7):1531–1537

    Article  CAS  PubMed  Google Scholar 

  14. Silber SJ, Gosden RG (2007) Ovarian transplantation in a series of monozygotic twins discordant for ovarian failure. N Engl J Med 356(13):1382–1384

    Article  CAS  PubMed  Google Scholar 

  15. Silber SJ, Grudzinskas G, Gosden RG (2008) Successful pregnancy after microsurgical transplantation of an intact ovary. N Engl J Med 359(24):2617–2618

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Andersen CY, Silber SJ, Bergholdt SH, Jorgensen JS, Ernst E (2012) Long-term duration of function of ovarian tissue transplants: case reports. Reprod Biomed Online 25(2):128–132

    Article  PubMed  Google Scholar 

  18. Stoop D, Cobo A, Silber S (2014) Fertility preservation for age-related fertility decline. Lancet 384(9950):1311–1319

    Article  PubMed  Google Scholar 

  19. Homburg R, van der Veen F, Silber SJ (2009) Oocyte vitrification--women’s emancipation set in stone. Fertil Steril 91(4 Suppl):1319–1320

    Article  PubMed  Google Scholar 

  20. Nagy ZP, Chang CC, Shapiro DB, Bernal DP, Kort HI, Vajta G (2009) The efficacy and safety of human oocyte vitrification. Semin Reprod Med 27(6):450–455

    Article  CAS  PubMed  Google Scholar 

  21. Cobo A, Domingo J, Perez S, Crespo J, Remohi J, Pellicer A (2008) Vitrification: an effective new approach to oocyte banking and preserving fertility in cancer patients. Clin Transl Oncol 10(5):268–273

    Article  CAS  PubMed  Google Scholar 

  22. Silber S (2016) Ovarian tissue cryopreservation and transplantation: scientific implications. J Assist Reprod Genet

    Google Scholar 

  23. Lass A, Paul M, Margara R, Winston RM (1997) Women with one ovary have decreased response to GnRHa/HMG ovulation protocol in IVF but the same pregnancy rate as women with two ovaries. Hum Reprod 12(2):298–300

    Article  CAS  PubMed  Google Scholar 

  24. Zhai A, Axt J, Hamilton EC, Koehler E, Lovvorn HN III (2012) Assessing gonadal function after childhood ovarian surgery. J Pediatr Surg 47(6):1272–1279

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gosden RG, Telfer E, Faddy MJ, Brook DJ (1989) Ovarian cyclicity and follicular recruitment in unilaterally ovariectomized mice. J Reprod Fertil 87(1):257–264

    Article  CAS  PubMed  Google Scholar 

  26. Anderson EL, Baltus AE, Roepers-Gajadien HL, Hassold TJ, de Rooij DG, van Pelt AM, Page DC (2008) Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice. Proc Natl Acad Sci U S A 105(39):14976–14980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dittrich R, Mueller A, Maltaris T, Hoffmann I, Magener A, Oppelt PG, Beckmann MW (2009) Hormonal and histologic findings in human cryopreserved ovarian autografts. Fertil Steril 91(4 Suppl):1503–1506

    Article  PubMed  Google Scholar 

  28. Revel A, Laufer N, Ben Meir A, Lebovich M, Mitrani E (2011) Micro-organ ovarian transplantation enables pregnancy: a case report. Hum Reprod 26(5):1097–1103

    Article  PubMed  Google Scholar 

  29. Revelli A, Marchino G, Dolfin E, Molinari E, Delle Piane L, Salvagno F, Benedetto C (2013) Live birth after orthotopic grafting of autologous cryopreserved ovarian tissue and spontaneous conception in Italy. Fertil Steril 99(1):227–230

    Article  PubMed  Google Scholar 

  30. Stern CJ, Gook D, Hale LG, Agresta F, Oldham J, Rozen G, Jobling T (2013) First reported clinical pregnancy following heterotopic grafting of cryopreserved ovarian tissue in a woman after a bilateral oophorectomy. Hum Reprod 28(11):2996–2999

    Article  CAS  PubMed  Google Scholar 

  31. Deanesly R (1954) Immature rat ovaries grafted after freezing and thawing. J Endocrinol 11(2):197–200

    Article  CAS  PubMed  Google Scholar 

  32. Bruce HM, Parrott DM (1960) Role of olfactory sense in pregnancy block by strange males. Science 131(3412):1526

    Article  CAS  PubMed  Google Scholar 

  33. Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, Ho CH, Kawamura N, Tamura M, Hashimoto S, Sugishita Y, Morimoto Y, Hosoi Y, Yoshioka N, Ishizuka B, Hsueh AJ (2013) Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A 110(43):17474–17479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Oktay K, Economos K, Kan M, Rucinski J, Veeck L, Rosenwaks Z (2001) Endocrine function and oocyte retrieval after autologous transplantation of ovarian cortical strips to the forearm. JAMA 286(12):1490–1493

    Article  CAS  PubMed  Google Scholar 

  35. Aydin Y, Celiloglu M, Koyuncuoglu M, Ulukus C (2010) Follicular dynamics and apoptosis following unilateral oophorectomy. Syst Biol Reprod Med 56(4):311–317

    Article  PubMed  Google Scholar 

  36. Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF (1992) Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 7(10):1342–1346

    Article  CAS  PubMed  Google Scholar 

  37. Kaaijk EM, Hamerlynck JV, Beek JF, van der Veen F (1999) Clinical outcome after unilateral oophorectomy in patients with polycystic ovary syndrome. Hum Reprod 14(4):889–892

    Article  CAS  PubMed  Google Scholar 

  38. Kim SS (2003) Ovarian tissue banking for cancer patients. To do or not to do? Hum Reprod 18(9):1759–1761

    Article  PubMed  Google Scholar 

  39. Koskas M, Uzan C, Gouy S, Pautier P, Lhomme C, Haie-Meder C, Duvillard P, Morice P (2011) Fertility determinants after conservative surgery for mucinous borderline tumours of the ovary (excluding peritoneal pseudomyxoma). Hum Reprod 26(4):808–814

    Article  PubMed  Google Scholar 

  40. Meredith S, Dudenhoeffer G, Butcher RL, Lerner SP, Walls T (1992) Unilateral ovariectomy increases loss of primordial follicles and is associated with increased metestrous concentration of follicle-stimulating hormone in old rats. Biol Reprod 47(2):162–168

    Article  CAS  PubMed  Google Scholar 

  41. Saiduddin S, Rowe RF, Casida LE (1970) Ovarian follicular changes following unilateral ovariectomy in the cow. Biol Reprod 2(3):408–412

    Article  CAS  PubMed  Google Scholar 

  42. Yasui T, Hayashi K, Mizunuma H, Kubota T, Aso T, Matsumura Y, Lee JS, Suzuki S (2012) Factors associated with premature ovarian failure, early menopause and earlier onset of menopause in Japanese women. Maturitas 72(3):249–255

    Article  PubMed  Google Scholar 

  43. Silber S, Kagawa N, Kuwayama M, Gosden R (2010) Duration of fertility after fresh and frozen ovary transplantation. Fertil Steril 94(6):2191–2196

    Article  PubMed  Google Scholar 

  44. La Marca A, Giulini S, Tirelli A, Bertucci E, Marsella T, Xella S, Volpe A (2007) Anti-Mullerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology. Hum Reprod 22(3):766–771

    Article  CAS  PubMed  Google Scholar 

  45. Baird DT, Webb R, Campbell BK, Harkness LM, Gosden RG (1999) Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at −196 °C. Endocrinology 140(1):462–471

    CAS  Google Scholar 

  46. Kagawa N, Silber S, Kuwayama M (2009) Successful vitrification of bovine and human ovarian tissue. Reprod Biomed Online 18(4):568–577

    Article  PubMed  Google Scholar 

  47. Newton H, Aubard Y, Rutherford A, Sharma V, Gosden R (1996) Low temperature storage and grafting of human ovarian tissue. Hum Reprod 11(7):1487–1491

    Article  CAS  PubMed  Google Scholar 

  48. Keros V, Xella S, Hultenby K, Pettersson K, Sheikhi M, Volpe A, Hreinsson J, Hovatta O (2009) Vitrification versus controlled-rate freezing in cryopreservation of human ovarian tissue. Hum Reprod 24(7):1670–1683

    Article  CAS  PubMed  Google Scholar 

  49. Fuentes, F., Dubettier, R. (2004). Air Separation Method and Plant, United States Patent. Patent No. US 6,776,005 B2.

    Google Scholar 

  50. Bleyer WA (1990) The impact of childhood cancer on the United States and the world. CA Cancer J Clin 40(6):355–367

    Article  CAS  PubMed  Google Scholar 

  51. Ries, L. A. G., and SEER Program (National Cancer Institute (U.S.)). (1999). Cancer incidence and survival among children and adolescents: United States SEER program 1975–1995/[edited by Lynn A. Gloecker Ries ... et al.], Bethesda, MD: National Cancer Institute, SEER Program

    Google Scholar 

  52. Larsen EC, Muller J, Schmiegelow K, Rechnitzer C, Andersen AN (2003) Reduced ovarian function in long-term survivors of radiation- and chemotherapy-treated childhood cancer. J Clin Endocrinol Metab 88(11):5307–5314

    Article  CAS  PubMed  Google Scholar 

  53. Anderson RA, Themmen AP, Al-Qahtani A, Groome NP, Cameron DA (2006) The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod 21(10):2583–2592

    Article  CAS  PubMed  Google Scholar 

  54. Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, Beck LN, Brennan LV, Oktay K, American Society of Clinical, O (2006) American society of clinical oncology recommendations on fertility preservation in cancer patients. J Clin Oncol 24(18):2917–2931

    Article  PubMed  Google Scholar 

  55. Anderson RA, Cameron DA (2007) Assessment of the effect of chemotherapy on ovarian function in women with breast cancer. J Clin Oncol 25(12):1630–1631. author reply 1632

    Article  PubMed  Google Scholar 

  56. Jeruss JS, Woodruff TK (2009) Preservation of fertility in patients with cancer. N Engl J Med 360(9):902–911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Greve T, Clasen-Linde E, Andersen MT, Andersen MK, Sorensen SD, Rosendahl M, Ralfkiaer E, Andersen CY (2012) Cryopreserved ovarian cortex from patients with leukemia in complete remission contains no apparent viable malignant cells. Blood 120(22):4311–4316

    Article  CAS  PubMed  Google Scholar 

  58. Gook DA, Edgar DH, Stern C (1999) Effect of cooling rate and dehydration regimen on the histological appearance of human ovarian cortex following cryopreservation in 1, 2-propanediol. Hum Reprod 14(8):2061–2068

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Sherman Silber M.D. .

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Silber, S. (2017). Chapter 13 Human Ovarian Tissue Vitrification. In: Nagy, Z., Varghese, A., Agarwal, A. (eds) Cryopreservation of Mammalian Gametes and Embryos. Methods in Molecular Biology, vol 1568. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6828-2_13

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  • DOI: https://doi.org/10.1007/978-1-4939-6828-2_13

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6826-8

  • Online ISBN: 978-1-4939-6828-2

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