Skip to main content

Vitrification of Ovarian Tissue for Fertility Preservation

Abstract

While 80 % of young patients currently survive their cancers, devastating side effects of chemo- or radiotherapies leave females facing infertility due to ovarian failure. Cryopreservation of embryos, oocytes, and ovarian tissue is available to preserve fertility in female patients with cancer. Both embryo and oocyte freezing are established methods, and ovarian tissue cryopreservation has emerged as a promising hope for future fertility for patients who are prepubertal, adolescent, lacking partners, or those who require immediate cancer therapy. Autografting of cryopreserved ovarian tissue to women restored ovarian endocrine function and resulted in live births, but this fertility preservation option is still considered experimental. All but two of the 60 reported human births have resulted from ovarian tissue cryopreserved using a slow-rate freezing protocol. The slower progress for clinical implementation of ovarian tissue vitrification is due to the lack of a uniform vitrification protocol, in contrast to slow-rate freezing, that demonstrates consistent outcome. Recent advances in embryo and oocyte cryopreservation have driven clinical practice in the United States almost exclusively to vitrification, with the vast majority of infertility clinics no longer having access to programmable freezers in their embryology laboratories. Thus, there is a current demand for an ovarian tissue vitrification method that could extend the ability of clinics to offer this option for fertility preservation. This chapter compares and contrasts slow-rate freezing with vitrification, discusses the facts and fallacies surrounding ovarian tissue vitrification, and summarizes the steps necessary for optimizing a method for ovarian tissue vitrification using a logical approach based on cryobiological principles. Advantages and disadvantages of various endpoints used for assessing the morphology and function of vitrified ovarian tissue are also described. Emerging studies in nonhuman primates, whose ovarian structure and function are similar to women, reveal the first evidence of in vivo function of vitrified-thawed ovarian tissue after transplantation including restoration of ovarian cyclicity as well as collection of healthy mature oocytes capable of early embryonic development in vitro. The first reports of live births in women who underwent heterotopic transplantation with vitrified-thawed ovarian tissue unequivocally demonstrate that vitrification is an effective method of human ovarian tissue cryopreservation that preserves ovarian function, including the fertile potential of this tissue. Ovarian tissue vitrification using optimized protocols underscored by best manufacturing methods for vitrification solutions along with successful clinical practice for transplantation is an immediate need for patients whose sole option for one day becoming parents is ovarian tissue cryopreservation.

Keywords

  • Cancer patients
  • Fertility preservation
  • Nonhuman primates
  • Ovarian tissue cryopreservation
  • Ovarian tissue transplantation
  • Vitrification

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-319-32973-4_6
  • Chapter length: 19 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   109.00
Price excludes VAT (USA)
  • ISBN: 978-3-319-32973-4
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   139.99
Price excludes VAT (USA)
Hardcover Book
USD   149.99
Price excludes VAT (USA)
Fig. 6.1
Fig. 6.2
Fig. 6.3
Fig. 6.4
Fig. 6.5

References

  1. Amorim CA, Curaba M, Van Langendonckt A, Dolmans MM, Donnez J. Vitrification as an alternative means of cryopreserving ovarian tissue. Reprod Biomed Online. 2011;23(2):160–86.

    CrossRef  PubMed  Google Scholar 

  2. Amorim CA, Jacobs S, Devireddy RV, Van Langendonckt A, Vanacker J, Jaeger J, et al. Successful vitrification and autografting of baboon (Papio anubis) ovarian tissue. Hum Reprod. 2013;28(8):2146–56.

    CAS  CrossRef  PubMed  Google Scholar 

  3. Bielanski A, Vajta G. Risk of contamination of germplasm during cryopreservation and cryobanking in IVF units. Hum Reprod. 2009;24(10):2457–67.

    CAS  CrossRef  PubMed  Google Scholar 

  4. Dittrich R, Lotz L, Fehm T, Krussel J, von Wolff M, Toth B, et al. Xenotransplantation of cryopreserved human ovarian tissue – a systematic review of MII oocyte maturation and discussion of it as a realistic option for restoring fertility after cancer treatment. Fertil Steril. 2015;103(6):1557–65.

    CrossRef  PubMed  Google Scholar 

  5. Donnez J, Dolmans MM, Pellicer A, Diaz-Garcia C, Sanchez Serrano M, Schmidt KT, et al. 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.

    CrossRef  PubMed  Google Scholar 

  6. Donnez J, Dolmans MM. Ovarian cortex transplantation: 60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice. J Assist Reprod Genet. 2015;32(8):1167–70.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  7. Fahy GM, MacFarlane DR, Angell CA, Meryman HT. Vitrification as an approach to cryopreservation. Cryobiology. 1984;21(4):407–26.

    CAS  CrossRef  PubMed  Google Scholar 

  8. Fahy GM, Rall WF. Vitrification: an overview. In: Tucker MJ, Liebermann J, editors. Vitrification in assisted reproduction. London: Informa Healthcare; 2007. p. 1–20.

    CrossRef  Google Scholar 

  9. Grazul-Bilska AT, Banerjee J, Yazici I, Borowczyk E, Bilski JJ, Sharma RK, et al. Morphology and function of cryopreserved whole ovine ovaries after heterotopic autotransplantation. Reprod Biol Endocrinol. 2008;6:16.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  10. Hasegawa A, Mochida N, Ogasawara T, Koyama K. Pup birth from mouse oocytes in preantral follicles derived from vitrified and warmed ovaries followed by in vitro growth, in vitro maturation, and in vitro fertilization. Fertil Steril. 2006;86(4 Suppl):1182–92.

    CrossRef  PubMed  Google Scholar 

  11. Hashimoto S, Suzuki N, Yamanaka M, Hosoi Y, Ishizuka B, Morimoto Y. Effects of vitrification solutions and equilibration times on the morphology of cynomolgus ovarian tissues. Reprod Biomed Online. 2010;21(4):501–9.

    CrossRef  PubMed  Google Scholar 

  12. Hogg K, Etherington SL, Young JM, McNeilly AS, Duncan WC. Inhibitor of differentiation (Id) genes are expressed in the steroidogenic cells of the ovine ovary and are differentially regulated by members of the transforming growth factor-beta family. Endocrinology. 2010;151(3):1247–56.

    CAS  CrossRef  PubMed  Google Scholar 

  13. Hopkins JB, Badeau R, Warkentin M, Thorne RE. Effect of common cryoprotectants on critical warming rates and ice formation in aqueous solutions. Cryobiology. 2012;65(3):169–78.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  14. Hussein MR, Bedaiwy MA, Falcone T. Analysis of apoptotic cell death, Bcl-2, and p53 protein expression in freshly fixed and cryopreserved ovarian tissue after exposure to warm ischemia. Fertil Steril. 2006;85 Suppl 1:1082–92.

    CAS  CrossRef  PubMed  Google Scholar 

  15. Isachenko V, Lapidus I, Isachenko E, Krivokharchenko A, Kreienberg R, Woriedh M, et al. Human ovarian tissue vitrification versus conventional freezing: morphological, endocrinological, and molecular biological evaluation. Reproduction. 2009;138(2):319–27.

    CAS  CrossRef  PubMed  Google Scholar 

  16. Jeruss JS, Woodruff TK. Preservation of fertility in patients with cancer. N Engl J Med. 2009;360(9):902–11.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  17. Jin S, Lei L, Shea LD, Zelinski MB, Stouffer RL, Woodruff TK. Markers of growth and development in primate primordial follicles are preserved after slow cryopreservation. Fertil Steril. 2010;93(8):2627–32.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  18. Johnson MH, Pickering SJ. The effect of dimethyl sulphoxide on the microtubular system of the mouse oocyte. Development. 1987;100(2):313–24.

    CAS  PubMed  Google Scholar 

  19. Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, et al. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A. 2013;110(43):17474–9.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  20. Lee DM, Ting A, Thomas C, Bishop C, Xu F, Zelinski MB. Heterotopic transplants of vitrified ovarian tissue in macaques: assessment of follicular function, embryonic development and a novel microbubble assay for blood flow. Fertil Steril. 2012;98(3):S69.

    CrossRef  Google Scholar 

  21. Lee J, Kim SK, Youm HW, Kim HJ, Lee JR, Suh CS, et al. Effects of three different types of antifreeze proteins on mouse ovarian tissue cryopreservation and transplantation. PLoS One. 2015;10(5):e0126252.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  22. Mazur P. Kinetics of water loss from cells at subzero temperatures and the likelihood of intracellular freezing. J Gen Physiol. 1963;47:47–69.

    CrossRef  Google Scholar 

  23. Mazur P, Leibo SP, Chu EH. A two-factor hypothesis of freezing injury. Evidence from Chinese hamster tissue-culture cells. Exp Cell Res. 1972;71(2):345–55.

    CAS  CrossRef  PubMed  Google Scholar 

  24. Mazur P. Principles of cryobiology. In: Fuller BJ, Lane N, Benson EE, editors. Life in the frozen state. Boca Raton: CRC Press; 2004. p. 3–65.

    CrossRef  Google Scholar 

  25. Mullen SF, Li M, Li Y, Chen ZJ, Critser JK. Human oocyte vitrification: the permeability of metaphase II oocytes to water and ethylene glycol and the appliance toward vitrification. Fertil Steril. 2008;89(6):1812–25.

    CrossRef  PubMed  Google Scholar 

  26. Mullen SF, Fahy GM. Fundamental aspects of vitrification as a method of reproductive cell, tissue, and organ cryopreservation. In: Donnez J, Kim SS, editors. Principles and practice of fertility preservation. Cambridge: Cambridge University Press; 2011. p. 145–63.

    CrossRef  Google Scholar 

  27. Onions VJ, Mitchell MR, Campbell BK, Webb R. Ovarian tissue viability following whole ovine ovary cryopreservation: assessing the effects of sphingosine-1-phosphate inclusion. Hum Reprod. 2008;23(3):606–18.

    CAS  CrossRef  PubMed  Google Scholar 

  28. Otsuka F, McTavish KJ, Shimasaki S. Integral role of GDF-9 and BMP-15 in ovarian function. Mol Reprod Dev. 2011;78(1):9–21.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  29. Pegg DE. The role of vitrification techniques of cryopreservation in reproductive medicine. Hum Fertil (Camb). 2005;8(4):231–9.

    CAS  CrossRef  Google Scholar 

  30. Pegg DE. The relevance of ice crystal formation for the cryopreservation of tissues and organs. Cryobiology. 2010;60(3 Suppl):S36–44.

    CrossRef  PubMed  Google Scholar 

  31. Rall WF, Mazur P, McGrath JJ. Depression of the ice-nucleation temperature of rapidly cooled mouse embryos by glycerol and dimethyl sulfoxide. Biophys J. 1983;41(1):1–12.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  32. Sadeu JC, Smitz J. Growth differentiation factor-9 and anti-Mullerian hormone expression in cultured human follicles from frozen-thawed ovarian tissue. Reprod Biomed Online. 2008;17(4):537–48.

    CAS  CrossRef  PubMed  Google Scholar 

  33. Schmidt KL, Byskov AG, Nyboe Andersen A, Muller J, Yding Andersen C. Density and distribution of primordial follicles in single pieces of cortex from 21 patients and in individual pieces of cortex from three entire human ovaries. Hum Reprod. 2003;18(6):1158–64.

    CAS  CrossRef  PubMed  Google Scholar 

  34. Steif PS, Palastro MC, Rabin Y. The effect of temperature gradients on stress development during cryopreservation via vitrification. Cell Preserv Technol. 2007;5(2):104–15.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  35. Suzuki N, Hashimoto S, Igarashi S, Takae S, Yamanaka M, Yamochi T, et al. Assessment of long-term function of heterotopic transplants of vitrified ovarian tissue in cynomolgus monkeys. Hum Reprod. 2012;27(8):2420–9.

    CrossRef  PubMed  Google Scholar 

  36. Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, et al. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod. 2015;30(3):608–15.

    CrossRef  PubMed  Google Scholar 

  37. Ting AY, Yeoman RR, Lawson MS, Zelinski MB. Synthetic polymers improve vitrification outcomes of macaque ovarian tissue as assessed by histological integrity and the in vitro development of secondary follicles. Cryobiology. 2012;65(1):1–11.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  38. Ting AY, Yeoman RR, Campos JR, Lawson MS, Mullen SF, Fahy GM, et al. Morphological and functional preservation of pre-antral follicles after vitrification of macaque ovarian tissue in a closed system. Hum Reprod. 2013;28(5):1267–79.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  39. Toner M, Cravalho EG, Karel M, Armant DR. Cryomicroscopic analysis of intracellular ice formation during freezing of mouse oocytes without cryoadditives. Cryobiology. 1991;28(1):55–71.

    CAS  CrossRef  PubMed  Google Scholar 

  40. Vajta G, Nagy ZP. Are programmable freezers still needed in the embryo laboratory? Rev Vitrification Reprod Biomed Online. 2006;12(6):779–96.

    CrossRef  Google Scholar 

  41. Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, et al. Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod. 2004;10(2):77–83.

    CAS  CrossRef  PubMed  Google Scholar 

  42. Wowk B. Thermodynamic aspects of vitrification. Cryobiology. 2010;60(1):11–22.

    CAS  CrossRef  PubMed  Google Scholar 

  43. Wright CS, Hovatta O, Margara R, Trew G, Winston RM, Franks S, et al. Effects of follicle-stimulating hormone and serum substitution on the in-vitro growth of human ovarian follicles. Hum Reprod. 1999;14(6):1555–62.

    CAS  CrossRef  PubMed  Google Scholar 

  44. Xiao Z, Wang Y, Li L, Li SW. Cryopreservation of the human ovarian tissue induces the expression of Fas system in morphologically normal primordial follicles. Cryo Letters. 2010;31(2):112–9.

    PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Oncofertility Consortium NIH UL1 RR024926 (HD058293, HD058294, PL1-EB008542), U54-HD18185 (Eunice Kennedy Shriver Specialized Cooperative Centers Program in Reproduction and Infertility Research), and ONPRC 8P51OD011092.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alison Y. Ting PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Ting, A.Y., Mullen, S.F., Zelinski, M.B. (2017). Vitrification of Ovarian Tissue for Fertility Preservation. In: Woodruff, T., Gosiengfiao, Y. (eds) Pediatric and Adolescent Oncofertility. Springer, Cham. https://doi.org/10.1007/978-3-319-32973-4_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-32973-4_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-32971-0

  • Online ISBN: 978-3-319-32973-4

  • eBook Packages: MedicineMedicine (R0)