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Chapter 22 - Ovarian Cryopreservation and Transplantation


from Section 7 - Ovarian Cryopreservation and Transplantation

Published online by Cambridge University Press:  27 March 2021

Jacques Donnez
Catholic University of Louvain, Brussels
S. Samuel Kim
University of Kansas School of Medicine
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This book is primarily about prevention; its emphasis is on interventions that can be done at the time of cancer diagnosis – modifications of treatment and techniques for storing gametes, tissues or embryos for future use. By contrast, this chapter explores options open to cancer survivors after treatment has been completed. If preventive treatment was successful, either through medical interventions such as using less gonadotoxic regimens, fertility-sparing surgery, oophoropexy or gonadoprotective adjuncts like GnRH agonists, normal fertility has been preserved. Other survivors may be able to conceive using the gametes, embryos or tissue that was obtained and cryopreserved before their gonadotoxic treatment(s). However, in some cases, fertility preservation may not have been possible before treatment or, alternatively, the cryopreserved gametes, embryos or tissue may not have resulted in a successful pregnancy. This chapter provides insight into the fertility management of cancer survivors with compromised or absent ovarian function, who do not have cryopreserved gametes, embryos, or ovarian tissue.

Fertility Preservation
Principles and Practice
, pp. 243 - 259
Publisher: Cambridge University Press
Print publication year: 2021

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Andersen, CY, Rosendahl, M, Byskov, AG et al. Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue. Hum Reprod, 2008;23:22662272.CrossRefGoogle ScholarPubMed
Demeestere, I, Simon, P, Emiliani, S et al. Fertility preservation: successful transplantation of cryopreserved ovarian tissue in a young patient previously treated for Hodgkin’s disease. The Oncologist, 2007;12:14371442.CrossRefGoogle Scholar
Donnez, J, Dolmans, MM. Fertility preservation in women. N Engl J Med, 2017;377:16571665.CrossRefGoogle ScholarPubMed
Donnez, J, Dolmans, MM, Demylle, D et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. The Lancet, 2004;364:14051410.CrossRefGoogle ScholarPubMed
Gellert, S, Pors, S, Kristensen, SG et al. Transplantation of frozen-thawed ovarian tissue: an update on worldwide activity published in peer-reviewed papers and on the Danish cohort. J Assist Reprod Genet, 2018;35:561570.CrossRefGoogle ScholarPubMed
Meirow, D, Levron, J, Eldar-Geva, T et al. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med, 2005;353:318321.CrossRefGoogle Scholar
Roux, C, Amiot, C, Agnani, G et al. Live birth after ovarian tissue autograft in a patient with sickle cell disease treated by allogeneic bone marrow transplantation. Fertil Steril, 2010;93:2413. e15e19.CrossRefGoogle Scholar
Sánchez-Serrano, M, Crespo, J, Mirabet, V et al. Twins born after transplantation of ovarian cortical tissue and oocyte vitrification. Fertil Steril, 2010;93:268. e11e13.CrossRefGoogle ScholarPubMed
Silber, S, DeRosa, M, Pineda, Je et al. A series of monozygotic twins discordant for ovarian failure: ovary transplantation (cortical versus microvascular) and cryopreservation. Hum Reprod, 2008;23:15311537.CrossRefGoogle ScholarPubMed
Morris, RT. The ovarian graft. New York Medical Journal, 1895;62:697698.Google Scholar
Parrott, DM. The fertility of mice with orthotopic ovarian grafts derived from frozen tissue. J Reprod Fertil, 1960;1:230241.CrossRefGoogle Scholar
Gosden, R, Baird, D, Wade, J et al. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at-196 C. Hum Reprod, 1994;9:597603.CrossRefGoogle Scholar
Goding, J, McCracken, J, Baird, D. The study of ovarian function in the ewe by means of a vascular autotransplantation technique. J Endocrinol, 1967;39:37-NP.CrossRefGoogle Scholar
Winston, R, Browne, JM. Pregnancy following autograft transplantation of fallopian tube and ovary in the rabbit. The Lancet, 1974;304:494495.CrossRefGoogle Scholar
Scott, JR, Keye, WR, Poulson, AM et al. Microsurgical ovarian transplantation in the primate. Fertil Steril, 1981;36:512515.CrossRefGoogle ScholarPubMed
Leporrier, M, Von Theobald, P, Roffe, JL et al. A new technique to protect ovarian function before pelvic irradiation: heterotopic ovarian autotransplantation. Cancer, 1987;60:22012204.3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
Silber, SJ, Grudzinskas, G, Gosden, RG. Successful pregnancy after microsurgical transplantation of an intact ovary. N Engl J Med, 2008;359:26172618.CrossRefGoogle ScholarPubMed
Wang, X, Chen, H, Yin, H et al. Cryopreservation: fertility after intact ovary transplantation. Nature, 2002;415:385.CrossRefGoogle ScholarPubMed
von Wolff, M, Donnez, J, Hovatta, O et al. Cryopreservation and autotransplantation of human ovarian tissue prior to cytotoxic therapy–a technique in its infancy but already successful in fertility preservation. Eur J Cancer, 2009;45:15471553.CrossRefGoogle ScholarPubMed
Van der Ven, H, Liebenthron, J, Beckmann, M et al. Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates. Hum Reprod, 2016;31:20312041.CrossRefGoogle Scholar
Dittrich, R, Maltaris, T. A simple freezing protocol for the use of an open freezing system for cryopreservation of ovarian tissue. Cryobiology, 2006;52:166.CrossRefGoogle ScholarPubMed
Bagis, H, Aktoprakligil, D, Mercan, HO et al. Stable transmission and transcription of newfoundland ocean pout type III fish antifreeze protein (AFP) gene in transgenic mice and hypothermic storage of transgenic ovary and testis. Mol Reprod Devel, 2006;73:14041411.CrossRefGoogle ScholarPubMed
Arav, A, Natan, D. Directional freezing of reproductive cells and organs. Reprod Dom Anim, 2012;47:193196.CrossRefGoogle ScholarPubMed
Bos-Mikich, A, Marques, L, Rodrigues, JL et al. The use of a metal container for vitrification of mouse ovaries, as a clinical grade model for human ovarian tissue cryopreservation, after different times and temperatures of transport. J Assist Reprod Genet, 2012;29:12671271.CrossRefGoogle Scholar
Youm, HW, Lee, JR, Lee, J et al. Optimal vitrification protocol for mouse ovarian tissue cryopreservation: effect of cryoprotective agents and in vitro culture on vitrified–warmed ovarian tissue survival. Hum Reprod, 2013;29:720730.CrossRefGoogle ScholarPubMed
Lee, J, Kim, SK, Youm, HW et al. Effects of three different types of antifreeze proteins on mouse ovarian tissue cryopreservation and transplantation. PLoS One, 2015;10:e0126252.CrossRefGoogle ScholarPubMed
Lee, JR, Youm, HW, Lee, HJ et al. Effect of antifreeze protein on mouse ovarian tissue cryopreservation and transplantation. Yonsei Med J, 2015;56:778784.CrossRefGoogle ScholarPubMed
Pegg, D, Diaper, M. On the mechanism of injury to slowly frozen erythrocytes. Biophys J, 1988;54:471488.CrossRefGoogle ScholarPubMed
Newton, H, Aubard, Y, Rutherford, A et al. Ovary and ovulation: Low temperature storage and grafting of human ovarian tissue. Hum Reprod, 1996;11:14871491.CrossRefGoogle Scholar
Gook, DA, Edgar, D, 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;14:20612068.CrossRefGoogle ScholarPubMed
Kong, HS, Kim, EJ, Youm, HW et al. Improvement in ovarian tissue quality with supplementation of antifreeze protein during warming of vitrified mouse ovarian tissue. Yonsei Med J, 2018;59:331336.CrossRefGoogle ScholarPubMed
Yin, H, Kim, S, Fisher, J et al. Investigation of optimal conditions for equilibrating ovarian tissue with ethylene glycol prior to vitrification. Fertil Steril, 2001;76:S101.CrossRefGoogle Scholar
Kim, SS. Fertility preservation in female cancer patients: current developments and future directions. Fertil Steril, 2006;85:111.CrossRefGoogle ScholarPubMed
Dissen, G, Lara, H, Fahrenbach, W et al. Immature rat ovaries become revascularized rapidly after autotransplantation and show a gonadotropin-dependent increase in angiogenic factor gene expression. Endocrinology, 1994;134:11461154.CrossRefGoogle ScholarPubMed
Kim, SS, Yang, HW, Kang, HG et al. Quantitative assessment of ischemic tissue damage in ovarian cortical tissue with or without antioxidant (ascorbic acid) treatment. Fertil Steril, 2004;82:679685.CrossRefGoogle ScholarPubMed
Baird, D, Webb, R, Campbell, B et al. Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at − 196 C. Endocrinology, 1999;140:462471.CrossRefGoogle ScholarPubMed
Aubard, Y, Piver, P, Cognie, Y et al. Orthotopic and heterotopic autografts of frozen–thawed ovarian cortex in sheep. Hum Reprod, 1999;14:21492154.CrossRefGoogle Scholar
Nugent, D, Newton, H, Gallivan, L et al. Protective effect of vitamin E on ischaemia-reperfusion injury in ovarian grafts. J Reprod Fertil, 1998;114:341346.CrossRefGoogle ScholarPubMed
Kim, EJ, Lee, HJ, Lee, J et al. The beneficial effects of polyethylene glycol-superoxide dismutase on ovarian tissue culture and transplantation. J Assist Reprod Genet, 2015;32:15611569.CrossRefGoogle ScholarPubMed
Imthurn, B, Cox, S-L, Jenkin, G et al. Gonadotrophin administration can benefit ovarian tissue grafted to the body wall: implications for human ovarian grafting. Mol Cell Endocrinol, 2000;163:141146.CrossRefGoogle ScholarPubMed
Xia, X, Yin, T, Yan, J et al. Mesenchymal stem cells enhance angiogenesis and follicle survival in human cryopreserved ovarian cortex transplantation. Cell Transplant, 2015;24:19992010.CrossRefGoogle ScholarPubMed
Labied, S, Delforge, Y, Munaut, C et al. Isoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation. Transplantation, 2013;95:426433.CrossRefGoogle ScholarPubMed
Israely, T, Dafni, H, Granot, D et al. Vascular remodeling and angiogenesis in ectopic ovarian transplants: a crucial role of pericytes and vascular smooth muscle cells in maintenance of ovarian grafts. Biol Reprod, 2003;68:20552064.CrossRefGoogle ScholarPubMed
Adhikari, D, Liu, K. Molecular mechanisms underlying the activation of mammalian primordial follicles. Endocr Rev, 2009;30:438464.CrossRefGoogle ScholarPubMed
Roness, H, Kalich-Philosoph, L, Meirow, D. Prevention of chemotherapy-induced ovarian damage: possible roles for hormonal and non-hormonal attenuating agents. Hum Reprod Update, 2014;20:759774.CrossRefGoogle ScholarPubMed
Shaw, J, Bowles, J, Koopman, P et al. Ovary and ovulation: Fresh and cryopreserved ovarian tissue samples from donors with lymphoma transmit the cancer to graft recipients. Hum Reprod, 1996;11:16681673.CrossRefGoogle Scholar
Kim, SS, Radford, J, Harris, M et al. Ovarian tissue harvested from lymphoma patients to preserve fertility may be safe for autotransplantation. Hum Reprod, 2001;16:20562060.CrossRefGoogle ScholarPubMed
Meirow, D, Hardan, I, Dor, J et al. Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients. Hum Reprod, 2008;23:10071013.CrossRefGoogle ScholarPubMed
Dolmans, M-M, Marinescu, C, Saussoy, P et al. Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood, 2010: blood-2010–01-265751.CrossRefGoogle Scholar
Kyono, K, Doshida, M, Toya, M et al. Potential indications for ovarian autotransplantation based on the analysis of 5,571 autopsy findings of females under the age of 40 in Japan. Fertil Steril, 2010;93:24292430.CrossRefGoogle ScholarPubMed
Rosendahl, M, Andersen, CY, Ernst, E et al. 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;23:24752483.CrossRefGoogle ScholarPubMed
Harel, S, Ferme, C, Poirot, C. Management of fertility in patients treated for Hodgkin lymphoma. Haematologica, 2011: haematol. 2011.045856.CrossRefGoogle Scholar
Dolmans, M-M, Donnez, J, Camboni, A et al. IVF outcome in patients with orthotopically transplanted ovarian tissue. Hum Reprod, 2009;24:27782787.CrossRefGoogle ScholarPubMed
Donnez, J, Martinez-Madrid, B, Jadoul, P et al. Ovarian tissue cryopreservation and transplantation: a review. Hum Reprod Update, 2006;12:519535.CrossRefGoogle ScholarPubMed
Newton, H, Fisher, J, Arnold, J et al. Permeation of human ovarian tissue with cryoprotective agents in preparation for cryopreservation. Hum Reprod, 1998;13:376380.CrossRefGoogle ScholarPubMed
Fuller, B, Paynter, S. Fundamentals of cryobiology in reproductive medicine. Reprod Biomed Online, 2004;9:680691.CrossRefGoogle ScholarPubMed
Hovatta, O. Methods for cryopreservation of human ovarian tissue. Reprod Biomed Online, 2005;10:729734.CrossRefGoogle ScholarPubMed
Zhou, X-H, Zhang, D, Shi, J et al. Comparison of vitrification and conventional slow freezing for cryopreservation of ovarian tissue with respect to the number of intact primordial follicles: A meta-analysis. Medicine, 2016;95:e4095.CrossRefGoogle ScholarPubMed
Kawamura, K, Cheng, Y, Suzuki, N et al. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A, 2013;110:17474–17479.CrossRefGoogle ScholarPubMed
Suzuki, N, Yoshioka, N, Takae, S et al. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod, 2015;30:608615.CrossRefGoogle ScholarPubMed
McLaughlin, M, Albertini, D, Wallace, W et al. Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system. MHR: Basic Science of Reproductive Medicine, 2018;24:135142.Google Scholar
Demeestere, I, Simon, P, Emiliani, S et al. Orthotopic and heterotopic ovarian tissue transplantation. Hum Reprod Update, 2009;15:649665.CrossRefGoogle ScholarPubMed
Jensen, AK, Macklon, KT, Fedder, J et al. 86 successful births and 9 ongoing pregnancies worldwide in women transplanted with frozen-thawed ovarian tissue: focus on birth and perinatal outcome in 40 of these children. J Assist Reprod Genet, 2017;34:325336.CrossRefGoogle ScholarPubMed
Jadoul, P, Guilmain, A, Squifflet, J et al. Efficacy of ovarian tissue cryopreservation for fertility preservation: lessons learned from 545 cases. Hum Reprod, 2017;32:10461054.CrossRefGoogle ScholarPubMed
Callejo, J, Salvador, C, Miralles, A et al. Long-term ovarian function evaluation after autografting by implantation with fresh and frozen-thawed human ovarian tissue. J Clin Endocrinol Metab, 2001;86:44894494.CrossRefGoogle ScholarPubMed
Oktay, K, Economos, K, Kan, M et al. Endocrine function and oocyte retrieval after autologous transplantation of ovarian cortical strips to the forearm. JAMA, 2001;286:14901493.CrossRefGoogle ScholarPubMed
Kim, SS, Hwang, I-T, Lee, H-C. Heterotopic autotransplantation of cryobanked human ovarian tissue as a strategy to restore ovarian function. Fertil Steril, 2004;82:930932.CrossRefGoogle ScholarPubMed
Rosendahl, M, Loft, A, Byskov, A et al. Biochemical pregnancy after fertilization of an oocyte aspirated from a heterotopic autotransplant of cryopreserved ovarian tissue: case report. Hum Reprod, 2006;21:20062009.CrossRefGoogle ScholarPubMed
Kim, SS. Revisiting the role of heterotopic ovarian transplantation: futility or fertility. Reprod Biomed Online, 2014;28:141145.CrossRefGoogle ScholarPubMed
Oktay, K, Buyuk, E, Veeck, L et al. Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. The Lancet, 2004;363:837840.CrossRefGoogle ScholarPubMed
Kim, SS, Lee, WS, Chung, MK et al. Long-term ovarian function and fertility after heterotopic autotransplantation of cryobanked human ovarian tissue: 8-year experience in cancer patients. Fertil Steril, 2009;91:23492354.CrossRefGoogle ScholarPubMed
Kristensen, SG, Giorgione, V, Humaidan, P et al. Fertility preservation and refreezing of transplanted ovarian tissue – a potential new way of managing patients with low risk of malignant cell recurrence. Fertil Steril, 2017;107:12061213.CrossRefGoogle ScholarPubMed
Stern, C, Gook, D, Hale, L et al. First reported clinical pregnancy following heterotopic grafting of cryopreserved ovarian tissue in a woman after a bilateral oophorectomy. Hum Reprod, 2013;28:29962999.CrossRefGoogle Scholar
Kim, SS. Assessment of long term endocrine function after transplantation of frozen-thawed human ovarian tissue to the heterotopic site:10 year longitudinal follow-up study. J Assist Reprod Genet, 2012;29:489493.CrossRefGoogle ScholarPubMed
Snow, M, Cox, S-L, Jenkin, G et al. Generation of live young from xenografted mouse ovaries. Science, 2002;297:2227.CrossRefGoogle ScholarPubMed
Gook, DA, Edgar, D, Borg, J et al. Oocyte maturation, follicle rupture and luteinization in human cryopreserved ovarian tissue following xenografting. Hum Reprod, 2003;18:17721781.CrossRefGoogle ScholarPubMed
Kim, SS, Soules, MR, Battaglia, DE. Follicular development, ovulation, and corpus luteum formation in cryopreserved human ovarian tissue after xenotransplantation. Fertil Steril, 2002;78:7782.CrossRefGoogle ScholarPubMed
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;20:25022508.Google ScholarPubMed
Seli, E, Tangir, J. Fertility preservation options for female patients with malignancies. Curr Opin Obstet Gynecol, 2005;17:299308.CrossRefGoogle ScholarPubMed
Courbiere, B, Caquant, L, Mazoyer, C et al. Difficulties improving ovarian functional recovery by microvascular transplantation and whole ovary vitrification. Fertil Steril, 2009;91:26972706.CrossRefGoogle ScholarPubMed
Imhof, M, Bergmeister, H, Lipovac, M et al. Orthotopic microvascular reanastomosis of whole cryopreserved ovine ovaries resulting in pregnancy and live birth. Fertil Steril, 2006;85:12081215.CrossRefGoogle ScholarPubMed
Onions, V, Mitchell, M, Campbell, B et al. Ovarian tissue viability following whole ovine ovary cryopreservation: assessing the effects of sphingosine-1-phosphate inclusion. Hum Reprod, 2008;23:606618.CrossRefGoogle ScholarPubMed
Bedaiwy, MA, Jeremias, E, Gurunluoglu, R et al. Restoration of ovarian function after autotransplantation of intact frozen-thawed sheep ovaries with microvascular anastomosis. Fertil Steril, 2003;79:594602.CrossRefGoogle ScholarPubMed

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