Fertility Preservation: The Rationale for Cryopreservation of the Whole Ovary

ABSTRACT

Recently, much progress has been made in the area of cryopreservation of ovarian tissue, one of the only options for fertility preservation available to women who require immediate gonadotoxic chemotherapy. Human ovarian cortical tissue strips have been cryopreserved, thawed, and autotransplanted with successful reproductive function. Cryopreservation of ovarian cortical strips, however, is limited by the ischemia that occurs at the time of retransplantation. Thus for patients that desire long-term resumption of endocrine function, cryopreservation of the whole ovary with an intact pedicle and vascular supply may be a better option. This article describes recent advances in whole ovary cryopreservation in both animal and human models, with a focus on surgical technique for removal, choice of cryoprotectants, freezing and thawing protocols, and preliminary results with organ retransplantation. Although no human cases of whole ovary retransplantation after cryopreservation have been performed to date, these preliminary studies have been encouraging, and it is likely that this option for fertility preservation will be a viable treatment option in the future.

KEYWORDS

Fertility preservation - cryopreservation - ovary - cryoprotectant

REFERENCES

• 1 Georgescu E S, Goldberg J M, du Plessis S S, Agarwal A. Present and future fertility preservation strategies for female cancer patients.  Obstet Gynecol Surv. 2008;  63(11) 725-732
• 2 Demirtas E, Elizur S E, Holzer H et al.. Immature oocyte retrieval in the luteal phase to preserve fertility in cancer patients.  Reprod Biomed Online. 2008;  17(4) 520-523
• 3 Donnez J, Martinez-Madrid B, Jadoul P, Van Langendonckt A, Demylle D, Dolmans M M. Ovarian tissue cryopreservation and transplantation: a review.  Hum Reprod Update. 2006;  12(5) 519-535
• 4 Bromer J G, Patrizio P. Preservation and postponement of female fertility: an overview and the initial Yale experience.  Placenta. 2008;  29(suppl B) 200-205
• 5 ACOG Committee Opinion No . ACOG Committee Opinion No. 405: ovarian tissue and oocyte cryopreservation.  Obstet Gynecol. 2008;  111(5) 1255-1256
• 6 Martin J R, Kodaman P, Oktay K, Taylor H S. Ovarian cryopreservation with transposition of a contra lateral ovary: a combined approach for fertility preservation in women receiving pelvic radiation.  Fertil Steril. 2007;  87(1) e185-187
• 7 Lee S J, Schover L R, Partridge A H American Society of Clinical Oncology et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients.  J Clin Oncol. 2006;  24(18) 2917-2931
• 8 Tao T, Del Valle A. Human oocyte and ovarian tissue cryopreservation and its application.  J Assist Reprod Genet. 2008;  25(7) 287-296
• 9 Oktay K, Sönmezer M. Fertility preservation in gynecologic cancers.  Curr Opin Oncol. 2007;  19(5) 506-511
• 10 von Wolff M, Strowitzki T, van der Ven H, Montag M. In vitro maturation is an efficient technique to generate oocytes and should be considered in combination with cryopreservation of ovarian tissue for preservation of fertility in women.  J Clin Oncol. 2006;  24(33) 5336-5337 author reply 5337-5338
• 11 Donnez J, Squifflet J, Van Eyck A S et al.. Restoration of ovarian function in orthotopically transplanted cryopreserved ovarian tissue: a pilot experience.  Reprod Biomed Online. 2008;  16(5) 694-704
• 12 Oktay K. Spontaneous conceptions and live birth after heterotopic ovarian transplantation: is there a germline stem cell connection?.  Hum Reprod. 2006;  21(6) 1345-1348
• 13 Kim S S, Hwang I T, Lee H C. Heterotopic autotransplantation of cryobanked human ovarian tissue as a strategy to restore ovarian function.  Fertil Steril. 2004;  82(4) 930-932
• 14 Oktay K, Buyuk E. Ovarian transplantation in humans: indications, techniques and the risk of reseeding cancer.  Eur J Obstet Gynecol Reprod Biol. 2004;  113(suppl 1) S45-S47
• 15 Oktay K, Karlikaya G. Ovarian function after transplantation of frozen, banked autologous ovarian tissue.  N Engl J Med. 2000;  342(25) 1919
• 16 Radford J A, Lieberman B A, Brison D R et al.. Orthotopic reimplantation of cryopreserved ovarian cortical strips after high-dose chemotherapy for Hodgkin's lymphoma.  Lancet. 2001;  357(9263) 1172-1175
• 17 Andersen C Y, Rosendahl M, Byskov A G et al.. Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue.  Hum Reprod. 2008;  23(10) 2266-2272
• 18 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) 1437-1442
• 19 Donnez J, Dolmans M M, Demylle D et al.. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue.  Lancet. 2004;  364(9443) 1405-1410
• 20 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(3) 318-321
• 21 Israely T, Dafni H, Nevo N, Tsafriri A, Neeman M. Angiogenesis in ectopic ovarian xenotransplantation: multiparameter characterization of the neovasculature by dynamic contrast-enhanced MRI.  Magn Reson Med. 2004;  52(4) 741-750
• 22 Israely T, Nevo N, Harmelin A, Neeman M, Tsafriri A. Reducing ischaemic damage in rodent ovarian xenografts transplanted into granulation tissue.  Hum Reprod. 2006;  21(6) 1368-1379
• 23 Qi S, Ma A, Xu D, Daloze P, Chen H. Cryopreservation of vascularized ovary: an evaluation of histology and function in rats.  Microsurgery. 2008;  28(5) 380-386
• 24 Oktay K. Ovarian tissue cryopreservation and transplantation: preliminary findings and implications for cancer patients.  Hum Reprod Update. 2001;  7(6) 526-534
• 25 Bedaiwy M A, Hussein M R, Biscotti C, Falcone T. Cryopreservation of intact human ovary with its vascular pedicle.  Hum Reprod. 2006;  21(12) 3258-3269
• 26 Martinez-Madrid B, Dolmans M M, Van Langendonckt A, Defrère S, Donnez J. Freeze-thawing intact human ovary with its vascular pedicle with a passive cooling device.  Fertil Steril. 2004;  82(5) 1390-1394
• 27 Silber S J, DeRosa M, Pineda J et al.. A series of monozygotic twins discordant for ovarian failure: ovary transplantation (cortical versus microvascular) and cryopreservation.  Hum Reprod. 2008;  23(7) 1531-1537
• 28 Gosden R G. Ovary and uterus transplantation.  Reproduction. 2008;  136(6) 671-680
• 29 Baird D T, Webb R, Campbell B K, Harkness L M, Gosden R G. Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at −196 C.  Endocrinology. 1999;  140(1) 462-471
• 30 Martinez-Madrid B, Camboni A, Dolmans M M, Nottola S, Van Langendonckt A, Donnez J. Apoptosis and ultrastructural assessment after cryopreservation of whole human ovaries with their vascular pedicle.  Fertil Steril. 2007;  87(5) 1153-1165
• 31 Falcone T, Attaran M, Bedaiwy M A, Goldberg J M. Ovarian function preservation in the cancer patient.  Fertil Steril. 2004;  81(2) 243-257
• 32 Wang X, Chen H, Yin H, Kim S S, Lin Tan S, Gosden R G. Fertility after intact ovary transplantation.  Nature. 2002;  415(6870) 385
• 33 Yin H, Wang X, Kim S S, Chen H, Tan S L, Gosden R G. Transplantation of intact rat gonads using vascular anastomosis: effects of cryopreservation, ischaemia and genotype.  Hum Reprod. 2003;  18(6) 1165-1172
• 34 Winston R M, Browne J C. Pregnancy following autograft transplantation of Fallopian tube and ovary in the rabbit.  Lancet. 1974;  2(7879) 494-495
• 35 Goding J R, McCracken J A, Baird D T. The study of ovarian function in the ewe by means of a vascular autotransplantation technique.  J Endocrinol. 1967;  39(1) 37-52
• 36 Jeremias E, Bedaiwy M A, Gurunluoglu R, Biscotti C V, Siemionow M, Falcone T. Heterotopic autotransplantation of the ovary with microvascular anastomosis: a novel surgical technique.  Fertil Steril. 2002;  77(6) 1278-1282
• 37 Paldi E, Gal D, Barzilai A, Hampel N, Malberger E. Genital organs. Auto and homotransplantation in forty dogs.  Int J Fertil. 1975;  20(1) 5-12
• 38 Scott J R, Keye W R, Poulson A M, Reynolds W A. Microsurgical ovarian transplantation in the primate.  Fertil Steril. 1981;  36(4) 512-515
• 39 Mhatre P, Mhatre J, Magotra R. Ovarian transplant: a new frontier.  Transplant Proc. 2005;  37(2) 1396-1398
• 40 Leporrier M, von Theobald P, Roffe J L, Muller G. A new technique to protect ovarian function before pelvic irradiation. Heterotopic ovarian autotransplantation.  Cancer. 1987;  60(9) 2201-2204
• 41 Hilders C G, Baranski A G, Peters L, Ramkhelawan A, Trimbos J B. Successful human ovarian autotransplantation to the upper arm.  Cancer. 2004;  101(12) 2771-2778
• 42 Bedaiwy M A, 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(3) 594-602
• 43 Falcone T, Bedaiwy M A. Cryopreservation of intact ovaries—size is a variable?.  Fertil Steril. 2005;  83(5) 1587, author reply 1588
• 44 Revel A, Elami A, Bor A, Yavin S, Natan Y, Arav A. Whole sheep ovary cryopreservation and transplantation.  Fertil Steril. 2004;  82(6) 1714-1715
• 45 Grazul-Bilska A T, Banerjee J, Yazici I et al.. Morphology and function of cryopreserved whole ovine ovaries after heterotopic autotransplantation.  Reprod Biol Endocrinol. 2008;  6 16
• 46 Arav A, Revel A, Nathan Y et al.. Oocyte recovery, embryo development and ovarian function after cryopreservation and transplantation of whole sheep ovary.  Hum Reprod. 2005;  20(12) 3554-3559
• 47 Imhof M, Bergmeister H, Lipovac M, Rudas M, Hofstetter G, Huber J. Orthotopic microvascular reanastomosis of whole cryopreserved ovine ovaries resulting in pregnancy and live birth.  Fertil Steril. 2006;  85(suppl 1) 1208-1215
• 48 Fahy G M, Wowk B, Wu J et al.. Cryopreservation of organs by vitrification: perspectives and recent advances.  Cryobiology. 2004;  48(2) 157-178
• 49 Rall W F, Fahy G M. Ice-free cryopreservation of mouse embryos at −196 degrees C by vitrification.  Nature. 1985;  313(6003) 573-575
• 50 Kheirabadi B S, Fahy G M. Permanent life support by kidneys perfused with a vitrifiable (7.5 molar) cryoprotectant solution.  Transplantation. 2000;  70(1) 51-57
• 51 Courbiere B, Massardier J, Salle B, Mazoyer C, Guerin J F, Lornage J. Follicular viability and histological assessment after cryopreservation of whole sheep ovaries with vascular pedicle by vitrification.  Fertil Steril. 2005;  84(suppl 2) 1065-1071
• 52 Courbiere B, Caquant L, Mazoyer C, Franck M, Lorgage J, Salle B. Difficulties improving ovarian functional recovery by microvascular transplantation and whole ovary vitrification.  Fertil Steril. 2009;  91(6) 2697-2706
• 53 Jadoul P, Donnez J, Dolmans M M, Squifflet J, Lengele B, Martinez-Madrid B. Laparoscopic ovariectomy for whole human ovary cryopreservation: technical aspects.  Fertil Steril. 2007;  87(4) 971-975
• 54 Patrizio P, Gavish Z, Martel M et al.. Whole human ovary cryopreservation using a novel multi-gradient freezing device. Paper presented at: Annual Meeting of the American Society for Reproductive Medicine 2007 Washington, DC;
• 55 Patrizio P, Bromer J G, Johnson J et al.. Cryopreservation of eleven whole human ovaries: Histology, Immunohistochemistry, and technical details. Paper presented at: Annual Meeting of the American Society for Reproductive Medicine 2008 San Francisco, CA;
• 56 Patrizio P, Arav A, Bromer J G et al.. Cryopreservation of whole human ovaries together with fallopian tubes. Paper presented at: Annual Meeting of the American Society for Reproductive Medicine 2008 San Francisco, CA;