Abstract
Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.
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References
Armenian SH, Landier W, Hudson MM, Robison LL, Bhatia S, COG Survivorship and Outcomes Committee. Children’s oncology group’s 2013 blueprint for research: survivorship and outcomes. Pediatr Blood Cancer 2013; 60: 1063–1068.
Diller L, Chow EJ, Gurney JG, Hudson MM, Kadin-Lottick NS, Kawashima TI et al. Chronic disease in the childhood cancer survivor study cohort: A review of published findings. J Clin Oncol 2009; 27: 2339–2355.
Bhatia S, Constine LS . Late morbidity after successful treatment of children with cancer. Cancer J 2009; 15: 174–180.
Armstrong GT, Liu Q, Yasui Y, Neglia JP, Leisenring W, Robison LL et al. Late mortality among 5-year survivors of childhood cancer: a summary from the Childhood cancer survivor study. J Clin Oncol 2009; 27: 2328–2338.
Barton SE, Najita JS, Ginsburg ES, Leisenring WM, Stovall M, Weathers RE et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood cancer survivor study cohort. Lancet Oncol 2013; 14: 873–881.
Jadoul P, Donnez J . How does bone marrow transplantation affect ovarian function and fertility? Curr Opin Obstet Gynecol 2012; 24: 164–171.
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: 3045–3052.
Bakker B, Massa GG, Oostdijk W, van Weel–Sipman MH, Vossen JM, Wit JM . Pubertal development and growth after total-body irradiation and bone marrow transplantation for haematological malignancies. Eur J Pediatr 2000; 159: 31–37.
Jadoul P, Anckaert E, Dewandeleer A . Clinical and biologic evaluation of ovarian function in women treated by bone marrow transplantation for various indications during childhood or adolescence. Fertility and Sterility 2011; 96: 126–133.
Wallace WH, Kelsey TW . Human ovarian reserve from conception to the menopause. PLoS One 2010; 5: e8772.
Meirow D, Biederman H, Anderson RA, Wallace WH . Toxicity of chemotherapy and radiation on female reproduction. Clin Obstet Gynecol 2010; 53: 727–739.
Wallace WH, Anderson RA, Irvine DS . Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol 2005; 6: 209–218.
Green DM, Sklar CA, Boice JD Jr, Mulvihill JJ, Whitton JA, Stovall M et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol 2009; 27: 2374–2381.
Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC et al. Fertility of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2009; 27: 2677–2685.
The Ethics Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in patients facing gonadotoxic therapies: a committee opinion. Fertil Steril 2013; 100: 1224–1231.
Newton H, Aubard Y, Rutherford A, Sharma V, Gosden R . Low temperature storage and grafting of human ovarian tissue. Hum Reprod 1996; 11: 1487–1491.
Grynberg M, Poulain M, Sebag-Peyrelevade S, Le Parco S, Fanchin R, Frydman N . Ovarian tissue and follicle transplantation as an option for fertility preservation. Fertil Steril 2012; 97: 1260–1268.
Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J et al. Restoration of ovarian function after orthotopic (intraovarian and periovarian) transplantation of cryopreserved ovarian tissue in a woman treated by bone marrow transplantation for sickle cell anaemia: case report. Hum Reprod 2006; 21: 183–188.
Meirow D, Fasouliotis SJ, Nugent D, Schenker JG, Gosden RG, Rutherford AJ . A laparoscopic technique for obtaining ovarian cortical biopsy specimens for fertility conservation in patients with cancer. Fertil Steril 1999; 71: 948–951.
Radford JA, Lieberman BA, Brison DR, Smith AR, Critchlow JD, Russell SA et al. Orthotopic reimplantation of cryopreserved ovarian cortical strips after high-dose chemotherapy for Hodgkin's lymphoma. Lancet 2001; 357: 1172–1175.
Poirot C, Vacher Lavenu MC, Helardot P, Guibert J, Brugières L, Jouannet P . Human ovarian tissue cryopreservation: indications and feasibility. Hum Reprod 2002; 17: 1447–1452.
Revelli A, Marchino G, Dolfin E, Molinari E, Delle Piane L, Salvagno F et al. Live birth after orthotopic grafting of autologous cryopreserved ovarian tissue and spontaneous conception in Italy. Fertil Steril 2013; 99: 227–230.
Donnez J, Dolmans M, 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: 1503–1513.
Teinturier C, Hartmann O, Valteau-Couanet D, Benhamou E, Bougneres PF . Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure. Bone Marrow Transplant 1998; 22: 989–994.
Borgmann-Staudt A, Rendtorff R, Reinmuth S, Hohmann C, Keil T, Schuster FR et al. Fertility after allogeneic haematopoietic stem cell transplantation in childhood and adolescence. Bone Marrow Transplant 2012; 47: 271–276.
Poirot CJ, Martelli H, Genestie C, Golmard JL, Valteau-Couanet D, Helardot P et al. Feasibility of ovarian tissue cryopreservation for prepubertal females with cancer. Pediatr Blood Cancer 2007; 49: 74–78.
Jadoul P, Dolmans MM, Donnez J . Fertility preservation in girls during childhood: is it feasible, efficient and safe and to whom should it be proposed? Hum Reprod Update 2010; 16: 617–630.
Anderson RA, Wallace WH, Baird DT . Ovarian cryopreservation for fertility preservation: indications and outcomes. Reproduction 2008; 136: 681–689.
Feigin E, Abir R, Fisch B, Kravarusic D, Steinberg R, Nitke S et al. Laparoscopic ovarian tissue preservation in young patients at risk for ovarian failure as a result of chemotherapy/irradiation for primary malignancy. J Pediatr Surg 2007; 42: 862–864.
Oktay K, Oktem O . Fertility preservation medicine: a new field in the care of young cancer survivors. Pediatr Blood Cancer 2009; 53: 267–273.
Borgstrom B, Hreinsson J, Rasmussen C, Sheikhi M, Fried G, Keros V et al. Fertility preservation in girls with turner syndrome: prognostic signs of the presence of ovarian follicles. J Clin Endocrinol Metab 2009; 94: 74–80.
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: 720–725.
Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet 2004; 364: 1405–1410.
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: 1437–1442.
Demeestere I, Simon P, Moffa F, Delbaere A, Englert Y . Birth of a second healthy girl more than 3 years after cryopreserved ovarian graft. Hum Reprod 2010; 25: 1590–1591.
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: 318–321.
Andersen CY, Rosendahl M, Byskov AG, Loft A, Ottosen C, Dueholm M et al. Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue. Hum Reprod 2008; 23: 2266–2272.
Ernst E, Bergholdt S, Jørgensen JS, Andersen CY . The first woman to give birth to two children following transplantation of frozen/thawed ovarian tissue. Hum Reprod 2010; 25: 1280–1281.
Silber SJ, DeRosa M, Pineda J, Lenahan K, Grenia D, Gorman K et al. A series of monozygotic twins discordant for ovarian failure: ovary transplantation (cortical versus microvascular) and cryopreservation. Hum Reprod 2008; 23: 1531–1537.
Silber S, Kagawa N, Kuwayama M, Golden R . Duration of fertility after fresh and frozen ovary transplantation. Fertil Steril 2010; 94: 2191–2196.
Piver P, Amiot C, Agnani G, Pech J, Rohrlich PS, Vidal E et al. Two pregnancies obtained after a new technique of autotransplantation of cryopreserved ovarian tissue, In 25th Annual Meeting of ESHRE, 28 June–1 July, 2009 Oxford University Press: Amsterdam, the NetherlandsAmsterdam, the NetherlandsHum Reprod 2009.
Roux C, Amiot C, Agnani G, Aubard Y, Rohrlich PS, Piver P . Live birth after ovarian tissue autograft in a patient with sickle cell disease treated by allogeneic bone marrow transplantation. Fertil Steril 2010; 93: 2413.
Sanchez-Serrano M, Crespo J, Mirabet V, Cobo AC, Escriba MJ, Simon C et al. Twins born after transplantation of human ovarian cortical tissue and oocyte vitrification. Fertil Steril 2010; 93: 268.
Revel A, Laufer N, Ben Meir A, Lebovich M, Mitrani E . Micro-organ ovarian transplantation enables pregnancy: a case report. Hum Reprod 2011; 26: 1097–1103.
Dittrich R, Lotz L, Keck G, Hoffmann I, Mueller A, Beckmann MW et al. Live birth after ovarian tissue autotransplantation following overnight transportation before cryopreservation. Fertil Steril 2012; 97: 387–390.
Burmeister L1, Kovacs GT, Osianlis T . First Australian pregnancy after ovarian tissue cryopreservation and subsequent autotransplantation. Med J Aust 2013; 198: 158–159.
Callejo J, Salvador C, Miralles A, Vilaseca S, Lailla JM, Balasch J . Long-term ovarian function evaluation after autografting by implantation with fresh and frozen-thawed human ovarian tissue. J Clin Endocrinol Metab 2001; 86: 4489–4494.
Stern CJ, Toledo MG, Hale LG, Gook DA, Edgar DH . The first Australian experience of heterotopic grafting of cryopreserved ovarian tissue: evidence of establishment of normal ovarian function. Aust N Z J Obstet Gynaecol 2011; 51: 268–275.
Rosendahl M, Loft A, Byskov AG, Ziebe S, Schmidt KT, Andersen AN et al. Biochemical pregnancy after fertilization of an oocyte aspirated from a heterotopic autotransplant of cryopreserved ovarian tissue: case report. Hum Reprod 2006; 21: 2006–2009.
Oktay K, Türkçüoğlu 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: 804.
Poirot C, Abirached F, Prades M, Coussieu M, Bernaudin F, Piver P . Induction of puberty by autograft of cryopreserved ovarian tissue. Lancet 2012; 379: 588.
Ernst E, Kjærsgaard M, Birkebæk NH, Clausen N, Andersen CY . Case report: stimulation of puberty in a girl with chemo- and radiation therapy induced ovarian failure by transplantation of a small part of her frozen/thawed ovarian tissue. Eur J Cancer 2013; 49: 911–914.
Dolmans MM, Luyckx V, Donnez J, Andersen CY, Greve T . Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue. Fertil Steril 2013; 99: 1514–1522.
Sonmezer M, Oktay K . Fertility preservation in female patients. Hum Reprod Update 2004; 10: 251–266.
Slasky BS, Straub WH, Deutsch M . Acute lymphocytic leukemia of the ovary: the value of sonography. J Comput Tomogr 1982; 6: 161–165.
Dolmans MM, Marinescu C, Saussoy P, Van Langendonckt A, Amorim C, Donnez J . Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood 2010; 116: 2908–2914.
Greve T, Clasen-Linde E, Andersen MT, Andersen MK, Sørensen SD, Rosendahl M et al. Cryopreserved ovarian cortex from patients with leukemia in complete remission contains no apparent viable malignant cells. Blood 2012; 120: 4311–4316.
Vanacker J, Luyckx V, Dolmans MM, des Rieux A, Jaeger J, Van Langendonckt A et al. Transplantation of an alginate-matrigel matrix containing isolated ovarian cells: first step in developing a biodegradable scaffold to transplant isolated preantral follicles and ovarian cells. Biomaterials 2012; 33: 6079–6085.
Dolmans MM, Martinez-Madrid B, Gadisseux E, Guiot Y, Yuan WY, Torre A et al. Short-term transplantation of isolated human ovarian follicles and cortical tissue into nude mice. Reproduction 2007; 134: 253–262.
Hovatta O . Cryopreservation and culture of human primordial and primary ovarian follicles. Mol Cell Endocrinol 2000; 169: 95–97.
Picton HM, Harris SE, Muruvi W, Chambers EL . The in vitro growth and maturation of follicles. Reproduction 2008; 136: 703–715.
Smitz J, Cortvrindt R . Oocyte in-vitro maturation and follicle culture: current clinical achievements and future directions. Hum Reprod 1999; 14: 145–161.
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Biasin, E., Salvagno, F., Berger, M. et al. Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell transplant: experience of a single centre. Bone Marrow Transplant 50, 1206–1211 (2015). https://doi.org/10.1038/bmt.2015.111
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DOI: https://doi.org/10.1038/bmt.2015.111
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