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Pregnancies and live births after 20 transplantations of cryopreserved ovarian tissue in a single center

      Objective

      To report the results of 20 orthotopic retransplantations of cryopreserved ovarian tissue after cancer treatment.

      Design

      Retrospective analysis.

      Setting

      Tertiary gynecology department.

      Patient(s)

      Twenty patients with malignant disease: 11 with hematological malignancies (55%), four with breast cancer (20%), three with anal cancer (15%), and two with ovarian cancer (10%); the mean age before oncological treatment was 30.5 years.

      Intervention(s)

      Ovarian tissue was removed from patients in various centers in Germany in 2005–2009. All patients received chemotherapy and/or radiotherapy. Afterward, 17 patients had complete premature ovarian insufficiency, while three still showed some ovarian activity. Overnight transportation of tissue before freezing was necessary in eight cases. Cryopreservation followed slow freezing protocols in all cases. Retransplantation was performed at Erlangen University Hospital 3.75 years after extraction, on average. Thawed tissue was transplanted into a peritoneal pouch in the broad ligament region, below the tube, in 16 cases. Fragments were sutured both onto the remaining ovary and into a peritoneal pouch in four cases.

      Main Outcome Measure(s)

      Restoration of ovarian activity, pregnancy, birth.

      Result(s)

      Ovarian activity resumed in all patients except one. Seven patients conceived, with one miscarriage and four ongoing pregnancies. Four patients delivered healthy babies. One pregnancy and live birth after oocyte donation need to be considered separately.

      Conclusion(s)

      These data clearly demonstrate that preserving fertility by cryopreserving ovarian tissue is a successful and safe clinical option that can be considered for selected cancer patients.

      Key Words

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      References

        • West E.R.
        • Zelinski M.B.
        • Kondapalli L.A.
        • Gracia C.
        • Chang J.
        • Coutifaris C.
        • et al.
        Preserving female fertility following cancer treatment: current options and future possibilities.
        Pediatr Blood Cancer. 2009; 53: 289-295
        • Dittrich R.
        • Maltaris T.
        • Hoffmann I.
        • Oppelt P.G.
        • Beckmann M.W.
        • Mueller A.
        Fertility preservation in cancer patients.
        Minerva Ginecol. 2010; 62: 63-80
        • Cobo A.
        • Garcia-Velasco J.A.
        • Domingo J.
        • Remohí J.
        • Pellicer A.
        Is vitrification of oocytes useful for fertility preservation for age-related fertility decline and in cancer patients?.
        Fertil Steril. 2013; 99: 1485-1495
        • Jeruss J.S.
        • Woodruff T.K.
        Preservation of fertility in patients with cancer.
        N Engl J Med. 2009; 360: 902-911
        • Von Wolff M.
        • Donnez J.
        • Hovatta O.
        • Keros V.
        • Maltaris T.
        • Montag M.
        • 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 Oxf Engl. 2009; 45: 1547-1553
        • Maltaris T.
        • Beckmann M.W.
        • Binder H.
        • Mueller A.
        • Hoffmann I.
        • Koelbl H.
        • et al.
        The effect of a GnRH agonist on cryopreserved human ovarian grafts in severe combined immunodeficient mice.
        Reprod Camb Engl. 2007; 133: 503-509
        • Donnez J.
        • Dolmans M.M.
        • Demylle D.
        • Jadoul P.
        • Pirard C.
        • Squifflet J.
        • et al.
        Livebirth after orthotopic transplantation of cryopreserved ovarian tissue.
        Lancet. 2004; 364: 1405-1410
        • Müller A.
        • Keller K.
        • Wacker J.
        • Dittrich R.
        • Keck G.
        • Montag M.
        • et al.
        Retransplantation of cryopreserved ovarian tissue: the first live birth in Germany.
        Dtsch Ärztebl Int. 2012; 109: 8-13
        • Donnez J.
        • Dolmans M.-M.
        • Pellicer A.
        • Diaz-Garcia C.
        • Sanchez Serrano M.
        • Schmidt K.T.
        • 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
        • Dittrich R.
        • Lotz L.
        • Keck G.
        • Hoffmann I.
        • Mueller A.
        • Beckmann M.W.
        • et al.
        Live birth after ovarian tissue autotransplantation following overnight transportation before cryopreservation.
        Fertil Steril. 2012; 97: 387-390
        • Isachenko V.
        • Isachenko E.
        • Keck G.
        • Dittrich R.
        • Montag M.
        • van der Ven H.
        • et al.
        First live birth in Germany after re-transplantation of cryopreserved ovarian tissue: original device for initiation of ice formation.
        Clin Lab. 2012; 58: 933-938
        • 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
        • Donnez J.
        • Silber S.
        • Andersen C.Y.
        • Demeestere I.
        • Piver P.
        • Meirow D.
        • et al.
        Children born after autotransplantation of cryopreserved ovarian tissue. a review of 13 live births.
        Ann Med. 2011; 43: 437-450
        • Andersen C.Y.
        • Rosendahl M.
        • Byskov A.G.
        • Loft A.
        • Ottosen C.
        • Dueholm M.
        • et al.
        Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue.
        Hum Reprod Oxf Engl. 2008; 23: 2266-2272
        • 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
        • Meirow D.
        • Hardan I.
        • Dor J.
        • Fridman E.
        • Elizur S.
        • Ra'anani H.
        • et al.
        Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients.
        Hum Reprod Oxf Engl. 2008; 23: 1007-1013
        • 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 Oxf Engl. 2010; 25: 1590-1591
        • Silber S.
        • Kagawa N.
        • Kuwayama M.
        • Gosden R.
        Duration of fertility after fresh and frozen ovary transplantation.
        Fertil Steril. 2010; 94: 2191-2196
        • Roux C.
        • Amiot C.
        • Agnani G.
        • Aubard Y.
        • Rohrlich P.-S.
        • 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.e15-2413.e19
        • Sánchez-Serrano M.
        • Crespo J.
        • Mirabet V.
        • Cobo A.C.
        • Escribá M.-J.
        • Simón C.
        • et al.
        Twins born after transplantation of ovarian cortical tissue and oocyte vitrification.
        Fertil Steril. 2010; 93: 268.e11-268.e13
        • Revel A.
        • Laufer N.
        • Ben Meir A.
        • Lebovich M.
        • Mitrani E.
        Micro-organ ovarian transplantation enables pregnancy: a case report.
        Hum Reprod Oxf Engl. 2011; 26: 1097-1103
        • García Rada A.
        Spanish woman becomes pregnant through ovarian tissue transplantation.
        Br Med J. 2012; 344: d8350
        • 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
        • Devi K.P.
        • Kumar L.
        Live-birth after transplantation of cryopreserved ovarian tissue.
        Natl Med J India. 2005; 18: 257-258
        • 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: 17474-17479
        • Ernst E.
        • Bergholdt S.
        • Jørgensen J.S.
        • Andersen C.Y.
        The first woman to give birth to two children following transplantation of frozen/thawed ovarian tissue.
        Hum Reprod Oxf Engl. 2010; 25: 1280-1281
        • Callejo J.
        • Salvador C.
        • González-Nuñez S.
        • Almeida L.
        • Rodriguez L.
        • Marqués L.
        • et al.
        Live birth in a woman without ovaries after autograft of frozen-thawed ovarian tissue combined with growth factors.
        J Ovarian Res. 2013; 6: 33
        • Dolmans M.-M.
        • Jadoul P.
        • Gilliaux S.
        • Amorim C.A.
        • Luyckx V.
        • Squifflet J.
        • et al.
        A review of 15 years of ovarian tissue bank activities.
        J Assist Reprod Genet. 2013; 30: 305-314
        • Yang X.R.
        • Chang-Claude J.
        • Goode E.L.
        • Couch F.J.
        • Nevanlinna H.
        • Milne R.L.
        • et al.
        Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.
        J Natl Cancer Inst. 2011; 103: 250-263
        • Practice Committee of American Society for Reproductive Medicine
        Ovarian tissue cryopreservation: a committee opinion.
        Fertil Steril. 2014; 101: 1237-1243
        • Kim S.S.
        • Lee W.S.
        • Chung M.K.
        • Lee H.C.
        • Lee H.H.
        • Hill D.
        Long-term ovarian function and fertility after heterotopic autotransplantation of cryobanked human ovarian tissue: 8-year experience in cancer patients.
        Fertil Steril. 2009; 91: 2349-2354
        • Rosendahl M.
        • Schmidt K.T.
        • Ernst E.
        • Rasmussen P.E.
        • Loft A.
        • Byskov A.G.
        • et al.
        Cryopreservation of ovarian tissue for a decade in Denmark: a view of the technique.
        Reprod Biomed Online. 2011; 22: 162-171
        • Donnez J.
        • Dolmans M.-M.
        Preservation of fertility in females with haematological malignancy.
        Br J Haematol. 2011; 154: 175-184
        • Liebenthron J.
        • Köster M.
        • Drengner C.
        • Reinsberg J.
        • van der Ven H.
        • Montag M.
        The impact of culture conditions on early follicle recruitment and growth from human ovarian cortex biopsies in vitro.
        Fertil Steril. 2013; 100: 483-491.e5
        • Telfer E.E.
        • McLaughlin M.
        In vitro development of ovarian follicles.
        Semin Reprod Med. 2011; 29: 15-23
        • Huang J.Y.J.
        • Tulandi T.
        • Holzer H.
        • Tan S.L.
        • Chian R.-C.
        Combining ovarian tissue cryobanking with retrieval of immature oocytes followed by in vitro maturation and vitrification: an additional strategy of fertility preservation.
        Fertil Steril. 2008; 89: 567-572
        • Kim S.S.
        • Kang H.G.
        • Kim N.H.
        • Lee H.C.
        • Lee H.H.
        Assessment of the integrity of human oocytes retrieved from cryopreserved ovarian tissue after xenotransplantation.
        Hum Reprod. 2005; 20: 2502-2508
        • Luyckx V.
        • Dolmans M.-M.
        • Vanacker J.
        • Legat C.
        • Fortuño Moya C.
        • Donnez J.
        • et al.
        A new step toward the artificial ovary: survival and proliferation of isolated murine follicles after autologous transplantation in a fibrin scaffold.
        Fertil Steril. 2014; 101: 1149-1156
        • Larsen E.C.
        • Schmiegelow K.
        • Rechnitzer C.
        • Loft A.
        • Müller J.
        • Andersen A.N.
        Radiotherapy at a young age reduces uterine volume of childhood cancer survivors.
        Acta Obstet Gynecol Scand. 2004; 83: 96-102
        • Arrivé L.
        • Chang Y.C.
        • Hricak H.
        • Brescia R.J.
        • Auffermann W.
        • Quivey J.M.
        Radiation-induced uterine changes: MR imaging.
        Radiology. 1989; 170: 55-58
        • Von Wolff M.
        • Montag M.
        • Dittrich R.
        • Denschlag D.
        • Nawroth F.
        • Lawrenz B.
        Fertility preservation in women—a practical guide to preservation techniques and therapeutic strategies in breast cancer, Hodgkin’s lymphoma and borderline ovarian tumours by the fertility preservation network FertiPROTEKT.
        Arch Gynecol Obstet. 2011; 284: 427-435