title: Transplantations of frozen-thawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria.
abstract: To report the single-center results of orthotopic retransplantations of cryopreserved ovarian tissue in cancer survivors and evaluate the validity of commonly accepted procedure limitations.
  
  
  
  Prospective cohort study.
  
  
  
  Tertiary university-affiliated assisted reproduction technology (ART) and oncology centers.
  
  
  
  Twenty cancer survivors who underwent ovarian transplantation of frozen-thawed ovarian tissue with the aim to conceive.
  
  
  
  Ovarian tissue cryopreservation (OTCP) and transplantation, endocrine monitoring, in vitro fertilization (IVF).
  
  
  
  Endocrine profile, IVF, pregnancies, live births.
  
  
  
  The patient ages at tissue harvesting ranged from 14 to 39 years. Fifteen women had hematologic malignancies, and two had leukemia (chronic myelogenous leukemia and acute myelogenous leukemia). Ten patients were exposed to nonsterilizing chemotherapy before OTCP. After transplantation, the endocrine recovery rate was 93%. Fourteen patients underwent IVF treatments with a fertilization rate of 58%. Sixteen pregnancies were achieved (10 after IVF, 6 spontaneous), resulting in 10 live births, two (twins) after harvesting from the mother at the age of 37. Two pregnancies are currently ongoing. After transplantation, 53% of patients conceived, and 32% delivered at least once. One patient conceived four times. Preharversting chemotherapy exposure was not associated with inferior outcomes. All patients, including two leukemia survivors, remained cancer free.
  
  
  
  Orthotopic transplantation of thawed ovarian tissue is a highly effective measure to restore fertility in sterilized cancer patients. Chemotherapy exposure before harvesting and age >35 is a realistic option in selected patients. Retransplantation in leukemic patients is possible after application of maximal safety measures. These results have led the national ethical and professional authorities to decide for the first time not to consider OTCP as an experimental modality for fertility preservation.
  
  
  
  NCT02659592.
authors.affiliation: Fertility Preservation, IVF Unit, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Obstetrics and Gynecology, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: meirow@post.tau.ac.il.
authors.forename: Dror
authors.initials: D
authors.lastname: Meirow
authors.affiliation: Fertility Preservation, IVF Unit, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Obstetrics and Gynecology, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Ra'anani
authors.affiliation: Fertility Preservation, IVF Unit, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Obstetrics and Gynecology, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Shapira
authors.affiliation: Fertility Preservation, IVF Unit, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Obstetrics and Gynecology, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Masha
authors.initials: M
authors.lastname: Brenghausen
authors.affiliation: Fertility Preservation, IVF Unit, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Derech Chaim
authors.affiliation: Department of Pathology and Talpiot Medical Leadership Program, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Sarit
authors.initials: S
authors.lastname: Aviel-Ronen
authors.affiliation: Cancer Research Center, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.affiliation: Division of Obstetrics and Gynecology, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Schiff
authors.affiliation: Fertility Preservation, IVF Unit, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Obstetrics and Gynecology, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Raoul
authors.initials: R
authors.lastname: Orvieto
authors.affiliation: Fertility Preservation, IVF Unit, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Obstetrics and Gynecology, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Jehoshua
authors.initials: J
authors.lastname: Dor
mesh_terms: D000046:Academic Medical Centers; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015925:Cryopreservation; D005260:Female; D059247:Fertility Preservation / Q000009:adverse effects / Q000379:methods*; D005307:Fertilization in Vitro; D006801:Humans; D007247:Infertility, Female / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D007557:Israel; D050498:Live Birth; D008423:Maternal Age; D009369:Neoplasms / Q000188:drug therapy*; D010053:Ovary / Q000637:transplantation*; D010298:Parity; D011247:Pregnancy; D018873:Pregnancy Rate; D011446:Prospective Studies; D012092:Replantation; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects; D012307:Risk Factors; D017741:Survivors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: Cryopreserved Ovarian Tissue; Fertility Preservation; Pregnancy; Safety; Transplantation