Transplantation of frozen thawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria

Authors:
Dror Meirow, M.D.correspondenceemail, Hila Ra’anani, M.D., Moran Shapira, M.D., Masha Brenghausen, Ph.D., Chaim Sanaz Derech, B.Sc., Sarit Aviel-Ronen, M.D., Ph.D., Ninette Amerilgio, M.D., Eyal Schiff, M.D., Raoul Orvieto, M.D., Jehoshua Dor, M.D.

Abstract:

Objective:
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.

Design:
Prospective cohort study.

Setting:
Tertiary university-affiliated assisted reproduction technology (ART) and oncology centers.

Patient(s):
Twenty cancer survivors who underwent ovarian transplantation of frozen-thawed ovarian tissue with the aim to conceive.

Intervention(s):
Ovarian tissue cryopreservation (OTCP) and transplantation, endocrine monitoring, in vitro fertilization (IVF).

Main Outcome Measure(s):
Endocrine profile, IVF, pregnancies, live births.

Result(s):
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.

Conclusion(s):
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.

Clinical Trial Registration Number:
NCT02659592.

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