Cryopreserved ovarian tissue autotransplantation in an acute myeloid leukaemia survivor following extensive minimal residual disease screening: first reported live birth in Europe.
Michelle Soares, Ingrid Segers, Michael De Brucker, Alessandra Camboni, Camille Hossay, Ileana Mateizel, Iebe De Quick, Ellen Van Moer, Dominik Selleslag, Steven Hellebaut, Marie-Madeleine Dolmans, Michel De Vos
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Abstract
Purpose: We report successful autotransplantation of ovarian tissue in a sterile acute myeloid leukaemia survivor after comprehensive minimal residual disease (MRD) screening.
Methods: At age 18, the patient underwent ovarian tissue cryopreservation while in complete remission prior to allogeneic stem cell transplantation. Premature ovarian failure and the wish to conceive led her to request transplantation of her cryopreserved ovarian tissue 12 years later. Extensive MRD screening of frozen-thawed biopsy specimens, including histology, immunohistochemistry, PCR and 6-month xenotransplantation to immunodeficient mice, was conducted before ovarian tissue transplantation (OTT).
Results: Histology and immunohistochemistry (MPO, p53, CD4, CD45) of thawed ovarian fragments showed no malignant cell contamination. Nested RT-PCR (MLL::AF9) was negative and the mouse grafted with ovarian tissue showed no disease after 6 months. The xenografted tissue was analyzed again (histology, immunohistochemistry and RT-PCR) and showed no contamination. Laparoscopic transplantation to the patient restored ovarian function after 4 months. Modified natural cycle IVF resulted in pregnancy. At 29 weeks, the patient had preterm premature rupture of membranes and delivered a healthy boy at 34.5 weeks. Three years post-transplantation, the patient remains disease-free.
Conclusions: Concerns about malignant cell contamination limit cryopreserved OTT in leukemia survivors. This is the first reported European live birth in an acute myeloid leukemia survivor following frozen-thawed OTT. Safe OTT was achieved by retrieving ovarian tissue during complete remission and conducting thorough screening before transplantation. Obstetrical risks in leukemia survivors who had total body irradiation should also be thoroughly discussed during decision making before attempting motherhood.
期刊介绍：
The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species.
The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.
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