First pregnancy and live birth in Turkey following frozen-thawed ovarian tissue transplantation in a patient with acute lymphoblastic leukemia who underwent cord blood transplantation

Purpose To report the first live birth after frozen-thawed ovarian transplantation in Turkey and the second case for an acute lymphoblastic leukemia (ALL) survivor in the world. Methods A 19-year-old patient underwent ovarian tissue cryopreservation (OTC) before cord blood transplantation in 2010. She was diagnosed as ALL with a bone marrow biopsy revealing 90% blast ALL-L2 type, and karyotype analyses indicated reciprocal translocation at t(9;22)(q34;q11). The patient received the Berlin-Frankfurt-Munster (BFM) protocol, and complete remission was achieved before fertility preservation. Serum AMH level was measured as 1.5 ng/ml, and 12 antral follicles were counted on ultrasound. She was informed about fertility preservation options and decided to proceed with OTC, with her signed consent before cord blood transplantation in April 2011. Ovarian tissue transplantation (OTT) was performed in 2017 when the patient was menopausal with serum FSH levels > 100 IU/ml and estradiol < 20 pg/ml and hematologically in molecular remission. Detailed molecular analysis, standard histology, and immunohistochemistry demonstrated that the thawed tissue is free of malignant cells. Results Six months following OTT, she had spontaneous menstruation with serum FSH 11 IU/ml and estradiol 53 pg/ml. Two consecutive IVF cycles yielded three top-quality embryos. Following three embryo transfer cycles, one fresh and two frozen, a healthy term live birth was achieved. Frozen-thawed-transplanted tissues were extracted during caesarean delivery upon the patient's request after a total period of 25 months in vivo, and histopathological evaluation revealed that the tissue was free of leukemic infiltration. Conclusion The authors report the first pregnancy and live birth in Turkey and the second live birth in the world following transplantation of frozen-thawed ovarian tissue in a leukemia survivor. As the transplanted tissues were removed during caesarean delivery, histological findings prove the functionality and the malignant-free status of the transplanted tissue during the grafted period.