The Outcome of Fertility Preservation Strategy in Female Hematopoietic Stem Cell Transplant Recipients of Reproductive Age. Retrospective Study from the Kanto Study Group for Cell Therapy

Background: Conditioning regimens including high-dose chemotherapy and/or total body irradiation (TBI) often harm the gonads leading to infertility after hematopoietic stem cell transplantation (HSCT). Therefore, strategies to preserve fertility have been investigated to improve the quality of life of patients after HSCT. For female patients, oocyte collection followed by cryopreservation of oocytes or embryos is recommended in guidelines, but collecting oocytes before or during chemotherapy is challenging in patients with acute leukemia. For patients planned to receive TBI, ovarian shielding has been shown to achieve early ovarian function recovery after HSCT. However, only a few large-scale studies have evaluated the outcome of these strategies. Methods: We retrospectively investigated information on fertility preservation strategy and its outcome using a questionnaire among female recipients aged 16-42 years at HSCT, performed between 2001 and 2020 at 18 institutions in the Kanto Study Group for Cell Therapy. Results: This study included 201 autologous and 1421 allogeneic HSCT in 1379 patients with a median age of 32 years at HSCT. Oocytes or embryos were cryopreserved in 76 patients in total. Ovarian tissue cryopreservation was performed in 12. Of the 286 and 193 patients who underwent allogeneic HSCT with reduced-intensity conditioning (mainly for aplastic anemia) and who underwent autologous HSCT, respectively, 52 (18.2%) and 20 (10.3%) recovered menstruation and 8 (2.8%) and 13 (6.7%) became pregnant. On the other hand, of the 900 patients who underwent allogeneic HSCT with myeloablative conditioning, 26 (2.9%) recovered menstruation exclusively using TBI-regimens (>8Gy, 19 with ovarian shielding), but none who received busulfan-based regimens did so, and 10 (1.1%) became pregnant including spontaneous pregnancy in 5 (all after TBI with ovarian shielding), and 2 each using cryopreserved oocytes and egg donation, respectively. Overall, 42 pregnancies in 31 patients resulted in 32 deliveries. With regard to the feasibility of oocytes/embryos cryopreservation, 125 (11%) of the 1147 patients with available information were referred to a fertility specialist. The oocyte or ovarian tissue collection for cryopreservation was actually attempted in 49% (61 of 125 cases). Among patients with an available information on the number of cryopreserved oocytes/embryos, the median number of cryopreserved oocytes and embryos was 5 and 3, respectively, and the rate of cryopreserving at least 10 oocytes or at least 3 embryo was 41% of patients with cryopreserved oocytes/embryos. Information on the reason for no-referral was not collected, but may include low probability to harvest enough oocytes, refusal by the patients including those who already had children, and so on.Conclusion: Although cryopreservation of oocytes and embryos is challenging in patients with hematological malignancies, these assisted reproductive technologies and ovarian shielding during TBI appeared to contribute to pregnancy and delivery after HSCT.

Inamoto:Meiji Seika Pharma: Honoraria, Research Funding; Janssen: Honoraria. Hatta:Chugai Pharmaceutical Co., LTD.: Honoraria; Nihon Servier Co., LTD: Honoraria; Bristol-Myers Squibb Co: Honoraria; Phizer Japan Inc: Honoraria; Kyowa Hakko Kirin CO. LTD: Honoraria. Kanda:Asahi-kasei, MSD, Novartis, Pfizer, Sanofi, Chugai, Astellas, Kyowa-Kirin: Honoraria; Chugai, Kyowa-kirin, Asahi-kasei, Otsuka: Research Funding.