Ovarian tissue oocyte-in vitro maturation combined with ovarian tissue cryopreservation: a promising urgent fertility preservation strategy for hematological patients before HSCT

BACKGROUND: Hematological diseases to be treated with HSCT are a definite indication for fertility preservation (FP). Ovarian tissue oocyte in vitro maturation (OTO-IVM) combined with ovarian tissue cryopreservation (OTC) may be a promising and urgent FP strategy for this population. This study aims to evaluate the efficacy of OTO-IVM for this population and identify which hematological diseases are more likely to benefit from OTO-IVM. METHODS: This study included 44 hematological patients before HSCT who underwent the OTO-IVM combined with OTC for urgent FP. Patients were divided into the malignant hematological disease (MHD) and non-MHD groups and the OTO-IVM outcomes were retrospectively analysed. Donated ovarian tissues from MHD, non-MHD and control group were subjected to further molecular and pathological study. RESULTS: Patients with non-MHD exhibited significantly higher serum anti-Müllerian hormone (AMH) levels (4.36 ± 3.14 vs. 2.08 ± 1.57, p = 0.017) and a greater number of retrieved immature oocytes (10.58 ± 7.54 vs. 4.85 ± 3.26, p = 0.012) than those with MHD. Although the maturation rate showed a non-significant decreasing trend in the non-MHD group (35.80 ± 28.12 vs. 49.83 ± 33.96, p = 0.163), multivariable analysis demonstrated that non-MHD was associated with a lower per-patient IVM rate. The final number of MII oocytes did not differ significantly between groups (3.58 ± 4.07 vs. 2.23 ± 2.01, p = 0.264). Notably, increased apoptosis of ovarian stromal cells may contribute to impaired oocyte maturation competence in patients with aplastic anemia (AA). Consistently, AA ovarian tissues displayed activation of apoptotic signalling pathways and dysregulated T cell activation-associated gene expression compared with MHD and impaired oocyte development and maturation compared with control group. CONCLUSIONS: OTO-IVM combined with OTC appears feasible for urgent fertility preservation in hematological patients prior to HSCT. Our exploratory findings suggest that ovarian stromal cell apoptosis may contribute to reduced oocyte maturation competence in AA, which warrants further validation and optimization of maturation rates.