Optimizing in vitro maturation outcomes of oocytes following gonadotropin priming in premenarcheal girls undergoing ovarian tissue cryopreservation.

Objective: To investigate the impact of gonadotropin (Gn) priming on oocyte maturation outcomes during in vitro maturation (IVM) in premenarcheal girls undergoing ovarian tissue cryopreservation for fertility preservation.

Design: A retrospective cohort study conducted at a university-affiliated tertiary care medical center.

Subjects: A total of 167 premenarcheal girls aged 3-18 years scheduled for hematopoietic stem cell transplantation between July 2021 and September 2024. None of the patients had been exposed previously to chemotherapy.

Exposure: Administration of exogenous Gn for 3 days prior to ovarian tissue cryopreservation.

Main Outcome Measures: Oocyte maturation rate of IVM.

Results: Ovarian tissue from premenarcheal girls expressed Gn receptors and responded to exogenous Gn stimulation. Although the number of retrieved oocytes was comparable between the Gn and control groups (median [interquartile range]: 9.5 [6.0-14.0] vs. 8.0 [6.0-11.0]), higher maturation rates were observed in the Gn group than in the control group (49.2% vs. 36.2%). Subgroup analysis revealed the greatest benefit in the youngest age group (3-5 years; odds ratio [OR] = 3.04, 95% confidence interval [CI]: 1.21-7.65), whereas a moderate effect was observed in children aged 6-11 years (OR = 1.67, 95% CI: 1.03-2.69). In adolescents aged 12-18 years, the improvements were less pronounced and were not significant (OR = 2.04, 95% CI: 0.78-5.36). No significant difference in maturation rates of IVM was observed between Gn doses of 150 IU (47.3%) and 225 IU (51.1%) (OR = 0.99, 95% CI: 0.69-1.43). Transcriptomic analysis of granulosa cells suggested that Gn priming may enhance oocyte maturation by modulating pathways related to mitochondrial function, steroidogenesis, deoxyribonucleic acid repair, and spindle assembly.

Conclusion: Gn priming improves oocyte maturation rates of IVM in premenarcheal girls undergoing fertility preservation, with the most pronounced benefit observed in younger children. These findings highlight the potential of Gn priming as an adjunct to optimize fertility preservation protocols in premenarcheal girls, particularly in those under 6 years of age. Further studies are warranted to elucidate the molecular mechanisms underlying these effects and to refine Gn-based stimulation strategies for this unique population.