Optimizing In Vitro Maturation Outcomes of Oocytes Following Gonadotropin Priming in Premenarcheal Girls Undergoing Ovarian Tissue Cryopreservation

Weie Zhao; Yingchun Guo; Chuanchuan Zhou; Peng Sun; Tingting Li; Haitao Zeng; Jingjie Li; Cong Fang; Xiaoyan Liang

doi:10.1016/j.fertnstert.2025.06.038

Optimizing In Vitro Maturation Outcomes of Oocytes Following Gonadotropin Priming in Premenarcheal Girls Undergoing Ovarian Tissue Cryopreservation

Fertil Steril. 2025 Jun 28:S0015-0282(25)00543-6. doi: 10.1016/j.fertnstert.2025.06.038. Online ahead of print.

Authors

Weie Zhao¹, Yingchun Guo¹, Chuanchuan Zhou¹, Peng Sun¹, Tingting Li¹, Haitao Zeng¹, Jingjie Li¹, Cong Fang¹, Xiaoyan Liang²

Affiliations

¹ Reproductive Medicine Research Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; GuangDong Engineering Technology Research Center of Fertility Preservation, Guangzhou, China; Biochemical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
² Reproductive Medicine Research Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; GuangDong Engineering Technology Research Center of Fertility Preservation, Guangzhou, China; Biochemical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address: Liangxy2@mail.sysu.edu.cn.

PMID: 40588149
DOI: 10.1016/j.fertnstert.2025.06.038

Abstract

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 (OTC) 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 OTC.

Main outcome measure: Oocyte maturation rate of IVM.

Results: Ovarian tissue from premenarcheal girls expressed Gn receptors and responded to exogenous Gn stimulation. While 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], P=0.338), higher maturation rates were observed in the Gn group than in the control group (49.2% vs. 36.2%, P < 0.001). 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, P=0.019), whereas a moderate effect was observed in children aged 6-11 years (OR= 1.67, 95% CI: 1.03-2.69, P=0.037). In adolescents aged 12-18 years, the improvements were less pronounced and were not significant (OR = 2.04, 95% CI: 0.78-5.36, P=0.146). 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, P = 0.965). Transcriptomic analysis of granulosa cells suggested that Gn priming may enhance oocyte maturation by modulating pathways related to mitochondrial function, steroidogenesis, DNA repair, and spindle assembly.

Conclusions: 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 gonadotropin-based stimulation strategies for this unique population.

Keywords: fertility preservation; gonadotropin; in vitro maturation; ovarian tissue cryopreservation; premenarcheal girls.