卵巢组织卵母细胞体外成熟在恶性肿瘤患者生育力保存中的应用

Feasibility analysis and application of ovarian tissue oocyte-in vitro maturation in the patients with malignant tumors undergoing fertility preservation

目的探讨卵巢组织卵母细胞体外成熟(ovarian tissue oocyte-in vitro maturation,OTO-IVM)在肿瘤患者中的临床效果与应用前景。方法回顾性分析2017年3月至2022年8月期间于中山大学附属第六医院生殖医学研究中心行卵巢组织冷冻(ovarian tissue cryopreservation,OTC)并同时行OTO-IVM的27例肿瘤患者的临床资料。分析总结OTO-IVM的临床结局,包括成熟卵母细胞数、成熟率、成熟时间;IVM来源成熟卵母细胞的受精率、卵裂率和胚胎发育情况;探讨卵巢组织获取前短期使用促性腺激素(gonadotropin,Gn)在OTO-IVM中的应用。结果81.48%(22/27)的患者至少有1枚卵母细胞成熟,成熟卵母细胞中位数为3.00(1.50,7.00)枚,成熟率为38.81%(104/268)。4.85%(13/268)的卵母细胞在24 h内成熟,14.93%(40/268)在24~36 h之间成熟,16.79%(45/268)在36~48 h之间成熟,仅有2.24%(6/268)卵母细胞在48 h后成熟。4例患者的41枚卵母细胞行卵胞质内单精子注射(intracytoplasmic sperm injection,ICSI)授精,受精率为85.37%(35/41),卵裂率为94.29%(33/35),可利用胚胎率为54.29%(19/35),优质胚胎率为34.29%(12/35)。术前短暂使用Gn患者的IVM率63.16%(48/76)显著高于未使用者[29.17%(56/192),P<0.001]。结论OTO-IVM可获得一定数量的卵母细胞与胚胎,可作为肿瘤患者生育力保存的补充方法。卵巢组织获取前短暂使用Gn可提高卵母细胞成熟率,由于样本量尚少,但还需要进一步研究,验证Gn在OTO-IVM中的应用价值。

Objective To explore the prospects of ovarian tissue oocyte-in vitro maturation(OTO-IVM)in fertility preservation for patients with malignancy.Methods OTO-IVM outcomes from 27 malignant tumor patients who underwent fertility preservation in Reproductive Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-Sen University from March 2017 to August 2022 were analyzed,including the number of mature oocytes(MII oocytes),maturation rate,and maturation time.The fertilization rate,the cleavage rate,and the embryonic development potential of IVM-derived MII were also analyzed.Further,the short-term use of gonadotropin(Gn)in OTO-IVM before ovarian tissue acquisition was initially explored.Results After OTO-IVM,81.48%(22/27)of patients had at least one MII oocyte,with a mean number of MII oocytes of 3.00(1.50,7.00)and a maturation rate of 38.81%.About 4.85%(13/268)of oocytes matured within 24 h;14.93%(40/268)matured between 24 h and 36 h;16.79%(45/268)matured between 36 h and 48 h,and only 2.24%(6/268)matured after 48 h.A total of 41 MII oocytes from 4 patients were fertilized by intracytoplasmic sperm injection(ICSI),with a fertilization rate of 85.37%(35/41),cleavage rate of 94.29%(33/35),variable embryo rate of 54.29%(19/35),and high-quality embryo rate of 34.29%(12/35).The IVM rate was significantly higher in patients who used Gn than in those who did not[63.16%(48/76)vs.29.17%(56/192),P<0.001].Conclusion OTO-IVM can be used as a complementary method for fertility preservation in oncology patients and obtain a certain number of oocytes and embryos.Short-term use of Gn before ovarian tissue acquisition can improve oocyte maturation rate,but further studies are needed to verify the value of Gn in OTO-IVM.