国产重组人绒毛膜促性腺激素用于中国女性控制性超促排卵治疗中的有效性与安全性:一项随机对照研究

Efficacy and safety of domestic produced recombinant human chorionic gonadotropin in Chinese women undergoing controlled ovarian hyperstimulation:a randomized controlled trial

目的评价国产重组人绒毛膜促性腺激素(recombinant human chorionic gonadotropin,r-hCG)用于中国女性辅助生殖技术(assisted reproductive technology,ART)控制性超促排卵(controlled ovarian hyperstimulation,COH)治疗的有效性与安全性。方法本试验为多中心、随机、双盲、阳性药平行对照临床研究,于2017年7月至2018年10月期间选取中国7家生殖医学中心纳入卵巢储备功能正常、拟进行ART-COH治疗的不孕女性。应用中央随机化系统按照完全随机化原则将受试者随机分为试验组(国产r-hCG,n=112)和对照组(进口r-hCG,n=116),比较两组受试者COH周期中获得卵母细胞数、分裂中期卵母细胞率、卵裂细胞数、双原核受精数、移植周期中血清hCG阳性率、早期移植胚胎丢失率、临床妊娠率、持续妊娠率及不良反应发生率等指标。结果试验组和对照组在COH周期中获得的卵母细胞数分别为(12.1±5.6)枚和(12.0±6.7)枚,差异无统计学意义(P>0.05);两组间分裂中期卵母细胞率、卵裂细胞数、双原核受精数、移植周期中血清hCG阳性率、早期移植胚胎流失率、临床妊娠率、持续妊娠率差异均无统计学意义(均P>0.05),且两组差值的90%置信区间(confidence interval,CI)均落在预先设定的等效性界值(-3,+3)范围内;两组间免疫原性评估的差异无统计学意义(P>0.05);治疗期间卵巢过度刺激综合征(ovarian hyperstimulation syndrome,OHSS)及其他不良反应发生率差异均无统计学意义(均P>0.05),且试验组不良反应均为进口r-hCG的已报道的不良反应。结论在卵巢储备功能正常的中国不孕女性COH周期中,国产r-hCG有效性及安全性与进口r-hCG相当。

Objective To evaluate the efficacy and safety of domestic recombinant human chorionic gonadotropin(r-hCG)for injection in Chinese women undergoing assisted reproductive technology(ART)of controlled ovarian hyperstimulation(COH).Methods In a multicenter,randomized,double-blind,positive,parallel controlled clinical trial,the infertile women with normal ovarian reserve who received COH in seven reproductive medical centers from July 2017 to October 2018 were randomly divided into two groups:experimental group(domestic r-hCG,n=112)and control group(imported r-hCG,n=116).Interactive web response system was used to randomize.The total number of oocytes obtained,cleavage cells,two pronuclei fertilization,mid-division oocytes rate,positive serum hCG rate,early embryo loss rate,clinical pregnancy rate,sustained pregnancy rate and the incidence of adverse reactions were compared between the two groups during the cycle of COH.Results During the initiation cycle of ovulation induction therapy,the total number of oocytes obtained in experimental group and control group were(12.1±5.6)and(12.0±6.7)respectively,with no statistically significant difference(P>0.05).There were no significant differences in the rate of mid-division oocytes,the number of cleavage cells,the number of double pronuclear fertilization,the positive rate of serum hCG during the transplantation cycle,the loss rate of early embryo,the clinical pregnancy rate,and the sustained pregnancy rate between the two groups(all P>0.05),and the 90%confidence interval(CI)of the difference between the two groups fell within the preset equivalence threshold(-3,+3).The difference in immunogenicity assessment between the two groups was not statistically significant(P>0.05).The incidence of ovarian hyperstimulation syndrome(OHSS)and other adverse reactions in treatment period were not significantly different between the two groups(all P>0.05),which were known adverse reaction occurred in the imported r-hCG.Conclusion In the COH cycle of Chinese infertile women with normal ovarian reserve,the effectiveness and safety of domestic r-hCG are equivalent to imported r-hCG.