国产重组人促卵泡激素在辅助生殖技术控制性超促排卵的临床应用

目的评价国产重组人促卵泡激素(recombinant human follicle-stimulating hormone,rhFSH)用于辅助生殖技术(assisted reproductive technology,ART)控制性超促排卵(controlled ovarian hyperstimulation,COH)的有效性及安全性。方法本试验采用多中心、随机、双盲、阳性平行对照、非劣效研究方法,于2017年7月至2019年6月间选取6家生殖医学中心纳入卵巢储备正常的不孕女性进行ART的COH治疗。受试者随机分为试验组(国产rhFSH,n=134)和对照组(进口rhFSH,n=133),研究过程中因各种因素排除受试者共8例,试验组7例,对照组1例,最终依照研究方案完成试验的受试者试验组127例,对照组132例。比较两组受试者COH周期中获得的卵母细胞总数、rhFSH用药情况、卵母细胞受精率、优质胚胎数、临床妊娠率、活产率、新生儿情况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总数分别为(13.0±5.8)枚和(12.9±5.7)枚,差异无统计学意义(P>0.05);在82例卵胞质内单精子显微注射(intracytoplasmic sperm injection,ICSI)受试者中,试验组(39例)获得MII卵母细胞数(9.9±3.9)枚]显著高于对照组(43例)(7.5±3.0)枚,P=0.003];卵母细胞受精率试验组63.82%(1048/1642)]显著高于对照组56.19%(958/1705),P<0.001]。rhFSH用药时间和总量、优质胚胎数、临床妊娠率、早产率、活产率、新生儿异常发生率、新生儿体质量、Apgar评分等两组间差异无统计学意义(P均>0.05);治疗期间卵巢过度刺激综合征(ovarian hyperstimulation syndrome,OHSS)和其他不良反应发生率差异无统计学意义(P均>0.05),且均为进口rhFSH已知的不良反应。结论在卵巢储备正常的不孕女性中使用相同卵巢刺激治疗方案,国产rhFSH有效性及安全性与进口rhFSH相当。

Clinical application of domestic recombinant human follicle-stimulating hormone in controlled ovarian hyperstimulation with assisted reproductive technology

Objective To evaluate the efficacy and safety of domestic recombinant human follicle-stimulating hormone(rhFSH)in assisted reproductive technology(ART)of controlled ovarian hyperstimulation(COH).Methods In a multicenter,randomized,double-blind,positive,parallel controlled non-inferiority clinical trial,the infertile women with normal ovarian reserve who received ART-COH in six reproductive medical centers from July 2017 to June 2019 were randomly divided into two groups:experimental group(domestic rhFSH,n=134)and control group(imported rhFSH,n=133).Eight subjects were excluded due to various reasons during the experimental process,7 in experimental group and 1 in control group.At last,127 subjects in experimental group and 132 subjects in control group complete the experiment following the research protocol.The total number of oocytes,usage of FSH,fertilization rate of oocytes,the number of high-quality embryos,clinical pregnancy rate,live birth rate,neonatal characteristics 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 13.0±5.8 and 12.9±5.7,respectively,with no statistically significant difference(P>0.05).Among the 82 intracytoplasmic sperm injection(ICSI)patients,the number of MII oocytes obtained in experimental group(39 cases)was markedly higher than that in control group(43 cases)(9.9±3.9 vs.7.5±3.0,P=0.003).The fertilization rate of oocytes in experimental group was obviously higher than that in control group63.82%(1048/1642)vs.56.19%(958/1705),P<0.001].There were no significant differences of stimulated duration and dosage of rhFSH,number of high-quality embryos,clinical pregnancy rate,preterm rate,live birth rate,incidence of neonatal abnormalities,neonatal weight or Apgar score between the two groups(all P>0.05).The incidence of ovarian hyperstimulation syndrome 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 rhFSH.Conclusion The efficacy and safety of domestic rhFSH were the same as that of imported rhFSH in infertile patients with normal ovarian reserve under the same ovarian stimulation regimen.