国产与进口重组人FSH用于WHOII类排卵功能障碍患者促排卵的多中心、盲法、随机对照Ⅲ期临床试验

A randomized, single-blind, parallel-controlled and multicentre study： compare the efficacy and safety of domestic and imported human recombinant FSH in WHO group II anovulatory infertility

目的评价国产重组人FSH（rhFSH）用于WHO1I类无排卵性患者促排卵的临床有效性及安全性。方法多中心、随机、盲法、平行阳性对照的非劣效试验。2008年5月-2009年8月在13家医院确诊的531例WHOⅡ类无排卵性不孕症育龄期妇女被纳入统计学分析，随机分为试验组（予国产rhFSH，n=352）和对照组（予进口rhFSH，n=179）。比较两组患者在启动周期内达到成熟卵泡（B超下卵泡直径〉118mm）的有效率、排卵率、临床妊娠率、多胎妊娠率、卵巢过度刺激综合征（OHSS）发生率及不良反应发生率等指标。结果启动周期内达到成熟卵泡的有效率，试验组和对照组分别为91．8％（323，352）和88．8％（159／179），两组比较，差异无统计学意义（P〉0．05）。基于成熟卵泡周期的排卵率和临床妊娠率，试验组为91．3％（295／323）和19．2％（62／323），对照组为90．6％（144／159）和18．2％（29／159），分别比较，差异均无统计学意义（P〉0．05）。直径〈14mm的卵泡数、hCG日LH和孕酮水平、hCG日子宫内膜厚度，两组比较，差异均无统计学意义（P〉0．05）；14mm≤直径〈18mm、直径≥18mm的卵泡数及hOG日雌二醇水平，试验组均显著高于对照组（P〈0．05）。试验组患者rhFSH总用量和刺激天数分别为（879±419）U、（9．8±2．2）d，对照组分别为（1043±663）U、（11．4±0．6）d，分别比较，差异均有统计学意义（P〈0．05）。试验组的多胎妊娠率高于对照组，分别为21％（13／62）和10％（3／29），两组比较，差异有统计学意义（P〈0．05）。治疗期间，OHSS和不良反应发生率，两组比较，差异均无统计学意义（P〉0．05）。试验组未出现进口rhFSH不良反应以外的事件。结论针对WHOII类无排卵性患者采用国产rhFSH促排卵治疗有效、安全、经济，值得推广。

Objective To evaluate the efficacy and safety of domestic human recombinant FSH （rhFSH） in women with anovulation of WHO group Ⅱ. Methods A randomized, blind, parallel-controlled, non-inferiority and multicenter study was performed. A total of 534 admitted to 13 hospitals from May 2008 to August 2009. There were 531 women with ovulatory disorder was included in the statistical analysis, were randomly divided into test group （domestic rhFSH, n=352） and control group （imported rhFSH, n=179）. Percentage of cycle with mature follicle, ovulation rate, clinical pregnancy rate, multiple pregnancy rate, ovarian hyperstimulation syndrome （OHSS） and adverse events were observed. Results No statistical significant differences （P〉0.05） were observed between the two groups in terms of the efficiency on mature follicle [91.8% （323/352） versus 88.8% （159/179）], ovulation rate [91.3% （295/323） verus 90.6% （144/159）], clinical pregnancy rate [19.2% （62/323） verus 18.2% （29/159）], the number of the follicles〈 14 mm, the level of serum LH and progesterone, the thickness of endometrium on the day of hCG administration. The number of follicle≥18 mm and 14 mm≤.folliele〈18 mm and the level of serum estradiol on the day of hCG in the test group were significantly higher than those in the control group （P〈0.05）. The number of days of rhFSH administration in the test group was significantly less than that in the control group [（9.8±2.2） versus （11.4±0.6） days, P〈0.05], the dosage of rhFSH was significantly lower than that in the control group [（879±419） versus （1 043±663） U, P〈0.05]. The multiple pregnancy rate in the test group was significantly higher than that in the control group [21% （13/62） versu 10% （3/29）, P〈0.05]. The incidence of OHSS and adverse events were similar between the two groups （P〉0.05）, and no other adverse events were observed in test group during treatment. Conclusion Ovarian stimulation with domestic rhFSH is effective, safe and economical in women with anovulation of WHO group Ⅱ.