GnRH激动剂长方案与GnRH拮抗剂方案用于中国不孕患者有效性和安全性比较的系统评价和meta分析

Comparison of effectiveness and safety of GnRH agonist long protocol with GnRH antagonist protocol in Chinese infertile women:a systematic review and meta-analysis

目的系统比较促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)激动剂长方案与GnRH拮抗剂方案应用于中国不孕患者辅助生殖治疗中的有效性及安全性,为临床实践提供科学参考。方法计算机检索PubMed、EMBASE、CENTRAL、CBM、CNKI和Wanfang Data数据库,检索时限均为建库至2019年6月,纳入相关随机对照试验(randomized controlled trial,RCT)。由两名经方法学培训的研究者独立完成文献筛选、偏倚风险评价及数据提取后,采用RevMan5.3软件进行meta分析。结果共纳入14项RCT,共2335例中国不孕患者,年龄为29.0~38.9岁,不孕年限为3.8~6.8年。纳入研究偏倚风险为中到高。在中国不孕患者中,应用GnRH激动剂长方案与GnRH拮抗剂方案相比获卵数更多(MD=0.60,95%CI=0.07~1.13,P=0.030)。而两种方案的M_(Ⅱ)卵率(RR=1.03,95%CI=0.99~1.07)、受精率(RR=1.02,95%CI=0.99~1.05)、可移植胚胎数(MD=-0.05,95%CI=-0.15~0.04)、优质胚胎率(MD=-0.17,95%CI=-0.66~0.33)、种植率(RR=0.96,95%CI=0.80~1.15)和临床妊娠率(RR=1.07,95%CI=0.93~1.22)差异均无统计学意义(均P>0.05)。在安全性方面,应用两种方案的周期取消率(RR=1.74,95%CI=0.98~3.10)和流产率(RR=1.08,95%CI=0.68~1.72)差异均无统计学意义(均P>0.05),但GnRH激动剂长方案的卵巢过度刺激综合征发生率高于GnRH拮抗剂方案(RR=2.77,95%CI=1.59~4.81,P<0.001)。结论在中国不孕患者中,与GnRH拮抗剂方案相比,应用GnRH激动剂长方案可能增加获卵数,增加卵巢过度刺激综合征发生风险。而在M_(Ⅱ)卵率、受精率、可移植胚胎数、优质胚胎率、种植率、临床妊娠率、周期取消率和流产率上,尚不能认为两种促排卵方案存在差异。

Objective To systematically compare the effectiveness and safety of gonadotropin-releasing hormone(GnRH)agonist long protocol and GnRH antagonist protocol in Chinese infertile women,thus providing scientific support for clinical practice.Methods We systematically searched PubMed,EMBASE,CENTRAL,CBM,CNKI and Wanfang Data for eligible randomized controlled trials from inception to June 2019.Two well-trained reviewers who had full understanding of the study protocol conducted the literature screening,risk of bias assessment and data extraction independently.Meta analyses were conducted by RevMan5.3 software.Results Totally 14 randomized controlled trials were identified for analysis,including 2335 Chinese infertile women patients,with age ranged from 29.0 to 38.9 years and 3.8-6.8 years duration of infertility.Bias risk of included studies was moderate to high.Meta analyses suggested that in Chinese infertile women,compared with GnRH antagonist protocol,application of GnRH agonist long protocol increased the number of retrieved oocytes(MD=0.60,95%CI=0.07-1.13,P=0.030),but there were no significant differences between the two protocols when referred to M_(Ⅱ) oocyte rate(RR=1.03,95%CI=0.99-1.07),fertilization rate(RR=1.02,95%CI=0.99-1.05),number of embryos transferred(MD=-0.05,95%CI=-0.15-0.04),good-quality embryo rate obtained(MD=-0.17,95%CI=-0.66-0.33),implantation rate(RR=0.96,95%CI=0.80-1.15)and clinical pregnancy rate(RR=1.07,95%CI=0.93-1.22).As for safety evaluation,there were no significant differences between the two protocols in cancellation rate(RR=1.74,95%CI=0.98-3.10)and abortion rate(RR=1.08,95%CI=0.68-1.72),while the ovarian hyperstimulation syndrome(OHSS)rate of GnRH agonist long protocol was significantly higher than that of GnRH antagonist protocol(RR=2.77,95%CI=1.59-4.81,P<0.001).Conclusion Current available evidence showed that in Chinese infertile women,application of GnRH agonist long protocol may result in more retrieved oocytes and higher OHSS risk than GnRH antagonist protocol,while there were no significant differences between the two protocols in M_(Ⅱ) oocyte rate,fertilization rate,number of embryos transferred,good-quality embryo rate,implantation rate,clinical pregnancy rate,cancellation rate and abortion rate.