新鲜周期与不同内膜准备方案冻融胚胎移植周期母胎结局比较

Comparison of the maternal-fetal outcomes between the fresh embryo transfer and different endometrial preparation protocols for the frozen-thawed embryo transfer

目的探讨新鲜周期与不同内膜准备方案冻融胚胎移植(frozen-thawed embryo transfer,FET)周期对母胎结局的影响,以指导临床咨询与应用。方法本研究为回顾性队列研究,分析2014年1月至2017年6月期间在北京大学第三医院妇产科生殖医学中心进行体外受精-胚胎移植(in vitro fertilization and embryo transfer,IVF-ET)助孕,获得分娩22395个连续周期的临床资料,根据不同移植方案分为3组:新鲜周期组、自然周期(natural cycle,NC)-FET组、激素替代治疗(hormone replacement therapy,HRT)-FET组。研究主要结局指标为产科母胎结局,次要结局指标为各组生殖相关临床资料、实验室相关指标等基本资料情况,并进一步采用logistic回归分析周期对各产科结局的影响。结果本研究新鲜周期组12118个,NC-FET组6648个,HRT-FET组3629个。基本特征中:①三组间不孕年限差异有统计学意义(P=0.007),女方年龄、女性体质量指数(body mass index,BMI)、男方年龄、不孕类型比例、人绒毛膜促性腺激素(human chorionic gonadotropin,hCG)注射日/转化日内膜厚度差异均有显著统计学意义(均P<0.001),其中内膜厚度在新鲜周期组最厚[(11.13±1.63)mm],NC-FET组次之[(10.61±1.74)mm],HRT-FET组[(9.77±1.58)mm]最低。②FET周期囊胚移植比例[NC-FET组54.8%(3646/6648)、HRT-FET组52.4%(1901/3629)]较新鲜周期组[3.8%(461/12118)]增加(P<0.001)。③囊胚移植后单卵双胎的发生率增加(P<0.001)。母胎结局:①三组间活产率差异有统计学意义(P=0.011)。②三组间分娩孕周差异有统计学意义[新鲜周期组(38.39±2.08)周、NC-FET组(38.69±1.87)周、HRT-FET组(38.40±2.31)周,P<0.001];NC-FET组和HRT-FET组的足月引产率[19.8%(1315/6648)、19.0%(690/3629)]、新生儿体质量[(3168.05±607.90)g、(3124.70±683.53)g]、巨大儿出生率[7.8%(521/6648)、8.5%(309/3629)]均高于新鲜周期组[16.6%(2017/12118)、(3007.61±627.60)g、6.6%(804/12118),均P<0.001]。③HRT-FET组早产率[16.9%(615/3629)]、剖宫产率[75.7%(2748/3629)]、低出生体质量儿率[12.1%(438/3629)]显著高于NC-FET组[12.6%(838/6648)、69.4%(4611/6648)、9.6%(637/6648),均P<0.001]。④HRT-FET组的妊娠高血压疾病发生率为5.0%(182/3629)、妊娠期糖尿病发生率为6.7%(244/3629)及胎膜早破发生率为3.4%(124/3629),新鲜周期组分别为1.6%(198/12118)、2.4%(198/12118)、2.9%(351/12118)],NC-FET组分别为2.0%(134/6648)、6.2%(410/6648)、2.1%(140/6648),三组间差异均有统计学意义(P<0.001)。⑤胎盘异常/产后出血发生率在HRT-FET组[1.0%(37/3629)]较NC-FET组升高[0.6%(41/6648)],差异有统计学意义(P=0.042)。结论FET是辅助生殖技术中安全、有效的治疗方案,胎儿并发症少于新鲜移植周期,但HRT-FET周期中母亲产科并发症增加。因此,不同内膜准备方案FET中,在可进行NC-FET的情况下,建议其作为首选治疗。

Objective To perform a comparative study of obstetric outcomes in fresh cycles and different endometrial preparation protocols in frozen-thawed embryo transfer(FET)cycles,in order to guide the follow-up clinical consulting service and applications.Methods This retrospective cohort study was conducted in a cohort of 22395 consecutive cases with live birth following successful in vitro fertilization and embryo transfer(IVF-ET)/FET performed at the Center for Reproductive Medicine,Department of Obstetrics and Gynecology of Peking University Third Hospital from January 2014 to June 2017.According to the method of embryo transfer cycles,they were divided into fresh cycle group,natural cycle(NC)-FET cycle group and hormone replacement therapy(HRT)-FET cycle group.The primary outcome indicators of the study were the maternal and fetal outcomes in obstetrics,and the secondary outcome indicators were the basic data such as reproductive-related clinical data and laboratory-related indicators in each group.Logistic regression was used to analyze the influence of cycles on the obstetrical outcomes.Results Among the 22395 cycles,there were 12118 cycles in fresh group,6648 cycles in NC-FET group,and 3629 cycles in HRT-FET group.Among the basic characteristics:1)There was a statistical difference in infertility duration among the three groups(P=0.007),and differences were also found in female age,female body mass index(BMI),male age,the proportion of infertile type,and mean endometrial thickness on human chorionic gonadotropin(hCG)/conversion day among the three groups(all P<0.001);the mean endometrial thickness among the women with the fresh cycles[(11.13±1.63)mm]was the thickest,followed by the NC-FET cycles[(10.61±1.74)mm]and the lowest in the HRT-FET cycles[(9.77±1.58)mm].2)The proportion of blastocysts transferred increased in the FET cycles[NC-FET cycles 54.8%(3646/6648),HRT-FET cycles 52.4%(1901/3629)]compared with fresh cycles[3.8%(461/12118),P<0.001].3)The incidence of monozygotic twins after blastocyst transfer increased(P<0.001).Maternal-fetal outcomes:1)The difference was observed in the live birth rate among the three groups(P>0.001).2)There was a statistical difference in the gestational age of delivery among the three groups[fresh cycles(38.39±2.08)weeks,NC-FET cycles(38.69±1.87)weeks,HRT-FET cycles(38.40±2.31)weeks,P<0.001],the full-term pregnancy induction rate(greater than 40 weeks)[19.8%(1315/6648),19.0%(690/3629)],the newborn weight[(3168.05±607.90)g,(3124.70±683.53)g]and the macrosomia rate[7.8%(521/6648),8.5%(309/3629)]were higher in the NC-FET and HRT-FET cycles than those in fresh cycles[16.6%(2017/12118),(3007.61±627.60)g,6.6%(804/12118),all P<0.001].3)In HRT-FET cycles,the premature birth rate[16.9%(615/3629)],the cesarean section rate[75.7%(2748/3629)],and the low birth weight rate[12.1%(438/3629)]were significantly higher than those in NC-FET cycles[12.6%(838/6648),69.4%(4611/6648),9.6%(637/6648),all P<0.001].4)The incidence of gestational hypertension,the incidence of gestational diabetes and the incidence of premature rupture of membranes in HRT-FET cycles[5.0%(182/3629),6.7%(244/3629),3.4%(124/3629)]were significantly different from those in NC cycles[1.6%(198/12118),2.4%(198/12118),2.9%(351/12118)]and NC-FET cycles[2.0%(134/6648),6.2%(410/6648),2.1%(140/6648),P<0.001].5)The incidence of placental abnormalities/postpartum hemorrhage also increased significantly in HRT-FET cycles[1.0%(37/3629)]compared with NC-FET cycles[0.6%(41/6648),P=0.042].Conclusion The application of FET in assisted reproductive technology is safe and becoming widespread.Fetal complications are less than the fresh cycles,but maternal obstetric complications increase during HRT-FET cycles.Therefore,in different protocols of FET,when NC-FET is available,it is recommended as the first choice.