应用自然周期与激素替代疗法行首次冻融胚胎移植的年轻患者临床结局分析

Analysis of the first frozen-thawed embryo transfer clinical outcomes in young patients applying natural cycle and hormone replacement therapy

目的分析应用自然周期(natural cycle,NC)与激素替代疗法(hormone replacement therapy,HRT)行首次冻融胚胎移植(frozen-thawed embryo transfer,FET)的<35岁患者的临床结局。方法回顾性队列研究分析2016年1月至2021年6月期间在郑州大学第一附属医院生殖医学中心接受首次FET助孕的年轻不孕症患者4814例,根据内膜准备方案的不同分为NC组和HRT组,使用倾向性评分匹配(propensity score matching,PSM)法按1∶1的比例匹配两组的基线数据后,比较基线特征、妊娠结局及围产期结局,通过单因素及多因素logistic回归分析调整影响活产率的混杂因素后,根据窦卵泡计数(antral follicle count,AFC)、移植胚胎数和移植优质胚胎数进一步分层,分别分析NC和HRT对活产率的影响。结果PSM前,纳入NC组2131例,HRT组2683例,两组间的女方年龄、男方年龄、体质量指数(body mass index,BMI)、基础卵泡刺激素(basal follicle-stimulating hormone,bFSH)、抗苗勒管激素(anti-Müllerian hormone,AMH)、AFC、转化日子宫内膜厚度、移植胚胎数差异均存在统计学意义(均P<0.05),两组间的移植优质胚胎数和移植胚胎类型差异均无统计学意义(均P>0.05);PSM后,纳入NC组和HRT组各1441例,两组患者的女方年龄、男方年龄、BMI等基线特征差异均无统计学意义(均P>0.05),NC组的活产率[50.66%(730/1441)]和临床妊娠率[60.31%(869/1441)]显著高于HRT组[44.69%(644/1441),P=0.001;54.27%(782/1441),P=0.001],极低出生体质量儿发生率NC组[0.34%(3/871)]显著低于HRT组[1.69%(13/769),P=0.006],余各项指标两组差异均无统计学意义(均P>0.05)。把bFSH、AMH、AFC、转化日子宫内膜厚度、移植胚胎数及移植优质胚胎数纳入多因素logistic回归模型矫正混杂因素后,结果显示NC为影响首次FET周期活产的独立保护因素(aOR=1.280,95%CI:1.103~1.486,P=0.001)。分层分析结果显示,在AFC<11、11~20,移植胚胎数为2及移植优质胚胎数为2的人群中,NC组的活产率[49.03%(151/308),49.09%(349/711),56.38%(442/784),57.85%(350/605)]显著高于HRT组[36.36%(120/330),P=0.001;43.14%(286/663),P=0.027;48.97%(379/774),P=0.003;48.68%(294/604),P=0.001]。结论对于年轻FET助孕患者,NC-FET比HRT-FET有更高的活产率和临床妊娠率。

Objective To analyze the clinical outcomes of the first frozen-thawed embryo transfer(FET)in patients<35 years old applying natural cycle(NC)and hormone replacement therapy(HRT).Methods A retrospective cohort study was conducted to analyze 4814 young infertility patients who underwent the first FET in Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2016 to June 2021.According to different endometrial preparation protocols,they were divided into 2 groups:NC group and HRT group,who were matched the baseline data using 1∶1 propensity score matching(PSM).After the matching,the two groups of their baseline data,pregnancy outcomes and perinatal outcomes were compared,and then we adjusted the confounding factors which affect live birth rate by univariate and multivariate logistic regression analysis.Based on antral follicle count(AFC),number of embryos transferred and number of high-quality embryos transferred,the effect of NC and HRT on the live birth rate were further analyzed.Results Before PSM,2131 patients in NC group and 2683 patients in HRT group were included.The differences in female age,male age,body mass index(BMI),basal follicle-stimulating hormone(bFSH),anti-Müllerian hormone(AMH),AFC,endometrial thickness on conversion day,and number of embryos transferred were all statistically significant between the two groups(all P<0.05).And the differences in number of high-quality embryos transferred and type of embryos transferred between the two groups were not statistically significant(all P>0.05).After PSM,1441 patients in each of NC group and HRT group were included,and there were no significant differences in their baseline characteristics such as female age,male age and BMI between the two groups(all P<0.05).The live birth rate[50.66%(730/1441)]and the clinical pregnancy rate[60.31%(869/1441)]in NC group were significantly higher than those in HRT group[44.69%(644/1441),P=0.001;54.27%(782/1441),P=0.001],and the incidence of very low birth weight in NC group was significantly lower than that in HRT group,and there were no statistical significances in other indicators between the two groups(all P>0.05).After adjusting confounders including bFSH,AMH,AFC,endometrial thickness on conversion day,number of embryos transferred and high-quality embryos transferred using multivariate logistic regression analysis,the results showed that NC was an independent protective factor for live birth rate in the first FET cycle(aOR=1.280,95%CI:1.103-1.486,P=0.001).Stratified analysis showed that those with AFC<11,AFC 11-12,2 embryos transferred and 2 high-quality embryos tranferred in NC group had significantly higher live birth rate[49.03%(151/308),49.09%(349/711),56.38%(442/784),57.85%(350/605)]than those in HRT group[36.36%(120/330),P=0.001;43.14%(286/663),P=0.027;48.97%(379/774),P=0.003;48.68%(294/604),P=0.001].Conclusion NC-FET had higher live birth rate and clinical pregnancy rate than HRT-FET in young patients.