子宫内膜转化日血清雌二醇浓度对激素替代周期冻融胚胎移植结局的预测价值

The value of serum estradiol concentration on the day of endometrial transformation in predicting the outcome of frozen-thawed embryo transfer in hormone replacement cycle

为探讨黄体酮转化子宫内膜日的血清雌二醇浓度能否预测激素替代周期冻融胚胎移植的妊娠结局。本文采用病例对照研究,回顾性分析首都医科大学附属北京妇产医院生殖医学科于2018年1月至2020年12月进行的激素替代疗法冻融胚胎移植(hormone replacement therapy-frozen thawed embryo transfer,HRT-FET)共230个周期,血清雌二醇浓度在139.5~3 941.0 pg/ml之间。根据子宫内膜转化日血清雌二醇浓度的百分位数将患者分为3组:对照组(<第25百分位数,n=58例),高雌二醇组(第25~75百分位数,n=112例)和超高雌二醇组(>第75百分位数,n=60例)。比较3组的基本特征及妊娠结局,主要观察指标是活产率,次要观察指标是临床妊娠率。数据分析采用F检验和Kruskal-Wallis(H)检验进行计量资料组间比较,采用χ2检验进行计数资料组间比较。结果显示,一般情况:3组取卵周期时的年龄、抗苗勒管激素(anti-Müllerian hormone,AMH)、基础窦卵泡数(antral follicle count,AFC)、体重指数(body mass index,BMI)、不孕年限、原发不孕占比等方面的差异无统计学意义(F=2.375,H=5.479,H=5.374,F=1.391,H=4.779,χ2=1.969,P>0.05)。FET周期治疗情况:3组子宫内膜转化前的孕酮(P)浓度、转化日子宫内膜厚度、单胚胎移植占比、囊胚移植占比之间的差异无统计学意义(H=5.359,H=5.957,χ2=0.626,χ2=4.532,P>0.05);3组在FET周期中子宫内膜转化前的雌激素用药天数,高雌二醇组为13.0(12.0,14.0)d、超高雌二醇组为13.0(12.0,15.0)d,均比对照组13.0(12.0,13.3)d的时间长,差异有统计学意义(H=8.897,P<0.05);高雌二醇组在内膜转化前的E2浓度为1 560.4(1 170.2,1 848.2)pg/ml、超高雌二醇组E2浓度为2 420.9(2 131.0,2 849.2)pg/ml,明显高于对照组的E2浓度238.8(206.9,287.0)pg/ml,差异有统计学意义(H=194.84,P<0.05)。3组的妊娠结局:3组的临床妊娠率,对照组37.9%、高雌二醇组51.8%、超高雌二醇组40.0%,其中高雌二醇组临床妊娠率最高,其次是超高雌二醇组,但3组间的差异无统计学意义(χ2=3.853,P>0.05);3组的胚胎种植率分别为19.3%、25.0%、32.8%,其中超高雌二醇组的胚胎种植率最高,但3组间的差异无统计学意义(χ2=5.544,P>0.05);3组活产率分别为37.9%、39.3%、40.0%,差异亦无统计学意义(χ2=0.055,P>0.05);104例临床妊娠病例中共发生了14(13.5%)例流产,均发生在高雌二醇水平组。104例临床妊娠病例中双胎妊娠24例(23.1%),发生在高雌二醇水平组(10例)和超高雌二醇水平组(14例),对照组无双胎妊娠病例。230个FET周期中有4例发生了宫外孕(1.7%),对照组和高雌二醇水平组各有2例,超高雌二醇组无宫外孕病例。

To analyze whether the serum concentration of estradiol on the day of progesterone conversion could predict the pregnancy outcome of frozen-thawed embryo transfer in hormone replacement cycle.In this paper,a case-control study was conducted to retrospectively analyze the 230 cycles of hormone replacement therapy-frozen thawed embryo transfer(HRT-FET)conducted by the Department of Reproductive Medicine,Beijing Obstetrics and Gynecology Hospital,Capital Medical University from January 2018 to December 2020.The concentration of serum estradiol was between 139.5-3941.0 pg/ml.According to the percentile of serum estradiol concentration on the day of endometrial transformation,patients were divided into three groups:control group(<25th percentile,n=58),high estradiol group(25th-75th percentile,n=112)and ultra-high estradiol group(>75th percentile,n=60).Comparing the basic characteristics and pregnancy outcome of the three groups,the main observation index was the live birth rate,and the secondary observation index was the clinical pregnancy rate.F test and Kruskal-Wallis(H)test were used to compare the measurement data,andχ2 test was used to compare the counting data.The results showed that there was no significant difference in age,anti-Müllerian hormone(AMH),antral follicle count(AFC),body mass index(BMI),years of infertility and the proportion of primary infertility among the three groups(F=2.375,H=5.479,H=5.374,F=1.391,H=4.779,χ²=1.969,P>0.05).FET cycle treatment:There was no significant difference in the concentration of progesterone(P)before transformation,the thickness of endometrium on the day of transformation,the proportion of single embryo transfer and blastocyst transfer among the three groups(H=5.359,H=5.957,χ²=0.626,χ²=4.532,P>0.05).The days of estrogen administration before endometrial transformation in the three groups during the FET cycle were 13.0(12.0,14.0)days in the high estradiol group and 13.0(12.0,15.0)days in the ultra-high estradiol group,which were significantly longer than those in the control group 13.0(12.0,13.3)days.The E2 concentration before intimal transformation in high estradiol group was 1560.4(1170.2,1848.2)pg/ml,while that in ultra-high estradiol group was 2420.9(2131.0,2849.2)pg/ml,which was significantly higher than that in control group 238.8(206.9,287.0)pg/ml.The pregnancy outcome of the three groups:the clinical pregnancy rate of the three groups was 37.9%in the control group,51.8%in the high estradiol group and 40.0%in the ultra-high estradiol group,of which the high estradiol group had the highest clinical pregnancy rate,followed by the ultra-high estradiol group.But there was no significant difference among the three groups(χ²=3.853,P>0.05).The embryo implantation rate of the three groups was 19.3%,25.0%,32.8%,respectively,and the embryo implantation rate of the ultra-high estradiol group was the highest,but there was no significant difference among the three groups(χ²=5.544,P>0.05).The live birth rate of the three groups was 37.9%,39.3%,40.0%,respectively,and the difference was not statistically significant(χ²=0.05,P>0.05).A total of 14(13.5%)abortions occurred in 104 clinical pregnancies,all of which occurred in the high estradiol level group.Of the 104 clinical pregnancies,24(23.1%)had twin pregnancies,which occurred in the high estradiol level group(10 cases)and the ultra-high estradiol level group(14 cases).There were no twin pregnancies in the control group.Ectopic pregnancy occurred in 4 of 230 FET cycles(1.7%),2 in control group and 2 in high estradiol group,and no ectopic pregnancy in ultra-high estradiol group.