低抗苗勒管激素水平与卵巢储备功能下降不孕患者冻胚移植临床结局的相关性

Correlation between low serum AMH level and clinical outcomes of patients with diminished ovarian reserve undergoing frozen embryo transfer

目的探讨卵巢储备功能下降(DOR)不孕患者低抗苗勒管激素(AMH)水平与冻融胚胎复苏移植临床结局的关系。方法以2018年1月至2019年6月在东南大学附属中大医院生殖医学科行冻融胚胎复苏移植周期的256例DOR患者为研究对象,回顾性分析患者血清AMH、年龄、身体质量指数(BMI)、不孕年限、基础卵泡刺激素(FSH)、基础雌二醇(E2)、移植日子宫内膜厚度、移植胚胎类型(卵裂胚/囊胚)及移植胚胎数与临床结局的相关性。结果共纳入386个周期,临床妊娠率为33.68%(130/386);流产率为26.15%(34/130),活产率为16.05%(56/349,除随访暂未完成的37个周期)。临床妊娠组患者年龄小于未妊娠组、基础FSH值低于未妊娠组(P<0.05),AMH值、移植日子宫内膜厚度高于未妊娠组(P<0.05),且囊胚移植的比例高于未妊娠组(P<0.05);临床妊娠组和未妊娠组BMI、不孕年限、基础E2、移植胚胎数差异未见统计学意义(P>0.05)。活产组年龄小于流产组(P<0.05)。根据AMH值将患者分为低(1.01~1.50 ng/mL)、中低(0.51~1.00 ng/mL)、极低(0.01~0.50 ng/mL)3组并比较,AMH中低、低组的一般情况差异均无统计学意义(P>0.05);AMH极低组和中低、低组间年龄、基础FSH、移植胚胎类型差异有统计学意义(P<0.05);AMH极低组临床妊娠率和继续妊娠率低于中低、低组(P<0.05);3组间流产率和活产率差异无统计学意义(P>0.05)。进一步对可能影响临床结局的因素行Logistic回归分析,修正混杂因素显示,临床妊娠率、活产率均与年龄呈负相关(P<0.05),流产率与年龄呈正相关(P<0.05),移植囊胚可提高临床妊娠率(P<0.05)。结论在DOR患者中,低AMH值与冻融胚胎复苏移植临床结局无关;用AMH无法预测复苏周期临床结局;影响临床结局的主要因素是女性年龄,年龄越大,临床妊娠率、活产率越低,流产率越高。

Objective To investigate the correlation between low serum anti-müllerian hormone(AMH) and the clinical outcomes of frozen embryo transfer(FET) in the infertile women with diminished ovarian reserve(DOR). Methods In this retrospective study, the clinical outcomes were followed in 256 patients with DOR undergoing FET cycles in the Department of Reproductive Medicine, Zhongda Hospital from January 2018 to June 2019. The possible influencing factors, including serum AMH, age, body mass index(BMI), duration of infertility, basal follicle stimulating hormone(FSH), basal estradiol(E2), endometrial thickness on the day of FET, embryo type(cleavage embryo/blastocyst), and the number of embryos transferred, were analyzed for evaluating the correlation with clinical outcomes of frozen embryo transfer. Results A total of 386 cycles were included. The clinical pregnancy rate was 33.68%(130/386) and the abortion rate was 26.15%(34/130). The live birth rate was 16.05%(56/349) excluding 37 uncompleted follow-up pregnant cycles. In the comparison between clinical pregnant and non-pregnant groups, the female age of the clinical pregnancy group was obviously younger and basal FSH was significantly lower(P<0.05), but serum AMH level and thickness of endometrium on the day of FET in the clinical pregnancy group was obviously higher(P<0.05), and the proportion of blastocyst transferring was significantly higher(P<0.05). There were no significant differences of BMI, duration of infertility, basal E2 and number of transferred embryos between two groups(P>0.05). In the comparison of basic characteristics between abortion and live birth groups, the age of the live birth group was significantly younger(P<0.05). The patients were stratified into three groups based on AMH concentration: low(1.01 to 1.50 ng/mL), middle-low(0.51 to 1.00 ng/mL) and very-low(0.01 to 0.50 ng/mL) groups. The results of analysis revealed that the age, basal FSH, and embryo type in very-low AMH group were significantly different from those of the other two groups(P<0.05), but no significant difference of general information was found between the low AMH group and the middle-low group(P>0.05). In the terms of clinical outcomes, the clinical pregnancy rate of very-low AMH group was significantly lower than that of middle-low and low AMH group(P<0.05) while no significant difference of abortion rate and live birth rate was found among the 3 groups(P>0.05). The multiple logistic regression was used to further analyze the factors that might affect the clinical outcomes and the results revealed that the female age was the common factor having effect on clinical outcomes after adjustment for confounders. The clinical pregnancy rate and live birth rate were negatively correlated with age(P<0.05), and the abortion rate was positively correlated with female age(P<0.05). Blastocyst transferring could improve clinical pregnancy rate(P<0.05). Conclusion Low AMH level is not associated with clinical outcomes of frozen embryo transfer in the patients with DOR, and serum AMH level can not predict the clinical outcomes of frozen embryo transfer. The main factor that affects the clinical outcomes should be the age of patients. The older the age of the patients, the lower the probability of clinical pregnancy and live birth, and the higher the risk of abortion.