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中华妇幼临床医学杂志(电子版) ›› 2024, Vol. 20 ›› Issue (03) : 276 -283. doi: 10.3877/cma.j.issn.1673-5250.2024.03.006

生殖医学专辑

高龄女性冻胚移植周期临床妊娠结局的影响因素分析
李欣1, 魏艺1, 张娟1, 张娟娟1, 凌秀凤1, 赵纯1, 张媔秋1,†()   
  1. 1. 南京医科大学附属妇产医院（南京市妇幼保健院）生殖医学中心，南京　210004
  • 收稿日期:2024-01-02 修回日期:2024-05-15 出版日期:2024-06-01
  • 通信作者: 张媔秋

Influencing factors on clinical pregnancy outcomes of frozen-thaw embryo transfer cycle in women of advanced age

Xin Li1, Yi Wei1, Juan Zhang1, Juanjuan Zhang1, Xiufeng Ling1, Chun Zhao1, Mianqiu Zhang1,†()   

  1. 1. Reproductive Medicine Center, Women′s Hospital of Nanjing Medical University (Nanjing Women and Children′s Healthcare Hospital), Nanjing 210004, Jiangsu Province, China
  • Received:2024-01-02 Revised:2024-05-15 Published:2024-06-01
  • Corresponding author: Mianqiu Zhang
  • Supported by:
    National Natural Science Foundation of China(81971386); Jiangsu Maternal and Child Health Association Scientific Research Project(FYX202204)
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引用本文：

李欣, 魏艺, 张娟, 张娟娟, 凌秀凤, 赵纯, 张媔秋. 高龄女性冻胚移植周期临床妊娠结局的影响因素分析[J]. 中华妇幼临床医学杂志(电子版), 2024, 20(03): 276-283.

Xin Li, Yi Wei, Juan Zhang, Juanjuan Zhang, Xiufeng Ling, Chun Zhao, Mianqiu Zhang. Influencing factors on clinical pregnancy outcomes of frozen-thaw embryo transfer cycle in women of advanced age[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(03): 276-283.

目的

探讨影响高龄(分娩年龄≥35岁)女性冷冻胚胎移植(FET)临床妊娠结局的因素。

方法

选择2018年1月至2020年12月于南京医科大学附属妇产医院生殖中心接受体外受精-胚胎移植(IVF-ET)治疗，采取全胚胎冷冻进行FET，并且35岁<分娩年龄<45岁的1 135例不孕患者及其1 135个周期为研究对象。采取回顾性分析方法，根据临床妊娠结局，将1 135例不孕患者分为妊娠组(n＝476，FET后成功妊娠者)和非妊娠组(n＝659，FET后未成功妊娠者)。对2组不孕患者血清基础性激素水平、临床妊娠率、囊胚移植率及优质胚胎率等进行统计学分析。对高龄女性FET临床妊娠结局的影响因素分析，采用单因素logistic及多因素非条件logistic回归分析法。采用受试者工作特征(ROC)曲线，评估分娩年龄及血清抗苗勒管激素(AMH)水平对高龄女性FET临床妊娠结局的预测价值。本研究经南京医科大学附属妇产医院伦理委员会批准(审批文号：2020KY-020)，所有患者签署临床研究知情同意书。

结果

①妊娠组不孕患者分娩年龄、血清基础卵泡刺激素(FSH)水平低于非妊娠组，而血清基础AMH水平则高于非妊娠组，并且差异均有统计学意义(P<0.05)。②1 135例不孕患者中，35岁<分娩年龄<40岁患者临床妊娠率为50.0%(383/766)，显著高于40≤分娩年龄<45岁患者的临床妊娠率(25.2%，93/369)，并且差异有统计学意义(χ2＝27.60，P<0.001)。③2组不孕患者4个内膜准备方案的患者比例及移植日内膜厚度比较，差异均无统计学意义(P>0.05)；妊娠组患者囊胚移植率高于非妊娠组，并且差异有统计学意义(P<0.001)。④多因素非条件logistic回归分析结果显示，患者血清AMH水平高(OR＝1.054，95%CI：1.004～1.106，P＝0.033)，进行囊胚移植(OR＝1.981，95%CI：1.524～2.575，P<0.001)，均为高龄女性FET妊娠成功的独立保护因素；而40岁≤分娩年龄<45岁(OR＝0.469，95%CI：0.349～0.630，P<0.001)，则为独立危险因素。⑤妊娠组476例不孕患者中，40岁≤分娩年龄<45岁患者的卵裂期FET占比高于囊胚期FET，而35岁<分娩年龄<40岁患者，则反之。⑥受试者工作特征(ROC)曲线分析显示，分娩年龄、血清AMH水平预测高龄女性FET临床妊娠成功的曲线下面积(AUC)分别为0.642、0.630，敏感度分别为80.5%、68.6%，特异度分别为41.9%、52.1%，最佳临界值分别为分娩年龄为39.5岁、血清AMH水平为1.805 ng/mL。

结论

对于高龄FET不孕患者的分娩年龄及血清AMH水平，可作为其临床妊娠成功的预测指标。

关键词: 不育，女(雌)性, 胚胎移植, 体外受精, 妊娠结局, 影响因素分析, 高龄, 冻融胚胎移植
Objective

To explore the influencing factors on the clinical pregnancy outcomes of frozen embryo transfer (FET) in women at advanced maternal age (≥35 years old).

Methods

A total of 1 135 cycles of 1 135 infertile patients aged 35 years old< delivery age < 45 years old from January 2018 to December 2020 who underwent in vitro fertilization-embryo transfer (IVF-ET) cycles and took whole embryo freezing for FET at the Reproductive Medicine Center of the Women′s Hospital of Nanjing Medical University, were selected as research objects. With retrospective analysis, according to clinical pregnancy outcomes, 1 135 infertile patients were divided into pregnancy group (n=476, successful pregnancy after FET) and non-pregnancy group (n=659, unsuccessful pregnancy after FET). The basal serum sex hormone levels, clinical pregnancy rate, blastocyst transfer rate and high quality embryo rate between two groups were statistically analyzed. Univariate and multivariate logistic regression analysis were used to analyze the influencing factors on clinical pregnancy outcomes of FET in women with advanced age. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of delivery age and serum Mullerian hormone (AMH) level for clinical pregnancy outcomes of FET in women with advanced age. This study was approved by the Ethics Committee of Women′s Hospital of Nanjing Medical University (Approval No. 2020KY-020), and all patients signed the informed consent forms for clinical research.

Results

① The delivery age and basal serum follicle stimulating hormone (FSH) level of infertile patients in pregnancy group were lower than those of in non-pregnancy group, while the basal serum AMH level was higher than that of in non-pregnancy group, and the differences were statistically significant (P<0.05). ② Among the 1 135 infertile patients in this study, the clinical pregnancy rate of patients with delivery age of over 35 years old and less than 40 years old was 50.0% (383/766), which was significantly higher than that of patients with delivery age of greater than or equal to 40 years old and less than 45 years old (25.2%, 93/369), and the difference was statistically significant (χ2=27.60, P<0.001). ③ There were no significant differences in the proportion of patients with 4 endometrial preparation protocols and the endometrial thickness on the day of transplantation between two groups (P>0.05). The blastocyst transfer rate in pregnancy group was higher than that in non-pregnancy group, and the difference was statistically significant (P<0.001). ④ Multivariate unconditional logistic regression analysis showed that patients with high serum AMH level (OR=1.054, 95%CI: 1.004-1.106, P=0.033) and took blastocyst transfer (OR=1.981, 95%CI: 1.524-2.575, P<0.001) were independent protective factors for successful FET pregnancy in women with advanced age, while delivery age of greater than or equal to 40 years old and less than 45 years old (OR=0.469, 95%CI: 0.349-0.630, P<0.001) was independent risk factor. ⑤ Among the 476 patients in pregnancy group, the proportion of cleavage stage FET was higher than that of blastocyst stage FET in the patients with delivery age of 40 to 45 years old, while the opposite was observed in the patients with delivery age of 35 to 40 years old. ⑥ ROC curve analysis showed that the area under the curve (AUC) of delivery age and serum AMH level in predicting clinical pregnancy success of FET in women with advanced age was 0.642 and 0.630, the sensitivity was 80.5% and 68.6%, the specificity was 41.9% and 52.1%, respectively. The optimal cut-off values were 39.5 years old for delivery age and 1.805 ng/mL for serum AMH level.

Conclusions

The delivery age and serum AMH level of the advanced age infertile patients with FET can be used as predictors of successful clinical pregnancy.

Key words: Infertility, female, Embryo transfer, Fertilization in vitro, Pregnancy outcome, Root cause analysis, Advanced age, Frozen-thaw embryo transfer
表1 2组不孕患者一般临床资料及血清基础性激素水平比较
组别 例数 分娩年龄(岁，±s) 不孕年限[年，M(Q1，Q3)] BMI(kg/m2，±s) 血清基础AMH水平[ng/mL，M(Q1，Q3)] 血清基础FSH水平[IU/mL，M(Q1，Q3)] 血清基础LH水平[IU/mL，M(Q1，Q3)] 血清基础雌二醇水平[pg/mL，M(Q1，Q3)]
妊娠组 476 37.6±2.5 3.0(2.0，5.0) 23.1±3.3 2.7(1.5，4.4) 7.7(6.6，9.2) 3.9(2.9，5.3) 41.0(28.0，56.0)
非妊娠组 659 39.5±3.8 2.0(2.0，6.0) 23.1±5.4 1.8(0.8，3.4) 8.6(7.0，10.8) 4.1(3.0，5.5) 44.0(31.0，61.0)
统计量   t＝117.09 Z＝－0.70 t＝0.27 Z＝－7.46 Z＝－5.65 Z＝－1.52 Z＝－1.99
P值   <0.001 0.482 0.602 <0.001 <0.001 0.130 0.052
表2 2组不孕患者内膜准备方案、移植日内膜厚度及囊胚移植率比较
组别 例数 自然周期[例数(%)] 促排卵周期[例数(%)] 人工周期[例数(%)] 降调节＋人工周期[例数(%)] 移植日内膜厚度(mm，±s) 囊胚移植率[例数(%)]
妊娠组 476 70(14.7) 50(10.5) 244(51.3) 112(23.5) 6.1±3.9 292(61.3)
非妊娠组 659 103(15.6) 92(14.0) 315(47.8) 149(22.6) 6.1±3.5 244(37.0)
统计量   χ2＝0.13 χ2＝2.36 χ2＝0.45 χ2＝0.08 t＝3.20 χ2＝23.05
P值   0.714 0.125 0.503 0.774 0.075 <0.001
表3 影响高龄女性FET临床妊娠结局的单因素logistic分析
影响因素 B SE Wald值 P值 OR值 OR值95%CI
血清FSH水平(连续变量) －0.099 0.019 26.101 <0.001 0.906 0.872～0.941
血清AMH水平(连续变量) 0.132 0.024 29.580 <0.001 1.141 1.088～1.197
40岁≤分娩年龄<45岁(vs 35岁<分娩年龄<40岁) －1.088 0.140 60.380 <0.001 0.337 0.256～0.443
是囊胚移植(vs否) 0.993 0.124 64.156 <0.001 2.699 2.117～3.441
表4 影响高龄女性FET临床妊娠结局的多因素非条件logistic回归分析
影响因素 B SE Wald值 P值 OR值 OR值95%CI
血清FSH水平(连续变量) －0.034 0.021 2.669 0.102 0.966 0.928～1.007
血清AMH水平(连续变量) 0.052 0.025 4.536 0.033 1.054 1.004～1.106
40岁≤分娩年龄<45岁(vs 35岁<分娩年龄<40岁) －0.757 0.151 25.240 <0.001 0.469 0.349～0.630
是囊胚移植(vs否) 0.683 0.134 26.110 <0.001 1.981 1.524～2.575
表5 妊娠组2个分娩年龄段不孕患者卵裂期与囊胚期胚胎移植构成比及优质胚胎率比较
分娩年龄段(岁) 例数 胚胎移植构成比[例数(%)] 优质胚胎率[%(n/n′)]
卵裂期 囊胚期 卵裂期 囊胚期
>35～40 383 135(35.3) 248(64.7) 79.1(208/263) 65.5(245/374)
≥40～45 93 49(52.7) 44(47.3) 80.8(84/104) 52.8(38/72)
χ2值   9.60 0.01 1.00
P值   0.002 0.903 0.318
图1 分娩年龄及血清AMH水平预测高龄女性FET临床妊娠成功的ROC曲线分析注：AMH为抗苗勒管激素，FET为冷冻胚胎移植。ROC曲线为受试者工作特征曲线，AUC为曲线下面积
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