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

doi:10.3877/cma.j.issn.1673-5250.2024.03.006

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′)]
分娩年龄段(岁)	例数	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

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′)]
分娩年龄段(岁)	例数	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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