Department of Obstetrics and Gynecology, Beijing Tongren Hospital, The Capital Medical University, Beijing, China.
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China.
Acta Obstet Gynecol Scand. 2023 Aug;102(8):1073-1083. doi: 10.1111/aogs.14618. Epub 2023 Jun 28.
Miscarriage is a major concern in early pregnancy among women having conceived with assisted reproductive treatments. This study aimed to examine potential miscarriage-related biophysical and biochemical markers at 6 weeks' gestation among women with confirmed clinical pregnancy following in vitro fertilization (IVF)/embryo transfer (ET) and evaluate the performance of a model combining maternal factors, biophysical and biochemical markers at 6 weeks' gestation in the prediction of first trimester miscarriage among singleton pregnancies following IVF/ET.
A prospective cohort study was conducted in a teaching hospital between December 2017 and January 2020 including women who conceived through IVF/ET. Maternal mean arterial pressure, ultrasound markers including mean gestational sac diameter, fetal heart activity, crown rump length and mean uterine artery pulsatility index (mUTPI) and biochemical biomarkers including maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), kisspeptin and glycodelin-A were measured at 6 weeks' gestation. Logistic regression analysis was carried out to determine significant predictors of miscarriage prior to 13 weeks' gestation and performance of screening was estimated by receiver-operating characteristics curve analysis.
Among 169 included pregnancies, 145 (85.8%) pregnancies progressed to beyond 13 weeks' gestation and had live births whereas 24 (14.2%) pregnancies resulted in a miscarriage during the first trimester. In the miscarriage group, compared to the live birth group, maternal age, body mass index, and mean arterial pressure were significantly increased; mean gestational sac diameter, crown rump length, mUTPI, serum sFlt-1, glycodelin-A, and the rate of positive fetal heart activity were significantly decreased, while no significant differences were detected in PlGF and kisspeptin. Significant prediction for miscarriage before 13 weeks' gestation was provided by maternal age, fetal heart activity, mUTPI, and serum glycodelin-A. The combination of maternal age, ultrasound (fetal heart activity and mUTPI), and biochemical (glycodelin-A) markers achieved the highest area under the curve (AUC: 0.918, 95% CI 0.866-0.955), with estimated detection rates of 54.2% and 70.8% for miscarriage before 13 weeks' gestation, at fixed false positive rates of 5% and 10%, respectively.
A combination of maternal age, fetal heart activity, mUTPI, and serum glycodelin-A at 6 weeks' gestation could effectively identify IVF/ET pregnancies at risk of first trimester miscarriage.
流产是接受辅助生殖治疗的妊娠早期妇女的主要关注点。本研究旨在检查体外受精（IVF）/胚胎移植（ET）后确认临床妊娠的妇女在 6 周妊娠时与流产相关的生物物理和生化标志物，并评估在 IVF/ET 后单胎妊娠中结合母体因素、6 周妊娠时的生物物理和生化标志物的模型在预测早期流产中的表现。
2017 年 12 月至 2020 年 1 月，在一家教学医院进行了一项前瞻性队列研究，包括通过 IVF/ET 受孕的妇女。在 6 周妊娠时测量母体平均动脉压、超声标志物（包括平均孕囊直径、胎儿心脏活动、头臀长和平均子宫动脉搏动指数（mUTPI））和生化生物标志物（包括母体血清可溶性 fms 样酪氨酸激酶-1（sFlt-1）、胎盘生长因子（PlGF）、 kisspeptin 和糖蛋白-A）。进行逻辑回归分析以确定 13 周前流产的显著预测因子，并通过接受者操作特征曲线分析评估筛查性能。
在 169 例纳入的妊娠中，145 例（85.8%）妊娠进展至 13 周以上并分娩活产，而 24 例（14.2%）妊娠在早期流产。在流产组中，与活产组相比，母体年龄、体重指数和平均动脉压明显升高；平均孕囊直径、头臀长、mUTPI、血清 sFlt-1、糖蛋白-A 和胎儿心脏活动阳性率明显降低，而 PlGF 和 kisspeptin 无明显差异。母体年龄、胎儿心脏活动、mUTPI 和血清糖蛋白-A 对 13 周前流产有显著预测作用。母体年龄、超声（胎儿心脏活动和 mUTPI）和生化（糖蛋白-A）标志物的组合获得了最高的曲线下面积（AUC：0.918，95%CI 0.866-0.955），在固定的假阳性率为 5%和 10%时，13 周前流产的检测率分别为 54.2%和 70.8%。
6 周妊娠时母体年龄、胎儿心脏活动、mUTPI 和血清糖蛋白-A 的组合可有效识别 IVF/ET 妊娠早期流产的风险。
