Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology

Abstract Introduction 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 pre...

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Main Authors: Jun Guo, Qiaoli Feng, Piya Chaemsaithong, Kubi Appiah, Daljit S. Sahota, Bo Wah Leung, Jacqueline P. Chung, Tin Chiu Li, Liona C. Poon
Format: Article
Language:English
Published: Wiley 2023-08-01
Series:Acta Obstetricia et Gynecologica Scandinavica
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Online Access:https://doi.org/10.1111/aogs.14618
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author Jun Guo
Qiaoli Feng
Piya Chaemsaithong
Kubi Appiah
Daljit S. Sahota
Bo Wah Leung
Jacqueline P. Chung
Tin Chiu Li
Liona C. Poon
author_facet Jun Guo
Qiaoli Feng
Piya Chaemsaithong
Kubi Appiah
Daljit S. Sahota
Bo Wah Leung
Jacqueline P. Chung
Tin Chiu Li
Liona C. Poon
author_sort Jun Guo
collection DOAJ
description Abstract Introduction 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. Material and methods 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. Results 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. Conclusions 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.
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spelling doaj-art-e548e8ca455741829bedab0005bbe8c82025-08-20T02:36:39ZengWileyActa Obstetricia et Gynecologica Scandinavica0001-63491600-04122023-08-0110281073108310.1111/aogs.14618Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technologyJun Guo0Qiaoli Feng1Piya Chaemsaithong2Kubi Appiah3Daljit S. Sahota4Bo Wah Leung5Jacqueline P. Chung6Tin Chiu Li7Liona C. Poon8Department of Obstetrics and Gynecology, Beijing Tongren Hospital The Capital Medical University Beijing ChinaDepartment of Obstetrics and Gynecology Peking University Shenzhen Hospital Shenzhen ChinaDepartment of Obstetrics and Gynecology, Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok ThailandDepartment of Obstetrics and Gynecology The Chinese University of Hong Kong Shatin Hong Kong SARDepartment of Obstetrics and Gynecology The Chinese University of Hong Kong Shatin Hong Kong SARDepartment of Obstetrics and Gynecology The Chinese University of Hong Kong Shatin Hong Kong SARDepartment of Obstetrics and Gynecology The Chinese University of Hong Kong Shatin Hong Kong SARDepartment of Obstetrics and Gynecology The Chinese University of Hong Kong Shatin Hong Kong SARDepartment of Obstetrics and Gynecology The Chinese University of Hong Kong Shatin Hong Kong SARAbstract Introduction 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. Material and methods 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. Results 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. Conclusions 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.https://doi.org/10.1111/aogs.14618embryo transferfetal heart activityglycodelin‐Ain vitro fertilizationmaternal agemiscarriage
spellingShingle Jun Guo
Qiaoli Feng
Piya Chaemsaithong
Kubi Appiah
Daljit S. Sahota
Bo Wah Leung
Jacqueline P. Chung
Tin Chiu Li
Liona C. Poon
Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology
Acta Obstetricia et Gynecologica Scandinavica
embryo transfer
fetal heart activity
glycodelin‐A
in vitro fertilization
maternal age
miscarriage
title Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology
title_full Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology
title_fullStr Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology
title_full_unstemmed Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology
title_short Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology
title_sort biomarkers at 6 weeks gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology
topic embryo transfer
fetal heart activity
glycodelin‐A
in vitro fertilization
maternal age
miscarriage
url https://doi.org/10.1111/aogs.14618
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