The transfer of double morphologically good Day 5 blastocysts increases the risk of clinical pregnancy loss in singleton pregnancies following frozen-thawed embryo transfer

BackgroundTo investigate whether double embryo transfer (DET) increases the risk of spontaneous clinical pregnancy loss (CPL) in singleton pregnancies following frozen-thawed embryo transfer (FET), compared to single embryo transfer (SET).MethodsThis retrospective cohort study included 2,448 females...

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Main Authors: Yufeng Wang, Qin Wan, Xiaohui Lu, Lingjun Li, Huihui Wang, Li Chen, Xiuliang Dai
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1508014/full
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author Yufeng Wang
Qin Wan
Qin Wan
Xiaohui Lu
Lingjun Li
Huihui Wang
Li Chen
Xiuliang Dai
author_facet Yufeng Wang
Qin Wan
Qin Wan
Xiaohui Lu
Lingjun Li
Huihui Wang
Li Chen
Xiuliang Dai
author_sort Yufeng Wang
collection DOAJ
description BackgroundTo investigate whether double embryo transfer (DET) increases the risk of spontaneous clinical pregnancy loss (CPL) in singleton pregnancies following frozen-thawed embryo transfer (FET), compared to single embryo transfer (SET).MethodsThis retrospective cohort study included 2,448 females with singleton pregnancies (excluding vanishing twin cases) resulting from frozen-thawed single or double embryo transfers between January 2017 and September 2022. The CPL rate was the sole outcome measure. We compared CPL rates between SET and DET across three populations with increasing embryo developmental potential using binary logistic regression analysis: P1, comprising transfers of Day 3 cleavage-stage embryos; P2, comprising transfers of blastocysts; and P3, comprising transfers of top-quality blastocysts, defined as morphologically good Day 5 blastocysts.ResultsAfter adjusting for confounding factors, the comparison between SET and DET revealed the following findings: in P1, DET had a slightly higher CPL rate compared to SET [OR (95% CI): 1.18 (0.74-1.90), p=0.46]; In P2, DET showed a moderately higher CPL rate [OR (95% CI): 1.34 (0.96-1.87), p=0.08]; In P3, DET had a significantly higher CPL rate [OR (95% CI): 1.55 (1.02-2.37), p=0.04]. A combined analysis indicated that as the developmental potential of the transferred embryo increased (from P1 to P2 and further to P3), the impact of DET on CPL also increased, as reflected by the rising OR values and decreasing p-values. We proposed that in singleton pregnancies resulting from DET, the loss of a non-viable embryo at a later stage, when it has a larger cell mass, may trigger excessive intrauterine inflammation, thereby increasing the risk of CPL for the remaining full developmental potential embryo. In singleton pregnancies resulting from DET, a higher-quality embryo that fails is more likely to die at a later stage. This could explain why the impact of DET on CPL increases with the developmental potential of the embryo.ConclusionSince a significant difference in CPL between SET and DET was only observed in P3 population. Therefore, we concluded that compared to SET, the transfer of double morphologically good Day 5 blastocysts is associated with increased clinical pregnancy loss in singleton pregnancies following FET.
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spelling doaj-art-795b37bd542a4e3bb2f8be0bd2d06df82025-08-20T03:10:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-04-011610.3389/fendo.2025.15080141508014The transfer of double morphologically good Day 5 blastocysts increases the risk of clinical pregnancy loss in singleton pregnancies following frozen-thawed embryo transferYufeng Wang0Qin Wan1Qin Wan2Xiaohui Lu3Lingjun Li4Huihui Wang5Li Chen6Xiuliang Dai7The Center for Reproductive Medicine, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, ChinaThe Center for Reproductive Medicine, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, ChinaDepartment of gynaecology and obstetrics, Xuancheng City Central Hospital, Xuancheng, Anhui, ChinaThe Center for Reproductive Medicine, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, ChinaThe Center for Reproductive Medicine, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, ChinaDepartment of Obstetrics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, ChinaThe Center for Reproductive Medicine, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, ChinaThe Center for Reproductive Medicine, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, ChinaBackgroundTo investigate whether double embryo transfer (DET) increases the risk of spontaneous clinical pregnancy loss (CPL) in singleton pregnancies following frozen-thawed embryo transfer (FET), compared to single embryo transfer (SET).MethodsThis retrospective cohort study included 2,448 females with singleton pregnancies (excluding vanishing twin cases) resulting from frozen-thawed single or double embryo transfers between January 2017 and September 2022. The CPL rate was the sole outcome measure. We compared CPL rates between SET and DET across three populations with increasing embryo developmental potential using binary logistic regression analysis: P1, comprising transfers of Day 3 cleavage-stage embryos; P2, comprising transfers of blastocysts; and P3, comprising transfers of top-quality blastocysts, defined as morphologically good Day 5 blastocysts.ResultsAfter adjusting for confounding factors, the comparison between SET and DET revealed the following findings: in P1, DET had a slightly higher CPL rate compared to SET [OR (95% CI): 1.18 (0.74-1.90), p=0.46]; In P2, DET showed a moderately higher CPL rate [OR (95% CI): 1.34 (0.96-1.87), p=0.08]; In P3, DET had a significantly higher CPL rate [OR (95% CI): 1.55 (1.02-2.37), p=0.04]. A combined analysis indicated that as the developmental potential of the transferred embryo increased (from P1 to P2 and further to P3), the impact of DET on CPL also increased, as reflected by the rising OR values and decreasing p-values. We proposed that in singleton pregnancies resulting from DET, the loss of a non-viable embryo at a later stage, when it has a larger cell mass, may trigger excessive intrauterine inflammation, thereby increasing the risk of CPL for the remaining full developmental potential embryo. In singleton pregnancies resulting from DET, a higher-quality embryo that fails is more likely to die at a later stage. This could explain why the impact of DET on CPL increases with the developmental potential of the embryo.ConclusionSince a significant difference in CPL between SET and DET was only observed in P3 population. Therefore, we concluded that compared to SET, the transfer of double morphologically good Day 5 blastocysts is associated with increased clinical pregnancy loss in singleton pregnancies following FET.https://www.frontiersin.org/articles/10.3389/fendo.2025.1508014/fullsingle embryo transferdouble embryo transferclinical pregnancy lossintrauterine inflammationdevelopmental defect
spellingShingle Yufeng Wang
Qin Wan
Qin Wan
Xiaohui Lu
Lingjun Li
Huihui Wang
Li Chen
Xiuliang Dai
The transfer of double morphologically good Day 5 blastocysts increases the risk of clinical pregnancy loss in singleton pregnancies following frozen-thawed embryo transfer
Frontiers in Endocrinology
single embryo transfer
double embryo transfer
clinical pregnancy loss
intrauterine inflammation
developmental defect
title The transfer of double morphologically good Day 5 blastocysts increases the risk of clinical pregnancy loss in singleton pregnancies following frozen-thawed embryo transfer
title_full The transfer of double morphologically good Day 5 blastocysts increases the risk of clinical pregnancy loss in singleton pregnancies following frozen-thawed embryo transfer
title_fullStr The transfer of double morphologically good Day 5 blastocysts increases the risk of clinical pregnancy loss in singleton pregnancies following frozen-thawed embryo transfer
title_full_unstemmed The transfer of double morphologically good Day 5 blastocysts increases the risk of clinical pregnancy loss in singleton pregnancies following frozen-thawed embryo transfer
title_short The transfer of double morphologically good Day 5 blastocysts increases the risk of clinical pregnancy loss in singleton pregnancies following frozen-thawed embryo transfer
title_sort transfer of double morphologically good day 5 blastocysts increases the risk of clinical pregnancy loss in singleton pregnancies following frozen thawed embryo transfer
topic single embryo transfer
double embryo transfer
clinical pregnancy loss
intrauterine inflammation
developmental defect
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1508014/full
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