The hidden causes of pregnancy loss: a closer look

Abstract Background Unexpected pregnancy loss can be a traumatic experience for fertile couples. The aim of the study was to assess the nature and type of chromosomal variants involved in early and late pregnancy loss and provide couples an explanation on the cause of their pregnancy loss. Methods I...

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Main Authors: Panlai Shi, Conghui Wang, Hongbin Liang, XiaoFan Zhu, Xinyan Wang, Yanting Ning, Don Leigh, David S. Cram, Xiangdong Kong
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-025-06678-x
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author Panlai Shi
Conghui Wang
Hongbin Liang
XiaoFan Zhu
Xinyan Wang
Yanting Ning
Don Leigh
David S. Cram
Xiangdong Kong
author_facet Panlai Shi
Conghui Wang
Hongbin Liang
XiaoFan Zhu
Xinyan Wang
Yanting Ning
Don Leigh
David S. Cram
Xiangdong Kong
author_sort Panlai Shi
collection DOAJ
description Abstract Background Unexpected pregnancy loss can be a traumatic experience for fertile couples. The aim of the study was to assess the nature and type of chromosomal variants involved in early and late pregnancy loss and provide couples an explanation on the cause of their pregnancy loss. Methods Investigations were conducted on 2928 pregnancy loss cases where products of conception (POC) samples could be retrieved for genetic analysis. Chromosomal variants were detected by low pass copy number variation sequencing (CNV-seq). Results In first-trimester miscarriages, 1272 of POC (60.4%) samples had a chromosome abnormality. Autosomal aneuploidy and monosomy X were the predominate variants (73.2%), followed by autosomal and sex chromosome mosaicism (10.7%), triploidy (9.6%), pathogenic CNVs (6.2%) and haploidy (0.3%). The chromosomal variants were similar in type and frequency regardless of whether the fetus had normal or abnormal ultrasound findings. In second trimester pregnancy loss where there was either a structural or non-structural ultrasound anomaly, only 15.3% of POC samples had a chromosome abnormality, involving mainly the smaller autosomes and monosomy X (55.7%), autosomal and sex chromosomal mosaicism (11.5%), triploidy (4.1%) and pathogenic CNVs (28.7%). Conclusion Chromosomal variants contribute to fetal demise in almost two thirds of pregnancy losses.
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spelling doaj-art-2af8a701e75d41ab998c581b64a949ac2025-08-20T03:04:15ZengBMCJournal of Translational Medicine1479-58762025-06-0123111110.1186/s12967-025-06678-xThe hidden causes of pregnancy loss: a closer lookPanlai Shi0Conghui Wang1Hongbin Liang2XiaoFan Zhu3Xinyan Wang4Yanting Ning5Don Leigh6David S. Cram7Xiangdong Kong8Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou UniversityGenetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou UniversityGenetics and Precision Medicine Center, First People’s Hospital of KunmingGenetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Obstetrics, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Ultrasound, The First Affiliated Hospital of Zhengzhou UniversityGenetics and Precision Medicine Center, First People’s Hospital of KunmingGenetics and Precision Medicine Center, First People’s Hospital of KunmingGenetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background Unexpected pregnancy loss can be a traumatic experience for fertile couples. The aim of the study was to assess the nature and type of chromosomal variants involved in early and late pregnancy loss and provide couples an explanation on the cause of their pregnancy loss. Methods Investigations were conducted on 2928 pregnancy loss cases where products of conception (POC) samples could be retrieved for genetic analysis. Chromosomal variants were detected by low pass copy number variation sequencing (CNV-seq). Results In first-trimester miscarriages, 1272 of POC (60.4%) samples had a chromosome abnormality. Autosomal aneuploidy and monosomy X were the predominate variants (73.2%), followed by autosomal and sex chromosome mosaicism (10.7%), triploidy (9.6%), pathogenic CNVs (6.2%) and haploidy (0.3%). The chromosomal variants were similar in type and frequency regardless of whether the fetus had normal or abnormal ultrasound findings. In second trimester pregnancy loss where there was either a structural or non-structural ultrasound anomaly, only 15.3% of POC samples had a chromosome abnormality, involving mainly the smaller autosomes and monosomy X (55.7%), autosomal and sex chromosomal mosaicism (11.5%), triploidy (4.1%) and pathogenic CNVs (28.7%). Conclusion Chromosomal variants contribute to fetal demise in almost two thirds of pregnancy losses.https://doi.org/10.1186/s12967-025-06678-xPregnancy lossFetal demiseCopy number sequencingWhole exome sequencingGenetic variants
spellingShingle Panlai Shi
Conghui Wang
Hongbin Liang
XiaoFan Zhu
Xinyan Wang
Yanting Ning
Don Leigh
David S. Cram
Xiangdong Kong
The hidden causes of pregnancy loss: a closer look
Journal of Translational Medicine
Pregnancy loss
Fetal demise
Copy number sequencing
Whole exome sequencing
Genetic variants
title The hidden causes of pregnancy loss: a closer look
title_full The hidden causes of pregnancy loss: a closer look
title_fullStr The hidden causes of pregnancy loss: a closer look
title_full_unstemmed The hidden causes of pregnancy loss: a closer look
title_short The hidden causes of pregnancy loss: a closer look
title_sort hidden causes of pregnancy loss a closer look
topic Pregnancy loss
Fetal demise
Copy number sequencing
Whole exome sequencing
Genetic variants
url https://doi.org/10.1186/s12967-025-06678-x
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