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. 2025 Jun 15;23(1):656.
doi: 10.1186/s12967-025-06678-x.

The hidden causes of pregnancy loss: a closer look

Panlai Shi #  1 , Conghui Wang #  1 , Hongbin Liang  2 , XiaoFan Zhu  1 , Xinyan Wang  3 , Yanting Ning  4 , Don Leigh  2 , David S Cram  5 , Xiangdong Kong  6
Affiliations

The hidden causes of pregnancy loss: a closer look

Panlai Shi et al. J Transl Med. .

Erratum in

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.

Keywords: Copy number sequencing; Fetal demise; Genetic variants; Pregnancy loss; Whole exome sequencing.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Zhengzhou University Ethics Committee (Protocol code: 2019-KY-418 and date of approval: December 28th, 2019). Informed consent was obtained from all subjects involved in the study. Consent for publication: Not applicable. Competing interests: The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Study design. CNV-seq outcomes for early and late pregnancy loss samples are shown. US: ultrasound; POC: products of conception; TOP: termination of pregnancy; SM: spontaneous miscarriage; WES: Whole exome sequencing
Fig. 2
Fig. 2
Nature and distribution of chromosomal variants associated with first trimester miscarriage. (I) and (III): Group A—pregnancy US anomalies; (II and IV): Group B—no pregnancy US anomalies
Fig. 3
Fig. 3
Nature and distribution of chromosomal variants associated with second trimester pregnancy loss. (I) and (III): Group C1—pregnancy US structural anomalies; (II and IV): Group C2—no pregnancy US structural anomalies
Fig. 4
Fig. 4
Whole exome sequencing findings in 34 fetuses with structural ultrasound anomalies. AD: autosomal dominant; AR: autosomal recessive; XLR: X-linked recessive
See this image and copyright information in PMC

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