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Prevalence of chromosomal alterations in first-trimester spontaneous pregnancy loss

ABSTRACT: Pregnancy loss is often caused by chromosomal abnormalities of the conceptus. The prevalence of these abnormalities and the allocation of (ab)normal cells in embryonic and placental lineages during intrauterine development remain elusive. We analyzed 1,745 spontaneous pregnancy losses and found that roughly half (50.4%) of the products of conception (POC) were karyotypically abnormal, with maternal and paternal age independently contributing to the increased genomic aberration rate in pregnancy loss. We applied genome haplarithmisis to a subset of 94 pregnancy losses with normal parental and POC karyotypes. Genotyping of parental DNA as well as POC extraembryonic mesoderm and chorionic villi DNA, representing embryonic and trophoblastic tissues, enabled characterization of the genomic landscape of both lineages. Of these pregnancy losses, 35.1% had chromosomal aberrations not previously detected by karyotyping, increasing the rate of aberrations of pregnancy losses to 67.8% by extrapolation. In contrast to viable pregnancies where mosaic chromosomal abnormalities are often restricted to chorionic villi, such as confined placental mosaicism, we found a higher degree of mosaic chromosomal imbalances in extraembryonic mesoderm rather than chorionic villi in pregnancy losses. Our results stress the importance of scrutinizing the full allelic architecture of genomic abnormalities in pregnancy loss to improve clinical management and basic research of this devastating condition.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228151 | GEO | 2023/10/05

REPOSITORIES: GEO

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Prevalence of chromosomal alterations in first-trimester spontaneous pregnancy loss

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