Prevalence of chromosomal alterations in first-trimester spontaneous pregnancy loss

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. In this study, we analyzed 1,745 spontaneous pregnancy losses and found that roughly half (50.4%) of the products of conception (POCs) were karyotypically abnormal, with maternal and paternal age independently contributing to the increased genomic aberration rate. 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 extra-embryonic 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 extra-embryonic mesoderm rather than chorionic villi. 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. Genomic analysis of products of conception collected after spontaneous pregnancy loss in the first trimester reveals previously undetected chromosomal aberrations and a higher degree of mosaic chromosomal imbalances.

Automated summary

This study analyzed 1,745 spontaneous pregnancy losses and found that approximately 50.4% of the products of conception (POCs) had chromosomal abnormalities. Parental age was identified as an independent factor contributing to the increased rate of genomic aberrations. By using genome haplarithmisis, the researchers discovered previously undetected chromosomal aberrations in 35.1% of the pregnancy losses. They also found a higher degree of mosaic chromosomal imbalances in the extra-embryonic mesoderm compared to the chorionic villi.