Genomic imbalance in euploid pregnancy loss

This study aims to investigate genomic imbalance in euploid products of conceptions (POCs) detected by chromosomal microarray analysis (CMA) and its association with clinical characteristics.

In a retrospective cohort study where all women with singleton pregnancy losses underwent CMA detection of POCs, only patients with euploid POCs were included in the analysis. The clinical features were compared between those with and without a copy number variant (CNV). The pathogenic CNVs and the variant of uncertain significance (VOUS) were analyzed, and the common pathogenic CNVs and uniparental disomy (UPD) were investigated.

A total of 610 POCs were detected as chromosomal euploid, of which 176 were euploid with CNVs and 434 were euploid without CNVs. Regarding maternal age, gestational age, and history of pregnancy loss, no significant differences were found between the two groups. Furthermore, 104 pathogenic CNVs were identified in 93 POCs, and the deletion of 8p23.3 was found in 10 subjects. All CNVs greater than 3 Mb and 39.5% of CNVs ranging from 1 to 2 Mb were pathogenic, and only 3 CNVs < 1 Mb were pathogenic. UPD was detected in 12 POCs.

Besides aneuploidy, 15.24% pregnancy loss might have an association with pathogenic genomic imbalance, and the occurrence of genomic imbalance is not related to clinical characteristics. CNVs greater than 3 Mb in pregnancy losses have a high probability to be pathogenic, and approximately 40% of CNVs ranging from 1 to 2 Mb are pathogenic. The deletion of 8p23.3 is the most common pathogenic CVN in POCs of Chinese-Han women. The clinical significance of UPD in pregnancy loss needs further study.