Genetic Etiology of Miscarriage in a Vietnamese Cohort Using CNV-Seq and Exome Sequencing.

OBJECTIVE

Pregnancy loss affects approximately 15% of pregnancies worldwide, with genetic abnormalities being a major cause. This study aimed to investigate the genetic etiologies of pregnancy loss in Vietnam and to characterize associated clinical features.

METHOD: This retrospective study included 636 pregnancy loss cases from a multicenter Vietnamese cohort across 18 centers (2022-2024). Products of conception were analyzed using copy number variant sequencing (CNV-seq, n = 636) and clinical exome sequencing (CES, n = 401).

RESULTS

Genetic etiologies were identified in 209 of 636 cases (32.9%). Numerical chromosomal abnormalities accounted for 27%, structural abnormalities for 3%, and single-gene variants for 2%. Sixteen pathogenic variants in 12 genes were detected, with FGFR3 and skeletal dysplasia being the most common monogenic finding. CNV-seq and CES detected abnormalities in 30.7% and 3.5% of cases, respectively. Among cases with identified genetic anomalies, 71.3% presented with early pregnancy loss (≤ 12 weeks), 47.4% had a history of prior pregnancy loss, 31.1% were of advanced maternal age.

CONCLUSION

This study provides a preliminary descriptive analysis of genetic causes of pregnancy loss in a Vietnamese cohort. The application of CNV-seq and CES may be helpful in identifying genetic causes and can help inform the management of future pregnancies.