Comprehensive genetic analysis in first or second trimester pregnancy loss using chromosomal microarray with single nucleotide polymorphism probes

Abstract

To explore possible genetic causes associated with early pregnancy loss using chromosomal microarray analysis (CMA) with single nucleotide polymorphism (SNP) probes. A retrospective review was performed by the CMA of samples from 961 patients who spontaneously aborted in our hospital before the 20th week of pregnancy. (1) The total chromosome abnormality rate in miscarriage samples was 54.44% (515/946), including single chromosome abnormality (39.53%), two chromosome abnormality (2.22%), multi-chromosome abnormality (0.42%), triploidy or hypertriploidy (4.86%), copy number variants (CNVs) in 41 cases (4.33%), regions of homozygosity (ROH, 0.74%), mosaic (2.22%) and chimera (0.11%). (2) CNV analysis of 41 cases showed that 85.36% were pathogenic and likely pathogenic, 12.20% were classified as clinical significance unknown and 2.44% were interpreted as likely benign; (3) Among the cases of ROH, 2 cases shown whole-genome homozygosity and 1 case had completely homozygous at chromosome 21. The homozygous regions in 2 cases were located at the end of the short arm of chromosome 16, suggesting the mechanism of ROH in such cases could be the result of isodisomy. Chromosome abnormality is an important genetic factor causing pregnancy loss. The application of CMA with SNP probes can indeed improve the detection rate of chromosome abnormalities and evaluate the risk of reproductive fertility in patients with pregnancy loss.