Clinical utilization of chromosomal microarray analysis for the genetic analysis in subgroups of pregnancy loss

Abstract

Objective

The underlying etiologies of pregnancy loss are heterogeneous and in many cases unexplained. This study was to explore the genetic causes of early and late pregnancy loss using chromosomal microarray analysis (CMA).

Methods

A cohort of 222 specimens of conceptions underwent genetic analysis using Affymetrix CytoScan 750 K arrays, which includes both SNP markers and copy number markers.

Results

Of the 222-products of conception (POC), the overall detection rate for clinical significantly chromosomal anomalies was 40.54%, including 53 autosomal aneuploidy (23.87%), 16 sex chromosome aneuploidy (7.21%), 5 mutiple aneuploidy (2.25%), 4 triploidy (1.80%), and 12 pathogenic copy number variants (pCNVs) (5.41%). In addition, variants of uncertain significance and loss of heterozygosity were detected in 9 samples and 2 samples, respectively. The detection rates for total chromosomal abnormalities, autosomal aneuploidy, sex chromosome aneuploidy, multiple aneuploidy, and triploidy in specimens of early pregnancy loss was higher than that of late pregnancy loss, while had lower detection rate of pCNVs. Moreover, the detection rate in POC of mothers younger than 35 years was lower than that of advanced maternal age. The detection rate was 40.57% in POC of mothers with adverse pregnancy histories, in which was comparable with that of mothers without adverse pregnancy histories.

Conclusions

CMA yielded a superior detection rate in early pregnancy loss than that of late pregnancy loss. Moreover, the incidence of chromosome abnormality in cases with advanced maternal age was higher than that of cases with younger maternal age, while adverse pregnancy history seemed not to be the factors affecting the detection rate for chromosomal abnormality in pregnancy loss.

Keywords:

• Pregnancy loss
• chromosomal microarray analysis
• copy number variant
• maternal age
• adverse pregnancy history

Acknowledgments

We thank all the participants for their generosity in agreeing to take part in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was funded by Medical Science Foundation of Jiangsu Province[H2019007], Maternity and Child Health Care Science Foundation of Jiangsu Province [F201819], National Natural Science Foundation of China [81703493], Natural Science Foundation of Jiangsu Province [BK20170258], China Postdoctoral Science Foundation-funded projects [2019M661943] and Science & Technology Foundation of Xuzhou [KC18027, KC18175].