Clinical utility of chromosomal microarray analysis for genetic diagnosis in 708 cases of spontaneous abortion tissues

To evaluate the diagnostic yield, abnormality spectrum, and clinical interpretation value of chromosomal microarray analysis (CMA) in products of conception from pregnancy loss, and to explore the associations of maternal age and gestational age with different categories of chromosomal abnormalities.

This study involved a retrospective cohort analysis of chorionic villus or fetal tissue samples obtained from patients with spontaneous abortion who visited our center between 2017 and 2025. Genomic DNA was extracted from all samples and subjected to genome-wide screening using CMA to detect chromosomal aneuploidies and copy number variations (CNVs). The pathogenicity of detected CNVs was evaluated according to the guidelines established by the American College of Medical Genetics and Genomics (ACMG). Furthermore, clinical characteristics such as maternal age were used as stratification variables to compare the chromosomal abnormality rates across different subgroups.

Of the 708 samples analyzed, 348 cases (49.15%) were found to have clinically significant chromosomal abnormalities, comprising 347 pathogenic and one likely pathogenic variants. In the 705 samples with successful testing results, there were 365 detected chromosomal abnormalities, yielding a detection rate of 51.77%. This finding highlights that chromosomal abnormalities constitute a major genetic etiology of spontaneous abortion. Furthermore, within the successfully tested cohort, numerical chromosomal abnormalities were the most prevalent type, identified in 287 cases (40.71%). This was followed by microdeletions in 37 cases (5.25%) and microduplications in 27 cases (3.83%). However, mosaicism, whole-genome uniparental disomy (UPD), and long contiguous stretches of homozygosity (LCSH) were rare, being detected in only four cases in total. Among the numerical anomalies, autosomal trisomy was the primary subtype, with trisomy 16 being the most frequently observed autosomal trisomy.

Chromosomal microarray analysis plays a pivotal role in the etiological diagnosis of spontaneous abortion. As a high-resolution, high-throughput detection method, it enables genome-wide identification of CNVs, particularly submicroscopic deletions and duplications that are difficult to detect with conventional karyotyping. CMA showed a high testing success rate and provided clinically useful information for the genetic evaluation of products of conception. Its advantages include direct DNA-based analysis without the requirement for viable cell culture and the ability to detect submicroscopic CNVs that may be missed by conventional karyotyping. However, because this study did not include a direct comparison with conventional karyotyping, cost-effectiveness analysis, or systematic parental validation for all clinically relevant findings, the results should be interpreted as supporting the clinical utility of CMA rather than establishing it as a universal routine test for all pregnancy loss cases.