[Combined CNV-seq and STR polymorphism analysis for the genetic diagnosis of 553 cases of spontaneous abortion]

To evaluate the efficacy and clinical value of combining low-depth whole-genome copy number variation sequencing (CNV-seq) with short tandem repeat (STR) polymorphism analysis in the genetic diagnosis of spontaneous abortion.

Products of conception and clinical data were retrospectively collected from 553 patients who underwent abortion surgery at Guiyang Maternal and Child Health Care Hospital between January 2023 and October 2024. All samples were tested by CNV-seq to detect copy number variations (CNVs) ≥ 100 kb and aneuploidies. STR analysis was performed in parallel to identify abnormalities undetectable by CNV-seq alone, such as triploidy and uniparental disomy (UPD). The correlation between the detection rate of chromosomal abnormalities and factors including maternal age, gestational week, conception method, and history of adverse pregnancy was analyzed. This study was approved by the Medial Ethics Committee of the Guiyang Maternal Child Health Care Hospital (Ethics No.: 2025-10).

The initial detection rate of chromosomal abnormalities by CNV-seq alone was 52.98% (293/553). After integrating STR results, 23 cases of triploidy and 1 case of UPD were additionally identified, increasing the overall detection rate to 57.32% (317/553). Autosomal aneuploidy was the most common abnormality (48.26%, 153/317), followed by aneuploidy mosaicism (20.82%, 66/317), sex chromosome aneuploidy (10.41%, 33/317), and pathogenic CNVs (10.41%, 33/317). The most frequent numerical abnormalities were trisomy 16 (9.15%), 45,X (7.57%), and triploidy (7.26%). The chromosomal abnormality detection rate was significantly higher in women of advanced maternal age (≥ 35 years) (67.55%, 102/151) than in those < 35 years (53.73%, 215/402), and significantly higher in the early miscarriage group (< 12 weeks) (60.20%, 307/510) than in the late miscarriage group (20.93%, 9/43) (both P < 0.05). No significant differences in chromosomal abnormality rates were found between the assisted reproductive technology (ART) and natural conception groups, or between groups with ≤ 2 or > 2 previous adverse pregnancies (both P > 0.05).

The combined application of CNV-seq and STR polymorphism analysis improves the detection rate of genetic causes in spontaneous abortion. Advanced maternal age and early miscarriage are key risk factors for embryonic chromosomal abnormalities, while ART conception and a limited history of previous abortions showed no significant impact in this study. This integrated strategy provides a reliable basis for the precise etiological diagnosis of abortion and subsequent genetic counseling.