Chromosomal abnormalities are a leading cause of early pregnancy loss (EPL). While copy number variation sequencing (CNV-seq) is gradually applied in clinical practice, its sensitivity for detecting triploidy and uniparental disomy (UPD) remains limited. This study aimed to evaluate whether integrating CNV-seq with short tandem repeat (STR) genotyping could improve diagnostic performance in EPL. In this study, 572 EPL samples were examined using CNV-seq combined with STR genotyping to detect chromosomal abnormalities, including triploidy and UPD, and to explore STR-based approaches for identifying the origin of abnormal chromosomes. Selected results were validated using karyotyping, CMA, MLPA, or FISH when necessary. Chromosomal abnormalities were identified in 313 cases (54.7%), including autosomal aneuploidies (52.4%), CNVs (13.4%), sex chromosome aneuploidies (11.5%), multiple trisomies (3.5%), and mosaicism (3.5%). STR genotyping identified 38 additional cases (35 triploidy, 3 UPD) missed by CNV-seq, elevating the overall diagnostic yield by 6.6% (p < 0.05). Parental origin analysis revealed distinct distribution patterns: 69,XXY triploidies were predominantly of paternal origin (80.8%), whereas 69,XXX cases were mostly maternal (88.9%); all detected UPD cases were paternally derived. Among 134 common autosomal aneuploidies, maternal meiotic errors accounted for 91.8% of occurrences. The combination of CNV-seq and STR genotyping significantly improves the detection efficiency of triploidy, mosaicism, and other complex chromosomal anomalies, compensating for crucial limitations of conventional CNV-seq. Further STR-based parental tracing facilitates the identification of chromosomal aberration origins and reveals error formation patterns, thereby providing robust evidence for clinical etiological interpretation of early pregnancy loss.
Zhang et al. (Fri,) studied this question.