Chromosomal microarray analysis reveals the genetic etiology spectrum of pregnancy loss in 849 products of conception samples

Objective: To characterize the spectrum and distribution of chromosomal abnormalities detected by chromosomal microarray analysis (CMA) in products of conception (POC) from pregnancy loss, and to assess the association between maternal age and the detection rate of these abnormalities, providing evidence for genetic counseling and recurrence risk assessment. Methods: A total of 852 POC samples from women with pregnancy loss were received at Beijing Jiaen Hospital from January 2016 to December 2025; 849 were successfully analyzed using the Affymetrix CytoScan 750K array following the manufacturer’s standard protocols, while 3 samples were cancelled because immersion in formalin or alcohol had rendered the DNA unsuitable for testing. All detected copy number variants (CNVs) were evaluated for pathogenicity according to ACMG/ClinGen guidelines through comprehensive database queries. The types, frequencies, and distribution characteristics of chromosomal abnormalities were summarized descriptively, and the association between maternal age and the detection rate of pathogenic abnormalities was assessed using the chi-square test, the Cochran–Armitage test for trend, and univariable logistic regression. Results: Abnormalities were detected in 62.19% (528/849) of samples, with numerical abnormalities—trisomies, double trisomies, monosomies, and polyploidies (47 triploid and 6 tetraploid cases)—accounting for the vast majority (82.58% of abnormal samples, 436/528). Trisomy 16 and trisomy 22 were the most prevalent, followed by monosomy X. The remaining 92 samples included other aneuploid abnormalities (n = 35), CNVs (n = 52), and complete hydatidiform moles (genome-wide uniparental disomy, n = 5). The detection rate of pathogenic abnormalities increased with maternal age, from 48.99% in women aged <30 years to 73.81% in women aged ≥40 years ( P for trend <0.001), with the ≥40-year group showing significantly elevated odds relative to the <30-year group (odds ratio = 2.93, 95% confidence interval: 1.76–4.89). Conclusion: Chromosomal or genomic abnormalities detectable by CMA were identified in 62.19% of the 849 POC samples analyzed. Because CMA does not require cell culture and can detect submicroscopic CNVs, loss of heterozygosity, and uniparental disomy, it is well suited for the genetic evaluation of POC; however, the incremental diagnostic yield of CMA over conventional karyotyping was not assessed in this study.