Chromosomal copy-number variation analysis of villous tissues using molecular karyotyping in early missed abortions

Abstract Karyotype abnormalities are the most common etiology of early spontaneous miscarriage. However, traditional karyotyping of chorionic villus samples (CVSs) is limited by cell culture and its low resolution. The objective of our study was to investigate the efficiency of molecular karyotyping technology in detecting the CNVs of early missed abortion tissues. Chromosome analysis of 1160 abortion CVSs in early pregnancy, collected by hysterosuction, was conducted in Fujian, China, with informed consent secured from the participants; 449 chromosomal CNV analyses were conducted via CNV-seq and 711 analyses were conducted using microarray. Clinically submicroscopic CNVs of abortion villous tissues were identified to clarify the cause of the abortion and to guide the participants’ subsequent pregnancies. Among the 1160 samples, 754 cases (65.0%) with genetic abnormalities were identified, of which, 531 (45.8%) were single aneuploidies, 31 (2.7%) were multiple aneuploidies, 50 (4.3%) were polyploidies, 53 (4.6%) were partial aneuploidies, 78 (6.7%) had a microdeletion or microduplication, and 8 cases (0.7%) were uniparental disomies. However, compared with the young maternal age group, the embryotic numerical and structural chromosomal rate was significantly different in the advanced maternal age group, while there was no significant positive correlation between maternal age and other types of genetic abnormalities. A higher detection rate of embryotic chromosomal abnormalities, especially submicroscopic CNVs, was achieved using CNV-seq and microarray. Our results indicate that embryonic CNVs cause early miscarriage and highlight the importance of CNV analysis in CVSs, irrespective of maternal age.