Experience of Copy number variation sequencing applied in production of conception from first- and second- trimester miscarriage

Abstract Background We evaluated the application value of copy number variation sequencing (CNV-seq) to analyze chromosomal abnormalities in products of conception (POCs) from first- and second- trimester miscarriages. Methods Approximately 650 POCs from spontaneous abortion were collected from April 2018 to May 2020. CNV-seq and QF-PCR were performed to determine the characteristics and frequencies of copy number variants (CNVs) with clinical significance. Clinical features were recorded. Results Clinically significant chromosomal abnormalities were identified in 355 (54.6%) POCs, including 217 (33.4%) autosomal trisomies, 42(6.5%) chromosomal monosomy and 40 (6.2%) pathogenic CNVs (pCNVs). Chromosomal trisomy mainly occurred on chromosomes 16, 22, 21, 18, and 15. Gestational week was a negative correlative factor for chromosome abnormality.Maternal age was the positive correlative factor of chromosome abnormality. However the occurrence of monosomy X was not related to maternal or gestational age. The frequency of chromosomal abnormalities in women with a normal live birth history was 55.3%, vs 54.4% in women without a normal live birth history (P > 0.05). There were no significant differences among women without, with 1, and ≥ 2 previous miscarriages history regarding the rate of chromosomal abnormalities (P > 0.05); CNVs were less frequently detected in women with advanced maternal age than in women aged ≤ 29 years and 30–34 years (P < 0.05). Conclusion Chromosomal abnormalities are the most common causes of pregnancy loss, maternal and gestational age are strongly associated with fetal autosomal trisomy aberrations. Embryo chromosomal examination is recommended regardless of gestational age, modes of conception or previous abortion status.