The purpose of this study was to explore the copy number variations (CNVs) associated with miscarriage during early and middle pregnancy and provide useful genetic guidance for pregnancy and prenatal diagnosis. A total of 505 fetal specimens were collected and CNV sequencing (CNV-seq) analysis was performed to determine the types and clinical significance of CNVs, and relevant medical records were collected. The chromosomal abnormality rate was 54.3% (274/505), among which the numerical chromosomal abnormality rate was 40.0% (202/505) and structural chromosomal abnormality rate was 14.3% (72/505). Chromosomal monosomy mainly occurred on sex chromosomes, and chromosomal trisomy mainly occurred on chromosomes 16, 22, 21, 15, 13, and 9. The incidence of numerical chromosomal abnormalities in ≥35 year-old age pregnant women was significantly higher than <35 year-old age group. The highest incidence of pathogenic CNV (pCNV) was found in fetuses at ≤6 weeks of pregnancy (5.26%), and the incidence of variants of unknown significance (VOUS) CNVs decreased gradually with the increase of gestational age. The rate of chromosomal abnormalities of fetuses in early pregnancy (59.5%) was higher than that of fetuses in middle pregnancy (27.2%) (p < 0.001). There were 168 genes in VOUS + pCNV regions. 41 functions and 12 pathways (p < 0.05) were enriched of these genes by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Some meaningful genetic etiology information such as genes and pathways has been obtained, it may provide useful genetic guidance for pregnancy and prenatal diagnosis.

本研究的目的是探索与妊娠早期和中期流产相关的拷贝数变异（CNV），并为妊娠和产前诊断提供有用的遗传指导。共收集505个胎儿标本，进行CNV测序（CNV-seq）分析，确定CNV的类型和临床意义，并收集相关病历。染色体异常率为54.3%（274/505），其中染色体数值异常率为40.0%（202/505），染色体结构异常率为14.3%（72/505）。染色体单体性主要发生在性染色体上，染色体三体性主要发生在16、22、21、15、13、9号染色体上。≥35岁孕妇染色体数值异常发生率显着高于<35岁年龄组。病原性CNV（pCNV）发生率最高的是妊娠≤6周的胎儿（5.26%），并且显着性未知变异（VOUS）CNV的发生率随着胎龄的增加而逐渐降低。妊娠早期胎儿染色体异常率（59.5%）高于妊娠中期胎儿（27.2%）（磷< 0.001)。VOUS + pCNV 区域有 168 个基因。41 种功能和 12 条通路（磷< 0.05) 通过基因本体论 (GO) 分析和京都基因和基因组百科全书 (KEGG) 分析富集这些基因。已经获得了一些有意义的遗传病因学信息，如基因和通路，可为妊娠和产前诊断提供有益的遗传指导。