Application Of Chromosome Copy Number Variation Sequencing (CNV-seq) In The Diagnosis Of Spontaneous Abortion Tissues

Objective:The CNV-seq technique was applied to detect chorionic villus tissue in early and mid-term spontaneous abortions,analyze the distribution characteristics of CNV in the genome of spontaneously aborted embryos,explore the correlation between maternal age,gestational week and number of miscarriages and embryonic genomic CNV,and provide genetic guidance for reducing the risk of recurrent miscarriage and the next pregnancy.METHODS:A total of 300 patients with early to mid-term pregnancy miscarriage attending the First Affiliated Hospital of Xinjiang Medical University from November 2020 to April 2022 were selected for the study.CNV-seq assays were performed on miscarriage tissues with informed consent,and the results were analyzed bioinformatically.Results:1 Chromosomal abnormalities detected:The success rate of CNV-seq in detecting 300 spontaneous abortion tissues was 100%,with 204 cases(68%)of chromosomal abnormalities,including 149 cases(49.67%)of chromosomal number abnormalities,including 98 cases(32.67%)of chromosome trisomies,22 cases(7.33%)of haplogroups,21 cases(7%)of haplogroups,7 cases of chimerism(2.33%)and 2 cases(0.67%)of complex chromosomes(containing 2 or more chromosomal abnormalities);53cases(17.67%)of chromosomal structural abnormalities,including 29 cases(9.67%)of large segment deletions/duplications and 24 cases(8%)of small segment micro/deletion microduplications.2 Distribution of chromosomal abnormalities:204 chromosomal abnormalities affected all chromosomes except chromosome 19,with the trisomic type having the highest incidence of chromosomal abnormalities,accounting for 48.04% of all chromosomal abnormalities.Monosomal type abnormalities were most prevalent in X monosomy,accounting for 8.82% of all chromosomal abnormalities.Among the chromosomal structural abnormalities,there were 27 cases(9%)of pathogenic CNVs and10 cases(3.33%)of microdeletions/microduplications of p CNVs.3 Age,gestational week and miscarriage correlation:the prevalence of chromosomal abnormalities was 79.71% and64.50% in patients aged ≥ 35 years and <35 years,respectively,with a statistical difference between the two groups(P<0.05).There was a positive correlation between maternal age and chromosomal number abnormalities(P=0.014)and no correlation with chromosomal structure abnormalities(P=0.136).The rate of chromosomal abnormalities was 40.47% and 72.48% in the patient’s ≥ 12 weeks gestation group and <12 weeks group respectively,with a statistically significant difference between the two(P<0.01).4Correlation between number of miscarriages and spontaneous abortions:there was no statistical difference between the number of spontaneous abortions(1,2,3 and ≥4)and chromosomal abnormalities(P> 0.05).Conclusion:Chromosomal aneuploidy is the most common cause of spontaneous abortion in early and mid pregnancy,and pathogenic CNV is also an important cause of spontaneous abortion.Maternal age is positively associated with chromosomal number abnormalities in the embryo and less so with chromosomal structure abnormalities.There is little correlation between the number of spontaneous abortions and the chromosomes of the embryos.