Copy Number Variation Sequencing And Whole-exome Sequencing In Recurrent Spontaneous Abortion

Objective Along with the growing population,the number of infertility patients is also rapidly increasing,and it is estimated that more than 5% of couples need to suffer ≥2spontaneous abortions.How to perform effective prenatal screening and diagnosis is an important concern for the search of genetically related causes of unexplained recurrent miscarriage in China and worldwide reproductive medicine health.The aim of this study is to investigate the clinical significance of copy number variation sequencing(CNV-seq)combined with whole exome sequencing(WES)in patients with recurrent spontaneous abortion(RSA).MethodSixty-seven patients with a history of spontaneous abortion and their embryonic abortion products who attended the Reproductive Medicine and Prenatal Diagnostic Center of Maanshan Maternal and Child Health Hospital from June 1,2021 to August31,2022 were selected and divided into RSA group and one spontaneous abortion group according to the number of abortions,both were tested with CNV-seq.For the RSA samples with negative CNV-seq test results,due to the cost of testing For reasons of testing cost,some samples were selected for additional testing with the WES technique.The clinical application of the CNV-seq technique in combination with the WES technique in patients with RSA was explored.ResultsOf the 67 samples studied,CNV-seq results were suggestive of positive specimens in 37 cases,accounting for 55.22%.There were 34 cases of primary spontaneous abortion,of which 19 had abnormalities in the abortion tissue,3 were of unknown clinical significance,3 were triploid,1 was sex chromosome haploid,13 were aneuploid and 2had more than two copy number variations(CNVs).33 patients with RSA,of which 18 had abnormalities in the abortion tissue,2 were triploid,2 were sex chromosome haploid,10 were aneuploid and 4 had more than two copy number variations(CNVs).Of the 15 samples with negative CNV-seq results in RSA patients,10 were randomly selected for WES testing due to the cost of testing,accounting for 66.67% of the 15 samples,of which three were pathogenic,one was clinically significant,and six were clinically significant.The rate of positive WES results was: 30%.Conclusion1.The CNV-seq technique provides ideas and methods for the treatment of genetically related causes of miscarriage.2.The rate of chromosomal abnormalities in embryos with recurrent miscarriage was comparable to the rate of chromosomal abnormalities in embryos with one spontaneous miscarriage,with no statistically significant difference.3.There was no statistically significant relationship between maternal age and chromosomal abnormalities in recurrent miscarriage.4.Whole exome sequencing technology has revealed new pathogenic gene mutations related to embryo termination and malformations.Combined with the CNV-seq technique,it can improve the diagnosis of genetic factors related to recurrent miscarriage and has important value for eugenics consultation and guidance in the next pregnancy.