Objective To explore the application value of copy number variation sequencing（CNV-seq）combined with quantitative fluorescent polymerase chain reaction（QF-PCR），compared with conventional karyotyping analysis and single nucleotide polymorphism（SNP）array，in genetic diagnosis of spontaneous abortion. Methods Chromesome detection by conventional karyotyping analysis，CNV-seq combined with QF-PCR，and SNP array analysis was performed on tissue samples from 286 cases of spontaneous abortion undergoing curettage，which were collected from Fujian Maternity and Child Health Hospital between April 2018 and May 2020.The detection rates of chromosome abnormalities and the accuracy of the three methods were analyzed. Results Among the 286 products of conception，the detection success rates of conventional karyotyping，CNV-seq，and SNP array were 80.1%（229/286），100%（286/286），and 100%（286/286），respectively. Among the 229 samples with valid results obtained by all three methods，the detection rates of chromosomal abnormalities were 52.0%，55.4%，and 51.1%，respectively，while the detection rate of aneuploidy was 45.0% for all three methods. CNV-seq detected six cases of mosaicism，whereas SNP array detected one. The five additional microdeletions/microduplications identified by CNV-seq were all variants of uncertain significance（VUS）. Five cases of tetraploidy detected by conventional karyotyping were not identified by either CNV-seq or SNP array. Conclusions CNV-seq combined with QF-PCR has a high detection success rate and can identify some low-level mosaicism and submicroscopic copy number variants，however，it may fail to detect certain cases of tetraploidy. Given the respective advantages and limitations of different detection techniques，the choice of testing strategy in clinical practice should be guided by the diagnostic objectives，sample characteristics，and technical performance. When necessary，combined application of multiple techniques may improve the accuracy of identifying the genetic causes of spontaneous miscarriage.