Copy number variation sequencing combined with quantitative fluorescence polymerase chain reaction in clinical application of pregnancy loss

Purpose In this study, we evaluated the feasibility of the combining CNV-seq and quantitative fluorescence polymerase chain reaction (QF-PCR) for miscarriage analysis in clinical practice. Methods Over a 35-month period, a total of 389 fetal specimens including 356 chorionic villi and 33 fetal muscle tissues were analyzed by CNV-seq and QF-PCR. Relationships between the risk factors (e.g., advanced maternal age, abnormal pregnancy history, and gestational age) and incidence of these chromosomal abnormalities were further analyzed by subgroup. Results Clinically significant chromosomal abnormalities were identified in 58.95% cases. Aneuploidy was the most common abnormality (46.84%), followed by polyploidy (8.16%) and structural chromosome anomalies (3.95%). In sub-group analysis, significant differences were found in the total frequency of chromosomal abnormalities between the early abortion and the late abortion group, as well as in the distribution of chromosomal abnormalities between the advanced and the younger maternal age group. Meanwhile, the results of the logistic regression analysis identified a trend suggesting that the percentage of fetal chromosomal abnormalities is significantly higher in advanced maternal age, lesser gestational age, and lesser number of prior miscarriages. Conclusion Our study suggests that CNV-seq and QF-PCR are efficient and reliable technologies in the fetal chromosome analysis of miscarriages and could be used as a routine selection method for the genetic analysis of spontaneous abortion.