Identification of chromosomal abnormalities in early pregnancy loss using a high-throughput ligation-dependent probe amplification-based assay.

Abstract Embryonic chromosomal abnormalities are the major cause of miscarriage. An accurate, rapid, and inexpensive method for chromosome analysis in miscarriage is warranted in clinical practice. Thus, we developed a high-throughput ligation-dependent probe amplification (HLPA)-based method for detecting aneuploidies and copy number variations in miscarriage. A total of 1060 cases of miscarriage were enrolled. Each specimen was subjected to quantitative fluorescent-polymerase chain reaction (QF-PCR)/HLPA and chromosomal microarray analysis (CMA) in parallel. All 1060 samples were successfully analyzed by both methods; of these samples, 1.7% (18/1060) were identified with significant maternal cell contamination (MCC). Among the remaining 1042 cases without significant MCC, QF-PCR/HLPA reached a diagnostic yield of 59.6% (621/1042), which is comparable to the yield of 60.3% (628/1042) by CMA. Compared with CMA results, the sensitivity and specificity of QF-PCR/HLPA for identification of total pathogenic chromosomal abnormalities were 98.9% and 100.0%, respectively. Furthermore, the overall incidence of chromosomal abnormalities in cases of spontaneous abortion was not significantly different from that in cases of recurrent miscarriage (61.3% vs. 58.5%, P > 0.05). In summary, QF-PCR/HLPA can rapidly and accurately identify chromosomal abnormalities at a comparable performance and lower cost as compared with CMA. Combining simplicity and accuracy with cost-effectiveness, QF-PCR/HLPA may serve as a promising approach for a routine genetic test of miscarriage in clinical practice.