Clinical Utility of a High-Resolution Melting Test for Screening Numerical Chromosomal Abnormalities in Recurrent Pregnancy Loss

Abstract

Recurrent pregnancy loss (RPL) occurs in approximately 5% of clinically identified pregnancies. Determining the cause of RPL is essential. Genetic testing, accompanied by an evidence-based workup, is the well-accepted process for evaluating RPL; however, current genetic tests have limitations in clinical practice. We, thus, developed a high-resolution melting analysis-based test (HRM test) to screen for the most common numerical chromosomal abnormalities present in the products of conception. We examined 765 products-of-conception samples with known karyotypes retrospectively using the HRM test, which showed high technical sensitivity (96.1%) and specificity (96.3%) as well as a high positive predictive value (95.9%) for the screening of chromosomal abnormalities. The cost-effectiveness of four RPL evaluation strategies that employ different genetic tests, karyotyping, chromosomal microarray/next-generation sequencing, the HRM test, and a combination of the HRM test and chromosomal microarray/next-generation sequencing, was then compared. The costs of diagnosing an explained RPL using karyotyping or the HRM test alone were similar. Performance of the HRM screening test before chromosomal microarray/next-generation sequencing analysis improved cost-effectiveness by approximately 30%. Cost-effectiveness was more prominent in the advanced maternal age group. Thus, the HRM test could be used as an initial screening tool, followed by other diagnostic methods to improve the cost-effectiveness of RPL evaluation, or as an alternative genetic test when other methods are unavailable or unaffordable.