Utility Of A High-Resolution Melting Test For Screening Numerical Chromosomal Abnormalities In Recurrent Pregnancy Loss

The incidence of recurrent pregnancy loss(RPL)is approximately 5%in clinically identified pregnancies.It is particularly important to identify the etiology of RPL that assists the doctor to make a reasonable treatment plan and relieves the mental burden of patients.At present,genetic testing for products of conception(POC)combined with an evidence-based workup has been widely accepted in RPL evaluation.However,the current genetic tests have been limited in clinical application due to the time-consuming,expensive and low throughout.Thus,this research developed a high-resolution melting analysis-based test(HRM test)to screen for the most frequent numerical chromosome abnormalities(NCA)meanwhile proposed a new model of genetic analysis of POC with screening before diagnosis.In this study,765 retrospective clinical POC samples with known karyotypes were screened for chromosomal abnormalities by HRM test.All of POC samples were successful examined(100%),which had a high technical sensitivity(96.1%)and specificity(96.3%)as well as a high positive predictive value(95.9%).After that,the cost-effectiveness analysis of four RPL evaluation strategies were compared that employ different genetic tests,including chromosome karyotype analysis,chromosomal microarray(CMA)/next generation sequencing(NGS),HRM screening and a combination of the HRM test and CMA/NGS.The results showed that the cost of karyotyping or HRM screening alone was highly similar for diagnosis an explained RPL(1495.3 vs1417.8 yuan),while the cost-effectiveness of adding HRM screening strategy before CMA/NGS diagnosis is about 30%higher than that of using CMA/NGS(2542.5 vs 3613.5 yuan)for RPL evaluation.In addition,the cost-effectiveness of four RPL evaluation strategies were better in the elderly group than in the non-elderly group.In conclusion,HRM can be used as an initial screening tool to improve the costeffectiveness of RPL evaluation strategy that followed by other diagnostic methods;or as an alternative genetic test when other detection methods are unavailable or unaffordable.