The use of cell-free DNA technology in pregnancy loss

Pregnancy loss is the most common pregnancy complication, occurring in up to 70% of fertilised eggs and approximately 15–20% of clinically recognised pregnancies. 1 Branch DW Humphreys MA Recurrent pregnancy loss. in: Lockwood CJ Copel JA Dugoff L Creasy and Resnik's maternal-fetal medicine: principles and practice. 9th edn. Elsevier, Philadelphia, PA2022 Google Scholar The causes of pregnancy loss can provide important information for medical management, reproductive counselling, and supportive patient care. 2 Sahoo T Dzidic N Strecker MN et al. Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges. Genet Med. 2017; 19: 83-89 Summary Full Text Full Text PDF PubMed Scopus (103) Google Scholar Genetic factors constitute the largest single category of known factors that cause pregnancy loss, with fetal chromosomal abnormalities accounting for approximately 50–60% of early pregnancy losses. 3 Hardy K Hardy PJ Jacobs PA Lewallen K Hassold TJ Temporal changes in chromosome abnormalities in human spontaneous abortions: results of 40 years of analysis. Am J Med Genet A. 2016; 170: 2671-2680 Crossref PubMed Scopus (50) Google Scholar Although fetal karyotyping has been used for many years to evaluate pregnancy tissues, it is limited because it requires live cells and cell culture. The success rate of karyotyping pregnancy tissues may be as low as 53%, largely due to a 32% culture failure rate and a 15% rate of maternal cell contamination. 4 Pauta M Grande M Rodriguez-Revenga L Kolomietz E Borrell A Added value of chromosomal microarray analysis over karyotyping in early pregnancy loss: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018; 51: 453-462 Crossref PubMed Scopus (33) Google Scholar , 5 Lathi RB Gustin SL Keller J et al. Reliability of 46,XX results on miscarriage specimens: a review of 1222 first-trimester miscarriage specimens. Fertil Steril. 2014; 101: 178-182 Summary Full Text Full Text PDF PubMed Scopus (66) Google Scholar Chromosomal microarray of pregnancy tissues using single nucleotide polymorphisms (SNPs) can overcome the challenges of culture failure and false-negative results due to maternal cell contamination. In addition to identifying whole chromosome aneuploidy and triploidy, SNP-based microarray can identify uniparental disomy and segmental imbalances below the standard resolution of karyotyping. Cell-free fetal DNA for genetic evaluation in Copenhagen Pregnancy Loss Study (COPL): a prospective cohort studyThis validation of cffDNA-based testing in pregnancy loss shows the potential and feasibility of the method to distinguish euploid and aneuploid pregnancy loss for improved clinical management and benefit of future reproductive medicine and women's health research. Full-Text PDF