Cell‐Free DNA Screening After Euploid Embryo Transfer: Concordance With Amniocentesis and Residual Aneuploidy Risk

ABSTRACT Objective To assess concordance between cell‐free DNA screening and invasive prenatal diagnosis after single euploid embryo transfer following pre‐implantation genetic testing for aneuploidy (PGT‐A), and estimate residual chromosomal risk. Method This retrospective cohort included 1079 singleton ongoing pregnancies after PGT‐A between August 2019 and March 2024. Prenatal testing comprised cell‐free DNA screening alone ( n = 317), amniocentesis alone ( n = 500), or both tests ( n = 262). Chromosomal microarray analysis of amniocytes was the reference standard. Results In the dual‐testing cohort, eight pregnancies had high‐risk cell‐free DNA results, of which one was confirmed as 47, XXX. One low‐risk result was subsequently diagnosed as sex chromosome mosaicism. Sensitivity, specificity, positive predictive value and negative predictive value were 50.0% (95% CI, 2.7–97.3), 97.3% (94.3–98.8), 12.5% (0.6–53.3) and 99.6% (97.5–99.9), respectively. Among 762 pregnancies undergoing amniocentesis, residual confirmed aneuploidy risk after euploid embryo transfer was 0.1% (1/762). The overall yield of clinically relevant CMA findings was 0.5% (4/762), including two pathogenic microdeletions. One pregnancy loss within 7 days after amniocentesis occurred (0.1%). Conclusion After PGT‐A, cell‐free DNA screening showed high negative predictive value but limited positive predictive value. These findings support risk‐stratified prenatal testing, while invasive diagnosis remains indicated after high‐risk screening, abnormal ultrasound, or patient preference.