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

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.

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.

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%).

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.