Maternal plasma DNA testing for aneuploidy in pregnancies achieved by assisted reproductive technologies

Purpose: We sought to compare measurements of circulating cell-free DNA as well as Down syndrome test results in women with naturally conceived pregnancies with those conceived using assisted reproductive technologies. Methods: Data regarding assisted reproductive technologies were readily available from seven enrollment sites participating in an external clinical validation trial of nested case/control design. Measurements of circulating cell-free fetal and total DNA, fetal fraction (ratio of fetal to total DNA), chromosome-specific z -scores, and karyotype results were available for analysis. Results: Analyses were restricted to 632 euploid (5.2% assisted reproductive technologies) and 73 Down syndrome (13.7% assisted reproductive technologies), including 16 twin pregnancies. No differences were found for fetal or total circulating cell-free DNA, or for the fetal fraction in euploid ( P = 0.70) or Down syndrome ( P = 0.58) pregnancies by method of conception. There appeared to be systematic z -score reductions for chromosomes 21, 18, and 13 in assisted reproductive technologies versus natural euploid pregnancies ( P = 0.048, 0.0032, and 0.36, respectively). Conclusion: Assisted reproductive technologies and naturally conceived pregnancies contribute similar levels of circulating cell-free DNA into maternal circulation. Small differences in the z -scores of pregnancies achieved by assisted reproductive technologies were observed and do not appear to be test-related artifacts. However, the findings need confirmation before any consideration of changes to testing and reporting protocols. Genet Med 16 5, 419–422.