Geralyn Lambert-Messerlian1, Edward M Kloza1, John Williams2, Jaroslav Loucky3, Barbara O'Brien4, Louise Wilkins-Haug5, Maurice J Mahoney6, Pierangela De Biasio7, Antoni Borrell8, Mathias Ehrich9, Dirk van den Boom9, Allan T Bombard10, Cosmin Deciu11, Glenn E Palomaki1. 1. Department of Pathology and Laboratory Medicine, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA. 2. Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA. 3. IMALAB s.r.o. Medical Laboratories, Zlin, Czech Republic. 4. Department of Obstetrics and Gynecology, Prenatal Diagnosis Center, Women and Infants Hospital and the Alpert Medical School of Brown University, Providence, Rhode Island,USA. 5. Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, USA. 6. Department of Genetics, Yale University, New Haven, Connecticut, USA. 7. Istituto G. Gaslini, Genova, Italy. 8. Hospital Clinic Barcelona, Barcelona, Spain. 9. Sequenom, San Diego, California, USA. 10. 1] Sequenom, San Diego, California, USA [2] Sequenom Center for Molecular Medicine, San Diego, California, USA. 11. Sequenom Center for Molecular Medicine, San Diego, California, USA.
Abstract
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.
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.