TY - JOUR
T1 - Cell-based non-invasive prenatal testing for monogenic disorders
T2 - confirmation of unaffected fetuses following preimplantation genetic testing
AU - Toft, Christian Liebst Frisk
AU - Ingerslev, Hans Jakob
AU - Kesmodel, Ulrik Schiøler
AU - Hatt, Lotte
AU - Singh, Ripudaman
AU - Ravn, Katarina
AU - Nicolaisen, Bolette Hestbek
AU - Christensen, Inga Baasch
AU - Kølvraa, Mathias
AU - Jeppesen, Line Dahl
AU - Schelde, Palle
AU - Vogel, Ida
AU - Uldbjerg, Niels
AU - Farlie, Richard
AU - Sommer, Steffen
AU - Østergård, Marianne Louise Vang
AU - Jensen, Ann Nygaard
AU - Mogensen, Helle
AU - Kjartansdóttir, Kristín Rós
AU - Degn, Birte
AU - Okkels, Henrik
AU - Ernst, Anja
AU - Pedersen, Inge Søkilde
N1 - © 2021. The Author(s).
PY - 2021/8
Y1 - 2021/8
N2 - PURPOSE: Proof of concept of the use of cell-based non-invasive prenatal testing (cbNIPT) as an alternative to chorionic villus sampling (CVS) following preimplantation genetic testing for monogenic disorders (PGT-M).METHOD: PGT-M was performed by combined testing of short tandem repeat (STR) markers and direct mutation detection, followed by transfer of an unaffected embryo. Patients who opted for follow-up of PGT-M by CVS had blood sampled, from which potential fetal extravillous throphoblast cells were isolated. The cell origin and mutational status were determined by combined testing of STR markers and direct mutation detection using the same setup as during PGT. The cbNIPT results with respect to the mutational status were compared to those of genetic testing of the CVS.RESULTS: Eight patients had blood collected between gestational weeks 10 and 13, from which 33 potential fetal cell samples were isolated. Twenty-seven out of 33 isolated cell samples were successfully tested (82%), of which 24 were of fetal origin (89%). This corresponds to a median of 2.5 successfully tested fetal cell samples per case (range 1-6). All fetal cell samples had a genetic profile identical to that of the transferred embryo confirming a pregnancy with an unaffected fetus, in accordance with the CVS results.CONCLUSION: These findings show that although measures are needed to enhance the test success rate and the number of cells identified, cbNIPT is a promising alternative to CVS.TRIAL REGISTRATION NUMBER: N-20180001.
AB - PURPOSE: Proof of concept of the use of cell-based non-invasive prenatal testing (cbNIPT) as an alternative to chorionic villus sampling (CVS) following preimplantation genetic testing for monogenic disorders (PGT-M).METHOD: PGT-M was performed by combined testing of short tandem repeat (STR) markers and direct mutation detection, followed by transfer of an unaffected embryo. Patients who opted for follow-up of PGT-M by CVS had blood sampled, from which potential fetal extravillous throphoblast cells were isolated. The cell origin and mutational status were determined by combined testing of STR markers and direct mutation detection using the same setup as during PGT. The cbNIPT results with respect to the mutational status were compared to those of genetic testing of the CVS.RESULTS: Eight patients had blood collected between gestational weeks 10 and 13, from which 33 potential fetal cell samples were isolated. Twenty-seven out of 33 isolated cell samples were successfully tested (82%), of which 24 were of fetal origin (89%). This corresponds to a median of 2.5 successfully tested fetal cell samples per case (range 1-6). All fetal cell samples had a genetic profile identical to that of the transferred embryo confirming a pregnancy with an unaffected fetus, in accordance with the CVS results.CONCLUSION: These findings show that although measures are needed to enhance the test success rate and the number of cells identified, cbNIPT is a promising alternative to CVS.TRIAL REGISTRATION NUMBER: N-20180001.
KW - Adult
KW - Aneuploidy
KW - DNA Mutational Analysis
KW - Embryo Transfer
KW - Female
KW - Fetus/pathology
KW - Genetic Carrier Screening
KW - Genetic Diseases, Inborn/classification
KW - Germ Cells/growth & development
KW - Humans
KW - Male
KW - Microsatellite Repeats/genetics
KW - Noninvasive Prenatal Testing
KW - Pedigree
KW - Preimplantation Diagnosis
UR - http://www.scopus.com/inward/record.url?scp=85102315918&partnerID=8YFLogxK
U2 - 10.1007/s10815-021-02104-5
DO - 10.1007/s10815-021-02104-5
M3 - Journal article
C2 - 33677749
SN - 1058-0468
VL - 38
SP - 1959
EP - 1970
JO - Journal of Assisted Reproduction and Genetics
JF - Journal of Assisted Reproduction and Genetics
IS - 8
ER -