Cell-based non-invasive prenatal testing for monogenic disorders: confirmation of unaffected fetuses following preimplantation genetic testing

Toft et al., 2021, Journal of Assisted Reproduction and Genetics.

Toft CLF1,2, Ingerslev HJ3, Kesmodel US2,3, Hatt L4, Singh R4, Ravn K4, Nicolaisen BH4, Christensen IB4, Kølvraa M4, Jeppesen LD4, Schelde P4, Vogel I5, Uldbjeg N6, Farlie R7, Sommer S8, Østergård MLV9, Jensen AN10, Mogensen H11, Kjartansdóttir KR12, Degn B1, Okkels H1, Ernst A1, Pedersen IS1,2.

Journal of Assisted Reproduction and Genetics, 2021, volume 38, pages 1959-1970.


1Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark

2Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

3Fertility Unit, Aalborg University Hospital, Aalborg, Denmark

4ARCEDI Biotech ApS, Vejle, Denmark

5Department of Clinical Genetic, Aarhus University Hospital, Aarhus, Denmark

6Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark

7Department of Obstetrics and Gynecology, Viborg Regional Hospital, Viborg, Denmark

8Department of Obstetrics and Gynecology, Horsens Regional Hospital, Horsens, Denmark

9Department of Obstetrics and Gynecology, Randers Regional Hospital, Randers, Denmark

10Department of Obstetrics and Gynecology, Aalborg University Hospital, Aalborg, Denmark

11Department of Obstetrics and Gynecology, Kolding Regional Hospital, Kolding, Denmark

12Molecular Genetics Laboratory, Department of Clinical Genetics, University Hospital Copenhagen, Copenhagen, Denmark

DOI: 10.1007/s10815-021-02104-5

PMID: 33677749


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).

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.

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.

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.

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