The Number of Circulating Fetal Extravillous Trophoblasts Varies from Gestational Week 6 to 20
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PLACENTA: ORIGINAL ARTICLE
The Number of Circulating Fetal Extravillous Trophoblasts Varies from Gestational Week 6 to 20 Katarina Ravn 1 Niels Uldbjerg 3
Ripudaman Singh 1 4 & Johnny Hindkjær
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Lotte Hatt 1
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Mathias Kølvraa 1
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Palle Schelde 1
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Ida Vogel 2
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Received: 24 April 2020 / Revised: 8 June 2020 / Accepted: 22 June 2020 # The Author(s) 2020
Abstract Cell-based non-invasive prenatal testing (cbNIPT) based on circulating fetal extravillous trophoblasts (fEVTs) has shown to be possible in gestational week (GW) 10–13. Prenatal testing is relevant for a wider time period than GW 10–13, but it is unclear if fEVTs are present in sufficient numbers for cbNIPT at other time points during pregnancy. We present the first longitudinal study where the number of circulating fEVTs was determined from the mid first trimester to the mid second, specifically GW 6–8, 12– 13, and 19–20. Blood samples from 13 women opting for assisted reproduction were collected at GW 6–8, 12–13, and 19–20. fEVTs were enriched using a magnetic-activated cell sorting system, stained with anti-cytokeratin antibodies, and fEVTs were identified with the use of a MetaSystem fluorescence microscope scanner. Blood samples drawn at GW 6–8 yielded an average of 5.5 fEVTs per 30 mL of blood. This increased significantly to an average of 11.8 in GW 12–13 (P value: 0.0070, Mann-Whitney test), and decreased significantly to an average of 5.3 in GW 19–20 (P value: 0.0063, Mann-Whitney test). In 9 out of 13 cases, the number of fEVTs peaked in GW 12–13 compared to GW 6–8 and GW 19–20. For the majority of cases, fEVTs can be identified at GW 6–8 and GW 19–20, but the highest number of fEVTs is observed at GW 12–13 indicating this is the optimal time point for cbNIPT. Keywords Cell-based non-invasive prenatal testing . Fetal cells in maternal blood . Extravillous trophoblasts . Trophoblast invasion
Introduction Non-invasive prenatal testing has gained more attention in the last decade as an alternative to invasive testing like chorionic villus sampling (CVS), which carries a slight procedural risk of miscarriage [1]. Today, non-invasive prenatal testing using cell-free fetal DNA (cfNIPT) has obtained widespread acceptance as a screening test for common trisomies. However, the fragmented fetal DNA and the presence of maternal
* Katarina Ravn [email protected] 1
ARCEDI Biotech ApS, Tabletvej 1, Vejle, Denmark
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Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
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Department of Obstetrics and Gynaecology, Aarhus University Hospital, Aarhus, Denmark
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Aagaard Fertility Clinic, Aarhus, Denmar
circulating DNA create limitations on the resolution of the test. Further complications arise with maternal malignancies, and maternal obesity causing low fetal DNA fractions leading to possible no-calls [2, 3]. Circulating fetal cell-based noninvasive prenatal testing (cbNIPT) represents an alternative, which can provide a pure source of the fetal genome and may develop into giving high-resolution diagnostic results [4–6]. Ho
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