Trophoblast Retrieval and Isolation from the Cervix to study genetic birth defects

The Non-Invasive Prenatal Testing (NIPT) allows early diagnosis of trisomies
with high sensitivity and specificity. However, it does have some limitations;
the fetal fraction must reach over 4% for accurate testing, an issue in e.g.
maternal obesity. Secondly, the low fetal fraction makes this technique highly
challenging in detecting a birth defect of genetic origin other than trisomies.
Prenatal testing for the other genetic birth defects is currently performed on
samples obtained invasively by chorionic villous sampling (CVS) or
amniocentesis, which have a 0.3-0.5% miscarriage risk. A new non-invasive
technique named TRIC is based on the principle that fetal trophoblast-like
cells are naturally shed from the placenta into the reproductive tract. By
endocervical sampling with a Papanicolaou (Pap) smear, intact fetal cells can
be collected as early as 5 weeks of gestation in number sufficient for genetic
testing. However, this technique has not yet been compared to the current gold
standard of sampling, CVS.

Main objective is to investigate if fetal DNA samples non-invasively obtained
by the TRIC method provide the same prenatal genetic test result as diagnostic
testing performed on samples obtained invasively by CVS, currently the gold
standard. This will be done by performing the TRIC method at the time of CVS
sampling to test if the genetic test result in samples obtained by TRIC are the
same as from samples obtained by CVS.

Non-inferiority study.

The burden consists of undergoing endocervical sampling (Papanicolaou smear)
at intake counselling and/or directly before CVS sampling. The additional risk
is harmless self-limited vaginal spotting. No significant increased risk of
serious adverse outcomes nor any trend in that direction have been observed in
previous studies.