Noninvasive detection of trophoblast protein signatures linked to early pregnancy loss using transcervical retrieval and isolation from the cervix

Protein biomarker expression in extravillous trophoblast cells obtained noninvasively at 5–10 weeks’ gestation differs between women having a normal term pregnancy and those with an early pregnancy loss.


Rani Fritz, D.O., Hamid-Reza Kohan-Ghadr, Ph.D., Jay M. Bolnick, M.D., Alan D. Bolnick, M.D., Brian A. Kilburn, B.S., Michael P. Diamond, M.D., Sascha Drewlo, Ph.D., D. Randall Armant, Ph.D.

Volume 104, Issue 2, Pages 339-346



To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells obtained noninvasively by transcervical retrieval and isolation from the cervix (TRIC) in patients with early pregnancy loss compared with control patients with uncomplicated term delivery.


Case-control study.


Academic medical center.


Women with either early pregnancy loss (EPL, n = 10) or an uncomplicated term delivery (N = 10).


Endocervical specimens obtained from ongoing pregnancies at gestational ages of 5–10 weeks to generate an archive of EVT cells isolated by TRIC, with medical records examined to select specimens matched for gestational age at the time of endocervical sampling.

Main Outcome Measure(s):

Known serum biomarkers for adverse pregnancy outcome that are expressed by EVT cells were evaluated by semiquantitative immunocytochemistry, using antibodies against endoglin (ENG), FMS-like tyrosine kinase-1 (FLT-1), α-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A), galectin-13 (LGALS13), galectin-14 (LGALS14), and placental growth factor (PGF).


The EVT purity was over 95% in all specimens, based on chorionic gonadotropin expression; however, the number of EVT cells obtained was significantly lower in women with EPL than the control group. There was a statistically significant elevation of AFP, ENG, and FLT-1, and statistically significant reduction of PAPP-A, LGALS14, and PGF in the EPL group compared with controls.


In this pilot study, EVT cells isolated by TRIC early in gestation exhibited altered protein expression patterns before an EPL compared with uncomplicated term pregnancies.

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