Transcervical retrieval of fetal cells in the practice of modern medicine: a review of the current literature and future direction

Abstract

Objective: To review published methods for transcervical collection of fetal cells and to assess the potential of this approach for application in prenatal diagnosis.

Main outcome measure(s): Retrospective analysis of efforts at prenatal diagnosis with trophoblast cells shed into the lower uterine pole that accumulate within the cervical mucus at the level of the internal os.

Result(s): Minimally invasive techniques that include cervical mucus aspiration, cervical swabbing, and cervical or intrauterine lavage can be used to retrieve trophoblast cells during the first trimester for diagnostic purposes, including for prenatal genetic analysis. Fetal cells have been identified in these specimens with success rates that vary from 40% to 90%. The disparity in reported success rates can be a function of gestational age, collection method, operator variability, detection sensitivity, or pregnancy status. Molecular approaches have been devised to determine fetal sex and identify aneuploidies. Antibody markers have proven useful to select trophoblast cells for genetic analysis and to demonstrate that the abundance of recoverable fetal cells diminishes in abnormal gestations, such as in ectopic pregnancy or blighted ovum.

Conclusion(s): Transcervical collection of fetal cells offers several avenues for prenatal diagnosis that with further refinement could one day provide valuable information for the management of ongoing pregnancies.

Keywords: Prenatal diagnosis; cervical mucus; ectopic pregnancy; fetal cells; genetic analysis; immunological markers; intrauterine lavage; transcervical cell collection; trophoblast.

Figure 1

Transcervical cell analysis and potential clinical applications by quantification of trophoblast cells or genetic analysis using fluorescence in situ hybridization (FISH) or the polymerase chain reaction (PCR).

Figure 2

HLA-G positive cytotrophoblast cell in a transcervical specimen. The slide was prepared as describe by Imudia et al. (18) from a specimen obtained during the first trimester of pregnancy. Antibody labeling was detected using monoclonal antibody G233 against HLA-G and a secondary antibody conjugated to peroxidase to produce a dark brown precipitate around the cytotrophoblast cell. Counterstaining with hematoxylin reveals nuclei (blue) of cervical cells, which are abundant in the specimen. Bar, 20 μm.