Trophoblast Retrieval and Isolation from the Cervix for Noninvasive, First Trimester, Fetal Gender Determination in a Carrier of Congenital Adrenal Hyperplasia

Alan D. Bolnick, Rani Fritz, Chandni Jain, Leena Kadam, Jay M. Bolnick, Brian A. Kilburn, Manvinder Singh, Michael P. Diamond, Sascha Drewlo, D. Randall Armant

Research output: Contribution to journalArticle

7 Scopus citations


Congenital adrenal hyperplasia (CAH) is an autosomal recessive defect in cortisol biosynthesis that elevates fetal androgen levels to cause genital ambiguity and external genital masculinization in newborn females. Introducing dexamethasone in utero by 7 weeks gestation precludes virilization of affected females. However, identification of a male fetus prior to week 7 could avert the necessity of steroid treatment in half of pregnancies at risk of CAH. We recently introduced trophoblast retrieval and isolation from the cervix (TRIC), an approach that noninvasively isolate homogeneous trophoblast cells from pregnant women as early as 5 weeks gestation, using a Papanicolaou test. Here, we have used TRIC to correctly identify male fetal DNA when both parents were carriers of the mutation that produces CAH and previously produced an affected child. Trophoblast cells (1400) obtained by TRIC were assessed using immunocytochemistry with an antibody against the trophoblast-specific β subunit of human chorionic gonadotropin, which labeled 100% (17 of 17) of isolated cells, while none of the excluded maternal cervical cells were labeled. The isolated cells were examined by fluorescent in situ hybridization for chromosomes 18, X, and Y at a clinical cytogenetics laboratory, demonstrating 100% (18 of 18) of cells to be diploid 18/XY. Aliquots of DNA obtained from the isolated cells assayed for SRY and RNASEH genes by TaqMan assays confirmed a male fetus. This case study demonstrates the utility of TRIC to accurately identify fetal gender as a means of reducing the need for prophylactic administration of exogenous steroids in pregnancies at risk of CAH.

Original languageEnglish (US)
Pages (from-to)717-722
Number of pages6
JournalReproductive Sciences
Issue number6
StatePublished - Jun 23 2016



  • 21-hydroxylase
  • congenital adrenal hyperplasia
  • fluorescence in situ hybridization
  • placenta
  • prenatal genetic diagnosis
  • steroids
  • trophoblast

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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