Detection of fetal DNA in trans‐cervical swabs from first trimester pregnancies by gene amplification: a new route to prenatal diagnosis?

Objective To determine whether fetal sex can be predicted from fetal DNA retrieved transcervically from the lower part of the uterine cavity in the first trimester of pregnancy. Design Prospective observational study. Setting St James's University Hospital, Leeds. Subjects 33 women undergoing legal termination of pregnancy at 9 to 13 weeks gestational age. Interventions Before termination of pregnancy samples for DNA analysis were obtained with cotton wool swabs from the vagina, cervix and transcervically in 26 women. In the other seven women samples were obtained using a transcervical cell retrieval (TraCeR) procedure involving flushing the lower uterine cavity with 5 ml saline. Main outcome measures Detection of Y-chromosome specific DNA sequences by the polymerase chain reaction (PCR) in cotton wool swabs taken from the lower uterus in the first trimester of pregnancy to predict fetal sex in comparison with standard cytogenetic analysis. Histological and immunohistochemical analysis of samples obtained by flushing of the lower uterine cavity (TraCeR) to confirm the presence of trophoblast. Results Fetal sex was predicted accurately in 25 of the 26 pregnancies investigated. Immunohistochemical analysis identified syncytial trophoblast fragments in all seven pregnancies investigated by TraCeR. Conclusion Trophoblast may be retrieved from the lower uterus in the first trimester by swabs or TraCeR. When purification of these syncytial fragments can be achieved using immuno-magnetic technology, this test will enable prenatal diagnosis of single gene defects in the fetus by the polymerase chain reaction.