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Minimally‐invasive early prenatal diagnosis using fluorescence in situ hybridization on samples from uterine lavage

A two‐phase study was undertaken to examine the efficiency of using transcervical cells (TCCs) collected by uterine lavage and fluorescence in situ hybridization (FISH) for early prenatal diagnosis of fetal chromosome aneuploidy. Uterine lavage was performed in 50 women scheduled for elective termination of pregnancy (TOP, n=35) or chorionic villus sampling (CVS, n=15) between 6 and 11 weeks of gestation. TCCS were dissociated by trypsin and collagenase, and interphase FISH was carried out for chromosomes X, Y, 13/21, and 18. The phase I study comprised 36 women. The FISH results were compared with the cytogenetic analysis from long‐term culture of villus samples collected at TOP or CVS. Among the 36 samples, 15 had a normal male karyotype and 21 had a normal female karyotype. FISH on TCCs correctly identified 13 out of the 15 pregnancies with a male fetus. In phase II, uterine lavage was performed on 14 women. The samples were first tested for the presence of trophoblasts with an anti‐trophoblast antibody, GB25, by immunohistochemical staining. Among 12 GB25‐positive samples, the FISH results corresponded to the fetal karyotype. One of the GB25‐positive samples had five signals for the chromosome 13/21 probe. The cytogenetic analysis confirmed that the fetus had a karyotype of 47,XX,+21. In the GB25‐negative samples, FISH failed to identify one male pregnancy. Follow‐up was carried out on 13 ongoing pregnancies and no maternal or fetal complications were discovered. This study demonstrates that fetal chromosome numeration can be carried out using FISH on uterine lavage samples in early pregnancy. However, a specific fetal cell marker, such as specific anti‐trophoblast antibody, is necessary to avoid a false‐negative result. © 1997 John Wiley & Sons, Ltd.