Defining the role of fluorescence in situ hybridization on uncultured amniocytes for prenatal diagnosis of aneuploidies.

OBJECTIVE: This study examines the role of fluorescence in situ hybridization on uncultured amniocytes for prenatal diagnosis in a population at high risk for aneuploidies.

STUDY DESIGN: All patients undergoing amniocentesis for fetal structural abnormality on ultrasonographic examination (performed from 13 to 39 weeks), abnormal maternal serum aneuploidy screening results, or advanced maternal age with substantial parental anxiety were offered both fluorescence in situ hybridization on uncultured cells and conventional metaphase karyotyping on dividing cells.

RESULTS: From 1992 to 1995, 315 patients were studied. Mean time to obtain results was 2.8 days for fluorescence in situ hybridization and 8.3 days for karyotype. Fluorescence in situ hybridization was informative in 254 samples (80.6%), and within this group 21 aneuploidies were correctly identified. Among informative specimens there was 100% sensitivity and specificity, with 100% positive and negative predictive values. Of the 315 samples, 61 (19.4%) were uninformative or unreportable. Of 25 total cases of karyotype-proved aneuploidy, 4 were reported as uninformative by fluorescence in situ hybridization, for a total detection rate of 84%. Overall, amniocenteses performed after 24 weeks were significantly more likely to be uninformative than those performed in the second trimester (45% vs 16%, p = 0.01), peaking at a 56% uninformative rate after 33 weeks. Logistic regression analysis showed an 8% increase in the uninformative rate per week of gestational age (odds ratio 1.08, 95% confidence interval 1.04 to 1.14).

CONCLUSIONS: Fluorescence in situ hybridization on uncultured amniocytes is a rapid, clinically useful tool for prenatal diagnosis, with informative specimens being highly accurate. The combination of a structural fetal anomaly and an abnormal fluorescence in situ hybridization result should allow for definitive management decisions. The significant increase in uninformative specimens at later gestational ages limits its usefulness in the third trimester.