DEFINING THE ROLE OF FLUORESCENCE IN-SITU HYBRIDIZATION ON UNCULTUREDAMNIOCYTES FOR PRENATAL-DIAGNOSIS OF ANEUPLOIDIES

OBJECTIVE: This study examines the role of fluorescence in situ hybrid ization on uncultured amniocytes for prenatal diagnosis in a populatio n at high risk for aneuploidies. STUDY DESIGN: All patients undergoing amniocentesis for fetal structural abnormality on ultrasonographic ex amination (performed from 13 to 39 weeks), abnormal maternal serum ane uploidy screening results, or advanced maternal age with substantial p arental anxiety were offered both fluorescence in situ hybridization o n uncultured cells and conventional metaphase karyotyping on dividing cells. RESULTS: From 1992 to 1995, 315 patients were studied. Mean tim e to obtain results was 2.8 days for fluorescence in situ hybridizatio n and 8.3 days for karyotype. Fluorescence in situ hybridization was i nformative in 254 samples (80.6%), and within this group 21 aneuploidi es were correctly identified. Among informative specimens there was 10 0% sensitivity and specificity, with 100% positive and negative predic tive values. Of the 315 samples, 61 (19.4%) were uninformative or unre portable. Of 25 total cases of karyotype-proved aneuploidy, 4 were rep orted as uninformative by fluorescence in situ hybridization, for a to tal detection rate of 84%. Overall, amniocenteses performed after 24 w eeks were significantly more likely to be uninformative than those per formed in the second trimester (45% vs 16%, p = 0.01), peaking at a 56 % uninformative rate after 33 weeks. Logistic regression analysis show ed an 8% increase in the uninformative rate per week of gestational ag e (odds ratio 1.08, 95% confidence interval 1.04 to 1.14). CONCLUSIONS : Fluorescence in situ hybridization on uncultured amniocytes is a rap id, clinically useful tool for prenatal diagnosis, with informative sp ecimens being highly accurate. The combination of a structural fetal a nomaly and an abnormal fluorescence in situ hybridization result shoul d allow for definitive management decisions. The significant increase in uninformative specimens at later gestational ages limits its useful ness in the third trimester.