Detection of genetic abnormalities by using CVS and FISH prior to fetal reduction in sonographically normal appearing fetuses

Objective: To examine the ability of chorionic villus sampling (CVS) and fluorescence in situ hybridization (FISH) to detect aneuploidy before first trimester fetal reduction (FR) in sonographically normal-appearing fetuses. Methods: A retrospective review of 470 patients referred to our unit for FR from January 2007-March 2011. Prenatal diagnosis was offered to all. FR was performed after next-day FISH results. Abnormalities were categorized by ultrasound, FISH, and/or karyotype. Sensitivity, specificity, positive predictive value, and negative predictive value of pre-FR FISH were calculated. Results: Four hundred thirty-two of 470 patients seen were first trimester. 24/432 (5.2%) were excluded for abnormal ultrasound findings, including nuchal translucency (NT)>3.0mm, and 360 (88.2%) underwent CVS before FR. Ten fetuses were then excluded for euploid sex mosaicism. 10/350 (2.9%) patients with normal ultrasounds had abnormal FISH confirmed by karyotype. 9/350 (2.6%) patients with normal FISH had an abnormal karyotype necessitating follow up amniocentesis in which the clinically relevant discordancy was confirmed in one case (1/350, 0.3%). Pre-FR FISH had a 90% sensitivity, 99.4% specificity, 83.3% positive predictive value, and 99.7% negative predictive value. Conclusions: 3.1% of patients with normal-appearing fetuses prior to first trimester FR had a fetus with an abnormal karyotype of which FISH detected 90%. CVS with FISH prior to FR adds significant information that can guide reduction decisions.