An assessment of the use of interphase FISH with chromosome specific probes as an alternative to cytogenetics in prenatal diagnosis.

We have assessed the effects that would have been observed if we had changed from standard prenatal diagnosis to interphase fluorescence in situ hybridization (FISH) on our amniocentesis samples. We aimed to estimate the number of cases with aberrations other than chromosomes 13, 18, 21, X and Y, which would not have been detectable by FISH and to assess the potential clinical implications for these cases. In 1687 prenatal diagnoses, 111 cases had abnormal cytogenetic reports (6.5% aneuploidy rate). Out of those 111 cases, 14 had chromosomal abnormalities not detectable by FISH but four of these had major structural abnormalities diagnosed on ultrasound, which would have lead to counselling of a very poor prognosis anyway. In 10 cases without abnormal ultrasound findings, if FISH had been used rather than cytogenetics, it appears that there may have had no detrimental effects on the clinical outcomes of the cases studied. Out of those 10 cases, two pregnancies were terminated because of abnormal cytogenetic results (one was due to maternal age and the second one was due to abnormal biochemical screening) (mosaic 46,XY, /47,XY,+mar and 46,X,del(8)(p21) respectively) and their post-mortem results also did not show any abnormalities. One pregnancy was continued in spite of a de novo chromosomal rearrangement and resulted in an apparently normal live birth. Five cases (including a set of twins) with inherited balanced translocations resulted in four normal live births and one unexplained intrauterine death at 32 weeks' gestation and post-mortem was declined. One case with a paternally derived abnormal chromosome 21, decided to continue the pregnancy and resulted in a normal live birth. The last case in this group resulted in a rhesus related intrauterine death in the second trimester, and although an abnormal chromosome 13 insertion (paternally derived known aberration) there was no abnormality found at post-mortem. Therefore, we suggest that it is reasonable to use FISH as an alternative prenatal diagnosis for indications such as advanced maternal age and abnormal maternal serum biochemical screening when high quality ultrasound scanning is performed, but FISH should only be used as an additional test to conventional cytogenetics for the other indications, especially when abnormalities are found on ultrasound scan. Copyright 2000 John Wiley & Sons, Ltd.