Accuracy of Genetic Diagnoses Made Using FISH Varies


INDIAN WELLS, CALIF. — Preimplantation genetic diagnosis using fluorescent in situ hybridization has a positive predictive value of 83% and a negative predictive value of 81% when a panel of probes for five chromosomes is used, Catherine M. De Ugarte, M.D., said at the annual meeting of the Pacific Coast Reproductive Society.

In a study that involved 241 IVF embryos, 34 of 198 embryos that were initially found to be abnormal with fluorescent in-situ hybridization (FISH) were later shown to be normal with subsequent FISH analyses. Of 43 embryos initially called normal with FISH, 8 were later shown to have an abnormality, said Dr. De Ugarte of the division of reproductive endocrinology and infertility at the University of California, Los Angeles, Medical Center.

Certain chromosomal abnormalities were more likely to be missed, including monosomies. Turner's syndrome, in particular, was highly likely to be falsely identified. Only 17% of embryos initially identified as affected with Turner's syndrome were confirmed as having the disorder.

Dr. De Ugarte said 45% of the time the initial FISH analysis indicated that an embryo was abnormal, confirmation revealed a different abnormality than initially diagnosed. There were various reasons for these misdiagnoses, including failure of the probes to hybridize when they should have and situations in which two chromosomes overlapped, preventing visualization of a probe.

One significant limitation is that the study used embryos that were initially found to be abnormal or unsuitable for freezing and preserving, said L. Michael Kettel, M.D., who commented on the study at the meeting.

Nevertheless, the study results, while perhaps disheartening, are “probably not surprising,” said Dr. Kettel, a reproductive endocrinologist in San Diego.

“As this technology is applied more and more often, it is important to understand the potential and significant limitations that this technology presents,” he said.

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