Human Reproduction, Vol. 15, No. 1, 229-230,
January 2000
© 2000 European Society of Human Reproduction and Embryology
Letters to the Editor |
Hutzel Hospital, 4707 St Antoine Boulevard, Detroit, MI 48201, USA
Dear Sir,
Van der Smagt et al. certainly make some interesting points in response to our article (Evans et al., 1999
). The authors suggest that: firstly, we did not divide our cases by method of referral. This is true, but it was not practical to do anything else given the large number of centres and the fact that not every centre receives complete information from all of its referral network. It certainly would be nice to have such information, but it is not reality to believe that this is going to happen in every case.
If ultrasound abnormalities are found along with a normal fluorescent in-situ hybridization (FISH), the karyotype will go on and, of course, be mandatory. This is an obvious point and actually supports our argument rather than refuting it.
Define the cytogenetic outcome other than being an `abnormal karyotype'. We have stated that it was impractical to do much more than that, simply because the clinical data on all the abnormalities are not available. The implications, for example, with ultrasound abnormalities are far different depending upon what those abnormalities happen to be. The authors argue that, maybe only 1/3 as opposed to 1/2 of non-13, 18, or 21 abnormalities would have `direct clinical significance'. Thus, the actual risk of missing a clinically significant abnormality in light of a negative FISH is perhaps less, and suggests that in the absence of ultrasound findings is probably <1%. Thus, reliance upon just FISH certainly is reasonable in high risk situations such as high order multiples in which a multifetal pregnancy reduction is about to be performed, pending genetic analysis.
The authors state we did not say what percentage of cases ended in termination. We do not have these data, but believe this is irrelevant. Prenatal diagnosis is for patient information, and what couples choose to do with that information is their business. We have previously reported wide variation in what couples choose to do with abnormalities, both cytogenetic and ultrasound.
The authors state that we argue that abnormal karyotypes, even if they are `of no consequence with respect to the phenotype of the fetus will be of importance to future genetic counselling'. They further state that it is `a matter of debate whether ascertained families for genetic counselling in itself should be a goal of prenatal diagnosis programmes'. We are flabbergasted by this statement. The goal of prenatal diagnosis programmes is to provide genetic information to parents, not only about their pregnancy but also about their future reproductive issues. We believe that taking the approach that `if it isn't in front of you, it doesn't matter' is simply shortsighted and unacceptable. The authors cite the case of confined placental mosaicism. We know, for example, that confined placental mosaicism can have profound effects in the management of pregnancy, including intra-uterine growth retardation, and risks of fetal compromise. As obstetricians (which many of us are in addition to being geneticists), we find this information to be extremely useful.
The authors argue that our economic analysis is flawed because the saved money could be used for other things like getting more patients screened by ultrasound. We argue that history shows that saved money from one element of a programme seldom gets used to support other elements.
We agree that both sides have used the assumption that the FISH would be 100% and that there would be no false negatives. Clearly this is not the case in reality, but this fact only strengthens our argument that as a general proposition FISH should be an adjunct to karyotype and not a replacement of one. Perhaps in the near future when detailed, molecular chromosome probes are available for the entire genome, the karyotype as we know it may disappear. Until such reliability and technology are developed, we believe the karyotype must remain the gold standard except in highly unusual circumstances. Lastly, we agree with Van der Smagt et al. that further large prospective studies evaluating interphase FISH use for routine prenatal diagnosis are needed to resolve some of the issues raised by our study.
Notes
1 To whom correspondence should be addressed 
References
Evans, M., Henry, G., Miller, W. et al. (1999) International, collaborative assessment of 146 000 prenatal karyotypes: expected limitations if only chromosome-specific probes and fluorescent in-situ hybridization (FISH) were used. Hum. Reprod., 14, 1213–1216.
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