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RESEARCH: Maureen T M Franssen, Johanna C Korevaar, Fulco van der Veen, Nico J Leschot, Patrick M M Bossuyt, and Mariette Goddijn Reproductive outcome after chromosome analysis in couples with two or more miscarriages: case-control study BMJ 2006; 332: 759-763 [Abstract] [Full text]

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Cohort not case control study

Anna C Goodman   (3 April 2006)

Chromosomal analysis in couples with recurrent miscarriages should be stopped.

Willem Vlaanderen   (12 April 2006)

Cohort not case control study 3 April 2006
Anna C Goodman, MSc Student of Epidemiology SE21 7EA Send response to journal: Re: Cohort not case control study	This is an extremely interesting paper which I enjoyed reading, but the authors are wrong to describe as a ‘case control’ study what is in fact a cohort study. The authors have recruited couples on the basis of their exposure (whether or not they had unbalanced chromosomal abnormalities) and then followed them up for at least 2 years to record their reproductive outcomes. Presumably the reason for this confusion is that, as the authors report, for each ‘exposed’ couple (i.e. with a chromosomal abnormality) they recruited two ‘unexposed’ couples (i.e. without any chromosomal abnormality). This is different, however, from genuine case-control studies in which recruitment is made, and participants are defined, on the basis of their outcome status not, as in this case, their exposure status. Competing interests: None declared
Chromosomal analysis in couples with recurrent miscarriages should be stopped. 12 April 2006
Willem Vlaanderen, gynaecologist ret. Malden, 6581 CK Send response to journal: Re: Chromosomal analysis in couples with recurrent miscarriages should be stopped.	Editor, The results of the investigation from Franssen et al(1) are very interesting. Advising couples with recurrent miscarriage to have chromosomal analysis is generally recommended although hard evidence about its efficacy is scarce. Now the results of a very large group that has been screened during 10 years is presented and for the first time this evidence is available: screening seems to be almost useless. Almost 12000 couples have been tested, in which a structural chromosomal abnormality was found in 382 couples: 3,2%. From 500 viable pregnancies in this group only 4 cases of unbalanced chromosomal abnormality were found: 0,8 %. It means that the risk for such an event in the total group before screening is 3,2 times 0,8 is 0.025 %. The average risk for the birth of a child with serious congenital anomalies is about 2 %, so the contribution of the 0,025 % is extremely small. From the 4 cases 2 were discovered by prenatal diagnosis, the other 2 were found after birth. One of these 2 children did not survive. To prevent (at most) 2 cases of severe abnormality 12000 couples have been counseled and tested, hundreds of pregnant women had invasive prenatal examinations, at a cost of an enormous amount of time, energy and money (estimated at least at 20 million Euro) and probably some normal pregnancies being lost by the procedure. The most interesting result however is that the cumulative success rate for couples in the group with the chromosomal aberration is just as high ( 83%) as in the group with the same history without structural abnormality (84%). That should be the most important message to give to those couples. We have to say: “ Some people seem to have a bigger chance to get a miscarriage than others but it is a waste of time and money to try to find out why. The best advise we can give you is to continue your attempts to conceive. When you get another miscarriage don’t be to disappointed. Realize that almost all abortions are abnormal products of conception and nature is extremely efficient in weeding these out. Just try once more, your chances for a fine result are very high”. The authors have to be complimented with this very important piece of research. However they seem to be a bit reluctant to draw the only possible conclusion from their results: chromosomal investigation in couples with recurrent miscarriage is a waste of time and money, gives the wrong signal to the people involved, and should therefore be stopped. 1. Maureen T M Franssen, Johanna C Korevaar, Fulco van der Veen, Nico J Leschot, Patrick M M Bossuyt, and Mariette Goddijn Reproductive outcome after chromosome analysis in couples with two or more miscarriages: case-control study BMJ, Apr 2006; 332: 759 - 763 Competing interests: None declared