BMJ, doi: 10.1136/bmj.38498.669595.8F, (Published 28 June 2005)

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Selective chromosome analysis in couples with two or more miscarriages: case-control study

Maureen T M Franssen ^1*, Johanna C Korevaar ², Nico J Leschot ³, Patrick M M Bossuyt ², Alida C Knegt ³, Klasien B J Gerssen-Schoorl ⁴, Cokkie H Wouters ⁵, Kerstin B M Hansson ⁶, Ron Hochstenbach ⁷, Kamlesh Madan ⁸, Fulco van der Veen ¹, Mariette Goddijn ¹

¹ Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, Netherlands
² Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam
³ Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam
⁴ Department of Clinical Genetics, University Hospital Groningen, Groningen
⁵ Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam
⁶ Department of Clinical Genetics, Leiden University Medical Centre, Leiden
⁷ Department of Clinical Genetics, University Medical Centre Utrecht, Utrecht
⁸ Department of Clinical Genetics, VU Medical Centre, University of Amsterdam

^* Correspondence to: maureen.franssen{at}planet.nl.

Objective To identify additional factors, such as maternal age or factors related to previous reproductive outcome or family history, and the corresponding probability of carrying a chromosome abnormality in couples with two or more miscarriages.

Design Nested case-control study.

Setting Six centres for clinical genetics in the Netherlands.

Participants Couples referred for chromosome analysis after two or more miscarriages in 1992-2000; 279 carrier couples were marked as cases, and 428 non-carrier couples served as controls.

Main outcome measures Independent factors influencing the probability of carrier status and the corresponding probability of carrier status.

Results Four factors influencing the probability of carrier status could be identified: maternal age at second miscarriage, a history of three or more miscarriages, a history of two or more miscarriages in a brother or sister of either partner, and a history of two or more miscarriages in the parents of either partner. The calculated probability of carrier status in couples referred for chromosome analysis after two or more miscarriages varied between 0.5% and 10.2%.

Conclusions The probability of carrier status in couples with two or more miscarriages is modified by additional factors. Selective chromosome analysis would result in a more appropriate referral policy, could decrease the annual number of chromosome analyses, and could therefore lower the costs.

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(Accepted 23 May 2005)
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