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Reproductive outcome after chromosome analysis in couples with two or more miscarriages: case-control study.

Franssen MT, Korevaar JC, van der Veen F, Leschot NJ, Bossuyt PM, Goddijn M

Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, Netherlands. maureen.franssen@planet.nl

OBJECTIVE: To compare reproductive outcomes in couples carrying a structural chromosome abnormality and non-carrier couples referred for chromosome analysis after two or more miscarriages. DESIGN: Case-control study. SETTING: Six centres for clinical genetics in the Netherlands. PARTICIPANTS: 278 carrier couples and 427 non-carrier couples referred for chromosome analysis between 1992 and 2000 after two or more miscarriages before 20 weeks of gestation. Couples were followed up for at least 24 months after chromosome analysis. MAIN OUTCOME MEASURES: The birth of at least one healthy child, at least one more miscarriage, and viable offspring with unbalanced chromosomal abnormalities after parental chromosome analysis. RESULTS: Mean follow-up after chromosome analysis was 5.8 years. 120 of 247 (49%) carrier couples had one or more miscarriage after chromosome analysis compared with 122 of 409 (30%) non-carrier couples (difference 19%, 95% confidence interval 11% to 26%; P < 0.01). The percentage of couples with at least one healthy child was not significantly different in carrier couples (83%) and non-carrier couples (84%) (difference -1%, - 7% to 5%). Among 550 pregnancies in carrier couples, two viable unbalanced chromosome abnormalities were detected at prenatal diagnosis (0.4%) and the fetuses aborted and two children with an unbalanced karyotype were born (0.4%). CONCLUSIONS: Couples whose carrier status was ascertained after two or more miscarriages have a low risk of viable offspring with unbalanced chromosomal abnormalities. Their chances of having a healthy child are as high as non-carrier couples, despite a higher risk of miscarriage.

Published 31 March 2006 in BMJ, 332(7544): 759-63.
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