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Hum. Reprod. Advance Access originally published online on April 16, 2008
Human Reproduction 2008 23(7):1607-1613; doi:10.1093/humrep/den118
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Fertility and pregnancy outcome in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

K. Hagenfeldt1, P.O. Janson2, G. Holmdahl3, H. Falhammar4,5, H. Filipsson6, L. Frisén7, M. Thorén4,5 and A. Nordenskjöld5,8,9

1 Department of Women and Child Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden 2 Department of Obstetrics and Gynaecology, Sahlgrenska Academy, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden 3 Department of Paediatric Surgery, Sahlgrenska Academy, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden 4 Department of Endocrinology, Metabolism and Diabetes, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden 5 Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden 6 Department of Endocrinology, Sahlgrenska Academy, Sahlgrenska University Hospital, 41345 Göteborg, Sweden 7 Department of Clinical Sciences, Division of Psychiatry, Karolinska Institutet, Danderyd Hospital, 182 87 Stockholm, Sweden 8 Department of Pediatric Surgery, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden

9 Correspondence address. Fax: +46 8 517 73620; E-mail: agneta.nordenskjold{at}ki.se

BACKGROUND: Low pregnancy rate has been reported in women with congenital adrenal hyperplasia (CAH) and little information on pregnancy and children is known.

METHODS: In a Swedish study, 62 adult women with CAH, aged 18–63 years, and 62 age-matched controls were followed-up. Medical records, including those concerning pregnancies and deliveries, were examined and the 21-hydroxylase genotype of patients was noted. All women answered a questionnaire concerning sexual and reproductive health including health of the children.

RESULTS: Pregnancy and delivery rates were significantly lower in women with CAH (P < 0.001, P < 0.0056, respectively), and the severity of the 21-hydroxylase-mutation correlated with the reduced number of children born. More women with salt-wasting CAH were single and had not attempted pregnancy. Pregnancies were normal except for a significantly increased incidence of gestational diabetes in CAH patients (P < 0.0024). The children had normal birthweight and no malformations were observed. A later follow-up of the children showed a normal intellectual and social development. The sex ratio of the offspring differed significantly, with 25% boys in the CAH group compared with 56% among controls (P < 0.016). CAH women had more gynaecological morbidity during menopause.

CONCLUSIONS: Pregnancy and delivery rates are reduced in women with CAH mainly due to psychosocial reasons. The outcome of children did not differ from controls. The unexpected sex ratio in children born to mothers with CAH warrants further research.

Key words: congenital adrenal hyperplasia/21-hydroxylase mutation/pregnancy/sex ratio/gestational diabetes

Submitted on October 11, 2007; resubmitted on March 9, 2008; accepted on March 12, 2008.


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