Fertility in women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
OBJECTIVE
In contrast to subfertility often reported in women suffering from the classical form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, fertility in nonclassical CAH (NC-CAH) has been rarely studied. Our objective was to evaluate fertility in NC-CAH women.


METHODS
We studied 190 NC-CAH women (161 probands + 29 first degree relatives). Only 20 probands had consulted for infertility (12%), either alone or associated with hirsutism or menstrual cycle disorders. The diagnosis was established on post-ACTH 17-hydroxyprogesterone 10 ng/ml or greater and further characterized by CYP21A2 gene analysis.


RESULTS
Ninety-five of the 190 women wanted pregnancy (aged 26.7 +/- 8.9 yr); 187 pregnancies occurred in 85 women, which resulted in 141 births in 82 of them. Ninety-nine pregnancies (52.9%) occurred before the diagnosis of NC-CAH (96 spontaneously and three with ovulation inducers) whereas 98 occurred after diagnosis (11 spontaneously and 77 with hydrocortisone treatment); 83% of pregnancies were obtained within 1 yr. The rate of miscarriages was 6.5% for pregnancies obtained with glucocorticoid treatment vs. 26.3% without. Two of the 141 infants (1.5%) were born with classical CAH.


CONCLUSIONS
Subfertility is mild in NC-CAH. However, the rate of miscarriages is lower in pregnancies occurring with glucocorticoid treatment and argues for treating NC-CAH women wanting pregnancy. In addition, considering the high rate of heterozygotes for CYP21A2 mutations in the general population, it is essential to genotype the partner of patients with a severe mutation to predict the risk of classical CAH and offer genetic counseling.
Bidet
Maud
M
Department of Reproductive Endocrinology, Hôpital Pitié-Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.
Bellanné-Chantelot
Christine
C
Galand-Portier
Marie-Béatrice
MB
Golmard
Jean-Louis
JL
Tardy
Véronique
V
Morel
Yves
Y
Clauin
Séverine
S
Coussieu
Christiane
C
Boudou
Philippe
P
Mowzowicz
Irene
I
Bachelot
Anne
A
Touraine
Philippe
P
Kuttenn
F
F
D000022:Abortion, Spontaneous / Q000235:genetics; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D000328:Adult; D016009:Chi-Square Distribution; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007247:Infertility, Female / Q000209:etiology*; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
D005938:Glucocorticoids; D013255:Steroid 21-Hydroxylase