Infertility reversed by glucocorticoids and full-term pregnancy in a couple with previously undiagnosed nonclassic congenital adrenal hyperplasia

Objective: To report the case of a couple with infertility and two unsuccessful previous attempts of ovarian stimulation for in vitro fertilization (IVF), whose nonclassic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (21-OHD) was diagnosed and verified by molecular studies. Design: Case report. Setting: Outpatient practice and academic hospital. Patient(s): A woman with hyperandrogenism, luteal phase deficiency, and polycystic ovaries, and a man with oligospermia, a high rate of abnormal forms of spermatozoa (>95%), decreased sperm motility, and normal testicular volume. Intervention(s): Ultrasonography, semen analysis, endocrinologic assays, corticosteroids. Main Outcome Measure(s): Increased basal and adrenocorticotropic hormone (ACTH) stimulated 17α-hydroxyprogesterone (17-OHP) values were detected in both partners. CYP21A2 genotyping revealed compound heterozygosity in both wife and husband (wife: p.P30L/p.P453S; husband: p.P453S /p.V281L). Result(s): Hydrocortisone, 30 mg/day orally, was administered to both wife and husband. Forty days later, a pregnancy was detected. The prospective mother continued to receive hydrocortisone (25 mg/day) adjusted according to her hormone status. After a full-term uneventful pregnancy, a completely normal female was born. The baby had NC-CAH (genotype p.P30L/p.V281L). Conclusion(s): Nonclassic congenital adrenal hyperplasia, a potential cause of infertility in couples, can be successfully treated with corticosteroids. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc

CYP21A2 mutations in women with polycystic ovary syndrome (PCOS)

The question of the contribution of CYP21A2 heterozygosity to the development of polycystic ovary syndrome (PCOS) has repeatedly been raised in the literature. The available data, however, do not offer a satisfactory answer. The discrepancy must be attributed, primarily, to the small number of subjects in the various studies, the type of selected phenotype, and the number of searched mutations. The aim of the study was to define the contribution of CYP21A2 heterozygous mutations to the pathogenesis of PCOS. We searched for 14 molecular defects of the CYP21A2 gene in 197 PCOS women, employing allele specific PCR. Androgen levels were determined at baseline by appropriate methodology in the follicular phase. PCOS women with 17-hydroxyprogesterone (17OHP) basal values >2 ng/ml and/or post-ACTH >10 ng/ml were excluded. Appropriate controls were included. The frequency of the CYP21A2 heterozygous mutations in PCOS women and in controls was 7.6% and 5.9%, respectively [p-value (PCOS vs. controls): 0.663]. Homozygosity for CYP21A2 gene defects was not detected. In conclusion, the contribution of CYP21A2 heterozygous mutations to the pathogenesis of PCOS is not substantiated by our data. Moreover, 17-hydroxyprogesterone values of < 10 ng/ml post-ACTH exclude homozygosity of CYP21A2 mutations. © Georg Thieme Verlag KG Stuttgart · New York