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.

Molecular defects of the CYP21A2 gene in Greek-Cypriot patients with congenital adrenal hyperplasia.

BACKGROUND/AIM: To determine the mutations in the CYP21A2 gene in Greek-Cypriots with congenital adrenal hyperplasia (CAH) and attempt a genotype-phenotype correlation. SUBJECTS AND METHODS: Molecular analysis was performed by multiplex ligation-dependent probe amplification and direct sequencing of PCR products of the CYP21A2 gene in 32 CAH patients. RESULTS: The most frequent genetic defect in the classic salt-wasting and simple virilizing forms was the IVS2-13A/C>G (55%) mutation, followed by Large lesion (20%) and in the non-classical form, the p.V281L (79.5%). Genotypes were categorized in 4 mutation groups (null, A, B and C). All 3 patients in the null group manifested the salt-wasting form and all 6 patients in mutation group A presented with the classical form. One patient in group B had the simple virilizing form and 22 patients in group C exhibited the non-classical form. CONCLUSION: The spectrum of mutations of the CYP21A2 gene in our population is comparable to the most common reported in similar ethnic groups. The knowledge of the ethnic specificity of the CYP21A2 mutations represents a valuable diagnostic tool for all forms of CAH.