Familial partial 17,20-desmolase and 17α-hydroxylase deficiency presenting as infertility

Purpose: Females with 17alpha-hydroxylase/17,20-desmolase deficiency normally present with amenorrhea, sexual infantilism, hypertension, and hypokalemia. We report on a new clinical presentation of this combined enzymatic defect. Methods: Four Jewish women from two unrelated families presented with primary infertility. All patients exhibited a normal phenotype, blood pressure, and serum potassium levels, with abnormally high follicular phase serum progesterone and low E-2 levels. In order to characterize the underlying defect, the following steps were undertaken: 1) ovarian suppression by GnRH agonist, 2) adrenal suppression by dexamethasone, 3) ovarian stimulation by gonadotropins, 4) adrenal stimulation by ACTH, 5) hormonal assessment of follicular fluid aspirates, and 6) assessment of in vitro E-2 production by luteinized granulosa cells. Results: The clinical characteristics and endocrine testing results support the diagnosis of a partial deficiency in 17alpha-hydroxylase/17,20-desmolase activities, shared by the adrenal gland and the ovaries. Conclusions: Female infertility can be the first and sole clinical manifestation of this enzymatic defect. Its exact nature and prevalence remain to be determined.