High serum progesterone associated with infertility in a woman with nonclassic congenital adrenal hyperplasia

Abstract

Nonclassic congenital adrenal hyperplasia (NCAH) is an autosomal-recessive disorder caused by 21-hydroxylase deficiency and manifests as hirsutism and oligomenorrhea due to excess adrenal androgen and progesterone. We report a case of a woman with NCAH who showed continuous high serum progesterone levels in the follicular phase associated with impaired folliculogenesis. NCAH was diagnosed based on high 17-hydroxyprogesterone levels after rapid adrenocorticotropic hormone loading, and three heterozygous missense mutations in CYP21A2, encoding 21-hydroxylase, were identified. Recurrent failure of in vitro fertilization programs occurred because of empty follicles and preterm rupture of leading follicles, and vaginal stenosis with a hypoplastic cervix. Glucocorticoid administration normalized serum progesterone levels, restored folliculogenesis, and stretched the vaginal wall, which contributed to the success of the in vitro fertilization program. The patient delivered at term following blastocyst transfer. Correction of hyperandrogenism and high progesterone levels using glucocorticoids may improve fertility in women with NCAH.

Approaching fertility in congenital adrenal hyperplasia: exploring P30L mutation-induced 21-hydroxylase deficiency with a presentation between non-classical and simple virilizing phenotypes. A case report

“…Excess androgen hormones can inhibit folliculogenesis and interfere with normal gonadotropin secretion. Increased levels of adrenal-derived progesterone perturb the menstrual cycle, sperm penetration and folliculogenesis, leading to empty follicles, thin endometrium and implantation difficulties [ 15 , 16 ]. In the case presented by Kawarai et al [ 16 ] substitution with GCs reduced the persistently elevated levels of follicular-phase progesterone and led to the normal restoration of folliculogenesis.…”

Drug substitution and adjuvant therapy in patients with genetics related infertility: A review

“…Through androgen receptors, androgens may directly influence follicular development, while aromatase expression and oestrogen aromatization indirectly influence follicular development (42). The viability of fallopian tubes, endometrial receptivity, and cervical thickness are also impacted by higher progesterone levels, which have an impact on embryo implantation (43).…”

“…Due to their ability to control excessive androgen expression by blocking adrenocorticotropic hormone activation, glucocorticoids have been the primary treatment for CAH. In people with non-classic adrenal hyperplasia, studies have shown that glucocorticoids can increase fertility by lowering excessive levels of testosterone and progesterone (43). Ovulation dysfunction in CAH women and supplemention with glucocorticoids may help to induce ovulation.…”

Factors affecting oocyte quality in New Zealand dairy cows

“…Plasma progesterone concentrations were not significantly different between the groups but did tend to be highest in the Low-NonCYC group, co-incident with the lowest CYP21 expression levels. The adrenal gland is a major secondary source of progesterone and in humans, genetic mutations that reduce adrenal CYP21 enzymatic activity can result in elevated circulating progesterone (Wendorf et al 1983;Kawarai et al 2017). Reduced CYP21 mRNA expression in the Low-NonCYC cows may also have resulted in less enzymatic activity, causing a rise in circulating progesterone.…”

“…Interestingly, CYP21 expression was negatively correlated with plasma progesterone concentrations. The adrenal gland is a major secondary source of progesterone and mutations that reduce adrenal CYP21 enzymatic activity can result in elevated circulating progesterone (Wendorf et al 1983;Kawarai et al 2017). Reduced CYP21 mRNA expression in the Low-FBV cows with long PPAIs may also have resulted in less enzymatic activity, causing a rise in circulating progesterone.…”