The origin of serum progesterone during the follicular phase of menotropin-stimulated cycles

The study was designed to investigate the source of progesterone secretion during pituitary suppression and ovarian stimulation. It involved 416 women undergoing in-vitro fertilization (IVF) who were treated with gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) (group I), 139 women undergoing ovulation induction with HMG only (group II) and nine women who were diagnosed previously as late-onset adrenal hyperplasia and treated continuously with dexamethasone, in addition to ovulation induction (group III). During HMG treatment, serum oestradiol and progesterone were measured every 1-2 days. If progesterone concentration exceeded 3.0 nmol/l, at least 36 h before human chorionic gonadotrophin (HCG) administration, the patients were prospectively randomized to treatment with dexamethasone or not and the hormones concentrations were measured again 12 h later. Mean age and pretreatment serum concentrations of dehydroepiandrosterone sulphate, androstenedione, testosterone and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, were not significantly different in the patients with and without progesterone elevation. Pituitary down-regulation did not reduce the incidence of progesterone elevation (13.9 and 12.2% in groups I and II respectively), while in group III, progesterone concentrations did not increase. After dexamethasone administration a significant decrease in serum progesterone concentration was demonstrated (mean +/- SD, -2.1 +/- 1.4 and -1.6 +/- 1.2 in groups I and II respectively, while in the untreated patients it increased (+1.9 +/- 1.9 and +4.2 +/- 4.8). The increase in serum progesterone concentrations was not accompanied by an increase in cortisol and 11-deoxycortisol but by an increase in LH. After dexamethasone administration the concentrations of cortisol, 11-deoxycortisol and LH significantly decreased. Progesterone concentration was positively correlated with both oestradiol concentration (r = 0.290; P < 0.05) and the number of oocytes retrieved (r = 0.207; P < 0.05). We conclude that at least a part of serum follicular-phase progesterone appears to be of adrenal origin. High oestrogen concentrations (or other ovarian factors) may cause changes in the hypothalamic-pituitary-adrenal axis and in adrenal enzyme activity as a part of the complex 'cross-talk' between the hypothalamic-pituitary-ovarian and the hypothalamic-pituitary-adrenal axes.