In vivo ovarian responses to recombinant follicle-stimulating hormone (FSH) with and without recombinant luteinizing hormone (LH) in polycystic ovary syndrome (PCOS).

Abstract

Objective: To contrast the effects of recombinant FSH (rFSH) with the added effects of recombinant LH (rLH) in a 1:1 ratio on ovarian secretion of 17α-hydroxyprogesterone (17OHP), androstenedione (δ4) and testosterone (T) in women with PCOS during ovulation-induction. Design: Prospective, controlled study in a University-based fertility centre. Materials/Methods: Forty-eight clomiphene-resistant women with PCOS were allocated to receive either daily injections of rFSH (n = 24) or rFSH+LH (n = 24) in a 1:1 ratio starting: 1) on day 2–3 of progestogen-induced menses (n = 8); 2) after 6 weeks of GnRH agonist treatment (nafarelin, 400 μg b.i.d; n = 8); or 3) after nafarelin treatment as in (2) plus dexamethasone (n = 8). After the initial 5-day fixed gonadotropin regimens, the dosage was adjusted according to serum E2 levels and follicle size and number on transvaginal ultrasound assessment. hCG was given [Congruent]24 hours after the last gonadotropin dose to trigger ovulation when the E2 levels were 2000 pg/ml and at least 1 leading follicle ≥15 mm (mean diameter) was seen on ultrasound examination. Between-regimen and within-subgroup interactions in serum levels of LH, 17OHP, δ4 and T were evaluated by ANOVA with specific treatment days as a repeated measures factor. Results: Pre-study hormone levels were similar for all groupings. Nafarelin significantly suppressed LH levels, which remained at the lower limit of assay sensitivity (0.5 IU/L) during stimulation with rFSH but increased significantly to >1 IU/L when rLH was added. Independent of exogenous rLH treatment, there was a small, but uniform increase in 17OHP, δ4 and T levels in the pre-ovulatory period. As expected, a greater increase occurred in subjects on rFSH + rLH. Dexamethasone further suppressed 17OHP, δ4 and T levels and unmasked a small, but significant rise in these ovarian steroids 24 hours following the first dose of rFSH + rLH, a rise that was absent with rFSH alone. Secretion of these steroids then appeared to “catch-up” after 5 days of rFSH stimulation. Conclusions: The differing secretion patterns would suggest greater reliance on compensatory paracrine mechanisms in production of these steroids when only rFSH is given following pituitary/adrenal suppression. Ideal ranges for LH levels during gonadotropin treatment remain to be explored but suppression of LH to suboptimal levels may increase the vulnerability of some of the processes involved in follicle development in the in vivo setting. Supported by: This work was supported by a research grant from the University of Alberta and Hospitals and Serono Canada Inc.