CONCENTRATIONS OF FREE ESTRADIOL AND PROGESTERONE IN HUMAN PREOVULATORY FOLLICULAR-FLUID

This study describes the distribution, based on computer calculations, of the total concentration of oestradiol (E2) and progesterone (P4) between a free and a protein-bound fraction in each of 98 preovulatory follicular fluids (FF). The FFs were obtained from 30 women undergoing in-vitro fertilization-embryo transfer (IVF-ET) treatment. The concentrations of free and total steroid were correlated to oocyte cleavage and establishment of pregnancies. In the FF, 4.3% of E2 was free, 1.5% was bound to sex-hormone-binding-globulin (SHBG), 94.2% to albumin and < 0.1% was bound to cortisol-binding-protein (CBP). The distribution of P4 in FF was 4.1% free, 5.6% bound to CBP, 90.3% bound to albumin and < 0.1% was bound to SHBG. These results demonstrate that albumin plays a central role in maintaining the concentration gradient of steroids between the preovulatory FF and the circulation. The concentration of free E2 in fluid from follicles in which the oocyte cleaved was significantly lower in patients who achieved pregnancy (133 +/- 9 nM) (+/- SEM) than in fluid from follicles in which the oocyte cleaved but where the patient did not become pregnant (169 +/- 13 nM: P < 0.05). Comparing the same two groups, the total concentration of E2 was also significantly lower in FF from patients who became pregnant. By contrast, no such correlation was found for either the free or the total concentrations of P4 in FF. A positive correlation was found between the concentrations of free and total E2 (r = 0.94, P < 0.001) and between the concentrations of free and total P4 (r = 0.93,; P < 0.001). These results indicate that physiological events within the follicle may equally well be related to the free or the total concentration of E2 and P4.