THE FOLLICLE-STIMULATING-HORMONE (FSH) THRESHOLD WINDOW CONCEPT EXAMINED BY DIFFERENT INTERVENTIONS WITH EXOGENOUS FSH DURING THE FOLLICULAR PHASE OF THE NORMAL MENSTRUAL-CYCLE - DURATION, RATHER THAN MAGNITUDE, OF FSH INCREASE AFFECTS FOLLICLE DEVELOPMENT/

According to the threshold concept, FSH concentrations need to surpass a distinct level to stimulate ovarian follicle growth. The window con cept stresses the significance of a limited duration of elevated FSH l evels above the threshold for single dominant follicle selection. The aim of this study was to investigate effects on follicle growth of inc reased FSH levels, differing in duration and magnitude of elevation, d uring the follicular phase. Twenty-three normo-ovulatory (cycle length , 26-31 days), young (age, 20-31 yr) women volunteered for this study. In all subjects a series of daily transvaginal sonography scans of th e ovaries and blood sampling [for FSH and estradiol (E-2) determinatio ns] were performed during two consecutive cycles. The first study cycl e (control cycle) star ted 10 days after urinary assessment of the LH surge in the preceding cycle (Day(LH)) and was concluded on the day of ovulation assessed by transvaginal sonography scans. The second serie s of daily monitoring (intervention cycle) started 10 days after Day(L H) in the control cycle. After randomization, subjects received either 375 IU urinary FSH, sc, as a single injection on Day(LH+14) (group A; n = 11) or 75 IU daily from Day(LH+19) until Day(LH+23) (group B; n = 12). In group A, FSH levels increased on the day after injection to a median concentration of 10.1 IU/L, which was 1.9 times higher (P < 0. 01) than levels on matching days during the control cycle. Concentrati ons returned to basal levels 3 days after injection. In group B, a mod erate elevation of FSH concentrations (15% increase; P < 0.05) was obs erved compared to levels during the control cycle. In group A, E-2 con centrations increased (P = 0.03) 1 day after FSH injection and returne d to baseline levels within 2 days. In group B, E-2 levels started to increase after the first injection of FSH and remained significantly h igher (P < 0.01) during the following 5 days compared to those on matc hing days in the control cycle. Compared to matching days in the contr ol cycle an increased number of follicles 8-10 mm in size was found in group A (P < 0.01) during the period from Day(LH+4) until Day(LH+19), without an increase in follicles 10 mm or larger thereafter. In contr ast, in group B, the numbers of both 8- to 10-mm and 10-mm or larger f ollicles were higher during the period from Day(LH+19) until Day(LH+24 ) in group B (P = 0.02 and P < 0.01, respectively). Results from the p resent study suggest that a brief, but distinct, elevation of FSH leve ls above the threshold in the early follicular phase does not affect d ominant follicle development, although the number of small antral foll icles did increase. In contrast, a moderate, but continued, elevation of FSH levels during the mid to late follicular phase (effectively pre venting decremental FSH concentrations) does interfere with single dom inant follicle selection and induces ongoing growth of multiple follic les. These findings substantiate the FSH window concept and support th e idea of enhanced sensitivity of more mature follicles for stimulatio n by FSH. These results may provide the basis for further investigatio n regarding ovulation induction treatment regimens with reduced compli cation rates due to over-stimulation.