Follicular Recruitment Although the inciting stimulus is unclear, cohorts of small antral follicles (<2 mm) become responsive to FSH stimulation only after 45 days of initial growth. They are then considered recruitable and begin to slowly enlarge in the late luteal phase of the cycle preceding ovulation. Once the antral follicle grows beyond 10 mm, FSH induces the appearance of LH receptors on the granulosa cells. At that point, somewhat contrary to the 2-cell2-gonadotropin model, LH can exert FSH-like actions on the granulosa cell, including stimulation of aromatase. With complete absence of endogenous LH, such as that seen with hypothalamic hypogonadism, exogenous FSH produces fewer preovulatory follicles, inadequate estradiol, lower ovulation rates, and thinner endometrium when compared to ovaries stimulated with exogenous HMG (FSH and LH). Therefore, in the setting of normal hypothalamic function, it seems likely that even with suppressive therapy, enough endogenous LH is present to synergize with exogenous FSH to provide adequate stimulation for recruitment (326).
Follicular Waves Seventy-five percent of unstimulated human menstrual cycles have two waves of follicular development: one major wave in which a dominant follicle is selected to the detriment of other follicles and one minor wave during which all follicles undergo atresia. When progesterone is available to block LH, the first wave is typically minor and occurs one day after ovulation in the previous cycle. The subsequent major wave occurs around the time of menses, with the dominant follicle being selected by its ability to reach a diameter of 10 mm by cycle day 6 or 7, which coincides with an estradiol rise that inhibits FSH. One-quarter of cycles will exhibit an additional wave that occurs 2 days prior to menses and may be minor or major. If the dominant follicle regresses or is removed, a new follicular wave begins 2 days later. In light of this, future efforts toward greater synchrony during stimulation might include ablation of the early dominant follicle using aspiration or administration of exogenous estrogen and progesterone during the follicular phase (333).