In a conventional Down-Regulation Protocol, the daily injection of GnRH agonist, such as Lupron, decreases FSH secretion. In theory, this protocol may recover the sensitivity of FSH receptors. Then, following high doses of Gonadotropin, such as Follistim, stimulation of follicles to grow should occur. Therefore, some doctors propose SLDR protocols (GnRH for 2-3 months, followed by high doses of gonadotropin stimulation) for patients with Primary Ovarian Insufficency (POF).
However, this SLDR protocol has no effect to severe cases of POF and only minimal effect to mild POF cases.
The prolonged pituitary suppression from daily GnRH agonist injections in SLDR protocols causes a lower serum FSH level, which causes the death of Granulosa cells in the follicles. Without adequate functional Granulosa cells in the follicle, no Ovarian Follicle growth will be observed even after high doses of FSH stimulation. Additionally, endogenous FSH (occurring internally, naturally) is secreted in a pulsatile (pulsating) pattern. Down regulation protocol suppresses this endogenous pattern; however, exogenous FSH or FSH/LH injections cannot mimic this pattern. Therefore, the SLDR protocol causes less follicle growth and risks poor egg quality.