Leuprolide acetate (Lupron) is a gonadotropin-releasing hormone (GnRH) agonist. In Assisted Reproductive Technology (ART), the “microdose” protocol uses a specific, low dosage almost exclusively during In Vitro Fertilization (IVF) cycles. This approach differs from the standard long-suppression Lupron protocol, which aims to temporarily shut down natural hormone production. The primary purpose of the microdose is to initiate a rapid, temporary surge of the body’s own reproductive hormones to enhance the ovarian response to subsequent medications.
The Dual Hormonal Effect
The microdose Lupron protocol exploits the initial stimulatory effect of the GnRH agonist, known as the “flare” effect. When a small, diluted dose of leuprolide is administered frequently, it initially overwhelms the pituitary gland’s receptors. This overstimulation causes the pituitary to release a large, immediate pulse of Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) into the bloodstream. This intense, short-lived surge is the intended therapeutic mechanism, acting as an internal “jump start” for the ovaries. The subsequent daily microdose injections continue alongside external injectable gonadotropins to maintain stimulation and prevent a premature LH surge and ovulation.
Achieving Synchronized Ovarian Stimulation
The goal of the microdose flare is to recruit a group of ovarian follicles to begin growth simultaneously. The surge of natural FSH and LH ensures that all follicles in the cohort develop at a synchronized pace. This synchronization is paramount in IVF because it increases the likelihood of retrieving multiple mature eggs in a single procedure. In a natural cycle, only one follicle becomes dominant, but the microdose flare, reinforced by injectable gonadotropins, overcomes this natural selection process. This coordinated growth ensures a greater number of follicles reach the desired size (17–20 mm) at the same time, maximizing the yield of mature oocytes for fertilization and embryo transfer.
Criteria for Patient Selection
The microdose flare protocol is selectively prescribed to specific populations who benefit from the initial hormonal boost. It is primarily recommended for patients classified as “poor responders,” defined as those who had a low egg yield (four or fewer oocytes) in previous standard IVF cycles. Patients with Diminished Ovarian Reserve (DOR), indicated by low Anti-Müllerian Hormone (AMH) levels or high basal FSH, are also strong candidates. The protocol is frequently advised for women of advanced reproductive age (38 years or older) because the flare effect maximizes the recruitment of their remaining follicles.
Administration Schedule and Common Effects
The microdose Lupron is administered via a small, subcutaneous injection, typically into the upper thigh or lower abdomen. The medication is usually diluted by a pharmacy and taken twice daily (morning and evening). This twice-daily dosing ensures constant, low-level exposure to the GnRH agonist, which maintains the flare effect and suppresses premature ovulation. Treatment often starts early in the menstrual cycle, such as on cycle day two, or after a short course of birth control pills. Frequent monitoring is required, involving transvaginal ultrasounds and blood tests, to track follicle growth and hormone levels. Side effects are generally mild but can include symptoms similar to Premenstrual Syndrome (PMS), such as headaches, mood swings, and hot flashes.