Which Types of Drug Protocols Are Used In IVF, and How Is the Most Appropriate Protocol Selected?

Although several drugs and protocols are available to stimulate the ovaries to produce extra eggs for IVF, most clinics utilize only a few of these stimulation protocols.

One of the more common IVF protocols is called luteal suppression (or long luteal or simply just long) and involves suppression of the ovaries using a GnRHanalog (Lupron) during the luteal phase of the menstrual cycle preceding the planned IVF treatment cycle. Once the ovaries are suppressed, ovarian stimulation is accomplished with daily injections of gonadotropins (e.g., Gonal-F, Follistim). Lupron is usually continued until the day of the HCG trigger shot. A common variation of this protocol is to stop Lupron at the time of starting stimulation. Not surprisingly, this protocol is called “stop Lupron.”

Another common protocol is called flare stimulation. In this case, the woman does not take any medications until the second day of her menstrual cycle. At that time, a microdose (most commonly) of Lupron is used to “flare” the pituitary gland and induce it to release its store of FSH and LH. Simultaneously, gonadotropins are started, producing a “one–two punch” in terms of ovarian stimulation. Premature ovulation of the eggs rarely occurs despite the low dose of GnRH agonist utilized in this protocol.

A third, more recent option is GnRH-antagonist stimulation, in which GnRH antagonists are added later in the stimulation to prevent premature ovulation. In this method, the gonadotropins are started on cycle day 2 of a normal menstrual period. Once the follicles have reached a specific size (usually 12 to 14 mm), the woman begins the GnRH-antagonist medication, which almost instantaneously prevents the pituitary gland from generating an LH surge.

Some reproductive endocrinologists prescribe oral contraceptive pills to their female patients prior to beginning the actual ovarian stimulation drugs, but this practice varies between patients and fertility clinics. We have found that the use of birth control pills often results in oversuppression of the ovaries and cycle cancellation except in those patients known to be high responders (women with PCOS, in particular).

The type of protocol selected for any patient (i.e., luteal suppression, flare stimulation or GnRH antagonist) depends on the individual patient and the philosophy of the fertility clinic. Factors that may influence the type of stimulation protocol selected include the patient’s age, her day 3 hormone levels, her follicle antral count as determined by ultrasound, and her previous responses to any other attempts at ovarian stimulation.