IVF Drug Treatment Protocols

Fertility drugs used to superovulate the ovaries by causing the production of numerous follicles may be given in a variety of combinations, which are called protocols. The physician determines the individualized specific treatment protocol for each patient. The following information describes the standard or initial protocol used for the majority of patients. Each patient’s protocol is individualized and may vary from the standard.

Standard IVF Protocol

With the standard IVF protocol, four types of fertility drugs may be given:

  1. Lupron: a gonadotropin-releasing hormone (GnRH) antagonist, which acts on the pituitary gland to inhibit gonadotropin (FSH and LH) secretion and prevent premature ovulation. Ganirelix is a GnRH agonist and may be used instead of Lupron to control ovulation timing.
  2. Progesterone:  helps supports endometrial development and maintain early pregnancy.
  3. Gonadotropins:   medications consisting of FSH alone or combined FSH/LH. They directly act on the ovaries to stimulate the development and maturation of the eggs
  4. Human chorionic gonadotropin (hCG):  known commercially as Pregnyl or Ovidrel, these medications act directly on the ovaries to cause the release of eggs from the ovarian follicles.

Down Regulation With Lupron

In order to optimize the stimulation of the ovaries, a fertility drug called Lupron is given starting one week before the expected period, on cycle day 21 of a 28-day cycle. Alternately, if instructed to initiate oral contraceptive pills (OCPs), then Lupron is administered beginning on day 14. Lupron acts by suppressing two hormones made in the pituitary gland, which normally cause the ovary to develop follicles and release eggs.

By suppressing these two hormones (follicle stimulating hormone (FSH) and luteinizing hormone (LH)), the ovaries should be quiet. They will not recruit eggs or produce the ovarian hormone called estradiol. Down regulation or ovarian suppression with Lupron allows the physician to have greater control over ovarian stimulation, which provides for an even growth of ovarian follicles and prevents a condition known as premature luteinization. This is a premature attempt by your body to ovulate.

Lupron is administered subcutaneously, meaning underneath the skin and not into the muscle. This medicine is typically injected into the thigh and is easily self-administered. Lupron is usually given 10 to 14 days before ovarian suppression occurs, but may also be given earlier without affecting the ovarian stimulation. Approximately 10 percent of patients require longer than 10 to 14 days of Lupron to completely suppress the ovaries. The Lupron dose will typically be reduced by half once the stimulation phase of the cycle begins.

Ganirelix Acetate/Cetrotide

Ganirelix and Cetrotide are both gonadotropin releasing hormone (GnRH) antagonists that suppress the pituitary gland’s LH secretion by binding to the GnRH receptor. These act immediately to suppress pituitary LH secretion to prevent premature ovulation. Depending on the patient, the physician may decide to use one of these medications in place of Lupron.
Ganirelix Acetate or Cetrotide is usually started after ovarian stimulation has begun, typically around stimulation day 6, or when the lead follicles are approaching 12 mm in mean diameter. Ovulation triggering is handled similarly to a Lupron cycle.

Ovarian Stimulation

A menstrual period should begin within 7 to 14 days from starting the Lupron injections. The clinic should be notified when the period starts so that a baseline ultrasound and blood estradiol test can be scheduled. The purpose of these tests is to confirm that the Lupron has successfully suppressed the ovaries to a baseline state.

Suppression means that the ovaries should contain no follicles that are greater than 15 mm in size, and the blood estradiol level should be less than 50 pg/ml. In approximately 10 to 15 percent of patients, one or both of these conditions are not met. Depending upon the results of these tests, the Lupron medication may be extended for another week and the patient may be asked to return for another sonogram and blood estradiol test. Occasionally an ovarian cyst aspiration may be performed for a persistent ovarian cyst.

After ovarian suppression has been achieved, ovarian stimulation using gonadotropin fertility drugs may commence at a scheduled time, which is referred to as the cycle start. These gonadotropin fertility drugs are continued throughout the stimulation phase of the cycle, that is, until hCG is administered.

The dose of gonadotropins will be based upon age, weight, number of follicles, cycle day 3 FSH and estradiol levels, and the response to previous stimulation cycles. The initial dose of medication will be taken for 2-3 days before returning to the clinic in the morning for an estradiol blood test. The dose of medication may be changed based upon the level of estradiol. Medication will usually be taken for two more days before for another estradiol blood test. Sonograms are conducted starting on day 6 or 7 of the stimulation. In general, return follow-up sonograms and estradiol blood tests occur every one to three days to monitor the growth of the follicles. Patients will be asked to return more frequently toward the end of their ovarian stimulation. Most people require eight to 12 days of ovarian stimulation, thus necessitating four to six sonograms and estradiol blood tests.

Ovulation Triggering (hCG)

When the follicles have met the criteria that indicate the eggs are mature, patients are instructed to administer hCG (Pregnyl or Ovidrel). In general, at least two follicles with a mean diameter of at least 18 mm and an appropriate estradiol level must be present before hCG is administered. Usually 5,000 to 10,000 units of hCG will be injected 36 hours before the planned oocyte retrieval. For example, Pregnyl or Ovidrel will be injected at 7:00 p.m. Monday evening, so that oocyte retrieval can occur at 7:00 a.m. Wednesday morning. Gonadotropins and Lupron/Ganirelix are discontinued after the hCG injection.

Administration of hCG is commonly called follicle triggering. The purpose of this medicine is to induce the final stages of oocyte maturation and the release of the eggs by the ovary. Timing the administration of this medication is extremely important and the physician/nurses instructions must be followed exactly.

Review Typical IVF Protocols: