Lupron, Ganirelix, Cetrotide
GnRH Agonists (Lupron)
Lupron is a fertility drug that was originally introduced for the treatment of prostate cancer in men and then for the treatment of endometriosis in women. Endometrial cells are dependent upon the hormone estrogen for growth and support. Lupron works by initially stimulating but then ultimately (after 10-12 days of therapy) inhibiting the production of gonadotropin releasing hormone (GnRH). This “down regulation” leads to reduced release of FSH and LH and thus lower estrogen levels.
Lupron is usually used in FSH ovarian stimulation cycles for IVF because it allows the physician to “control” follicular development and precisely time ovulation. The patient receives Lupron according to several treatment protocols that vary dependent upon factors such as age, FSH levels and desired timing. Lupron treatment results in lower levels of FSH and LH. This fertility drug prevents the LH surge and thus prevents premature release of the eggs.
External FSH (Repronex, Menopur, Bravelle, Follistim, or Gonal-F) is administered to cause follicular recruitment and development. Follicular development is monitored using transvaginal ultrasound and estradiol hormone measurements. If too few follicles are recruited, or they are developing “poorly”, the dosage of FSH will be increased. Estrogen levels are monitored to ensure that “quality” follicles are developing and to prevent the potentially serious side effect, ovarian hyperstimulation syndrome (OHSS).
A very important aspect of Lupron administration is that a patient will not usually ovulate while on this fertility drug (after the initial suppression phase). This is because the “spike” in LH production that normally causes ovulation is inhibited by Lupron. The physician can time ovulation based upon follicular maturity and schedule the egg retrieval accordingly. hCG injections are given in this case to mimic the LH surge and provide ideal timing. If the patient were not taking Lupron, she could ovulate “early”, before the eggs are retrieved, resulting in a “lost or cancelled” cycle.
Essentially, Lupron induces a temporary, reversible, menopausal state that leads to all of the side effects seen in the menopause including hot flashes, mood swings, etc.
The effects of these fertility drugs are similar to Lupron and they are specifically indicated and FDA approved for use in assisted reproductive technology cycles. The difference between Lupron and these products is that Lupron works by initially stimulating and then ultimately inhibiting the release of FSH and LH (by of process of down regulation of the receptors) whereas Ganirelix and Cetrotide work by immediately blocking GnRH’s effects at the pituitary gland (blocks the receptors). This blockade causes a more complete down regulated state (lower FSH and and LH levels) than does Lupron.
This “stronger down regulation” means that it is sometimes necessary to administer more FSH than if the patient were on Lupron to achieve the desired follicular recruitment and development. GnRH antagonists are typically started after the follicles have reached 14-15 mm in size (5-7 days after starting FSH injections).
Thus, Ganirelix and Cetrotide are also usually given for shorter periods. As with Lupron, an injection of hCG or LH is needed to initiate the “final maturation and ovulatory sequence” prior to egg retrieval. Usually 30-40 days of Lupron injections are needed while only 3-5 days of GnRH antagonist injections are needed. The GnRH antagonists are more expensive but because they are only used for a few days, the overall cost is similar.