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Gonal-F, Follistim, Menopur and other injectable FSH products stimulate the ovarian follicles directly. Clomid stimulates the ovary indirectly via the hypothalamic-pituitary interactions. Externally administered FSH is physiologically identical to the FSH produced by the pituitary. Gonal-F and Follistim are made using genetic recombinant therapy and are identical to the bodies FSH in all respects.
FSH is administered by subcutaneous injection in conjunction with assisted reproductive technologies (IVF) and intrauterine insemination (IUI) where multiple eggs are needed. Multiple egg development occurs because of the stimulatory effect of FSH on the follicles. Some women who have very low FSH levels (hypogonadotropic) and functional ovaries have an excellent response to FSH resulting in high pregnancy rates. FSH is usually administered at home by the patient or her partner.
Some products, such as Repronex and Humegon, contain FSH and small amounts of leutinizing hormone or other impurities whereas Gonal-F and Follistim are pure FSH products made with recombinant DNA technology. There is debate as to which class of these products (pure FSH vs. FSH/LH) is the most effective. Many embryologists believe higher quality eggs are obtained from pure FSH cycles.
The most serious potential side effect of the gonadotropins is ovarian hyperstimulation syndrome (OHSS). In this condition, the ovaries become enlarged and there is a "shift" of body fluid into the abdomen and pelvic cavity after ovulation. The decrease in fluid resulting from this "shift" can reduce blood perfusion and result in clots and poor circulation to the internal organs. The best predictor of hyperstimulation is elevated estrogen levels. This is why estrogen levels must be monitored in women undergoing ovulation induction with FSH. Fortunately, the incidence of OHSS is low (approximately 5%). This potential side effect in one reason that only highly trained infertility specialists should administer FSH.
Use of gonadotropins in IVF cycles significantly increases the chances of multiple births, usually twins. The incidence of higher order births is reduced when the drugs are properly administered and monitored. The incidence of twins is higher in stimulated IUI cycles because it is difficult to control the number of eggs ovulated. In fact, most high order multiple births reported in the media are due to stimulated IUI cycles.
FSH products should only be administered by a physician specially trained in their use. Much experience is required to become familiar with variable patient responses, interpret stimulation markers, adjust dosages, and prevent unwanted side effects. Reproductive endocrinologists undergo an additional two years of fellowship training after completing their OB/GYN residency to prepare them to safely use gonadotropins.
Lupron (leuprolide acetate), Ganirelix (Ganirelix Acetate), Cetrotide (cetrorelix acetate)
GnRH agonists (Lupron), interfere with the production of FSH and LH. Lupron is a GnRH agonist which works at the hypothalamus (a small gland located at the base of the brain ) whereas Ganirelix and Cetrotide are GnRH antagonists which completely block the effect of gonadotropin releasing hormone at the pituitary gland thus creating a "more complete "down regulation" and reduction in gonadotropin levels.
Leuprolide acetate is a long-acting GnRH analog. An injection of Lupron results in an initial stimulation followed by a prolonged suppression of pituitary gonadotropins. This action inhibits the release of pituitary gonadotropins and FSH, LH, and estrogen levels are lowered. Endometrial tissue is dependent upon the presence of estrogen for growth. When endometrial tissue enters the body cavity it can attach to organs such as the tubes and ovaries thus creating endometriosis. Since Lupron lowers estrogen levels is an effective treatment for endometriosis which depends upon estrogen for support and growth.
In in vitro fertilization cycles, Lupron, Ganirelix or Cetrotide is used to lower gonadotropin levels (FSH, LH) during the stimulation cycle. External FSH is administered by injection to replace that suppressed by the GnRH agonist or antagonist allowing for precise control of the stimulation cycle. These drugs are administered in different protocols dependent upon the patient's response. The amount of Gonal-F or Follistim required for a stimulation cycle is patient specific. In most cases more FSH is required in cycles where Ganirelix or Cetrotide is used. These drugs are administered until the eggs are mature and the retrieval is scheduled.
It is critical that ovulation not occur before egg retrieval in a stimulated IVF cycle. If ovulation does occur, the eggs cannot be retrieved and the IVF cycle is “lost”. LH is responsible for signaling the ovary to ovulate and is suppressed with Lupron, Ganirelix and Cetrotide until the physician judges that the eggs are mature. Once mature, an injection of hCG is given and the egg retrieval is scheduled.
GnRH agonists and antagonists have similar side effects and can include hot flashes, vaginal dryness, painful intercourse, headache, mood swings, fatigue, lowered libido, and insomnia. These side effects mimic the symptoms induced by the menopause.
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