FSH FERTILITY DRUGS
FSH causes the recruitment, and supports the development, of the ovarian follicles, which contain an egg each. The pituitary gland produces FSH after it is stimulated with gonadotropin releasing hormone (GnRH). Injectable FSH is used in assisted reproductive technology cycles, usually for 7-10 days, to stimulate the recruitment and development of multiple eggs, which are needed for procedures such as IVF and IVF/ICSI.
Patients undergoing ovulation induction with FSH are carefully monitored using vaginal probe ultrasound and E2 hormone measurements to check follicular development and avoid serious side effects. The ultrasound determines follicle size and count. It is also used to assess the thickness of the endometrium (lining of the uterus). If the lining is thin, it may indicate a hormonal problem.
The most severe adverse effect associated with FSH products is ovarian hyperstimulation syndrome (OHSS), which occurs in approximately 1% if cases. These drugs must always be administered by a specialist (reproductive endocrinologist) thoroughly trained in their use.
Once the ovarian follicles mature, the hypothalamus signals the pituitary gland to release a surge of luteinizing hormone (LH). The LH surge is responsible for initiating ovulation of the mature eggs. The ovary responds to an injection of human chorionic gonadotropin (hCG) in the same manner as LH, thus ovulation will occur after an injection, or spike, of hCG.
hCG is available as Pregnyl, which is natural product, derived from placental tissue. hCG is also available as Ovidrel, which is pure r-hCG, manufactured using genetic recombinant technology.
Progesterone is a hormone that supports the development of the endometrium, which is the lining of the uterus. The endometrium must thicken and become more vascular to support the growth of a developing embryo. When the endometrium does not develop properly it is sometimes due to inadequate progesterone during the luteal phase, known as a luteal phase defect. When additional progesterone is needed it can be administered as an injection, vaginal troche, vaginal suppositories and oral micronized capsules.
Once a woman becomes pregnant, the pituitary gland increases the production of prolactin, which is known as the “breast milk” hormone. As the name implies, prolactin is responsible for stimulating the production of breast milk in pregnant women.
When the prolactin level is elevated in women who are not pregnant, the condition is known as hyperprolactinemia, which can lead to irregular, or no ovulation. In some cases, hyperprolactinemia is caused by a small non-malignant tumor within the pituitary gland. When a tumor is present, surgical removal is usually the “first line” treatment. In other cases, the fertility drug bromocriptine is administered to medically lower prolactin levels.
The fertility drug letrozole is as an aromatase inhibitor and is used to induce ovulation. Letrozole is used in women who do not ovulate or in women with unexplained infertility. It works by blocking the enzyme that converts androstendione and testosterone to estrone and estradiol.
A proposed mechanism of action. Its effects mimic those seen when clomiphene citrate is administered. By lowering circulating estrogen it will release the hypothalamus from the negative feedback of estrogen causing an increase in GnRH (Gonadotropin releasing hormone) which leads to an increase in FSH (Follicle stimulating hormone) and LH (luteinizing hormone) secretion. The secretion of these two hormones stimulates the growth of ovarian follicles.
A second mechanism of action of letrozole in promoting ovulation is increased ovarian follicle sensitivity to FSH. Letrozole has also been shown to not have the adverse effects on the endometrium and cervical mucus that are typically seen with Clomid. Side effects from letrozole are rare but hot flashes, headaches, and leg cramps have been reported.
(GnRH Agonist), Ganirelix, Cetrotide (GnRH antagonist)
In order for ovulation to occur, the hypothalamus must signal the pituitary gland to release a surge of LH. This cannot occur while a patient is taking Lupron, Ganirelix or Cetrotide because the action of GnRH on the pituitary is blocked. This is the primary reason these drugs are used as adjuvant to control the assisted reproductive technology (ART) cycles. Ovulation must not occur prior to egg retrieval or the stimulation cycle would be “lost”. When the eggs are mature an injection of hCG (the body reacts to hCG like LH) is given and retrieval is scheduled.
Lupron (Lucrin), a commonly used fertility drug, works by competing with receptors at the hypothalamus while Cetrotide and Ganirelix work to directly block GnRH at the pituitary. Since Ganirelix and Cetrotide block GnRH, they produce a more profound, and quicker, down regulation. Patients undergoing ovulation induction with the fertility drug FSH must come to our office regularly for estradiol hormone measurements and ultrasound evaluation.