Other Fertility Medications
Fertility drugs exist for a variety of reasons, but most work to correct, stimulate, or regulate ovulation.
Additional drugs used in Stimulation Cycles
- Lupron, Ganirelix, and Cetrotide
- Glucophage (metformin)
- Pregnyl, Ovidrel (Human Chorionic Gonadotropin, hCG)
- Parlodel (bromocriptine) and Dostinex (cabergoline)
- Birth control pills
Follicle stimulating hormone (FSH) and luteinizing hormone (LH) are hormones produced by the pituitary gland that control the recruitment and development of ovarian follicles, each of which contains one egg (oocyte). FSH and LH secretion are regulated by the hypothalamus in the brain. The hypothalamus releases another hormone, called gonadotropin releasing hormone (GnRH) that stimulates the pituitary to produce FSH and LH.
When a woman undergoes controlled ovarian hyperstimulation for an in vitro fertilization (IVF) cycle, fertility specialists want to control the pituitary gland so that natural production of FSH and LH do not interfere with the cycle. During controlled ovarian hyperstimulation, FSH is given by injection until the follicles are mature and ready for retrieval. In a natural cycle, the hypothalamus then signals the pituitary gland to release LH, thus initiating ovulation. This surge of LH must not occur in an IVF cycle before the eggs are retrieved or the cycle is “lost.”
Lupron is given during an IVF cycle to suppress the pituitary gland, thereby preventing an LH surge from interfering with the cycle. Lupron also essentially blocks the production of estrogen, which is why it is effective in treating endometriosis. Ganirelix Acetate and Cetrotide produce the same effects as Lupron, albeit by different mechanisms. These products are known as GnRH antagonists. They block the production of LH and FSH by the pituitary. Ganirelix Acetate and Cetrotide act more rapidly to block FSH/LH production compared to Lupron, and thus can be given in lower doses for shorter periods of time.
Since all of these products produce a down-regulated state (natural production of reproductive hormones is blocked), they produce side effects similar to menopause if taken for an extended time. These side effects can include hot flashes, mood swings, nausea, headaches and many others. See the manufacturer’s Website for detailed information.
Polycystic ovarian syndrome (PCOS) is a condition characterized by irregular or absent menstrual cycles due to oligo- or anovulation, as well as excess androgens (male hormones) that may lead to excess body hair. The ovaries of PCOS patients are typically covered with numerous small follicles, which are cysts that contain eggs. Many PCOS patients are overweight and usually find it very difficult to effectively diet. However, PCOS can also occur in thin women.
PCOS patients usually have elevated insulin levels (hyperinsulinemia) due to a condition known as insulin resistance. Insulin resistance occurs because the insulin receptors that are found in all the body’s cells are resistant to the hormone insulin. This means the insulin doesn’t function as efficiently as it should. The body tries to compensate for this by secreting more insulin, leading to elevated levels of the hormone.
Hyperinsulinemia causes the ovaries to over-produce androgens, leading to the classic symptoms of PCOS. Chronically elevated insulin levels may also increase the long-term health risk for diseases such as diabetes. Metformin belongs to a class of drugs known as “insulin-sensitizing agents,” and is routinely used to treat diabetes. It improves the effectiveness of insulin while maintaining or decreasing insulin levels. Once insulin levels are lowered, the corresponding production of androgens by the ovaries decreases. Natural ovulation will often resume once androgen levels are normalized.
Although Metformin is FDA-approved for diabetes, it is considered off-label when used by women with PCOS. Numerous studies have been published that support the use of metformin for women with PCOS. Although most of these studies to date have evaluated metformin usage in overweight women with PCOS, a few studies have supported the use for thin women as well.
Women with PCOS have an increased risk of having a miscarriage, and studies have shown Metformin effectively decreases this risk. Metformin usage alone has also been shown to induce ovulation and pregnancy in women with PCOS, without requiring further treatment. About 25 percent of women who do not have any other causes of infertility except for PCOS conceive with metformin usage alone.
PCOS patients who have failed to ovulate with Clomid may ovulate with a combination of Clomid and Metformin. PCOS patients are often managed by a reproductive endocrinologist/fertility specialist due to the complexity of the condition and variable responses to medications.
The normal ovulatory cycle consists of several stages, beginning with the recruitment and development of ovarian follicles followed by a surge of luteinizing hormone (LH). LH stimulates the maturation of eggs and induces ovulation or the release of the egg(s).
Human Chorionic Gonadotropin (hCG) is known as the “pregnancy hormone,” as it is only produced by the placenta during an established pregnancy. The body responds to hCG in the same manner as LH, because they are structurally and biochemically similar. Therefore, an injection of hCG, called an hCG spike or the trigger shot, will initiate ovulation approximately 36 hours later. During an IVF cycle, the LH surge is impaired due to the administration of the fertility drugs Lupron or Ganirelix Acetate that optimize synchronized follicular growth and prevent spontaneous premature ovulation. Due to this impairment of LH, hCG is given to mimic the LH surge resulting in the final maturation of and ultimately the release of the eggs from the ovary.
hCG comes in two forms, natural and “recombinant”. The first form (natural) is derived and highly purified from the urine of pregnant women. Pregnyl and Novarel are natural forms that are supplied as a refined powder (“lyophilized”) that can easily be reconstituted, and then injected either subcutaneously or intramuscularly. The second form, Ovidrel, is “pure” hCG, as it is manufactured using recombinant biotechnology. In this formulation, the genetic coding sequence for hCG is inserted into specialized cells in culture, and the specialized cells can then ‘make’ pure hCG. Ovidrel comes in a pre-filled syringe for subcutaneous injection.
Once the follicles reach the appropriate size, an injection of hCG is given and egg retrieval is scheduled. If a patient is undergoing intrauterine insemination (IUI) with oral medications or gonadotropins, the hCG injection is administered and the insemination is scheduled accordingly.
Luveris (lutropin alpha) is another medication that is manufactured using recombinant technology.The LH in Luveris is identical to the body’s own luteinizing hormone and is used to treat patients who have severe deficiencies of LH. Luveris is not used to induce ovulation because the half-life is too short to be effective.
Progesterone is a hormone that is essential for the proper development of the endometrium and the maintenance of pregnancy. During the ovulatory cycle, the endometrium must thicken and become more vascular and receptive to the implantation of an embryo.
Progesterone is secreted by the corpus luteum: the name given an ovarian follicle after the release of the egg. Elevated levels of progesterone are an indication that quality ovulation has occurred, and low levels can be associated with a condition termed as luteal phase defect. Although the best way to treat this condition is to improve follicular growth, many patients can benefit from the administration of additional progesterone.
In early pregnancy, up until approximately seven weeks, progesterone production is sustained entirely by the corpus luteum. After this time, progesterone is increasingly secreted by the placenta. It is essential to maintaining an ongoing pregnancy. Progesterone is always administered in IVF cycles because medications, including Lupron and Ganirelix Acetate/Cetrotide, interfere with the body’s natural production of progesterone. Progesterone is available as an injection, a vaginal suppository or gel, or oral-micronized capsules.
Read a Detailed Article on Progesterone Written by Dr. Chantilis. This Article Includes a Discussion of the Luteal Phase Defect.
Prolactin is the hormone responsible for stimulating breast milk production in pregnant women. When prolactin levels are abnormally elevated in a woman who is not pregnant, a condition called hyperprolactinemia, ovulatory irregularities can result. This may include the absence of ovulation and may be associated with the abnormal production of breast milk.
There are many causes for hyperprolactinemia. A common one is undiagnosed thyroid disease. A variety of medications, including those used to control hypertension and depression/mood disorders, can also cause an elevation of prolactin. Hyperprolactinemia can also be caused by the presence of a small benign tumor at the base of the pituitary gland. Parlodel (Bromocriptine) and Dostinex (Cabergoline) are medications that are often effective in reducing prolactin levels and establishing normal ovulation. Both of these medications decrease the production of prolactin from the pituitary gland by stimulating dopamine receptors.
The major potential side effects of these medications include dizziness, drowsiness, nausea, vomiting and diarrhea. These adverse effects are usually dose-dependent, and rarer with the use of Dostinex, a newer medication. Please see the manufacturer’s Website for detailed information.
Birth control pills (Oral Contraceptive Pills or OCP’s) are sometimes used in IVF cycles, even though they are routinely administered to prevent pregnancy. Most birth control pills contain both estrogen and progesterone, which act to suppress the production of FSH and LH and prevent ovulation.
OCPs are given to prepare for an IVF cycle in order to prevent cysts from developing on the ovaries. Before starting an IVF cycle, it is important that no significant cysts are present as they may interfere with follicular development and response to medication. The use of OCPs also makes menstrual cycles more predictable and makes scheduling IVF appointments easier.