Fortunately, many fertility drugs are now available to help infertile couples. Several of these drugs are classified as ovulation-induction agents because they help to establish normal ovulation.
Depending on the type, length, and intensity of fertility treatment, many patients will take medications to support the reproductive process and/or procedure for successful pregnancy.
Medications for Ovulation Induction
Several medications are available to help induce ovulation in women who don’t ovulate, or stimulate more vigorous ovulation in those who do. We use these medications to create more eggs in an effort to boost natural fertility. Some of the more aggressive medications will require careful physician directed monitoring to ensure the response is good but not overly good (avoidance of multiple pregnancy).
As president of the Canadian Fertility and Andrology Society, Dr. Roberts is working closely with a variety of stakeholders on the issues surrounding the recent discontinuation of Serophene (clomiphene citrate). We will be providing regular updates on the situation and possibility for other sources of clomiphene citrate. Please read the EMD Serono Serophene Discontinuation Notice for more information.
Clomiphene citrate was first released for use in 1967 and is in the category of drugs known as SERMs (selective estrogen receptor modulators). Via feedback to the hypothalamus in the brain, it causes the pituitary gland in the brain to release more FSH (follicle stimulating hormone), and LH (luteinizing hormone), and provides more egg recruitment from the ovary. When combined with intrauterine insemination (IUI), pregnancy rates can approach 10-12% depending on the underlying fertility issue. Side effects include menopausal symptoms. It is only taken for 5 days of the month, starting on cycle day 3.
Follicle Stimulating Hormone (FSH) Injections
FSH is a protein made by the human pituitary gland and it has an effect on the ovary to push more follicles to develop. In the normal ovary, many follicles are recruited in the menstrual cycle, but only one or two will ovulate. With FSH, more of those follicles will come to maturity, giving a boost in background rates of pregnancy. These medications must be injected on a daily basis, and require very careful monitoring to ensure the response is adequate. There are three types of FSH available for purchase:
- Highly purified urinary FSH (trade name Bravelle)
- Recombinant Alpha Subunit (known as Gonal F)
- Recombinant Beta Subunit (known as Puregon)
Gonal F and Puregon are sold in ‘pen’ formats to allow for ease of preparation and injection, but are also generally a little more costly than Bravelle.
Luteinizing Hormone (LH) Injections
LH is another pituitary protein which is thought to help mature eggs in their development, and possibly provide higher quality eggs for fertilization during the IVF process. A variety of medications contain LH including:
- Menopur (highly purified urinary hCG which has LH and FSH effect)
- Repronex (similar to Menopur)
- Luveris (recombinant alpha subunit LH)
Lupron / Cetrotide / Orgalutran
Lupron, Cetrotide, and Orgalutran down-regulate the reproductive hormone system, resulting in profoundly low levels of FSH and LH. Ovulation cannot occur while taking these products unless hCG or LH is administered. Normally, a spike of LH causes ovulation 36 hours later; however, this spike cannot occur in women taking Lupron, Cetrotide, or Orgalutran. An injection of hCG or LH is given and egg retrieval is scheduled accordingly. Hence these medications are extremely useful during the IVF process, where we are attempting to cause the ovaries to develop follicles, but trying to prevent them from ovulating naturally.
hCG / Pregnyl / Ovidrel
Human chorionic gonadotropin (hCG) is known as the pregnancy hormone because its levels increase once a pregnancy is established. hCG is also used to initiate ovulation in assisted reproductive technology cycles where GnRH agonists or antagonists are used. Once a pregnancy is established, the placenta begins to produce hCG, which helps maintain the pregnancy. A spike in hCG levels initiates ovulation. Pregnancy outcomes can be determined by the rate that hCG rises over the course of the pregnancy. hCG/Pregnyl/ or ovidrel are administered 24-26 hours prior to an intrauterine insemination (IUI) or 36 hours prior to egg retrieval during an IVF treatment cycle.
Metformin is an insulin-sensitizing agent that is commonly used to treat Type II diabetes. It is used to lower insulin levels in hyperinsulinemic patients (insulin levels are too high). Most polycystic ovarian syndrome (PCOS) patients are hyperinsulinemic, which leads to increased male hormone production and irregular or no ovulation. Metformin normalizes insulin levels to allow natural ovulation to resume. Metformin facilitates the actions of insulin at the level of the cell and reverses many of the negative effects on the womans reproductive system, allowing the resumption of ovulation and reducing the risk of early pregnancy loss.
Prolactin is known as the breast milk hormone. When it occurs naturally and normally, it stimulates milk production in pregnant women. However if prolactin levels are too high in women who are not pregnant, it can lead to irregular or no ovulation. Parlodel is used to control (and lower) prolactin levels by stimulating dopamine receptors. Once prolactin levels normalize, regular ovulation often begins. Major side effects may include nausea, vomiting, and dizziness.
Progesterone is a hormone that plays an important role in several stages of the reproductive process. First, progesterone helps to prepare the endometrium for implantation of the embryo. The endometrium must thicken, become more vascular, and secrete nourishing substances in order to support a developing fetus. Once the eggs are ovulated, the corpus luteum produces progesterone. Once progesterone levels are elevated, it is a sign that ovulation has occurred. After the embryo implants, the placenta produces progesterone to continue to support the fetus throughout the pregnancy.
If the placenta produces an insufficient amount of progesterone it could cause “luteal phase defect”, which is thought to be associated with underdevelopment of the endometrium. It’s controversial whether or not luteal phase defect exists, but if it does, supplementation with progesterone would be the answer. Poor progesterone levels during early pregnancy can also mark a risk of miscarriage or ectopic pregnancy (pregnancy outside of the uterus). During IVF cycles, progesterone supplementation is prescribed until the pregnancy test and for an additional four weeks if the pregnancy test is positive.
Teaching of safe handling and injection of medications is the responsibility of the PCRM team. With the nursing teaching visit, and the educational materials provided, PCRM patients are able to take injectable medications with safety and confidence.
Further online resources are very helpful: