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Author: Lynn Westphal Infertility Medications
Ovulation Induction
Ovulation is the release of a mature egg from the ovary. In a normal menstrual cycle, the brain secretes follicle stimulating hormone (FSH) to cause an egg to develop in the ovary. When the egg develops, it secretes estrogen, which signals the brain that the ovary is responding appropriately. When the estrogen level reaches a certain level, the brain secretes a surge of luteinizing hormone (LH), which causes the egg to ovulate.
Some women are infertile because they ovulate infrequently or not at all. Medications that "induce ovulation" can be used to correct this problem. These medications are also used to increase the number of eggs that develop each month.
A. Clomiphene citrate (Serophene, Clomid) is a compound that was chemically synthesized in 1956. Although its exact mechanism of action is unknown, clomiphene citrate appears to be able to initiate ovulation because of its ability to bind to estrogen receptors. By displacing estrogen from its receptors, it can fool the brain into thinking that estrogen levels are too low. In response, the brain secretes even higher amounts of FSH (and LH), and this stimulates the ovary to develop one or more eggs.
Clomiphene citrate is a pill that is taken orally. Typically, it is started as one pill (50 milligrams) on day 3,4 or 5 of the cycle and continued for 5 days. If ovulation does not occur, the dose is then increased. Ovulation should occur around day fifteen and can be detected with the use of a urine ovulation predictor kit. Intercourse (or insemination) can be timed in this way. Clomiphene citrate can also be used in combination with some other medications, such as hCG and human menopausal gonadotropins.
Clomiphene citrate is a relatively inexpensive medication (compared to other infertility medications). It costs about $7-10/ tablet, so an initial course will be about $50.
Most women tolerate clomiphene citrate well, but there are some common side effects. Many women report hot flashes or feeling "premenstrual." Other problems that have been reported are headaches, visual symptoms, nausea, and bloating. Clomiphene citrate increases the number of eggs ovulated, so increases the possibility of multiple gestation (7-8% chance). If the ovaries produce too many eggs, the ovaries can become very large and cause severe abdominal discomfort. Clomiphene citrate can also have adverse effects on cervical mucus, which can decrease the efficacy of this therapy with intercourse.
B. Human Menopausal Gonadotropins (Pergonal, Metrodin, Humegon) have been used to induce ovulation since the late 1950's. Gonadotropins (FSH and LH) are elevated after menopause, and currently available gonadotropin preparations are extracted from the urine of postmenopausal women. Bioengineered recombinant FSH is being tested and awaiting FDA approval.
Gonadotropins are very expensive. Each ampule of medication can cost about $50. Women who are sensitive to the medication may need two ampules per day, and women whose ovaries are less responsive may need 6-8 ampules per day. Treatment usually consists of intramuscular injection of these medications for 8-12 days. Therefore, some women may spend more than $3,000 per month on these medications.
Since these are very powerful hormones, women on these medications need to be monitored closely. A pelvic sonogram is performed before initiating a course of treatment in order to determine whether there are any abnormal cysts in the ovaries. If the sonogram is normal, the injection of medication is begun early in the cycle (usually about day 3). After four or five days of the medication, the patient will be seen for a pelvic sonogram and blood test (estrogen level). The dose of medication may be adjusted if the response is not appropriate. The patient will usually be seen every 1-3 days after this and will have repeat sonograms and blood tests to evaluate the development of the eggs. When the eggs appear to be ready for ovulation, the patient will receive an injection of hCG, and this will cause the eggs to be released about 40 hours later. Intercourse or insemination can be timed in this manner. When these medications are being used for in vitro fertilization, the eggs are removed from the ovaries about 36 hours after the hCG injection (before ovulation can occur).
Ovarian overstimulation is the most common complication of gonadotropin therapy. Mild overstimulation is characterized by abdominal bloating, weight gain, and pelvic discomfort. This is a self-limiting condition and does not require treatment. Severe ovarian overstimulation is rare but can cause moderate to severe pain. It can also cause significant fluid retention, especially in the abdominal cavity and lungs. In its most severe form, ovarian overstimulation can result in ovarian rupture and a tendency to form blood clots. The other significant complication is the risk of multiple pregnancy (15-30%).
Other Medications
A. Gonadotropin releasing hormone (GnRH) agonists (Synarel, Lupron) are medications that inhibit the brain from secreting hormones that control the menstrual cycle. The ovaries enter into a state of rest, and the patient's cycle can be completely controlled. These medications prevent premature ovulation and allow the patient's cycle to be coordinated as needed.
Lupron is a subcutaneous injection and Synarel is a nasal spray. They are usually started one week before a patient's period is expected or in the very beginning of the cycle. The cost of these is about $250-350 per month.
These medications are usually well-tolerated, and most women do not have any side effects when taking these medications for a short time. However, some women may have hot flashes or headaches.
B. Progesterone is the hormone produced by the ovary after ovulation. This medication can be given to improve the uterine lining, which may improve implantaion of the embryo. It is usually started in the second half of the cycle, after insemination or embryo transfer. Progesterone can be given as an intravaginal suppository, oral capsule, or an intramuscular injection. Side effects can include bloating, irritability, and breast tnderness.
C. Human Chorionic Gonadotropin (hCG) is used to complete the final stages of egg maturation and to induce ovulation. It is given as an intramuscular injection. When used in conjunction with gonadotropins, it can contribute to ovarian overstimulation.
Donor Oocytes
A. Background
The first human pregnancy with egg donation was reported in 1983. Initially, the egg donor was inseminated with the partner's sperm and the embryos were retrieved by flushing the uterus. This technique was soon replaced by in vitro fertilization (IVF) with donor oocytes. In the past few years, this technique has been improved and has become much more popular. Currently, success rates with donor oocytes is higher than that for any other assisted reproductive technique. Many centers are finding that pregnancy rates with donor oocytes are close to 50% per cycle.B. Indications
Oocyte donation is the only treatment option for a number of disorders. Women may have ovarian failure due to surgery, chemotherapy, pelvic irradiation, or genetic disorders; or they may have poor ovarian function that prevents production of normal eggs. Donor eggs may also be used to prevent inheritable genetic disorders, and have also been used for women with recurrent miscarriages.C. Oocyte Donors
The first step in the oocyte donation process is recruitment of a donor. Donors can be anonymous (through an agency) or known (i.e. friend or sister). Women under 35 who have been pregnant are preferred. If the donor is found through an agency, there is usually a fee for both the donor and the agency. (This total fee varies, but is typically about $6,000). The degree of contact between the donor and the recipient varies greatly, and depends upon the desires of each individual. Some donor/recipient pairs never even know each other's name, and some become good friends.The donor undergoes a complete history and physical, psychologic evaluation, infectious disease testing, and extensive counselling about the risks of the procedure. When it is decided to proceed with the egg donation, the donor is started on a GnRH analog (Synarel or Lupron) in order to synchronize her cycle with the recipient. At the appropriate time, she starts injections of human menopausal gonadotropins (Pergonal, Metrodin, or Humegon). When the eggs are at the appropriate stage, the eggs are removed with a needle under ultrasound guidance. The eggs are then fertilized with sperm in the laboratory. Two to three days later, the embryos are placed into the recipient.
D.Oocyte Recipients
The recipient needs to undergo extensive screening similar to that of the oocyte donor. The age of the recipient is not as important as it is for the donor because the uterus does not age as quickly as the ovaries do. Therefore, menopausal women in their 50's have become pregnant with the use of donor oocytes. A gestational carrier can be used as the recipient if a gestational surrogate is needed.Similar to the oocyte donor, the recipient is started on a GnRH analog. When the donor starts injections of human menopausal gonadotropins, the recipient begins taking estrogen. Estrogen can be given as an oral tablet, intramuscular injection, or patch on the skin. At the time of the egg retrieval, the recipient is started on progesterone (most frequently given as an intramuscular injection daily). The embryos are then placed into the recipient's uterus two to three days after the egg retrieval. If the recipient becomes pregnant, she will continue on hormone replacement and be evaluated weekly to make sure her hormone levels are appropriate. She will usually continue homone therapy for 10-12 weeks.
Copyright 1996. The American Surrogacy Center, Inc.(TASC), Marietta, GA
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