Infertility In Women |
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DescriptionAn in-depth report on the causes, diagnosis, treatment, and prevention of female infertility. |
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Alternative NamesPelvic Inflammatory Disease; Polycystic Ovaries |
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MedicationsFertility drugs are often used alone as initial treatment to induce ovulation. If they fail as sole therapy, then they may be used with assisted reproductive procedures or artificial insemination to produce multiple eggs, a process called superovulation. ClomipheneClomiphene citrate (Clomid, Serophene) is usually the first fertility drug of choice for women with infrequent periods and long cycles. Unlike more potent agents used in superovulation, clomiphene is gentler and works by blocking estrogen, which tricks the pituitary into producing FSH and LH. This boosts follicle growth and the release of the egg. Clomiphene can be taken orally, is relatively inexpensive, and the risk for multiple births (about 5%, mostly twins) is lower than with other drugs. Women with the best chances for success with this drug are those with the following conditions:
Women with poorer chances to no chances with this drug have the following conditions:
One or two tablets are taken each day for five days, usually starting two to five days after the period starts. If successful, ovulation occurs about a week after the last pill has been taken. If ovulation does not occur, then a higher dose may be given for the next cycle. If this isn't successful, treatment may be prolonged or additional agents may be added. Experts usually do not recommend more than six cycles. The drug often reduces the amount and quality of cervical mucous and may cause thinning of the uterine lining. In such cases, other hormonal agents may be given to restore thickness. Other side effects include ovarian cysts, hot flashes, nausea, headaches, weight gain, and fatigue. There is a 5% chance of having twins with this agent, and a slightly increased risk for miscarriage. Superovulation with Gonadotropins and GnRH AgonistsSuperovulation, also called controlled ovarian stimulation, is generally used if clomiphene does not work. This approach is the direct administration of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), collectively called gonadotropins. The intent is to mimic the natural process leading to ovulation and produce multiple follicles. Superovulation is generally used in conjunction with assisted reproductive technologies. Many of the drugs used in superovulation are either taken from natural sources (menotropins) or are genetically developed:
Human Menopausal Gonadotropins (hMG). HMG (Pergonal, Repronal, Metrodin) is a menotropin that contains both FSH and LH and is obtained from the urine of postmenopausal women. HMG must be self-administered as an injection. It is one of the potent ovulation drugs now in use and is often used in assisted reproductive techniques. It may be effective in stimulating fertility in women with ovarian dysfunction, endometriosis, and unexplained infertility. HMG is administered as a series of injections two or three days after the period starts. Injections are usually given for seven to 12 days, but the time may be extended if ovulation does not occur. In such cases, an injection of human chorionic gonadotropin (hCG) may trigger ovulation. FSH. FSH stimulates the follicles directly and may be used with hCG to produce the LH and FSH surges that trigger ovulation. FSH is typically used alone for women who have taken clomiphene and failed. Such women often have polycystic ovaries, which is characterized by high LH and low FSH levels. Urofollitropin (Metrodin, Fertinex, Bravelle) is a menotropin extracted from the urine of postmenopausal women and has been the standard FSH agent. Recombinant follicle-stimulating hormone (Puregon, Gonal-F, Follistim) is genetically developed form of the natural FSH. Therefore it has no risk for contaminants, such as urinary proteins or traces of LH, which can occur with menotropins. (Bravelle is a highly-purified menotropin and may be as effective as recombinant FSH.) Human Chorionic Gonadotropin (hCG). Human chorionic gonadotropin or hCG is similar to luteinizing hormone and mimics the LH surge, which is to stimulate the follicle to release the egg. Standard hCG agents (APL, Follutein, Pregnyl, Profasi, Humegon) are derived from the urine of pregnant women. The recombinant (genetically developed) form of hCG (Ovridel) has fewer side effects at the injection site and its quality can be better controlled than the natural agents. It is generally used after hMG or FSH to stimulate the final maturation stages of the follicles. Ovulation, if it occurs, does so about 36 to 72 hours after administration. GnRH Analogs (Agonists or Antagonists). Gonadotropin-releasing hormone analogs (GnRH-a) can be either GnRH agonists or antagonists. They are synthetic agents that are similar to natural GnRH but have very different actions. While natural GnRH stimulate a surge in LH, these agents actually prevent the LH surge that occurs right before ovulation. This action helps prevent the premature release of the eggs before they can be harvested for assisted reproductive technologies.
GnRH-a agents are administered by injection or nasal spray. They increase the risk for ovarian cysts, but according to a 2000 study, they have no negative effect on pregnancy. These agents cause menopause-like effects, including hot flashes, vaginal dryness, insomnia, and possible osteoporosis (bone loss). Depression may be significant. Complications of SuperovulationMultiple Births. Overproduction of follicles can lead to ovarian enlargement. This event increases the risk for multiple births. There is a 25% chance of multiple births (about 17% for twins and 8% for triplets and over). Ovarian Hyperstimulation Syndrome. The most serious complication with superovulation is ovarian hyperstimulation syndrome (OHS), which is associated with the enlarged ovary (although the precise cause is unknown). This can result in dangerous fluid and electrolyte imbalances and endanger the liver and kidney. OHS is also associated with a higher risk for blood clots. In rare cases, it can be fatal. Symptoms include abdominal bloating, nausea, vomiting, and shortness of breath. Bleeding and Rupture of Ovarian Cysts. Overproduction of follicles, if unchecked, may result in bleeding and rupture of ovarian cysts. Cancer Concerns. There has been concern about an increased risk for ovarian and breast cancers in women taking fertility drugs, particularly clomiphene and human menopausal gonadotropins. In general, a strong body of evidence is finding no higher risk for either breast or ovarian cancer from the drugs themselves. Instead, such studies are suggesting that these cancers are caused by the same factors that contribute to the infertility itself. One exception, according to a 2003 study, may be a higher risk for breast cancer in women who took hMG for six or more months or cycles. The number of subjects was small, however, and more research is needed to confirm this finding. Other Agents Used or Under InvestigationTamoxifen. Tamoxifen (Nolvadex) is a drug known as a selective estrogen-receptor modulators (SERM). It is used to prevent breast cancer in high-risk women. Studies are also now suggesting that it may equal clomiphene in its ability to induce ovulation. It may be especially useful when used along with IVF for preserving fertility in breast cancer patients. This drug is less expensive than clomiphene and but poses some health hazards, including a risk for blood clots and uterine cancer. Aromatase Inhibitors.Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These agents include anastrozole (Arimidex) and letrozole. (Femara). Like tamoxifen, they are used for treating breast cancer and are being investigated for infertility in women. They do not appear to have the severe side effects of tamoxifen, however. In a 2002 comparison study between letrozole and clomiphene, the women who took letrozole had lower estrogen levels than those taking clomiphene. Evidence is suggesting that high estrogen levels may be harmful to the developing embryo. Therefore, letrozole may be more protective of the developing embryo than clomiphene.
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