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Medications for infertility
Medications to regulate ovulation are part of most infertility treatment plans. Find out how they work.
Medications for Ovulation InductionThe many medicines used to treat female infertility fall into two groups: drugs used to promote ovulation, and drugs used to treat other hormonal problems associated with infertility. Ovulation induction is the use of drugs to stimulate your ovary to produce and release an egg. This method is used to treat women who do not ovulate (anovulation) or who ovulate irregularly (oligoovulation). It's also used for women with unexplained infertility and women who are having assisted reproductive technology (ART) procedures, such as in vitro fertilization (IVF). These procedures require the woman to produce many eggs in a single cycle, a process known as superovulation. Medications used for ovulation induction include clomiphene citrate, which is taken as a pill; injectable gonadotropins, which are given as shots; and, less commonly, gonadotropin-releasing hormone (GnRH), which is given intravenously (pumped directly into a vein). If you are using injectable gonadotropins, you will also receive one or more drugs to trigger or control the release of the developed egg(s). Clomiphene citrate Clomiphene citrate (trade names Clomid, Serophene, Milophene) is the simplest, least expensive, and most common ovulation induction medicine. It works by blocking receptors for the female hormone estradiol. Your pituitary gland responds by making and releasing more follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This stimulates the ovary to produce and release an egg. Clomiphene comes as a pill. The usual starting dose is one 50 mg pill taken daily for five days. beginning on either Day 3 or Day 5 of your menstrual cycle. (Day 1 is the day your period starts.) You will need some form of monitoring for ovulation to determine whether the treatment is successful. This may be a basal body temperature graph (BBTG), urine LH testing, or a blood test for progesterone about 10 days after the expected time of ovulation. If ovulation does not occur, then your doctor will increase the dose of clomiphene by 50 mg increments, until you reach 200-250 mg per day. In women who have problems ovulating, clomiphene brings about ovulation in as many as 80 percent, and about half of these women get pregnant. In women taking clomiphene who fail to ovulate at doses of 100 mg daily, up to 70 percent will ovulate at higher doses, but less than 30 percent of these will become pregnant. In cases where clomiphene brings on ovulation but you do not get pregnant, it does not help to increase the dose of clomiphene. If you do not ovulate even at the increased dose, or if you ovulate but you do not get pregnant after up to six cycles of treatment, then your doctor will probably recommend that you stop using clomiphene and consider trying ovulation induction with gonadotropins. News reports occasionally warn that clomiphene and other medications used to induce ovulation may cause ovarian cancer. One study has shown a possible connection between the incidence of ovarian cancer and repeated treatment cycles (more than 12) using clomiphene. A problem with these findings is that women with infertility may be more likely to have underlying conditions — such as anovulation and obesity — that also increase their risk of ovarian cancer. Further research shows that women taking these drugs do not have a greater risk of developing ovarian cancer compared with childless women not taking these medications. Injectable gonadotropins These medications contain the hormones FSH and LH. There are several types. Human menopausal gonadotropins (hMG) and highly purified urine-derived FSH (hpFSH) are manufactured from the urine of postmenopausal women, while recombinant FSH (rFSH) is made with recombinant DNA technology. For women with ovulation problems who don't get pregnant with clomiphene, injectable gonadotropins succeed in causing ovulation in about 80 percent. Pregnancy rates with this treatment are about 40 percent per medication cycle. Injectable gonadotropins are typically used for:
Gonadotropins are given by injection. You generally start the injections on cycle Day 3 (or Day 2 if you are preparing for IVF or a related procedure). In ovulation induction cycles not involving IVF, the goal is to produce one or two good-quality eggs that may be fertilized normally through well-timed intercourse or IUI. Sometimes, even with low doses of gonadotropins, several follicles (fluid-filled sacs containing eggs) mature and release eggs. The release of several mature eggs may result in multiple gestation — a pregnancy involving two, three, or even more fetuses. Women who normally ovulate but are undergoing IVF receive higher doses of injectable gonadotropins to promote superovulation. The goal here is to bring about the release of multiple eggs, so the best-quality ones can be selected for insemination. Superovulation cycles require careful monitoring of egg development by a doctor with special expertise in reproductive endocrinology and infertility. This way, the doctor determines when to give an injection to induce egg release, while at the same time minimizing the risk of excessive stimulation. Excessive stimulation involves significant and sometimes dangerous enlargement of the ovaries. It can also prompt fluid retention and accumulation (edema) throughout the body, but especially in the abdomen and pelvis (ascites), lungs (pleural effusion), or even around the heart (pericardial effusion). This condition, called ovarian hyperstimulation syndrome (OHSS), occurs in approximately 1 out of 100 treatment cycles. Other more common side effects of injectable gonadotropins include discomfort with injection and soreness, redness, or bruising at the injection site. You may feel lightheaded or faint and occasionally bloated as you are going through a stimulation cycle. Other occasional side effects include fluid retention, mild nausea, headaches, and mood swings. After six to 15 days of daily injections of gonadotropins, when your eggs are ready, you will receive an injection of human chorionic gonadotropin (hCG) to prompt the ovary to release the eggs. This step mimics the body's normal mid cycle LH surge. hCG is a hormone of pregnancy, but it has the same stimulating effects on the ovary as LH, acts for a longer period, and costs less. Some women have a mid cycle LH surge on their own during ovulation induction with gonadotropins. In these cases, the eggs do not develop or ovulate properly. These LH surges, called premature LH surges, can be prevented with injections of medications called GnRH agonists or antagonists. These medications work by lowering or turning off your body's natural secretion of FSH and LH. There are several ways to use these drugs, so you might receive them either in the later part of the cycle before your stimulated cycle or at the same time you get your gonadotropin injections. GnRH induction of ovulation For women with certain types of hormone problems, the doctor may recommend inducing ovulation with pulsatile GnRH treatment. This involves giving frequent regular doses of GnRH through a portable pump attached to a needle placed into your body. GnRH is the hormone that stimulates the pituitary to release FSH and LH, which will induce ovulation. The major advantage of giving GnRH directly is the reduced need for cycle monitoring and the lower rates of multiple gestation and hyperstimulation. The disadvantage of this therapy is that you need to receive a dose of the hormone every 90 minutes until ovulation. That means you must wear the pump that delivers the medication around the clock for weeks at a time. Studies comparing injected gonadotropins to pulsatile GnRH therapy show equivalent success rates for both ovulation and pregnancy. However, the risk of multiple gestation (14 percent) is higher with gonadotropins than with pulsatile GnRH treatment (8 percent).
Other Medications for WomenAside from the use of drugs for ovulation induction, doctors also use various medications to treat specific hormonal conditions that can interfere with fertility. Among these conditions are PCOS and other disorders of overactive male hormone secretion (hyperandrogenism), excessive prolactin secretion (hyperprolactinemia), and thyroid dysfunction. If you have been diagnosed with polycystic ovarian syndrome (PCOS) or another hyperandrogen disorder, medication such as dexamethasone can lower the secretion of male hormones (androgens) by your adrenal glands. High levels of male hormones such as testosterone may cause such symptoms as hirsutism (excessive hair growth on your face, breasts and abdomen) as well as oily skin, acne, and ovulation problems. Your doctor will recommend medication depending on whether your primary goal is to treat symptoms such as hirsutism to improve fertility. If your goal is to treat hirsutism:
If your goal is to treat infertility: Standard therapy may involve weight loss, clomiphene citrate (Clomid, Milophene, Serophene), metformin (Glucophage), gonadotropins, or certain combinations of these. Alternative therapy may involve clomiphene citrate with dexamethasone, low-dose recombinant follicle-stimulating hormone (FSH), ovarian surgery, or in vitro fertilization (IVF). In one study of women with PCOS, the use of clomiphene plus dexamethasone caused 100 percent to ovulate and 85 percent to became pregnant. Those receiving clomiphene alone had a 50 percent ovulation rate and 33 percent pregnancy rate. For women with hyperandrogen disorders who don't have success with this approach, long term ovulation induction with low-dose FSH has a 74 percent chance of leading to pregnancy. Of those who fail to conceive with FSH, about 25 percent can become pregnant through IVF. Excess prolactin secretion (hyperprolactinemia) High levels of prolactin — a pituitary hormone involved in producing milk — may interfere with ovulation. This can happen whether or not you have milky breast discharge, a common symptom of hyperprolactinemia. Hyperprolactinemia is most often treated with a drug called bromocriptine (Parlodel), taken at bedtime to decrease the side effects of dizziness and lowered blood pressure upon standing. The dose may be increased every two weeks until your prolactin level is normal. If the side effects of blood pressure changes, dizziness, and nausea are too severe, you may be given an alternative prolactin-lowering medication. If you have high prolactin levels, your doctor may also recommend a magnetic resonance imaging (MRI) scan of your pituitary to check for a pituitary tumor. Thyroid disorders Thyroid disorders — especially hypothyroidism, in which the thyroid produces too little thyroid hormone — may cause ovulation problems, among many other symptoms. Hypothyroidism is treated by with supplements of thyroid hormone, called levothyroxine (Synthroid, Levoxyl), in the lowest dose needed to correct the deficiency.
Medications for MenDrugs are not generally effective for treating sperm problems except in certain men who have hormone deficiencies. Low levels of gonadotropins — follicle-stimulating hormone (FSH) and luteinizing hormone (LH) — can reduce testosterone production and lead to sperm abnormalities. Men with this problem can benefit from various medications, as follows:
In cases where sperm problems result from low testosterone levels, drug treatment produces excellent results. For men whose testosterone is already normal, however, these drugs do not help with fertility. In addition, hCG, hMG, GnRH, and clomiphene are not effective in improving sperm abnormalities in men whose FSH and LH levels are already normal.
The Eye and How It Works
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women in whom clomiphene fails to induce ovulation