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Problems With Ovulation

by Robert W. Rebar, MD

The ovaries do not release an egg each month (see Menstrual Cycle).

  • Ovulation problems can result from dysfunction of the part of the brain and the glands that control ovulation or dysfunction of the ovaries.

  • Women can determine whether ovulation is occurring and estimate when it occurs by measuring body temperature or using home predictor kits.

  • Doctors use ultrasonography or blood or urine tests to evaluate ovulation problems.

  • Drugs, usually clomiphene, can often stimulate ovulation, but pregnancy does not always follow.

In women, a common cause of infertility is an ovulation problem.

Causes

Reproduction is controlled by a system that includes the hypothalamus (an area of the brain), pituitary gland, ovaries, and other glands, such as the adrenal glands and thyroid gland. Ovulation problems result when one part of this system malfunctions. For example,

  • The hypothalamus may not secrete gonadotropin-releasing hormone, which stimulates the pituitary gland to produce the hormones that stimulate the ovaries to trigger ovulation (luteinizing hormone and follicle-stimulating hormone).

  • The pituitary gland may produce too little luteinizing hormone or follicle-stimulating hormone.

  • The ovaries may produce too little estrogen .

  • The pituitary gland may produce too much prolactin, a hormone that stimulates milk production. High levels of prolactin (hyperprolactinemia) may result in low levels of the hormones that trigger ovulation. Prolactin levels may be high because of a pituitary gland tumor (prolactinoma), which is almost always noncancerous.

  • Other glands may malfunction. For example, the adrenal glands may overproduce male hormones (such as testosterone ), or the thyroid glands can overproduce or underproduce thyroid hormones, which help keep the pituitary gland and ovaries in balance.

Ovulation problems may be due to many disorders. One of the most common causes is polycystic ovary syndrome, which is usually characterized by excess weight and excess production of male hormones by the ovaries. Other causes include diabetes and obesity. Problems may also result from excessive exercise, certain drugs (such as estrogens and progestins and antidepressants), weight loss, or psychologic stress. Sometimes the cause is early menopause—when the supply of eggs runs out early.

An ovulation problem is often the cause of infertility in women who have irregular periods or no periods (amenorrhea—see Absence of Menstrual Periods). Infrequently, an ovulation problem is the cause of infertility in women who have regular menstrual periods but do not have premenstrual symptoms, such as breast tenderness, lower abdominal swelling, and mood changes.

Diagnosis

Doctors ask women to describe their menstrual periods (menstrual history—see Menstrual Disorders and Abnormal Vaginal Bleeding:What the doctor does). Based on this information, doctors may be able to determine whether women are ovulating.

To determine if or when ovulation is occurring, doctors may ask a woman to take her temperature at rest (basal body temperature) each day. If possible, she should use a basal body temperature thermometer (which is highly accurate) or, if it is unavailable, a mercury thermometer. Electronic thermometers are the least accurate. Usually, the best time is immediately after awakening. A decrease in basal body temperature suggests that ovulation is about to occur. An increase of more than 0.9° F (0.5° C) in temperature usually indicates that ovulation has just occurred. However, this method is inconvenient for many women and is not reliable or precise. At best, it predicts ovulation only within 2 days. A more accurate method is an ovulation predictor kit for use at home. This kit detects an increase in luteinizing hormone in the urine 24 to 36 hours before ovulation. Urine is tested on several consecutive days.

Doctors can accurately determine whether and when ovulation occurs. Methods include ultrasonography and measurement of the level of progesterone in the blood or saliva or the level of one of its by-products in the urine. A marked increase in these levels indicates that ovulation has occurred.

Doctors may do other tests to check for disorders that can cause ovulation problems. For example, they may measure testosterone levels in the blood to check for polycystic ovary syndrome.

Treatment

A drug to trigger ovulation, such as clomiphene, aromatase inhibitors, or human gonadotropins, may be used. The particular drug is selected based on the specific problem. If the cause of infertility is early menopause, neither clomiphene nor human gonadotropins can stimulate ovulation.

Clomiphene

If ovulation has not occurred for a long time, clomiphene is usually preferred. A few days after menstrual bleeding begins, the woman takes clomiphene by mouth for 5 days. Usually, she ovulates 5 to 10 days after clomiphene is stopped, and she has a menstrual period 14 to 16 days after ovulation. Clomiphene is not effective for all causes of ovulation problems. It is most effective when the cause is polycystic ovary syndrome.

If a woman does not have a period after treatment with clomiphene, she takes a pregnancy test. If she is not pregnant, the treatment cycle is repeated. A higher dose of clomiphene is used in each cycle until ovulation occurs or the maximum dose is reached. When the dose that triggers ovulation is determined, the woman takes that dose for at least three or four more treatment cycles. Most women who become pregnant do so by the fourth cycle in which ovulation occurs. Although about 75 to 80% of women treated with clomiphene ovulate, only about 40 to 50% of those who ovulate become pregnant. About 5% of pregnancies in women treated with clomiphene involve more than one fetus, primarily twins.

Side effects of clomiphene include hot flashes, abdominal bloating, breast tenderness, nausea, vision problems, and headaches. Fewer than 1% of women treated with clomiphene develop ovarian hyperstimulation syndrome. In this syndrome, the ovaries enlarge greatly and a large amount of fluid moves out the bloodstream into the abdomen. This syndrome may be life threatening. To try to prevent it, doctors prescribe the lowest effective dose of clomiphene, and if the ovaries enlarge, they stop the drug.

Aromatase inhibitors

Aromatase inhibitors (such as letrozole) are usually used to treat breast cancer in women who have gone through menopause. But they may also be used to trigger ovulation when clomiphene does not work. These drugs have fewer side effects than clomiphene. However, these drugs are not yet considered standard treatment for ovulation problems. Birth defects of the genitals have occurred in fetuses of women who took an aromatase inhibitor during the pregnancy, so these drugs are used only after pregnancy has been ruled out.

Human gonadotropins

If a woman does not ovulate or become pregnant during treatment with clomiphene or an aromatase inhibitor, hormonal therapy with human gonadotropins, injected into a muscle or under the skin, can be tried. Human gonadotropins stimulate the follicles of the ovaries to mature. Follicles are fluid-filled cavities, each of which contains an egg (see Biology of the Female Reproductive System:Fallopian tubes). Ultrasonography can detect when the follicles are mature. Then, the woman is given an injection of a different hormone, human chorionic gonadotropin, to trigger ovulation. When human gonadotropins are used appropriately, more than 95% of women treated with them ovulate, but only 50 to 75% of those who ovulate become pregnant. About 10 to 30% of pregnancies in women treated with human gonadotropins involve more than one fetus, primarily twins.

Human gonadotropins are expensive and can have severe side effects, so doctors closely monitor the woman during treatment. About 10 to 20% of women treated with human gonadotropins develop ovarian hyperstimulation syndrome. If hyperstimulation occurs, doctors may not give the woman human chorionic gonadotropin to trigger ovulation.

Other drugs

If the hypothalamus does not secrete gonadotropin-releasing hormone, a synthetic version of this hormone (called gonadorelin acetate), given intravenously, may be useful. This drug, like the natural hormone, stimulates the pituitary gland to produce the hormones that trigger ovulation. The risk of ovarian hyperstimulation is low with this treatment, so close monitoring is not needed. However, this drug is not available in the United States.

When the cause of infertility is high levels of the hormone prolactin, the best drug to use is one that acts like dopamine, called a dopamine agonist, such as bromocriptine or cabergoline. (Dopamine is a chemical messenger that generally inhibits the production of prolactin.)

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • CLOMID
  • DELATESTRYL
  • CRINONE
  • FEMARA
  • No US brand name
  • PARLODEL