fertility news

Inducing Ovulation
2010

One of the most common barriers to becoming pregnant is an inability to ovulate (release eggs). Some women don’t ovulate at all, and others ovulate irregularly. Luckily, there are a number of highly successful treatments to overcome this problem, all with the same goal: to stimulate the ovaries to produce one or more eggs.

To understand ovulation induction, it helps to know how the ovaries work. A woman receives her entire lifetime supply of eggs – approximately 7 million – before she is even born. Throughout her lifetime, she will gradually use up this supply until she has no more eggs and reaches menopause.

Eggs rest in the ovaries until they are ready to mature and develop (in their immature state, the eggs are called “follicles”). Usually, only one follicle will mature and be released in a given monthly cycle. As it matures, the follicle depends on hormones such as FSH (follicle-stimulating hormone) and LH (luteinizing hormone) to continue its development. Follicles that do not mature simply stop growing and are reabsorbed by the body.

FSH, LH, and estrogen – another key female hormone - are regulated by the pituitary gland, an organ located at the base of the brain. When FSH levels are low, the pituitary releases more FSH to stimulate the follicle. Later in the monthly cycle, as the levels of estrogen and other hormones rise, the pituitary gland is inhibited and less FSH is released.

In some women, the pituitary gland does not produce enough LH and FSH to stimulate a follicle to mature. This sometimes occurs in women who exercise vigorously, are under a lot of stress, or who have anorexia or related eating disorders. Treatment usually consists of either stimulating the pituitary to release more LH and FSH, or simply replacing the missing hormones by injecting them directly.

Treatment With Clomiphene Citrate

The simplest and most common starting treatment is an oral medication called clomiphene citrate, which blocks the effects of estrogen throughout the body. Once the pituitary gland senses that estrogen is low, it responds by secreting more FSH and LH. This rise in FSH is stimulates the follicles to resume growth, mature, and eventually release. In properly selected patients, 80% can be expected to ovulate and approximately 40% become pregnant in response to this drug.

Generally, clomiphene citrate has few or mild side effects. They may include hot flashes, an upset stomach or bowels, headaches, sensitivity to bright light, visual disturbances, mood swings, and breast tenderness. Clomiphene citrate may also result in multiple pregnancy (five to ten percent of pregnancies will be twins). Prolonged use of clomiphene citrate may increase the risk of ovarian cancer. Women should discuss this concern, and all safety concerns, with their healthcare provider.

Women who take clomiphene citrate should also monitor their cycle closely to determine whether the treatment is working. Patients track their daily temperature with a specially sensitive thermometer known as a “basal body thermometer.” After a woman ovulates, her body temperature rises about 0.5 degrees F, and this slight rise can be detected by a basal body thermometer. Other methods for confirming ovulation include ultrasounds or blood tests.

However, these tests do not reveal when ovulation occurs. To predict the timing of ovulation, many women use an over-the-counter ovulation predictor kit. The kit tests for a surge in the pituitary hormone LH, which appears in the urine shortly before ovulation. The kit is able to predict ovulation approximately 18-24 hours in advance, allowing couples to schedule intercourse when the women is most fertile.

Treatment With Injectable Gonadotropins (FSH and LH)

Women who do not ovulate or get pregnant in response to clomiphene citrate have other treatment options. Instead of stimulating the pituitary to produce the necessary hormones, the hormones themselves can be given directly by injecting a type of medicine called a gonadotropin. Gonadotropins contain either FSH alone or FSH plus LH, which induce ovulation. They should be prescribed only by physicians who are experienced in infertility treatment.

Because gonadotropins act directly on the ovaries they can help the women attain higher levels of FSH levels which last for a longer time. However, this may cause some women to release more than one egg at a time. Women are monitored closely through ultrasounds and blood tests to avoid overstimulating the ovaries and producing high order multiples (triplets or more).

On the other hand, there are times when it is desirable for a woman to produce multiple eggs. A women who is undergoing in vitro fertilization (IVF) – a process in which eggs are removed from her ovaries, fertilized in a laboratory, and then implanted in her uterus – typically receives higher doses of injectable gonadotropins. Having multiple eggs increases her chances for successful implantation.

Because gonadotropins are injected some soreness, discomfort, and occasional redness or bruising may appear at the injection site. Some patients feel full or bloated as their ovaries enlarge during their stimulation cycle. Other common side effects include abdominal pain, flatulence, nausea and breast pain. Gonadotropins may cause a serious side effect called ovarian hyperstimulation syndrome (OHSS), in which the ovaries enlarge and fluid accumulates suddenly in the abdomen. Early warning signs of OHSS include severe pelvic pain, nausea, vomiting, sudden weight gain and reduced urine production. This risk can be reduced (but not entirely eliminated) by careful monitoring and adjustments of the medicine dosage.

The vast majority of patients are able to ovulate successfully in response to injectable gonadotropins. However, not all will conceive. Factors that influence pregnancy rates include the woman’s age, the presence of endometriosis or adhesions in her pelvis, any problems with her fallopian tubes, abnormalities of the lining of the uterus, and the quality of her partner’s sperm.

Treatment with Gonadotropin Releasing Hormone (GnRH)

Some women cannot ovulate because the hypothalamus (another part of the brain) doesn’t provide enough stimulation to their pituitary gland. Normally, the hypothalamus secretes a hormone called GnRH, which keeps the pituitary functioning. But during periods of high physical or psychological stress, the hypothalamus may not secrete GnRH.

To treat this problem, a patient is given GnRH directly through a small medication pump worn 24 hours a day for approximately 2 weeks, releasing small amounts of medication every hour or so through a series of needles. Pregnancy rates are excellent and side effects are uncommon, except for swelling or soreness at the injection site. Multiple pregnancies are also uncommon but may still occur.

Other Conditions

There are other conditions that can prevent a woman from ovulating. Some women with irregular periods have a condition called polycystic ovarian syndrome (PCOS). They have enlarged ovaries with multiple cysts inside, caused by an overproduction of androgens (male hormones), as well as abnormal levels of LH and FSH. Symptoms can include increased facial and body hair and acne. Women with these symptoms should be screened to rule out more serious problems. PCOS can be treated with medications that lower androgen production, such as low dose steroids or anti-diabetic drugs.

Other conditions that can prevent ovulation include high levels of prolactin (a hormone secreted by the pituitary) or thyroid problems. These conditions can often be corrected through medication.

Premature Ovarian Failure

Some women fail to ovulate simply because they have very few or no eggs remaining in their ovaries. This is normal at the time of menopause. But when a woman runs out of eggs before the age of 40, it is termed “premature ovarian failure” or “premature menopause.” This can result from prior chemotherapy or radiation therapy for cancer, prior surgical removal of the ovaries, or various genetic abnormalities. Usually, however, there is no obvious explanation and these women are believed to have simply exhausted their egg supply at a very young age. Because they have no eggs remaining, they are not candidates for ovulation induction.

But for most women who do not ovulate, ovulation induction is a safe and effective means of restoring fertility. Careful selection of treatment, combined with appropriate monitoring, may result in excellent rates of pregnancy.