The most commonly prescribed ovulation drug is clomiphene citrate (CC). Brand names include Clomid® and Serophene®. This drug is most often used to stimulate ovulation in women who have infrequent or absent ovulation. It is also used in combination with IUI as an empiric treatment for unexplained infertility and mild endometriosis, particularly in young couples with a short duration of infertility, and in those who are unwilling or unable to pursue more aggressive therapies involving greater costs, risk, or logistical demands.
The standard dosage is 50 milligrams (mg) of CC per day for five consecutive days. Treatment begins early in the cycle, usually on the second, third, fourth or fifth day after menstruation begins. If a woman does not have periods, a period can be induced by administering progesterone or some other progestin. Ovulation rates, pregnancy rates, and pregnancy outcomes are similar regardless of whether treatment begins on cycle day 2, 3, 4 or 5. Clomiphene works by causing the pituitary gland to secrete more FSH. The higher level of FSH spurs the development of ovarian follicles that contain eggs. As the follicles grow, they secrete estrogen into the bloodstream. If treatment is successful, about a week after the last tablet of CC is taken, the pituitary is hypersensitive to GnRH and releases an LH surge. The LH surge causes the egg to be released from the mature follicle in a process called ovulation.
It is important to determine whether a given dosage of CC results in ovulation. Most doctors rely on the menstrual pattern, ovulation prediction kits, measurement of serum progesterone levels or the BBTchart to monitor a patient’s response to the standard dose of clomiphene. A BBTchart is a chart in which the patient’s body temperature upon awakening is plotted every morning before she gets up. The readings help identify ovulation, which is indicated by a persistent temperature rise of one-half degree or more. If there is doubt, however, measuring the progesterone level about 14 to 18 days after the start of clomiphene, or examining the ovaries with ultrasound, can help to determine if and when ovulation occurred. If ovulation does not occur at the 50-mg dosage, CC may be increased by 50-mg increments in subsequent cycles until ovulation is achieved. Although dosages in excess of 100-mg are not approved by the Food and Drug Administration, your physician will determine the appropriate dose for you. Occasionally, the physician may choose to add other medications to clomiphene if the drug is not successful in inducing ovulation.
Clomiphene can reduce the quantity and wateriness of cervical mucus, making it a barrier for sperm. Intrauterine insemination frequently is used in conjunction with CC. Clomiphene sometimes can alter endometrial thickness, making it thin and unreceptive to implantation.
The lowest dose of clomiphene sufficient to induce ovulation in anovulatory women is usually used for at least four to six cycles to provide an adequate trial for most patients. Clomiphene will induce ovulation in about 80% of properly selected patients. About 40% to 45% of couples receiving clomiphene citrate will become pregnant within six cycles. Most authorities suggest that clomiphene be given for no more than six cycles, because the chance of success is much less after six cycles. After that, alternatives may be considered. Women who have irregular or absent ovulation due to hypothalamic disorders, or who have very low estrogen levels, generally do not respond well to clomiphene. Women who are obese may have better success if weight is lost.
Clomiphene is generally tolerated well. Side effects are relatively common, but generally mild. Hot flashes occur in about 10% of women taking CC, and typically disappear soon after treatment ends. Mood swings, breast tenderness, and nausea are also common. Severe headaches or visual problems, such as blurred or double vision, are uncommon, and virtually always reversible. If these side effects occur, it is prudent to stop treatment immediately and call the physician. Women who conceive with clomiphene have approximately a 10% chance of having twins. Triplet and higher order pregnancies are rare (<1%), but may occur. There is no increased risk of miscarriage in pregnancies conceived with clomiphene therapy. Ovarian cysts, which can cause pelvic discomfort, may form as a result of the drug’s overstimulation of the ovaries. A pelvic exam or ultrasound may be performed to look for ovarian cysts before beginning another clomiphene treatment cycle. A luteal phase defect may also occur. Side effects are more frequent with higher doses.