The most commonly prescribed ovulation drug is clomiphene citrate (CC). 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 50-100 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. 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.
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.