Ovulation Induction with Oral Medications

Clomiphene (CC, Clomid, Serophene)

Clomiphene (CC) has been used to induce ovulation since the 1960’s. Given as an oral tablet at doses 50-200 mg daily for 5 days each cycle (usually on days 5-9 or 3-7 of the cycle), it is the most commonly prescribed ovulation medication. CC is a synthetic medication that acts as an anti-estrogen and indirectly stimulates the production of LH and FSH, which are natural hormones from the pituitary gland that induce the ovary to produce mature eggs (ovulate). Approximately 80% of patients who do not normally ovulate will do so on CC. Approximately 40% of women that ovulate on CC will get pregnant.

CC is indicated in women who do not ovulate. These women most commonly have polycystic ovary syndrome (PCOS). Patients with ovarian failure, high prolactin levels, thyroid problems, or hypothalamic causes are unlikely to respond to CC. On occasion, CC may be used in normally-ovulating women to increase the number of mature eggs.

Contraindications and Adverse Effects
CC treatment must be closely monitored, usually with an examination or an ultrasound in the first days of the menstrual cycle before taking the medication to rule out large residual cysts. A basal body temperature chart and/or ovulation predictor test should be used to predict and confirm ovulation. An ultrasound in mid-cycle may be suggested as well. Pregnancy (diagnosed or undiagnosed), the presence of large ovarian cysts, or estrogen-dependent cancer are absolute contraindications to CC use. Common side effects include hot flashes, mood swings, headaches, or lower abdominal discomfort. Common adverse effects include drying of the cervical mucus and thinning of the uterine lining. CC increases the risk of multiple births (primarily twins) to 7-10% (compared to 1% without CC). If the medication is used for more than 3 consecutive cycles, a one month break may be advisable before the next CC treatment cycle. The medication is usually not effective in helping its user to conceive after 6 cycles.

Femara (letrozole)

This medication blocks the production of estrogen, thereby stimulating the pituitary to increase production of LH and FSH, which in turn induce ovulation. Though only approved in the U.S. for women previously treated for breast cancer, letrozole has been used extensively in the U.S. and Canada for ovulation induction. It is taken as an oral tablet at doses of 2.5-10 mg daily for 5 days each cycle. Ovulation and conception and multiple birth rates (7%) are similar to CC.

Similar to clomiphene (CC): lack of ovulation or the need to increase the number of mature eggs.

Contraindications and Adverse Effects
Side effects such as hot flashes, headaches, and mood swings ae usually less pronounced than with CC. Adverse effects on the cervical mucus and uterine lining are less severe than CC. The risk of twins (7%) is similar to CC. Femara (letrozole) is not approved by the FDA for ovulation induction at present. Please discuss its use for ovulation induction with your reproductive specialist.

Insulin-Sensitizing Medications (Metformin [Glucophage])

Metformin (Glucophage), commonly prescribed for the treatment of diabetes, causes reduction in insulin. This reduction may also lead to reduction of testosterone production by the ovary (testosterone excess may interfere with ovulation) and resultant ovulation in women with polycystic ovary syndrome (PCOS). Metformin may be used to induce ovulation by itself or in combination with clomiphene (CC) or letrozole or injectable gonadotropins at doses of 500-2500 mg daily. Unlike clomiphene, it is taken every day of the month and may be continued in the early stage of pregnancy. To reduce side effects, the dose of metformin should be gradually increased.

Patients with chronic lack of ovulation, especially those with PCOS, who failed to ovulate with CC or letrozole.

Contraindications and Side Effects
Nausea and diarrhea are very common but usually subside with continued use. Lactic acidosis is a very rare but serious complication in patients with previous kidney damage or patients who are severely dehydrated. In patients who are not diabetic, metformin rarely results in hypoglycemia (low blood sugar). Modest weight loss may occur, though metformin is not a weight-loss medication. Metformin is not approved by the FDA for ovulation induction. Please discuss its use with your reproductive specialist.

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