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Clomid was one of the first ovulation induction agents introduced. Clomid is used widely by OB/GYN’s as a first line treatment for infertility. Clomid is used to induce or regulate ovulation.


Infertility specialists complete a thorough workup to establish the cause(s) of infertility prior to starting therapy with Clomid or other fertility drugs.  Male infertility must be ruled out before any female therapy begins.


Clomid does not directly stimulate the ovaries; rather, it works in the brain at the hypothalamus and pituitary gland. The hypothalamus is the part of the brain that produces gonadotropin releasing hormone (GnRH) to stimulate the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH).  FSH and LH then act on the ovary to stimulate development of eggs.   Each egg is surrounded by cells and fluid that support development (a follicle).


When the hypothalamus measures lower levels of estrogen (produced by developing follicles), it responds by releasing GnRH to increase FSH production. Clomid works by “blocking” estrogen receptors at the hypothalamus. This blockade by Clomid causes the hypothalamus to “measure” lower estrogen levels thus increasing FSH production. Once ovulation is occurring regularly on Clomid there is no advantage to increasing the dosage.


Clomid should generally be used for a short time period. Clomid is usually started at 50mg per day on cycle days 3, 4, or 5 calculated from the first day of the menstrual period and continued for 5 days. If ovulation does not occur at 50mg, the dosage can be increased in 50mg increments to 150mg.


Historically, Clomid has sometimes been prescribed for long periods by generalists, which can lead to deleterious side effects.  Pregnancy is most likely to occur during the first three months and after this period success rates decline precipitously. Infertility specialists usually move to the next therapy, such as stimulated IUI, after 3 failed Clomid cycles.


Clomid can cause thickening of the cervical mucus making it more difficult for the sperm to reach the eggs, and it can produce other side effects such as moodiness, hot flashes, vaginal dryness, and headache. 


Many infertility specialists are using Femara (letrozole) as an ovulation induction drug, particularly for patients who have side effects with Clomid.  Letrozole is an aromatase inhibitor. Aromatase synthesizes the conversion of androgens to estrogen, so blockage lowers estrogen levels causing the hypothalamus to release GnRH thus increasing FSH. Letrozole is less likely to adversely affect the cervical mucus or endometrium.   Its use for ovulation induction is growing, but use of it for this purpose is considered “off label”, as it has not approved by the FDA for this specific purpose.


Letrozole must not be given to pregnant women.  It has a shorter half-life in the body and fewer side effects compared to Clomid, so its advantage is that patients can begin a second cycle of Letrozole in the month following the first cycle, with no drug leftover in the body.


Clomid is a useful first line fertility drug when used judiciously after a complete evaluation of the female and male.