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What is Clomid, and how does it work?

If you're facing infertility, you have probably heard about a number of different medications that are commonly used to help couples conceive. Fertility specialist Mark Kan, MD, tells you about Clomid -- one of the first treatments your doctor may try.

Your question
What is Clomid, and how does it work?

The expert answers
Clomiphene citrate (also known as Clomid or Serophene) is a medication that is commonly used in fertility treatment. Because it is relatively inexpensive and can be administered orally, clomiphene is generally one of the first medications prescribed for patients who do not ovulate regularly.

In women who do ovulate regularly, clomiphene may be used for "superovulation," where 2 or 3 eggs are produced. This increases the number of "targets" for the sperm, thereby increasing the chance of pregnancy.

Clomiphene is normally administered for five days during the follicular part of the cycle (the portion of the cycle following menstrual bleeding). Clomiphene is structurally similar to estrogen and acts on the estrogen receptor. First approved by the FDA in 1967, it has recently been reclassified as a selective-estrogen-receptor-modulator (SERM). How does clomiphene work? The hormonal signals that cause the ovarian follicles to grow are released from the pituitary gland. These hormones are named Follicle Stimulating Hormone (FSH) and Leutinizing Hormone (LH) for their actions in the ovary. The pituitary receives its signals from the hypothalamus in the brain. Clomiphene blocks the estrogen receptor and "tricks" the brain into thinking there are low levels of estrogen. The pituitary responds by releasing more FSH and LH, thus stimulating follicular growth in the ovaries.

Whereas clomiphene "tricks" the pituitary into producing more FSH and LH, gonadotropin injections of FSH and LH increase the amount of signals directly. Treatment with these injections requires more intensive monitoring than does therapy with clomiphene. In general, treatment with fertility medications is initiated to help women overcome ovulatory dysfunction, or to produce multiple eggs so there is a higher chance of achieving pregnancy.

In the "Clomiphene citrate challenge test" (CCCT), clomiphene is administered and FSH levels are compared before and after treatment. In theory, clomiphene blocks the negative feedback of estrogen, leaving only inhibin (a substance that inhibits FSH) to suppress FSH. In some women, inhibin alone is not able to block the high levels of FSH without the help of estrogen. The CCCT will therefore be abnormal and show high FSH levels after clomiphene in women with diminished ovarian reserve.

While the CCCT may help to identify some patients with diminished ovarian reserve, there is no single test that can predict which patients can or cannot become pregnant.

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