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Ask The Experts - Everything to Know About Clomiphene - aka Clomid

 **Q:** Is Clomid always the drug of first resort for treating infertility? **A:** Clomiphene citrate, aka "Clomid," is in a class of drugs known as anti-estrogens, meaning it binds to estrogen receptors in the hypothalamus region of the brain responsible for reproduction. As such, clomiphene fools the brain into thinking that there is little or no circulating estrogen in the bloodstream, and so the brain signals the pituitary gland to secrete more follicle stimulating hormone (FSH). **Why Clomid is So Common** Many women are prescribed clomiphene empirically, that is, without a specific cause, in hopes of enhancing fertility. For most women, this strategy is fine because clomiphene is a safe and inexpensive medication. However, no real benefit may be gained unless the clomiphene induces the ovulation of more than one follicle (or egg). Furthermore, as clomiphene is an anti-estrogen, for some women, it may bind to estrogen receptors in the uterine lining and cause it to be too thin, prohibiting pregnancy. To avert this, we perform at least one ultrasound in each clomiphene treatment cycle to check for normal endometrial thickness and hopefully, two or three follicles. We also have our patients monitor for their own LH surge with an over-the-counter ovulation predictor kit. Intercourse or intrauterine insemination is planned accordingly. **Best Candidates** Clomiphene is targeted to patients who do not ovulate regularly, especially if they have a condition known as polycystic ovarian syndrome or PCOS. These women have normally functioning ovaries but do not go through proper signaling of the brain to the pituitary and do not make adequate FSH and LH to induce ovulation. In these women, a small dose of clomiphene can trigger just enough FSH to accomplish ovulation of a single egg. While most women with PCOS will respond to clomiphene and ovulate, some will require the addition of an insulin sensitizing medication to enhance response. If a woman does not respond to clomiphene, she may have very low FSH and estrogen levels, a condition known as hypothalamic anovulation. These patients usually require injectable FSH to induce ovulation. **Normal Ovulators** Women who ovulate normally are also candidates for clomiphene to improve the hormonal response of their ovulatory cycles. If she is found to have a low luteal phase progesterone level, she may benefit from clomiphene making higher levels of progesterone to support embryo implantation. Unfortunately, many women are diagnosed with low progesterone because they are advised to check the level on "day 21" of the cycle. But because they don't have an exact 28 day cycle, the monitoring isn't exactly in the middle of the luteal, or post-ovulation phase of the cycle. A better way to do this is to have a patient use an ovulation predictor kit and have the progesterone level drawn 7 days after the LH surge. If this level is 10 ng/ml or greater, the level is normal and there is no "luteal phase defect." **Who Should Avoid Clomid** In general, we recommend that women 35 and older skip the Clomid step and consider more aggressive treatment, such as injectable FSH with intrauterine insemination or even in vitro fertilization. Women who experience a thinning of the uterine lining should not be given clomiphene. **Potential Side Effects** Many women will experience no side effects while others experience side effects similar to those seen in early menopause: hot flashes and irritability. These are rarely bothersome enough to discontinue treatment. Women who experience a rare side effect of significant visual changes (flashing lights) are advised to discontinue treatment immediately. Regarding risk of multiple pregnancy, Clomid doesn't have a large impact; the risk of twins is about 5% and triplets or more is 1% or less, depending on the patient's age.

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