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Fewer Multiples with Letrozole, More Pregnacies with Clomid

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Researchers at the Atlanta Center for Reproductive Medicine (ACRM) recently evaluated data from 16,001 intrauterine insemination (IUI) cycles from 2010-2013 that used the oral medications Letrozole or Clomid. The data showed that Letrozole was associated with lower multiple pregnancy rates for women of all age groups. In women under 38, pregnancy rates were higher with Clomid than Letrozole, but there were also higher multiple pregnancy rates. In women over the age of 40, pregnancy rates were higher with Letrozole.

According to Dr. Jim Toner, the director of third party reproduction at ACRM, his practice had been seeing these trends for many years, but with such a large sample size now available, the tune was right time to share their experience.

Diagnosis had a variable effect on the results. Toner said, “Some groups like PCO patients and unexplained infertility have better success than male factor or endometriosis patients. But overall, Clomid is better than Letrozole in younger patients.”

Letrozole and Clomid are often a first-line fertility treatment. A fertility doctor may prescribe one of the drugs to a patient who is ovulating but having a hard time getting pregnant, or to a patient who doesn’t ovulate (anovulation). Letrozole is an aromatase inhibitor, and Clomid blocks estrogen receptors; they achieve the same result by slightly different means.

The decision on whether to prescribe Letrozole or Clomid has generally been based on physician personal preference. Some physicians prescribe Clomid because it’s less expensive; others prescribe Letrozole because it has fewer side effect.

Toner says all patients at his fertility clinic have a semen analysis, AMH testing and a hysterosalpingogram (HSG). If they have unexplained fertility, or ovulatory issues they are usually advised to take Letrozole or Clomid for 2 to 3 cycles. “It’s the first step for almost everybody, and particularly those who do not have insurance coverage for fertility treatment.


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