Letrozole Produces More Babies in Women With Polycystic Ovary Syndrome: Study

By Gene Emery

July 10, 2014

NEW YORK (Reuters Health) - The breast cancer drug letrozole, used off label to stimulate ovulation, produces 44% more births among infertile women than standard treatment with clomiphene, according to a new study of 750 women.

In a double-blind trial in patients with polycystic ovary syndrome, 27.5% of the women getting letrozole gave birth compared to 19.1% given clomiphene (p=0.007) over the treatment period of up to five cycles.

The researchers, reporting in the July 10 New England Journal of Medicine, said the rate of congenital abnormalities was comparable in the two groups and the risk of pregnancy loss was similar.

As expected, letrozole recipients were less likely to deliver twins.

"Clomiphene is the granddaddy of all fertility drugs. But when you have a drug that is more than 40% better, that's going to open people's eyes and likely change practice," said the chief author, Dr. Richard Legro of Penn State College of Medicine in Hershey, Pennsylvania.

Because the drugs are far less expensive than in vitro fertilization, and letrozole's effectiveness has been demonstrated in the new trial, there's now "an additional option" for women with fertility problems, he told Reuters Health by phone. "You can argue whether clomiphene or letrozole should be tried first, but I think both of these drugs are now effective first-line treatments."

"It's a very powerful study. Clearly this is the best study to date," said Dr. Samantha Pfeifer, chairwoman of the practice committee of the American Society for Reproductive Medicine, who was not involved in the research. "Letrozole appears to be better than Clomid when it comes to live birth rates, and that's the outcome we're interested in."

Polycystic ovary syndrome affects 5% to 10% of reproductive-age women, making it the most common cause of anovulatory infertility, according to the researchers.

Clomiphene has been around for years, but a better alternative has been sought because treatment success rate is low and multiple births often result.

All of the women in the study had a normal uterine cavity, at least one patent fallopian tube, and a male partner with a sperm count of at least 14 million per milliliter.

The volunteers received either 50 mg of clomiphene daily for five days for up to five cycles or 2.5 mg daily of letrozole on the same schedule. If there was no response based on progesterone levels, the daily dose was increased to as high as 150 mg and 7.5 mg respectively.

The ovulation rate was significantly higher with letrozole. In the third treatment cycle, for example, the rate was 66.8% out of 268 women versus 50.0% of 282 women treated with clomiphene. The live birth rate in that cycle was 7.1% for letrozole therapy and 4.4% with clomiphene.

With letrozole, the miscarriage rate was 31.8%, and 3.4% of the pregnancies were twin pregnancies. The rates with clomiphene were 29.1% and 7.4% respectively.

There were four major infant congenital abnormalities with letrozole and one with clomiphene, a different that wasn't significant. "You also had more pregnancies with letrozole. You have to adjust the rate for the number of pregnancies," said Dr. Legro.

Clomiphene recipients tended to experience more hot flashes. Letrozole patients were more prone to fatigue and dizziness. Other side effects were comparable in the two groups.

Dr. Pfeifer, an associate professor of clinical reproductive medicine at the Weill Cornell Medical Center in New York, told Reuters Health that this is only the latest study to show that, despite earlier concerns, letrozole appears to be safe. "It's better tolerated than Clomid. Some people with Clomid have severe side effects and this seems to have less of a side effect profile."

SOURCE: http://bit.ly/1n1FwDv

N Engl J Med 2014.

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