For Unexplained Infertility, Breast Cancer Drug No Better Than Standard Treatment

Study found letrozole did not result in more pregnancies compared to two other fertility drugs

Wednesday, September 23, 2015

WEDNESDAY, Sept. 23, 2015 (HealthDay News) -- A breast cancer drug that is sometimes used to treat infertility may reduce a couple's risk of having a pregnancy with multiple babies -- but it might also slightly lower their chances of having a baby at all, a new clinical trial suggests.

The study did not find the cancer drug letrozole (Femara) more effective than standard fertility drugs for women with unexplained infertility.

In research reported last year, letrozole actually improved birth rates among women who were infertile due to polycystic ovarian syndrome compared to a widely used fertility drug called clomiphene (Clomid). In contrast, the new study focused on women age 40 and younger whose infertility had no clear cause.

"For them, we can't say that letrozole is as good as standard drugs when it comes to your chances of going home with a baby," said lead researcher Dr. Michael Diamond, professor and chair of the department of Obstetrics and Gynecology at Georgia Regents University, in Augusta.

The study was published Sept. 24 in the New England Journal of Medicine.

When a couple is unable to conceive and tests find no cause, doctors often try ovarian stimulation, where hormonal medications are used to encourage ovulation.

That's especially true when the woman is younger than 35, noted Dr. Sheeva Talebian, an infertility specialist and assistant clinical professor at the Icahn School of Medicine at Mount Sinai in New York City. The success rate with ovarian stimulation declines with age, so older women typically go straight to in-vitro fertilization, she added.

Traditionally, clomiphene has been the drug of choice for ovarian stimulation, explained Talebian.

If that failed, the next step would be gonadotropin, a more powerful injection drug.

"But in recent years, we've been shying away from gonadotropin because of the higher risk of multiples," Talebian said.

At the same time, more doctors have been turning to letrozole, a breast cancer drug that also stimulates ovulation in younger women.

Dr. Brooke Hodes-Wertz, a reproductive endocrinologist at NYU Langone Medical Center's Fertility Center in New York City, said, "In some centers, it's now the first-line therapy for unexplained infertility."

However, there have been no clinical trials to test whether letrozole is actually better, or even as good as clomiphene for unexplained infertility, Diamond said.

For the new study, Diamond and his team randomly assigned 900 women to undergo ovarian stimulation with either clomiphene, gonadotropin or letrozole -- for up to four treatment cycles.

In the end, 32 percent of women on gonadotropin gave birth, versus 23 percent of women on clomiphene, and 19 percent of those on letrozole, the study said.

However, the difference between the clomiphene and letrozole groups was not significant in statistical terms, Talebian pointed out. That means the result could be due to chance.

Gonadotropin led to a higher birth rate, but it also raised couples' odds of having twins or triplets. Eight percent of women on the drug had twins, and 2 percent had triplets, the research revealed.

One percent of women on clomiphene had twins, as did 3 percent of those taking letrozole, the study found. None of the women on either clomiphene or letrozole had triplets.

Both Talebian and Hodes-Wertz stressed that point. "As a field, we've been moving away from gonadotropins because of the risk of multiples," Hodes-Wertz said. "This study supports that."

She was not convinced, however, that the results prove clomiphene is better than letrozole for unexplained infertility.

Talebian agreed. "I think the findings suggest they are comparable," she said.

And Hodes-Wertz said the two drugs appear comparable in another important way: There were no differences in the risks of birth defects or newborn complications. That's reassuring, she explained, because past animal research had hinted that the risks might be higher with letrozole.

According to Talebian, some women do fare better on letrozole because it carries a lower risk of side effects like hot flashes and mood swings. So that's yet another factor to consider, she said.

Diamond agreed that individual couples have to talk to their doctors about the best drug option for them.

In some cases, though, the choice is not the doctors' or patients'. "Sometimes it's whatever insurance will pay for," Hodes-Wertz said.

The study was partly funded by the U.S. National Institutes of Health. None of the drugs' manufacturers had a role in the trial, the researchers said.

SOURCES: Michael Diamond, M.D., professor and chair, obstetrics and gynecology, Georgia Regents University, Augusta; Sheeva Talebian, M.D., assistant clinical professor, Icahn School of Medicine at Mount Sinai, New York City; Brooke Hodes-Wertz, M.D., M.P.H., reproductive endocrinologist, NYU Langone Medical Center's Fertility Center, New York City; Sept. 24, 2015, New England Journal of Medicine

HealthDay