Letrozole

PHILADELPHIA -- Researchers at New York's Cornell University have announced the first pregnancy after in vitro fertilization in a breast cancer patient whose ovaries were stimulated with letrozole and low-dose follicle stimulating hormone.

Standard ovarian stimulation agents are not considered safe in breast cancer patients because they increase estrogen levels. But letrozole, an aromatase inhibitor that is also used to treat breast cancer, can stimulate oocyte production with out raising estrogen levels, making it ideal for this patient population.

"We think this protocol can be given first priority in these patients," Kutluk Oktay, M.D., said at the annual meeting of the American Society for Reproductive Medicine.

"This could be a new twist in ovarian stimulation. I think this may be a protocol that we could possibly use for everybody," he said in an interview.

The pregnancy occurred during a study in breast cancer patients undergoing embryo freezing before chemotherapy. Sixty-five breast cancer patients were enrolled in the study, 33 of whom were undergoing ovarian stimulation, in vitro fertilization (IVF), and embryo freezing. A control group of 32 patients did not undergo IVF.

The IVF patients were divided into three groups, each of which received a different ovarian stimulation regimen: 60 mg/day of tamoxifen alone; 60 mg/day of tamoxifen plus low-dose FSH; or 5 mg/day of letrozole plus low-dose FSH.

Patients in the tamoxifen/FSH and letrozole/FSH groups had more eggs retrieved and more embryos created than did those on tamoxifen alone. In addition, the letrozole/FSH group had the lowest estrogen levels during stimulation but the highest yield of embryos per cycle--5.3--compared with 3.8 in the tamoxifen/FSH group and 1.3 in the tamoxifen alone group.

After a mean follow-up of 19 months, there were three cancer recurrences in the IVF and three in the control group.

In the IVF group, one patient had an embryo transferred to a gestational surrogate, resulting in the first pregnancy from a frozen embryo created from tamoxifen stimulation. In addition, one patient in the letrozole/FSH group became pregnant after transfer of an embryo.

Letrozole and tamoxifen, both aromatase inhibitors used in the treatment of breast cancer, work differently when it comes to stimulating the ovaries.

"Tamoxifen prevents breast cancer by blocking estrogen receptors, but it still stimulates ovaries to make estrogen. Letrozole works by shutting down estrogen production in the ovary, but when the body doesn't see enough estrogen it makes more FSH to stimulate the ovaries," he said.

Dr. Oktay noted that the study's secondary finding is that ovarian stimulation is possible with FSH and normal levels of estrogen. "You don't need your estrogen levels to go up sky high in IVF to have a successful outcome."

This finding also has important implications for patients without cancer who are undergoing IVF, because with lower estrogen levels the risk of ovarian hyperstimulation is also decreased.

"We have also found that if you start this drug you may actually shut down the symptoms of ovarian hyperstimulation, so I think letrozole may have promise for all IVF patients. It's cheaper, and you're not exposing people to unnecessary hyperstimulation." Dr. Oktay said.

BY KATE JOHNSON

Montreal Bureau

COPYRIGHT 2004 International Medical News Group
COPYRIGHT 2004 Gale Group