By Rick Weiss
Washington Post Staff Writer
Friday, May 15, 1998; Page A03

Federal health officials yesterday said a commonly used drug treatment for infertility may have caused a pregnant woman's death, and they asked doctors to report any similar cases so they could determine whether warnings ought to be issued.

The 38-year-old woman, whose identity was not released, was nine weeks pregnant with triplets when she died of a burst blood vessel in her brain. Like many women who undergo in-vitro fertilization (IVF), she was taking a combination of aspirin and a blood-thinning drug called heparin -- a popular but unproved regimen for preventing spontaneous abortion in women undergoing fertility treatments.

Officials from the Centers for Disease Control and Prevention in Atlanta said they were not sure the medicines had caused the fatal hemorrhage, which occurred in 1996 and has been under investigation until recently. Subsequent tests revealed that the burst vessel had been malformed since birth, and doctors have long known that abnormal vessels naturally become weaker during pregnancy.

But aspirin and heparin are potent clot busters that can initiate or exacerbate bleeding. That raised suspicions among medical investigators that the drug combination might have increased the woman's risk, and may also do so in women with normal vessels. Given the uncertainty, the CDC decided to publicize the case and ask doctors to be on the lookout for others.

"We really don't know if this is a single case or one of a few or one of many," said Fred Hopkins, a medical epidemiologist with the CDC in Atlanta. "I think this is a yellow flag rather than a red flag."

Hopkins said women who are using the drug combination should talk to their doctors about the drugs' possible risks and the limited evidence of their effectiveness. So far, he said, aspirin and heparin have only been proven to reduce the rate of spontaneous miscarriage in women who have repeatedly miscarried after natural pregnancy and who have an immune system disorder characterized by specific proteins in the blood, called antiphospholipid antibodies.

Only two studies have looked at the drug combination in women undergoing IVF. One showed some benefits and the other did not. But both studies included only women with the problematic antibodies in their blood, leaving unanswered the question of whether the drugs may help the vast majority of women who are infertile or miscarry for other reasons.

The Food and Drug Administration has not approved the drugs as a fertility treatment, but clinics have been offering the regimen to many women. A 1997 survey by the Society for Assisted Reproductive Technology in Birmingham, Ala., found that about three-quarters of fertility doctors had given the drugs; about half would consider giving them to women with a single unsuccessful IVF attempt; and about one in five would consider giving them to new patients with no history of IVF failure.

Judicious use of the drugs has not been helped by the many infertility Internet sites that tout the regimen for desperate patients, said Benjamin Younger, executive director of the American Society for Reproductive Medicine (ASRM) in Birmingham.

"Because they are paying for so much of this out of their pocket, and because they are so driven to become pregnant, patients make decisions and choices they might not normally make," Younger said. Use of the drugs in women not diagnosed with the immune system disorder should be considered experimental, Younger said, and ought to be limited to situations in which the women give informed consent and the work is overseen by an ethics review board.

Hopkins said he did not know whether the woman who died had been informed of the regimen's experimental nature. She was being monitored with standard coagulation tests, which had not detected any heightened risk of bleeding, according to a summary of the case in today's issue of the CDC's Morbidity and Mortality Weekly Report.

Robert J. Stillman, medical director of the Shady Grove Fertility Centers in Rockville and a member of the ASRM's board of directors, said he believes that use of the drugs has declined in recent years as evidence of their effectiveness has come into question.

"A baby aspirin alone may be as efficacious as the two together, and has much less risk," Stillman said.