Many women who have trouble conceiving turn to fertility drugs, but a Canadian-led research team warns there may be an underappreciated risk: The treatments most frequently prescribed to aid pregnancies have the potential to spread Creutzfeldt-Jakob disease.
The controversial research, which was funded in part by the federal government, tested dozens of samples of the most commonly available fertility drugs from around the world, and found that all those with pregnancy-enhancing hormones extracted from human urine contained prion proteins.
It is not known whether the proteins detected in the drugs were derived from infectious prions of the kind that cause CJD, or were normal, benign proteins. But the finding of the protein as a contaminant in these products indicates that infectious prions wouldn't be excluded from the manufacturing process if a urine donor was incubating the brain-wasting disease.
The discovery was worrisome enough for the researchers to conclude that "the risks of urine-derived fertility products could now outweigh their benefits" in their study published in the online journal PLoS One.
The finding "is a source of concern," said Neil Cashman, a neurologist at the University of British Columbia who led the team and is science director of PrioNet Canada, a research network funded by Ottawa and charged with developing strategies for minimizing the spread of prion-caused ailments.
Creutzfeld-Jakob disease involves prions attacking and destroying brain cells. Some people have a genetic predisposition for the disease, and it can also be spread through the blood or tissues of those infected. Up to now, urine has been considered to have minimal risk of transmission. But the cause of most cases is a mystery. The disease is best known for its bovine variant, commonly called mad cow disease.
Although it's not widely known, gonadotropin hormones excreted by women in their urine are the basic building blocks for about two-thirds of fertility drugs. Because of a quirk in female biology, more of the hormones are found in postmenopausal women. And because the hormones are found in such tiny amounts, drug makers have to pool the urine of thousands of donors to extract enough of the active ingredients.
An estimated 300,000 women in North America use fertility drugs each year. They are typically injected to help promote ovulation or other biological processes.
Health Canada said in an e-mailed statement that it's "reviewing this recent research, and continuing to monitor safety information as it becomes available to determine what additional action, if any, may be necessary."
Health Canada noted it updated its warning label on urine-derived fertility drugs in 2007 "as a precautionary measure .... to indicate that a theoretical risk of transmission of infectious agents cannot be completely excluded."
Ferring Pharmaceuticals Inc., a Swiss-based manufacturer of fertility drugs, disputed the contention that the products are a potential pathway for the brain-wasting disease to spread.
"There is a 50-year history of gonadotropin treatment, treating millions of women worldwide, and there has never been a case of prion-related disease," said Dennis Marshall, Ferring's executive director of medical affairs. He criticized the research, saying it may cause unjustified worries for women already anxious about trying to become pregnant.
Merck & Co. said its fertility drugs adhere to a rigorous testing process, high levels of care on donor selection, and Health Canada requirements.
"As indicated in the Health Canada-approved product monograph, 'no case of transmission of an infectious agent linked to the use of urine-derived gonadotropins has ever been identified,' " the company said.
But Dr. Cashman said the industry's view may be based on the fact that no donors have so far had the disease.
"We've been lucky that none of the donors have been incubators of Creutzfeld-Jakob disease. But if there was ... these batches of hormone would likely transmit CJD at a high percentage," Dr. Cashman said. "I think that it's a problem that needs attention, and as a society we need to be able to figure out how to deal with it."
He said one of the risks of using older women as donors is that prion-induced diseases could be incubating without yet having caused symptoms. Also, since the urine of thousands of women is pooled, it's possible for a single carrier to contaminate a large amount of the drug.
Researchers have been investigating urine after laboratory experiments with animals showed prions from urine are able to spread the brain ailment.