Toronto lab identifies proteins that could form basis of male infertility test

Embryologist Rick Slifkin displays some of the frozen sperm stored at Reproductive Medicine Associates of New York, in New York, Thursday, Oct. 3, 2013. (AP / Richard Drew)

TORONTO -- Scientists in Toronto have identified two proteins that could save men with infertility problems both pain and time.

They say the proteins could form the basis of tests to figure out what type of infertility a man has and whether he has a chance of fathering children.

More work will be needed before commercial tests using the proteins could be approved and marketed.

But one of the scientists says when they are ready the tests will dramatically reduce the need for testicular biopsies in men with fertility issues.

And Dr. Keith Jarvi says they will also be able to identify men for whom invasive sperm retrieval operations are likely to fail and therefore probably shouldn't be tried.

The work is being reported in the journal Science Translational Medicine and was funded by the Canadian Institutes of Health Research.

"We're trying to eliminate unnecessary surgery for the patients," says Jarvi, who is head of urology at Mount Sinai Hospital.

The scientists are from Mount Sinai and its Lunenfeld-Tanenbaum Research Institute, and University Health Network.

The field needs these kinds of diagnostics, Jarvi says. "I think our patients would flock to use this test. Anyone would prefer to do this rather than have the biopsy."

MaRS Innovation, which commercializes discoveries made by University of Toronto hospitals and research institutes, is already working on the project, which Jarvi believes may lead to commercial tests within the next couple of years.

Dolores Lamb, who directs a centre for reproductive medicine at Baylor College of Medicine in Houston, Tex., praised the work, which she predicts will lead to tests that clinics can use when assessing men with infertility.

"No one has taken it this far to be able to develop something that potentially could be used for clinical diagnostics," says Lamb, who was not involved in the research.

The work began when the team started looking for a test that could be used to see if a vasectomy was successful -- if it had actually stopped flow of sperm into the seminal fluid released when men ejaculate.

But they came to realize that proteins in seminal fluid could be used as clues with which to diagnose which type of infertility a man has -- obstructive or non-obstructive.

The researchers started by looking at 2,000 proteins, narrowing the search to 79 and then 18 and finally two, says Andrei Drabovich, first author of the paper and a post-doctoral fellow at the Lunenfeld-Tannenbaum Research Institute.

The researchers tested the predictive value of the proteins on first 30 patients, then an additional 119. Drabovich says they are working to draw on samples from other clinics to further validate the findings.

Urologists refer to obstructive infertility as a plumbing problem -- sperm are being produced, but they aren't getting released.

Non-obstructive infertility is a production problem; the testicles are making few, if any, sperm. There are three different types of non-obstructive infertility. Men with one of those types produce virtually no viable sperm.

Jarvi says currently men will take a series of expensive genetic tests to determine if they have obstructive or non-obstructive infertility. And some will undergo biopsies which involve inserting between one and three needles into testicles.

Men with obstructions can have the problem fixed in some circumstances or have sperm extracted from their testicles to be used in in vitro fertilization.

Things are more difficult -- though not always impossible -- for men in the non-obstructive category. Some produce small quantities of viable sperm. But locating it and extracting it requires an operation that can take several hours and involves cutting open a testicle and searching with a microscope for sperm.

Jarvi says that in about 55 to 60 per cent of such operations viable sperm will be harvested. "So about a little less than half the time we're in there for a few hours and we actually can't find any sperm that's usable."

Surgeons who do this type of work are highly skilled, and can often do the procedure without harming the testicle. But the operation can lead to damage and even loss of the testicle.

Jarvi says the tests cannot currently predict success, but one of the proteins, TEX101, can predict failure.

"It's very good at predicting the complete absence of sperm," he says. "It can tell you: If you don't have sperm, you shouldn't have the operation."

Lamb says that would be very useful. But though she was impressed by the work, she said she would like to see data on this aspect of the TEX101 protein.

Jarvi is hopeful the work will help male infertility clinics and the couples they counsel arrive at answers by a faster and simpler route than is currently available.

"You can avoid biopsies in many of the men," he says. "And I think for a lot of the men, they just want to know what their options are earlier on.

"That's very important for an infertile couple."