U.S. And Japanese Scientists Develop New Test For Male Infertility

The scientists have developed a method that could make diagnosis more accurate and lead to acorrect diagnosis in cases where doctors can find no apparent cause for a couple's inability toconceive.

Large trials are now starting in the United States and Japan and if these confirm the results ofresearch published today in Human Reproduction, the technology might even be developed as acommercial test kit for wide-scale use.

The researchers are Peter Sutovsky, M.S., Ph.D., and Gerald Schatten, Ph.D., of OregonHealth Sciences University and Yukihiro Terada M.D., Ph.D., from Tohoku University Schoolof Medicine in Sendai, Japan. The research was supported by US National Institutes of Health(NIH), National Institute of Occupational Safety and Health (NIOSH), National Institute ofChild and Human Development (NICHD), and US Department of Agriculture (USDA).

The method, called sperm-ubiquitin tag immunoassay (SUTI) is based on a small protein calledubiquitin. Ubiquitination is a process by which the body breaks down and recycles obsoletecellular proteins. The accumulation of ubiquitin in the sperm cells is evidence of damage ordefect. The researchers used specific antibodies against ubiquitin to screen sperm from 17infertility patients and two fertile donors by microscopy and flow cytometry.

They discovered high levels of ubiquitin antibodies on the surface of cells taken from 13 of the17 infertility patients tested, but not in the two fertile donors. Of the 17 infertility patients, thetest confirmed a previous clinical diagnosis of male infertility in five. Testing also revealedpossible reasons for infertility that had previously been inexplicable in five other patients. Inthree of the patients results suggested that there could be a male contribution to previouslydiagnosed maternal infertility. In another three, testing confirmed a previous diagnosis offemale-only infertility and in one case it showed that the man was unlikely to have been thecause of unexplained infertility.

"Ubiquitin appears to be a universal marker of semen abnormalities, recognising a wide rangeof sperm defects and also contaminants in semen," said Dr Sutovsky. "I think SUTI could bethe first truly objective assay for male infertility, based on an exact, fully automatedmeasurement of a single protein in sperm rather than a subjective analysis of sperm by lightmicroscopy. Its major advantage is its sensitivity. We were able even to diagnose a male factorin cases where conventional semen analysis could not explain infertility. In around one fifth ofall couples, current methods cannot identify a cause. SUTI will be able to provide an answer inat least a portion of these cases."

Dr Terada, whose hospital in Sendai provided the 17 patients, said that while traditional lightmicroscopic analysis of sperm had indisputable value, it often produced inconsistent resultsand did not always recognise some of the hidden intrinsic sperm defects. "This enables a moreaccurate diagnosis and could direct the treatment of infertility towards the man, sparing hispartner excessive examinations and possibly even unnecessary treatments," he said.

The research team believes SUTI may also have a role in future treatment. Dr Schatten said:"Since we now know a specific protein is associated with defective sperm and we haveantibodies against it, there is a chance that we could develop a technique for depleting most ofthe truly defective sperm from semen samples for IVF or intracytoplasmic sperm injection(ICSI) - the process by which an egg is fertilised by injecting a single sperm."