A team of US and Japanese experts in reproductive medicine has made a major advance in testing for male infertility that could prevent women seeking fertility treatment from taking unnecessary tests or having unnecessary treatments.
The scientists have developed a method that could make diagnosis more accurate and lead to a correct diagnosis in cases where doctors can find no apparent cause for a couple's inability to conceive.
Large trials are now starting in the United States and Japan and if these confirm the results of research published today* in Human Reproduction, the technology might even be developed as a commercial test kit for wide-scale use.
The researchers are Peter Sutovsky, M.S., Ph.D., and Gerald Schatten, Ph.D., of Oregon Health Sciences University and Yukihiro Terada M.D., Ph.D., from Tohoku University School of 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 of Child and Human Development (NICHD), and US Department of Agriculture (USDA).
The method, called sperm-ubiquitin tag immunoassay (SUTI) is based on a small protein called ubiquitin. Ubiquitination is a process by which the body breaks down and recycles obsolete cellular proteins. The accumulation of ubiquitin in the sperm cells is evidence of damage or defect. The researchers used specific antibodies against ubiquitin to screen sperm from 17 infertility 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 the 17 infertility patients tested, but not in the two fertile donors. Of the 17 infertility patients, the test confirmed a previous clinical diagnosis of male infertility in five. Testing also revealed possible reasons for infertility that had previously been inexplicable in five other patients. In three of the patients results suggested that there could be a male contribution to previously diagnosed maternal infertility. In another three, testing confirmed a previous diagnosis of female-only infertility and in one case it showed that the man was unlikely to have been the cause of unexplained infertility.
"Ubiquitin appears to be a universal marker of semen abnormalities, recognising a wide range of sperm defects and also contaminants in semen," said Dr Sutovsky. "I think SUTI could be the first truly objective assay for male infertility, based on an exact, fully automated measurement of a single protein in sperm rather than a subjective analysis of sperm by light microscopy. Its major advantage is its sensitivity. We were able even to diagnose a male factor in cases where conventional semen analysis could not explain infertility. In around one fifth of all couples, current methods cannot identify a cause. SUTI will be able to provide an answer in at least a portion of these cases."
Dr Terada, whose hospital in Sendai provided the 17 patients, said that while traditional light microscopic analysis of sperm had indisputable value, it often produced inconsistent results and did not always recognise some of the hidden intrinsic sperm defects. "This enables a more accurate diagnosis and could direct the treatment of infertility towards the man, sparing his partner 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 have antibodies against it, there is a chance that we could develop a technique for depleting most of the 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."
* Ubiquitin-based sperm assay for the diagnosis of male factor infertility. Human Reproduction. Vol 16. No 2. pp. 250-258
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