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RNA findings could diagnose male infertility

13 July 2015
Appeared in BioNews 810

A test to diagnose male infertility that uses RNA as a biomarker has been developed by researchers in the USA.

The scientists say the method could allow clinicians to bypass fertility treatments that are less likely to work, which could speed up the time to conception and avoid the financial and emotional cost of failed treatments.

Previous diagnosis of male infertility has focused on a physical examination of sperms' movement, volume and concentration.

As lead author Professor Stephen Krawetz from Wayne State University, Detroit, explains, this can miss more subtle causes of infertility: 'If you think about it, it's how good do the sperm look. That really doesn't tell you much about the quality. A sperm may look fantastic, but yet could not be up to the job of fertilisation.'

There are usually seven features used to diagnose male infertility, each requiring a different treatment or intervention. However, some couples struggle to conceive even when these features come back normal. Such couples are termed 'idiopathic infertile couples'.

It was previously thought that sperm contained as little as possible to make them more efficient DNA-carrying vehicles. However, recent research has shown that sperm carry a large amount of a different genetic molecule – RNA.

Krawetz's team hypothesised that a cause for idiopathic infertility may be found in this mass of RNA.

The team analysed sperm RNA elements (SREs) from 96 couples with idiopathic infertility and compared them to couples who had conceived naturally. They identified 648 SREs that correspond to genes involved in sperm development, motility and embryo formation.

Couples who conceived naturally were found to have a complete set of these SREs. Those missing certain SREs were significantly less likely to conceive naturally – the probability of conceiving dropped from 73 percent to 27 percent for men whose sperm were missing any of these SREs.

Importantly, the absence of these 'required' SREs did not affect the success rate of (more invasive) fertility methods such as IVF or ICSI. Therefore, the researchers say a diagnostic test based on this research could allow doctors to recommend more-invasive fertility therapies earlier on in treatment, if results suggest less-invasive therapies would be ineffective.

Sperm RNA element analysis may also diagnose female infertility. Where couples had the full set of SREs present but failed to conceive, researchers predicted a 'female factor may have been involved'. In most cases, this was confirmed by further testing.

Dr Rebecca Sokol, president of the American Society for Reproductive Medicine, cautions that there is still some way to go before a reliable diagnostic test becomes available. 'For this to be truly used as a screening test, it will have to be made more facile and less expensive,' she said. Dr Sokol also points out that the trial was small and lacked a randomised control group, and so the results need replicating.

The study was published in Science Translational Medicine.

Absence of sperm RNA elements correlates with idiopathic male infertility
Science Translational Medicine |  8 July 2015
Genetic Test May Help Spot Male Fertility Problems
HealthDay |  8 July 2015
Sequencing the RNA of sperm may better diagnose a man's infertility
The Verge |  8 July 2015
Sperm RNA, biomarker of male infertility, may predict success of fertility
Eurekalert (press release) |  9 July 2015
Sperm RNA-seq Study Reveals Potential Biomarkers for Diagnosing Male Infertility
GenomeWeb |  8 July 2015
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