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Could an obscure type of herpes virus trigger female infertility?

3:30pm Friday 8th July 2016 content supplied byNHS Choices

"Obscure virus may be cause of unexplained infertility," The Independent reports.

Italian researchers found copies of the HHV-6A virus - a type of herpes virus - in the womb lining of 43% of women with unexplained infertility compared to 0% in women with a history of successful pregnancy.

This small study analysed cells from the womb linings of 30 women with unexplained infertility and 36 women who'd had one successful pregnancy. Researchers found the HHV-6A virus in cells from almost half the women with unexplained infertility but none of the women who'd had babies had the HHV-6A virus.

There was also some difference in their levels of certain immune system molecules, which the researchers suggest could affect the ability to sustain a pregnancy - but this is only speculation.

Most people are infected with HHV-6 viruses in early childhood. These viruses (there's an A and B type), cause a usually mild childhood rash called roseola. Like other herpes viruses, they then live in the body and remain inactive for many years. However, reactivated forms of the virus have been linked by different researchers, in recent years, to more than 50 different conditions, ranging from amnesia to uveitis. Its impact on health outcomes remains uncertain. 

Ultimately, this is very early-stage research that leaves many questions unanswered and further studies are needed to find out whether HHV-6A really is a cause of infertility, and if so, whether treating the virus with antivirals would improve the chances of a successful conception.

 

Where did the story come from?

The study was carried out by researchers from the University of Geneva, University of Ferrara and Human Reproduction Centre Brunico Hospital and was funded by Regione Emila Romagna.

The study was published in the peer-reviewed journal PLOS One, an open-access journal, and is free to read online.

The Independent provides the most accurate summary of the study. Other news sources don't do as well.

The Mail Online's story, while basically accurate, may raise hopes of a cure before the cause of unexplained fertility is established.

The Times says: "Almost half of women with unexplained fertility problems are infected with a mysterious virus," although we don't know whether the proportion of women found to have HHV-6A infection in this small study would hold true of all women with unexplained infertility.

The Daily Telegraph has a bizarre headline which urges people to "Be careful who you kiss," on the basis that the virus may be passed on by saliva, despite the fact that most people are infected as toddlers.

The Telegraph's story also says unexplained primary infertility means "the inability ever to bear a child", when it actually means that a woman has been unable to become pregnant after one year or more of trying, without any obvious cause.

 

What kind of research was this?

This was an Italian cohort study, in which researchers took cells from the womb linings of women with and without infertility to look for DNA from HHV-6 viruses. HHV-6 (human herpes virus 6) is a virus that most people are infected with in childhood and then lies dormant in the body. It was discovered in 1986 and little is known about the role it may play in regards to human health.

Reactivation of the virus has been associated with various diseases, including immune and inflammatory conditions. Previous research has suggested the female genital and reproductive system could be a site for the virus to become reactivated and this was the basis for this research.

Cohort studies can show differences between groups, and links between one factor (in this case viral infection) and another (infertility) but they cannot prove that one causes the other.

 

What did the research involve?

The research involved analysing womb samples taken from 30 women who'd attended a clinic for infertility treatment, for whom no obvious cause of infertility had been found. These women were reportedly taking part in a randomised trial, though no further information on this is given. They were compared with another group of 36 women who'd had at least one child, who were within the same age range. The recruitment of the control cohort, or why they had womb samples taken, is unclear. 

They took samples of cells from the womb lining of each woman, during the same phase of the menstrual period. They analysed cells for the presence of HHV-6A and the linked HHV-6B virus, both in the cells and in the blood supply.

In further studies, researchers looked at how the cells infected with HHV-6A behaved and whether this was different from cells not infected with HHV-6A. They also looked at other factors such as hormone levels.

 

What were the basic results?

The researchers found:

  • similar numbers of women with and without infertility had HHV-6B DNA in their blood cells (8 infertile, 10 fertile)
  • no women with or without infertility had HHV-6B DNA in their womb lining cells
  • no women with or without infertility had HHV-6A DNA in their blood
  • 13 women (43%) with infertility had HHV-6A DNA in womb lining cells compared to none without infertility

In further research, they found that women with HHV-6A DNA in womb lining cells also had higher levels of one type of reproductive hormone (estradiol), and different levels of certain immune system signalling molecules compared to women without HHV-6A DNA, both in infertile and fertile women. 

 

How did the researchers interpret the results?

The researchers say: "further studies are required to confirm the association," but "our study indicates that HHV-6A infection might be an important factor in female primary unexplained infertility."

They suggest the reactivated virus in the womb might trigger changes to the immune system that promote "a dysfunctional uterine environment," or in other words, conditions in the womb that are unsuitable for pregnancy.

 

Conclusion

Unexplained infertility causes distress for thousands of couples trying for a baby. It can be hard to accept that doctors can find no reason for a couple's inability to get pregnant, and many couples spend a lot of time and money trying fertility treatments.

Finding a potential cause for unexplained infertility could raise a lot of people's hopes. This study has interesting results, but it was very small and needs to be replicated on a larger scale to be sure the results hold true. We also need to remember that this study cannot show causation - it can't tell us whether the virus is a cause of infertility, only that it seems to be more common in women with infertility not otherwise explained.

Having said that, these women had unexplained infertility and there is still a lot that we don't know about them. The researchers say that they didn't have endometriosis, any problems with ovulation or any structural abnormalities of the reproductive system.

However, we don't know any more than that, such as exploration of male factors for infertility, how long the woman/couple had been trying to conceive, prior miscarriages, or the success of future fertility treatment. We also know nothing about the control group - such as how they were recruited or why womb samples were taken - other than that they'd had a baby. They may have had problems conceiving themselves for all we know.

Overall, it can't be said that the women with infertility problems and HHV-6A would necessarily be less likely to become pregnant or have a successful outcome from assisted reproduction.

Even if we did find out that HHV-6A was responsible for some cases of infertility, that is not the same as being able to cure the condition. A range of antiviral drugs have been used to treat other conditions linked to HHV-6A reactivation, but none have been developed specifically for this virus and we don't know if they would be helpful in treating infertility.

A lot more research is needed before we know whether half of unexplained infertility, as claimed by some news sources, could be treated by targeting this virus.  

Summary

"Obscure virus may be cause of unexplained infertility," The Independent reports. Italian researchers found copies of the HHV-6A virus - a type of herpes virus - in the womb lining of 43% of women with.

Links to Headlines

Obscure virus may be cause of unexplained infertility. The Independent, July 7 2016

Is this why some women are infertile? Chicken pox-style virus that lurks in the womb 'may be to blame'. Mail Online, July 7 2016

Careful who you kiss: virus found in saliva associated with unexplained infertility. The Daily Telegraph, July 7 2016

Mysterious virus found in half of infertile women. The Times, July 8 2016 (subscription required)

Links to Science

Marci R, Gentili V, Bortolotti D, et al. Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility. PLOS One. Published online July 1 2016

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