Semen reshapes immune system to boost chances of pregnancy

Semen does more than fertilise eggs. In mice, it seems to prime the female’s  immune system for pregnancy, making it more likely that an embryo will successfully implant in the womb. It appears to prompt similar changes in women, a finding that could explain why IVF is more successful if couples have regular sex during treatment.

Sarah Robertson at the University of Adelaide, Australia, and her colleagues found that each time a female mouse copulates, it caused the release of immune cells called regulatory T-cells, which are known to dampen down inflammation in the body.

This process may be important for allowing embryos to implant in the womb, rather than being rejected as a foreign body. In people, low regulatory T-cell counts are linked to several reproductive problems, including unexplained infertility, miscarriage, pre-eclampsia and pre-term labour.

Does semen deserve more credit?

Examining the cervix in women, the team found signs that semen does seem to prompt immune system changes in people too. Shortly after sex, they detected the cervix begins to release immune signalling molecules, which may be a sign of increased levels of regulatory T-cells.

“It’s as if the seminal fluid is a Trojan horse that activates the immune cells to get things ready for conception,” says Robertson.

As well as making the embryo more likely to successfully implant in the womb lining, it’s possible that such effects also minimise the chances of a woman’s body rejecting the fetus later on in pregnancy, she says. Women who conceive after limited sexual activity are more likely to develop disorders during pregnancy, she adds.

IVF help

The findings, presented at the International Congress of Immunology in Australia this week, fit with observations that semen contains several signaling molecules – including cytokines, prostaglandins, and hormones – that can have an effect on female tissue.

The discovery has implications for IVF. After a woman’s eggs have been fertilised in the lab, an embryo is chosen for implantation and is surgically inserted into the womb. This is one of the points where IVF can fail, if an embryo is unable to implant in a woman’s uterine lining.

Many fertility clinics advise couples to abstain from sex during IVF treatment to minimise risk of infection from seminal fluid during the implantation surgery. This is a small risk outweighed by the benefits semen can have for the female immune system, Robertson says.

This is supported by a recent review of studies that concluded that sex during IVF improves embryo implantation rates by 23 per cent. “I think it’s really good for couples to know that there’s something they can do to help their chances – it allows them to take a bit of control back,” says Robertson.

Peter Illingworth of IVF Australia says the evidence is compelling. “I personally always say to IVF patients: ‘if you want to have sex, just have sex’.” But many couples choose not to during the treatment because IVF causes a lot of discomfort, he says.  “If you’ve got ovaries the size of baseballs, sex is a much less appealing prospect.”

Conception delay

The effect of semen on a woman’s immune system could also help explain why most couples do not fall pregnant straight away, says Robertson. “In humans, it seems that at least three months of sexual cohabitation is required to give you the priming that you need,” she says.

If low levels of regulatory T-cells are for a cause of infertility,  therapies that increase them may help women who have been trying unsuccessfully to get pregnant for a long time. Treatments like these are currently being developed for immune conditions like graft-versus-host disease, but they haven’t been tested for fertility yet.

“Our results suggest that the first-line approach to treating infertility should be to tell people to go home and practise,” Robertson says. “But if that doesn’t work, tackling regulatory T cells may be the way to go.”