The Fertility Time Bomb is Ticking

Sperm out of step in complex dance

Men are now as likely as women to be the infertile partner. Jerome Burne reports on the causes

IT'S THE time of the year when men's thoughts turn, if only fleetingly, to fitness. You might also have been prompted recently to consider your prowess in quite a different sporting arena - just how fit are your sperm?

Leading reproductive experts warn us that we are facing a "fertility time-bomb", both in Australia and other developed countries such as the UK and many European nations. The causes are unclear, but may have something to do with environmental chemicals, particularly some plastics which mimic the effects of the female hormone oestrogen.

What is not unclear are the effects. Fertility clinic records reveal that not only are men producing fewer sperm, but that the ones we do release are more bent and deformed and swim less vigorously.

In fact European males are now, for the first time, more likely to be the infertile half of couples attending fertility clinics, according to a report last year from the European Society for Human Reproduction and Embryology.

In Australia, it's thought men are just as likely to be the cause as their partner, but male infertility is rising faster and may soon become the main cause.

Then earlier this year came the launch in Britain of a kit that allows you to check the fitness of your sperm in your home. The test works by forcing the sperm to swim through mucus which mimics that found in the cervix; if 10 million per millilitre get through, you are normal, according to the World Health Organisation guidelines.

If you can't manage the numbers, the ultimate fix is a technique known as ICSI (intracytoplasmic sperm injection), which can freight a single sperm, however much of a couch potato, directly into an egg. In fact modern reproductive technology appears to be rendering men's role increasingly peripheral. All ICSI is interested in is the DNA compacted into the sperm's head, while researchers are now working on making sperm totally redundant by generating them from embryonic stem cells in the lab.

But by narrowly focusing on the athletic potential of individual sperm and their genetic load we could be ignoring other causes of infertility. Obviously numbers and performance are vital, but more than 30 per cent of men having trouble conceiving have perfectly adequate sperm; something else is going on.

What the current sperm fitness obsession misses is the other 99 per cent of an ejaculation. This is seminal fluid, a rich mix of chemicals that includes proteins, minerals and vitamins. It is discarded by the fertility clinics as being largely the sperm's energy pack; some researchers believe, however, that it is a key player in normal fertilisation.

"We have become very sophisticated about the mechanics of artificially fertilising an egg," says Stewart Irvine, consultant gynaecologist at the Royal Infirmary Edinburgh. "But we still know very little about the far more complicated dance that has to be done right if couples are going to conceive naturally." If we knew more about how that works, he says, a significant proportion of those who have to endure the gruelling process of IVF might be able to get pregnant far more enjoyably.

Recently there have been some intriguing glimpses of the kind of things to which Irvine is referring. For starters, sperm would normally be regarded by the woman's immune system as invading alien protein, and so would be rapidly destroyed. How do sperm get a safe-conduct pass?

Research by Sarah Robertson, a National Health and Medical Research Council senior research fellow and a reproductive biologist at the University of Adelaide, has shown how one of the many peptides in semen called TGF-beta is vital for ensuring that sperm doesn't get tagged for destruction by the woman's killer cells. In a paper last year in Cell and Tissue Research (2005;322:43-52), the associate professor suggested that some cases of male infertility could be the result of faulty interactions between the woman's body and TGF-beta and related peptides.

"There is growing evidence for what's been called 'male priming'," she says. "Prior exposure to seminal fluid seems to make conception more likely and increase the chance of a successful pregnancy."

Another of these proteins found in semen is known as PLCzeta and it has an equally vital function. At the end of the journey, once the sperm has penetrated the egg, it triggers a calcium cascade that allows the egg to start growing. "Faulty functioning of PLCzeta could be a root cause of male infertility," suggests Tony Lai, a professor and cardiologist at Cardiff University who discovered calcium signalling.

But these are just two of 83 proteins from the semen cocktail that have been found to play a crucial role in conception. Some are needed to follow the chemical trail that leads to the ovum, while others help to fight bacteria. But there is something else remarkable about these proteins; the genes controlling them are mutating faster than any others in the body, except for the corresponding ones in females.

It's this discovery that could lead to a much broader understanding of male fertility. "These reproductive proteins seem to be involved in an arms race," says Willie Swanson, geneticist and professor of Genome Sciences at the University of Washington, whose major review of this new field was published in January in the journal Reproduction (2006;131(1):11-22).

"When it comes to fertilisation, the interests of the male and female genes are not at all the same," she says. While the sperm's genes are all focused on fertilisation, the female's, with only a limited number of conceptions possible, have developed to be more cautious and have developed ways of delaying fertilisation.

"Many fertility problems could be about a mismatch between sperm-egg recognition molecules," Swanson says. "As in transplants, or skin grafts, some people's immune systems tolerate each other more easily; I suspect something similar is going on with the reproductive proteins in couples with fertility problems."

The success of IVF means that funding for research into the complexities of the natural version is hard to come by. But the long-term health of IVF babies is still unclear and all infertile couples would undoubtedly welcome a less drastic and gruelling solution.

The Times
Additional reporting: Adam Cresswell