Male infertility may be caused by a genetic defect

Up to a quarter of men around the world have a genetic defect that could reduce their chances of having children. Scientists have found some sperm lacks a protective protein that helps it to reach the egg.
The protein, DEFB126, coats the sperm and allows it to penetrate mucus in the female reproductive tract. It also protects the sperm from attack by the female immune system.

Without it, researchers believe it takes longer for a man with this defect to make his partner pregnant.

A study conducted in the U.S, the UK and China showed that up to a quarter of men worldwide carry defective copies of the protein gene. The discovery could help explain a significant proportion of male infertility worldwide. 'In 70 per cent of infertile men, you can't explain their infertility on the basis of sperm count and quality,' said lead researcher Professor Gary Cherr, from the University of California at Davis.

A test for defective DEFB126 could help fertility clinics decide whether couples should be given ICSI treatment (intracytoplasmic sperm injection), which involves injecting sperm directly into eggs. The research is published today in the journal Science Translational Medicine.

Sperm from men with the defective protein look normal under a microscope and appear to have no problem swimming. But they are far less able to swim through an artificial gel that resembles human cervical mucus. When the functional protein is added to the sperm, they recover their normal abilities.

About half of all men worldwide carry one defective copy of the protein gene and a quarter have two. A study carried out on couples trying to conceive found a significant decrease in pregnancy rate when the man had two copies of the defective DEFB126 gene.

It is still unclear how a mutation that adversely affects fertility can be so common. Men with one normal and one defective gene, but normal fertility, may be advantaged in some way, the scientists believe. Compared with sperm from monkeys and other mammals, human sperm is often of poor quality, slow swimming, and with a high rate of defective cells. But because humans tend to breed in long-term monogamous relationships, unlike most mammals, sperm quality may not be so important, according to Prof Cherr.

Fertility expert Dr Allan Pacey, at the University of Sheffield, said: 'We actually understand very little about the subtle molecular events which occur in sperm as they make their journey through the woman's body to fertilise an egg. 'We know even less about how a man's genes may contribute to how his sperm work, in the absence of an obvious defect that we can see down the microscope.

'Therefore, this paper is an important step forward and makes a significant contribution to our sperm knowledge. 'Although I doubt that testing for this genetic defect on its own will change clinical practice, in combination with other test information it may one day help guide doctors to suggest a couple start assisted conception treatment earlier than they might otherwise have done.'