/ 7 July 2008

Biological clock affects male fertility

The biological clock ticks for men as well as women, doctors warn on Monday, after research found that male fertility begins to decline when they reach their mid-30s.

Doctors said men who wait until their 40s before starting a family face a greater chance of their partner having a miscarriage, because of the poorer quality of their sperm.

Researchers examined patient records of more than 12 000 couples treated at a fertility clinic in Paris, and separated out the influence of male and female ages on the couples’ chances of having a baby.

They found that women whose partners were 35 or older had more miscarriages than those who were with younger men, regardless of their own age. The men’s ages also affected pregnancy rates, which were lower in the over-40s.

Doctors have long known that a woman’s fertility drops sharply in her mid to late 30s, but the effect of age on male fertility is less well understood. Among women, miscarriage rates typically double to 40% between the ages of 20 and 40.

The findings are a concern, researchers say, because of the trend for men to delay fatherhood. The latest figures from the Office for National Statistics show the typical age of married fathers rose from 29,1 in 1971 to 34,1 in 2003. The age of men having children outside marriage has remained stable at about 30. And, for the first time, more women in Britain are giving birth in their early 30s than in their late 20s.

Yves Ménézo, an embryologist at the Eylau Centre for Assisted Reproduction, said older men become less fertile because genetic defects build up in their sperm. In younger men, the damage is minor and can be repaired inside the fertilised egg. But in older men the amount of DNA damage can overwhelm the body’s natural repair mechanisms. ”We think there’s a critical threshold of DNA damage and above that, the damage can no longer be repaired. When that happens, genetic mistakes get through to the embryo and you get an increase in miscarriages,” Ménézo said.

The findings should cause fertility clinics to reconsider how they treat couples, Ménézo added. Those who fail to conceive after mild forms of fertility treatment, such as intra-uterine insemination (IUI), in which sperm is washed and transferred directly into the uterus, should move quickly to more advanced treatments, such as ICSI, where the best quality sperm are picked out and injected directly into the woman’s egg.

The study looked at pregnancies and miscarriages recorded for couples having IUI treatment at the clinic between 2002 and 2006. It found the risk of miscarriage was on average 16,7% when men were aged 30 to 34. That rate rose to 19,5% when men were 35 to 39 and 33% in men aged 40 or over.

Stéphanie Belloc, lead author of the study, which is due to be published in the journal RBM Online, said: ”Until now, gynaecologists only focus on maternal age, and the message was to get pregnant before the age of 35 or 38 because afterwards it would be difficult. But now the gynaecologists must also focus on paternal age and give this information to the couple.” She is to discuss her findings at the annual European Society of Human Reproduction and Embryology meeting in Barcelona on Monday.

Jacques de Mouzon, a co-author at the French National Institute for Medical Research, said: ”People say men are fertile into old age, 90 even. That may be true sometimes, but the product is different and there are more semen abnormalities as age advances. There is a decrease [in male fertility] and an increase in the spontaneous abortion rate after the age of 40 and especially after 45. It is necessary for men to try to have children before the ages of 40 to 45.”

Previous research has pointed to a slight increase in birth defects in babies born to older men. A 2005 study of 70 000 couples by epidemiologist Jorn Olsen at the University of California, Los Angeles, found a fourfold rise in Down’s syndrome among babies born to men aged 50 and older. They were also more likely to have limb deformities.

The chances of having a baby with Down’s syndrome increase rapidly with a woman’s age. About one in 1 000 babies born to mothers under 30 have it, a figure that rises to one in 400 by the age of 35 and one in 105 by the age of 40.

”There is growing evidence from a number of studies to show that men are not totally immune from reproductive ageing,” said Allan Pacey, an expert in male fertility at Sheffield University. ”Previous studies of couples trying to conceive naturally or undergoing IVF have shown that men over the age of about 40 are less fertile than younger men.” – guardian.co.uk