Dr. Sergey Moskovtsev, of the Mount Sinai Hospital, Toronto, Canada, told the conference that an increase in the average maternal and paternal ages at the time of attempted first pregnancy made this particularly significant. "Older men tend to reproduce with older women", he said, "and the combination of increased female factor infertility, increased sperm DNA damage, low levels of DNA repair, and increased abnormalities in conventional semen parameters present in this population will have a pronounced impact on their reproductive potential."
Dr. Moskovtsev and his team examined the relationship of DNA integrity, a novel semen parameter related to fertility potential, to age in 2134 men presenting for evaluation of their fertility. They identified damaged and normal sperm by means of a fluorescent dye that attaches to DNA, staining red when attached to damaged DNA and green to normal. Using 20 000 sperm per sample, they calculated DNA damage in each specimen via the ratio of red to green plus red. They found that DNA damage was significantly higher in men over 45 years old than in all younger age groups, and that the damage was doubled in those men 45 years and older compared with those less than 30 years old.
"Sperm DNA damage cannot be repaired", said Dr. Moskovtsev, "and appears to be a marker of reduced fertility potential rather than a predictor of fertility. Men with normal DNA integrity may be infertile for various reasons. We need to investigate the possibility of developing techniques to identify and select sperm without DNA damage for use in assisted reproduction techniques." IVF and ICSI cannot overcome abnormalities in DNA integrity, said Dr. Moskovtsev, who intends to follow up his work by investigating further the role of abnormalities in protamine, a protein found in sperm. This is one of the putative causes of reduced DNA integrity in sperm. He will also look at older and younger groups of men with abnormal DNA integrity to see if there are differences in the mechanism of DNA damage between the two groups.
"The effect of age on male fertility is particularly interesting because of the growth in the number of men choosing to father children at older ages", he said. "In the United States, the birth rate for fathers older than 35 years increased by almost 20% between 1980 and 1995. ESHRE has reported that there had been an increase in the number of men between 50 and 65 years of age attending andrology centres over the same time period, and our study confirms these observations - men over 40 made up almost 25% of our patient population.
"Many of these older couples will have trouble in conceiving and resort to IVF and ICSI", he said. "This will bypass the natural selection of normal, healthy sperm and may lead to fertilisation by sperm with damaged DNA which can result in early embryonic loss or the birth of unhealthy offspring."
An assessment of DNA damage in sperm should be an essential part of any examination of the fertility potential of older men, he said.