Male Age and Fertility by Richard Chetkowski, M.D.

The profound adverse impact of female age on live birth rates with IVF and all other fertility treatments as well as with natural conception (What is Age Factor?) has largely overshadowed discussion of advanced male age on reproductive outcomes. Even though quantitatively lower, several distinct unfavorable effects of advanced paternal age have been identified. In the developed countries both men and women are having children at an older age. In the United States since 1980, the birth rates for men aged 35-49 years have increased 40% while birth rates for men under 30 years of age have decreased by 20%. This demographic fact underlies the importance of the topic.

Older men exhibit an increased rate of de novo genetic point mutations, most of which are deleterious. Advanced paternal age is associated with increased frequency of autosomal dominant conditions which manifest themselves clinically in the presence of a single mutation. Among these rare conditions are: achondroplasia, which is a common cause of dwarfism, and Apert syndrome, which causes congenital malformations of the skull, face, hands and feet.

Two separate studies have found a significant association of advanced male age with increased risk of autism spectrum disorders and schizophrenia. In one report children of men older than 40 years were almost 6 times more likely to have autism than offspring of men under 30. One is tempted to speculate that the increased paternal age at reproduction might be a contributing factor to the large increase in the frequency of autism in children over the last couple of decades.

Whereas paternal age has only slight effect on the frequency of chromosomal abnormalities, which are primarily determined by maternal age, the father’s advanced age appears to be related to higher frequency of birth defects such as cleft palate, diaphragmatic hernia and some cardiac anomalies.

Sperm on the surface of an egg

Credit: Yorgos Nikas, Wellcome Images.

In addition to effects on the offspring, natural fertility appears to be reduced in men over 35 years resulting in longer interval to conception and an increase in the risk of spontaneous pregnancy loss. The majority of studies which examined the effect of advancing paternal age on the efficiency of IUI and IVF found lower live birth rates in older men. However, powerful laboratory techniques, such as ICSI, appear to level the fertilization field in vitro resulting in comparable pregnancy rates.

Since the ages of most men and women pursuing conception together are highly correlated, it is methodologically difficult to dissect the relative contributions of each partner’s age to the success rate of classic IVF. It seems that the effect of advanced paternal age is more pronounced when eggs from older women are used as opposed to donor eggs which are usually provided by younger women. This apparent attenuation of the adverse effect of high paternal age in donor egg cycles suggests the intriguing hypothesis that younger eggs might be able to compensate for functional abnormalities seen in aging sperm.

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