Effects of advanced paternal age on fertility
Owing to sociocultural and economic factors, there has been a considerable increase in recent years in the number of men over the age of 35 who wish to have children. As a couple ages, the probability that they will experience reproductive problems increases. The negative effect of maternal age on fertility has been widely documented and we know that fertility diminishes drastically after the age of 39. Maternal aging is also associated with miscarriage, pregnancy complications, congenital anomalies and an increase in perinatal mortality.
However, few studies analyse the effect of paternal age on success after the application of assisted reproduction technology (ART) and the results they provide are contradictory. It is true that the male reproductive function is less vulnerable than the female where the aging process is concerned, as is demonstrated by the fact that many babies have been born spontaneously to fathers who are in their seventies or eighties. However, some associations have been found in specific studies that relate a negative effect of advanced paternal age with:
- Reduction of the probability of gestation during the first year.
- Reduction of steroid levels, reflecting an alteration of testicular function.
- Increased risk of miscarriage.
- Increase in obstetric complications such as preeclampsia.
- Low birth weight.
- Neurocognitive abnormalities in the children born, such as autism.
- Psychiatric problems, diabetes mellitus and certain types of cancer in the offspring.
Complications of this type may, in part, be the result of genetic anomalies suffered in the germ cells of older fathers, including abnormalities in paternal genomic imprinting, or the peculiar mechanism for the regulation of paternal gene expression, as well as de novo mutations occurring in the sperm cells. An increase in numerical and structural chromosomal abnormalities has also been observed in men of advanced age.
Regarding semen parameters, ejaculate volume is associated with a lineal reduction as paternal age increases. However, the data published on sperm motility, morphology and concentration (millions/ml) are inconsistent. In recent years, the measure of sperm DNA fragmentation has been used as a complementary test to semen analysis, since it has been correlated in some cases with a reduction in fertilization rates, embryo arrest and miscarriage. However, the validity of this test is in the balance since the latest results published do not show it to be beneficial. Furthermore, there is no evidence of an association between paternal age and sperm DNA fragmentation.
Lastly, and regarding the results after ART, no effect on embryo quality has been found on the second and third day of development. However, a reduction has been observed in the number of embryos that reach the blastocyst stage. This phenomenon would appear to be related to abnormalities in paternal genome activation in the embryo which starts from the third day of development. Nevertheless, the main parameters for success, such as implantation rates and successful pregnancy, do not seem to be affected by the increase in paternal age.
An important problem when trying to determine the effect of paternal aging on fertility is that there are very few studies in which age is assessed above 50 years and furthermore the number of individuals is very low. This means that we cannot draw clear conclusions and that more studies are necessary with well-defined criteria and which report consistently on all the variables of interest.
Dr Jorge Ten, Director of the Reproductive Biology Unit, Instituto Bernabeu