The Aging Male and Infertility

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Couples delay starting a family for various reasons, including marriage at a later age and fulfilling career goals, among others. It is accepted that a woman’s fertility significantly decreases after age 40; in contrast, the effects of aging on male reproduction are more subtle. While there does not appear to be an age at which the reproductive capabilities of the male drop off sharply (as occurs normally in females), on the average sperm quality certainly decreases with age, making it difficult in some cases to initiate and maintain a pregnancy with their partner. An important point is that even if a man fathered children at an earlier age, at an older age he may not be as fertile simply due to the effects of age on decreased sperm quality. As discussed below, for the factor of sperm DNA integrity alone, a 50-year-old man has on the average, 30% less chance for a successful conception, compared to a man in his twenties.

The standard semen analysis of sperm count, motility (the ability of the sperm to reach the egg), and morphology (the shape of the sperm) has historically been used as an indicator of male fertility potential. However, there is a very large overlap in these values between proven fertile and infertile men, and thus the routine semen analysis is not a reliable indicator of fertility potential. A recent study found that sperm motility decreased by 0.7% per year and semen volume by 0.03 ml per year in men ages 22 to 80. Other studies suggest that sperm counts begin to decline at about age 25. A research group in California found that couples undergoing infertility treatments had an 11% less chance of not achieving a pregnancy with each additional year of age for the male (ranging from ages 22 to 55).

As couples begin planning for families later in life, genetic abnormalities and other disorders are also a concern. A large study found the risk of schizophrenia in offspring was related to increasing age of the father. The association was stronger in families with no history of schizophrenia, which indicates that the association between age and schizo- phrenia may be a result of a genetic mutation.

Down syndrome is a genetic condition caused by an extra chromosome 21 (trisomy 21). The influence of maternal age on Down syndrome has been well established; what is less clear is the effect from the father. In one study, an effect from both parents was found among Down syndrome offspring of couples age 35 or older. Interestingly, the paternal effect was very pronounced when the mother’s age was 40 years or older: in this older maternal group, the father contributed to the Down syndrome occurrence 50% of the time.

As a growing number of men are choosing to father children at a later age,   hormonal changes of the male are also a fertility concern. Andropause (similar to menopause in women) is associated with hormonal fluctuations in men and has recently been replaced with term “Androgen Decline in the Aging Male” (ADAM), which is associated with    hormonal fluctuations, fatigue, depression, erectile dysfunction and other symptoms.

Another well-recognized, and perhaps more important, factor for male infertility at an older age is the negative effect of sperm DNA fragmentation. Elevated levels of sperm DNA fragmentation have been shown to have a very significant negative effect on natural, IUI and routine IVF fertilization. A DNA Fragmentation Index (DFI) is the determination of the percent of sperm in the semen that have fragmented DNA. If the DFI is greater than 30% (i.e., more than 30% of sperm have measurable DNA fragmentation), there is a significant negative effect on pregnancy outcome using natural, IUI and routine IVF fertilization.

The Sperm Chromatin Structure Assay (SCSA®) is the most precise test for the determination of sperm DNA strand breaks providing data that are predictive for pregnancy. Results from several studies that used the SCSA® analysis indicate that couples whose DFI was less than 30% were 7.3 times more likely to become pregnant, using natural and IUI fertilization. If routine IVF was used, couples with a DFI of less than 30% were 2.2 times more likely to become pregnant.

The effect of age on sperm DNA fragmentation has now been established. A comprehensive male age study, soon to be published, shows an increase in sperm DNA fragmentation with age; the average age when men reach the important statistical threshold of 30% DFI is age 47. It   is important, however, to realize that some older men may have excellent sperm DNA integrity, while others who are much younger may have poor sperm DNA integrity.

Who should have a sperm DNA fragmentation test?

·        All couples with unexplained infertility

·        Couples with a history of spontaneous miscarriages

·        Men over 40 years of age

·        Men with exposure to toxic agents

·        Men with a questionable varicocele for repair

Many patients with elevated sperm DNA fragmentation want to know how to “fix” their fragmentation. Physician-guided treatment may include an improved healthy lifestyle; taking supplemental antioxidants in diet; avoidance of hot tubs, and not using a heat-generating notebook computer resting on their lap; and repair of a large varicocele.

The value of the SCSA® for infertility patients is that the SCSA clinical report allows the physician to optimize their patient’s infertility treatment plan saving emotional and financial cost. If a patient’s sperm DNA fragmentation is elevated; then based on current research, the physician may advise that the IUI assisted reproductive treatment procedure be skipped and the couple move on to routine IVF or preferably ICSI. u

About the authors: Donald P. Evenson, PhD, HCLD, is Distinguished Professor of Biochemistry at South Dakota State University and President of SCSA® Diagnostics, Inc. Dr. Evenson invented and developed the SCSA® test and has over 25 years of experience in this domain. Regina L. Wixon, PhD, is Assistant Director of SCSA Diagnostics. Her research interests are the structure and function of mammalian sperm nuclear chromatin as related to pregnancy outcome and reproductive toxicology. Web site: www.scsadiagnostics.com.