Older Dads and Fertility

Advanced Paternal Age

Older Dads and Male Infertility- Advanced Paternal Age

In recent decades, both men and women have been delaying having children until later in life. For a variety of socioeconomic reasons, many couples are simply choosing to wait longer to start a family than couples did in the past.  Since 1980, birth rates in the United States have increased by 40 percent for men ages thirty-five to forty-nine, and decreased by 20 percent for men under thirty. The proportion of men pregnancies from couples in which the man was 40 years or older increased from 1 in 11 in 1996 to 1 in 7 in 2010, and this percentage just continues to grow.

 

For women, there is a clear decrease in fertility as they age, with the relative fertility of women in their late 30’s being about half that compared with women who are in their early 20’s.  However, many women do conceive in their 40’s, and in the days before effective contraception, women routinely would have their last child in their early to mid 40’s.  Men do not have the same timeline for decreasing fertility potential, and stories abound of men fathering children well into their eighties and even nineties. At some point, however, a man’s fertility potential does begin to decrease, although the age at which this happens varies considerably.  Semen parameters as measured by semen analysis testing usually start to decrease after age 35, but most men do not experience a decrease in overall fertility potential until age 45 to 50 years and beyond.

 

Causes of Aging-Associated Changes in Male Fertility

 

A large number of factors associated with aging can play a role in decreasing reproductive potential in men. These include

        1)    Hormonal abnormalities, including decreased testosterone levels

        2)    Sexual dysfunction, including erectile dysfunction and decreased coital frequency

        3)    Accumulated environment toxin exposure

        4)    Increased oxidative stress on sperm cells

        5)    Aging spermatic germ cells with increasing levels of acquired genetic mutations

        6)    Increases in body fat and higher rates of obesity

        7)    Chronic health problems that can impact fertility (e.g. diabetes, hypothyroidism)

        8)    Prostate problems and treatment, such as BPH (benign enlargement) and cancer

        9)    Medication side effects

 

Furthermore, with increasing age come elevated levels of sperm fragmentation, as measured by the DNA fragmentation index, or DFI.  Below you’ll see how DFI changes with age; a normal DFI is under 30 percent.

            Age           Average DFI

          20–29            12.9%

          30–39            16.3%

         40–49            23.2%

         50–59            35.4%

         60–80            49.6%

                [A. J. Wyrobek et al., Proceedings of the National Academy of Sciences, 2006]

For more information on DFI, see “Advanced Sperm Testing” section of this website.


Changes in Semen Parameters

When men begin to reach their late 30’s, most begin to see some decreases in their semen parameters, though as mentioned above, this generally does not start to lower fertility potential until a decade later.  Aging has been associated with decreases in sperm counts, motility, and morphology.  Another common change in semen parameters seen over time is decreased ejaculate volume (because as men age, their prostate and seminal vesicles make less fluid). Of course, there is wide individual variation due to a multitude of factors, including genetics, lifestyle choices, and general health.

 

Natural Fertility

Studies have shown that men forty-five years and older have overall lower chances of success in establishing pregnancies through natural intercourse.  In addition, for older men who are successful at conceiving naturally, the time it takes to establish the pregnancy is often longer.  Studies have shown a four to five times greater chance of taking a year or longer to establish a pregnancy with advanced paternal age when compared to men who are twenty-five or younger.

 

Miscarriages and Stillbirth

Increased rates of pregnancy loss have been seen in pregnancies established by older men.  Compared to younger men, the risk of spontaneous abortion (pregnancy loss earlier than 20 weeks) is 1.58 times higher in men in their 40’s, and 1.9 times higher in men who are in their 50’s.  Rates of stillborn children (defined as a pregnancy loss at 20 weeks or later) is 1.23 times higher in men in their 40’s, and 1.36 times higher in men in their 50’s.  This makes sense, as 50% of spontaneous abortions and 25% of stillbirths are thought to be associated with either chromosomal and/or structural abnormalities in the fetus.  These chromosomal and structural abnormalities are known to be more common in the embryos of pregnancies established by older men.

 

Changes in IUI Outcomes

The impact of advanced paternal age on intrauterine insemination outcomes is controversial, although decreasing semen parameters in the fifth and sixth decades of a man’s life would be expected to have a negative impact on pregnancy rates, as well as an increased time to pregnancy.

 

Changes in IVF Outcomes

With IVF (including ICSI), success rates do seem to decrease as the father gets older.  Though controversial, studies have found lower rates of fertilization, blastocyst formation, implantation, and live birth rates in the offspring of older men utilizing IVF.  These findings may be associated with the higher rates of aneuploidy (chromosome abnormalities) seen in the embryos produced using the sperm of older men.  One study found embryo aneuploidy rates in men less than 40 years of age to be 59.1% vs. 73.9% in men aged 50 and older.

IVF success rates for older men may also be influenced by the age of the female partner as well.  Sperm DNA damage tends to be found in higher rates in older men, and a woman’s eggs are known to be able to repair some degree of this damage. However, this DNA repair ability of eggs may decrease as women get older, and therefore, eggs from an older woman may be less able to repair DNA damage in sperm from older men. Supporting evidence for this comes from studies that show no difference in IVF outcomes with advancing paternal age when donor eggs from younger women are used.

Some studies have shown that when ICSI is used with IVF, no significant decrease is seen in pregnancy rates in relation to paternal age when semen parameters are normal. However, in men with low sperm count (oligospermia), lower pregnancy rates for IVF/ICSI are seen as the man’s age rises.

Preimplantation genetic screening (PGS) is a technology that can be used in conjunction with IVF to screen for genetic abnormalities in the embryos in order to choose the “best” ones to transfer back into the woman’s uterus.  Advanced maternal age is one of the accepted indications for the use of PGS.  At this point in time, advanced paternal age is not considered an indication if the female is younger, but this recommendation may change as more data is collected.  See the “Genetics” section for more information on PGD/PGS


Increased Risk of Inherited Disorders

Traditionally, babies of older mothers are thought to have an elevated risk of birth defects and chromosomal abnormalities.  Recently, however, more attention has been focused on how the age of the father affects rates of birth defects and other developmental abnormalities. What follows is a list of those disorders that are seen in higher rates in the children of older fathers. It must be emphasized, however, that the vast majority of older men conceive children without any genetic abnormalities or birth defects whatsoever

 

Down Syndrome (Trisomy 21)

Older mothers have a well-described risk of having a child with Down syndrome:

           Age of Mother       Risk of Down Syndrome in Child

                   25                                1 in 1,250

                   35                                1 in 385

                  40                                1 in 106

                  45                                1 in 35

With men, being older seems to have a weak but positive correlation with an increased risk of Down syndrome in offspring (only about 10% of cases of Downs Syndrome are felt to be due to paternal causes). The risk is compounded when the mother is older as well (over thirty).

 

Schizophrenia

The risk of developing schizophrenia has been shown to be higher among children of older fathers, among other factors. Men who are fifty or older have about a three times greater risk of conceiving a child who will develop schizophrenia when compared to men less than twenty-five years old (1 in 47 for older fathers compared to 1 in 147 for younger fathers).

 

Autism

The risk of having a child with autism appears to be correlated (at least in part) with advancing paternal age. Men age forty year and older have a five to six times increased risk of having an autistic child in comparison to men who are thirty or younger.

 

Autosomal Dominant Mutations

Human beings have two copies of each chromosome, one inherited from each parent. Occasionally abnormal genes are inherited from one parent (or sometimes from both parents). Whether or not the abnormal gene will lead to a disorder in the child depends on multiple factors. Autosomal dominant disorders are chromosomal abnormalities in which only one abnormal copy of the gene is needed in order for the disease to show up. The risk of having a child with some types of these genetic abnormalities does appear to increase as the father’s age rises. A forty-year-old father has about a 0.3–0.5 percent chance of conceiving children with chromosomal abnormalities, and by age fifty the risk has double that of younger men.

Examples of chromosomal disorders (autosomal dominant as well as other types) that have been shown to increase with advancing paternal age include:

        1)    Abnormalities of growth- achondroplasia (dwarfism), osteogenesis imperfect, Marfan’s Syndrome

        2)    Craniosynostotic disease- Alpert syndrome, Pfeiffer syndrome, and Crouzon syndrome.

        3)    Polycystic kidney disease

        4)    Tuberous sclerosis

        5)    Neurofibromatosis

The rates of the above diseases are elevated, but since these are relatively rare, the absolute rates of these problems remain quite low overall in the children of older men.

 

Birth Defects

Being older may mildly increase the risk of fathering a child with cleft palate, diaphragmatic hernia, or right ventricular outflow tract obstruction of the heart, syndactyly, club foot, and possibly situs inversus.

 

Screening the Fetus for Abnormalities

Although the vast majority of older men will have normal children, there is accumulating evidence that the risk of certain abnormalities does increase with the age of the male partner. This increased risk seems to be amplified when the female partner is also older. At this point in time, there are no screening tests available to detect an elevated risk of such problems as autism or schizophrenia. Known genetic disorders can potentially be screened for using preimplantation genetic diagnosis (PGD) in conjunction with IVF (see above). Chorionic villus sampling (at 10–12 weeks of gestation), amniocentesis (at 15–20 weeks of gestation), and percutaneous umbilical cord blood sampling (after 17 weeks of gestation) are examples of tests that can be used to look for genetic abnormalities in fetuses, in addition to routine ultrasound screening and some types of blood tests (e.g., triple screen/quad screen). With some of these tests come the disadvantages of a small increase in the risk of pregnancy loss and the difficulties associated with making decisions about whether or not to let a pregnancy progress if a significant genetic abnormality is discovered.


Summary

Pregnancies in couples with older male partners is an increasingly common occurrence in modern society.  As discussed above, most of these older men will have no problems establishing a pregnancy, and most of the resulting children will be completely healthy and normal.  However, older men do have an increased risk of being unable to successfully establish and maintain a pregnancy, either naturally or with assistance such as IUI or IVF.  Also, their resulting children have a higher risk of having development, chromosomal, and/or structural abnormalities.  Recommendations for older men who are planning on having a child include consideration of earlier semen analysis testing, such as possibly checking after 6 months of trying (as opposed to the standard one year).  Also, a more aggressive approach for fetal health screening may be considered in conjunction with discussions with the female’s obstetrician.