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Try out PMC Labs and tell us what you think. Learn More. The trend in parenthood at an older age has also been seen in men. Age-related infertility will continue to be a problem. A basic understanding of the issues is critical for health care professionals so that they can effectively counsel patients who are considering a delay in childbearing for social reasons or for those seeking fertility treatments.
This review details the changes in fertility seen in the aging male. In recent decades, infertility has impacted an increasing of couples. The trend for parenthood at an older age has also been seen in men. Beyond the fact that older men tend to have older female partners, increasing male age is associated with increased time to conception. This reflects the age-related increase in acquired medical conditions, decreases in semen quality, and increasing rates of DNA fragmentation seen in sperm.
In addition, there is an association between age of the male partner and the incidence of birth defects and chromosomal abnormalities. Age-related infertility will continue to be a problem secondary to women delaying childbearing while obtaining advanced education and establishing a professional career. A basic understanding of these issues is critical for health care professionals so that they can effectively counsel patients who are considering a delay in childbearing for social reasons or for those seeking fertility treatments. Studies that have attempted to assess the impact of male age on fertility have been confounded by the age of the female partner.
It is well documented that women have a natural and inevitable decline in fecundity with age. Further studies have shown that, although there is a mild decrease in fertility in women in their late 20s, a more appreciable deterioration occurs after age 30, and fertility rapidly declines after age From a physiologic perspective, the greater impact of age on female fertility is understandable.
This falls through fetal development and at birth there are 1 to 2 million viable oocytes remaining. By the time she reaches puberty, there are only , to , oocytes remaining. The ovary has no capacity to regenerate oocytes. This is in stark contrast to the male, who can produce upwards of million sperm a day.
Studies have consistently shown that increasing male age is associated with an increased time to pregnancy and decreased pregnancy rates. However, only a few studies have examined these outcomes while adjusting for female age. Ford and colleagues performed a secondary data analysis of the Avon Longitudinal Study of Pregnancy and Childhood, a large population-based study in the United Kingdom.
Surveys from pregnancies were used to determine the effect of age on time to pregnancy. In addition to female age, coital frequency and sexual functioning are variables that affect time to conception and pregnancy rates. Decreased sexual activity can decrease the chances of conception, 10 and erectile dysfunction ED increases with age. Between ages 40 and 70, the probability of having severe ED increased threefold and the probability of moderate ED increased twofold. After adjusting for baseline sexual function, men engaged in sexual activity an average of 6.
This frequency decreased by one to two times per month after age 50 and by another one to two times per month after age In a survey study of British women controlled for female age, coital frequency, social history, and weight, an even stronger age effect on pregnancy rate was found than in the study by Ford and colleagues. To evaluate pregnancy rates in different age groups, a French study examined cycles of intrauterine artificial insemination.
They found that the most ificant factor contributing to probability of pregnancy was the age of the male partner. Male factor infertility is a term that encompasses a host of different conditions relating to sperm function that may make it difficult for a sperm to fertilize an egg under normal conditions. Problems in male factor fertility may be due to changes in semen quality as assessed by the semen analysis. The most ificant of these are a low sperm concentration oligospermia , poor sperm motility asthenospermia , and abnormal sperm morphology teratospermia.
Other factors less well associated with infertility include semen volume and other seminal markers of epididymal, prostatic, and seminal vesicle function. As men age, these variables are impacted and correlate with decreased fertility. In , Sasano and Ichijo first described the decrease in sperm concentration as men age. A study of 20, men found a statistically ificant increase in concentration of 0. In contrast to concentration, evidence consistently indicates that sperm motility decreases with advancing age.
Studies that adjusted for duration of abstinence revealed statistically ificant decreases in motility of 0. More recently, Sloter and colleagues used computer-assisted semen analysis in a population of 90 men aged 22 to 80 years with no history of infertility. Motility decreased 0. Because motility is acquired during sperm transit through the prostate and the epididymis, the decrease in motility is suspected to be due to age-related decline in the function of these posttesticular glands.
Similar to motility, morphology appears to decrease with advancing male age. Studies indicate declines in normal sperm morphology of 0. Evidence suggests there is a mild decrease in seminal volume with increasing age, although the clinical ificance of this finding is marginal. The decrease in volume may be related to seminal vesicle insufficiency because seminal vesicle fluid composes most of the ejaculate volume. The reports showing a decrease in volume have only identified a modest change of 0. Semen volume drops from a median of 2.
The association between age, the epididymal and accessory sex gland products, and their relation to sperm motility has also been examined. The specific seminal markers investigated were glucosidase secreted by the epididymis, prostate-specific antigen PSA and zinc secreted from the prostate, and fructose secreted by seminal vesicles. In a multiple regression analysis, glucosidase and PSA showed positive association with progressive motility, whereas zinc levels showed an inverse relationship with motility.
There has been a fair amount of recent literature pertaining to DNA sperm fragmentation and its effects on fertility. The evidence to date shows an increasing rate of fragmentation with increasing age. This is hypothesized to be a result of increasing oxidative stress over time, and is supported by animal models that show decreased epididymal antioxidant capacity with increasing age. Although the use of testicular sperm aspiration in combination with intracytoplasmic sperm injection in couples with otherwise unexplained infertility has been suggested when a high fragmentation index is found, the current evidence is not sufficient to recommend such invasive therapies.
The data relating to smoking is mixed, but in a meta-analysis of 20 observational studies, men who smoked cigarettes were more likely to have low sperm counts. The risk of developing a medical condition or of being exposed to environmental toxins increases with age. For men, viral orchitis and sexually transmitted infections can lead to infertility due to germinal cell damage, ischemia, or the immune response to the infection.
Men with a history of chronic illness such as sickle cell disease, chronic renal insufficiency, cirrhosis, celiac sprue, or malnutrition of any cause may have primary as well as secondary hypogonadism. Common medications that can impact semen parameters include antihypertensives spironolactone and calcium channel blockers , H2 blockers cimetidine , and antiandrogen treatments for the prostate flutamide. Testicular size is a surrogate marker of spermatogenesis. Germinal epithelium supports normal spermatogenesis. There is an overall disruption of the hypothalamic-pituitary-testicular HPT axis as a man ages and it is often referred to as late-onset hypogonadism.
This disruption is due to a combination of changes in testicular and germinal histology and HPT axis hormone levels. High levels of intratesticular testosterone, secreted by the Leydig cells, are necessary for spermatogenesis. Testosterone levels decrease with age, in what is termed the andropause , and this decline is initiated at approximately age Declining testosterone may be due to alterations of the HPT axis with aging, decreasing s of Leydig cells, or both.
For men enrolled in MMAS, total testosterone declined at 0. Sex hormone-binding globulin SHBG increased at 1. The increase in SHBG likely in a further decline in testosterone levels. Dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol, and estrone showed ificant declines, whereas dihydrotestosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin increased over time. Another recent study from the MMAS cohort controlled for confounding factors such as chronic illness, body mass index BMI , medications, and lifestyle when analyzing testosterone levels.
The authors report that chronic disease and high BMI ificantly decreased testosterone concentrations, whereas smoking tended to increase total, free, and bioavailable testosterone concentrations. Finally, declining testosterone may cause decline in libido, ED, and difficulty achieving ejaculation. The level of testosterone does appear to influence sexual function. Testosterone replacement therapy was found to improve erectile function for hypogonadal men in a randomized, placebo-controlled, double-blind, parallel group, multicenter study, 56 although exogenous testosterone obviously has severe adverse effects on spermatogenesis.
There is concern that the increased rate of DNA fragmentation ly discussed le to an increase in fetal abnormalities. It is difficult to demonstrate the effects that DNA fragmentation and paternal age have on genetic disorders for several reasons.
Genetic disorders are rare, which makes studying them difficult. Although more men are having children at later ages, the of older fathers is still relatively small, further impeding studying these rare outcomes. Many studies do not control for maternal age or lifestyle and health issues, which may confound their .
One study that showed an association between paternal age and a genetic mutation examined men aged 22 to 80 years. The revealed associations between age and the frequencies of sperm with DNA fragmentation and fibroblast growth factor receptor 3 gene FGFR3 mutations. FGFR3 mutation causes achondroplasia. The study found no associations between male age and sperm with aneuploidies or diploides. There has been recent evidence of increased rate of first trimester spontaneous abortion with older paternal age.
When divided by trimester, the risk of first trimester miscarriage was 1. This was illustrated by Singh and colleagues, who studied semen samples that were collected from men between the ages of 20 and 57 years visiting fertility clinics. They found that the percentage of sperm with highly damaged DNA was statistically ificantly higher in men aged 36 to 57 years than in those aged 20 to 35 years. It is clear that aging has a ificant impact on male sexual function, sperm parameters, and fertility.
These changes contribute to decreased fecundability, increased time to conception, and increased miscarriage rates. Despite the evidence discussed in this article, there are clearly many unknowns with regard to male aging and fertility. There is opportunity for further research in nearly all areas discussed in this article.
Further research will allow better understanding of the changes in the male reproductive axis and the impact on all areas of male fertility in relation to age.Is 39 old for a man
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Male Attractiveness and Aging