Male infertility


Male infertility refers to a sexually mature male's inability to impregnate a fertile female. Male infertility can wholly or partially account for 40% of infertility among couples who are trying to have children. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen. Semen quality is used as a surrogate measure of male fecundity. More recently, advanced sperm analyses that examine intracellular sperm components are being developed.

Age considerations

Sperm motility increases from puberty through one's mid-thirties. Research shows that, from the age of 36 onwards, sperm motility decreases from 40% Grade A & B to 31% in one's 50s. The effects of aging on semen quality is summarized below based on a study of 1,219 subjects:
Age group Number of subjects Motility
21–285747.5 ± 25.4
29–3545048.1 ± 30.4
36–4253240.0 ± 27.1
43–4916533.1 ± 25.1
50–601531.3 ± 23.9

90% of seminiferous tubules in men in their 20s and 30s contain spermatids, whereas men in their 40s and 50s have spermatids in 50% of their seminiferous tubules, and only 10% of seminiferous tubules from men aged over 80 contain spermatids. In a random international sample of 11,548 men confirmed to be biological fathers by DNA paternity testing, the oldest father was found to be 66 years old at the birth of his child. The ratio of DNA-confirmed versus DNA-rejected paternity tests around that age is in agreement with the notion of general male infertility above age 65–66.

Causes

Factors relating to male infertility include:

Immune infertility

have been considered as the cause of infertility in around 10–30% of infertile couples. ASA production are directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and acrosome reaction, impaired fertilization, influence on the implantation process, and impaired growth and development of the embryo. Risk factors for the formation of antisperm antibodies in men include the breakdown of the blood‑testis barrier, trauma and surgery, orchitis, varicocele, infections, prostatitis, testicular cancer, failure of immunosuppression and unprotected receptive anal or oral sex with men.

Genetics

Chromosomal anomalies and genetic mutations account for nearly 10–15% of all male infertility cases.

Mitochondrial DNA

Mature human sperm contains almost no mitochondrial DNA at all. An increased amount of mitochondrial DNA in the sperm cells has shown to have a negative impact on fertility.

Klinefelter syndrome

One of the most commonly known causes of infertility is Klinefelter syndrome, which affects one in 500–1000 newborn males. Klinefelter syndrome is a chromosomal defect that occurs during gamete formation due to a non-disjunction error during cell division. This results in males having smaller testes, reducing the amount of testosterone and sperm production. Males with this syndrome carry an extra X chromosome, meaning they have 47 chromosomes compared to the normal 46 in each cell. This extra chromosome directly affects sexual development before birth and during puberty. A variation of Klinefelter syndrome is when some cells in an individual have the extra X chromosome but others do not, referred to as mosaic Klinefelter syndrome. The reduction of testosterone in the male body normally results in an overall decrease in the production of viable sperm for these individuals, thereby making it hard for them to father children without fertility treatment.

Y chromosome deletions

is a direct cause of male infertility due to its effects on sperm production, occurring in approximately one in 2000 males. Usually, affected men show no symptoms, although they may have smaller testes. Men with this condition may exhibit azoospermia, oligozoospermia, or they may produce abnormally shaped sperm. This case of infertility occurs during the development of gametes in the male. Where a normal healthy male will have both an X and a Y chromosome, affected males have genetic deletions in the Y chromosome. These deletions affect protein production that is vital for spermatogenesis. Studies have shown that this is an inherited trait; if a male is fathered by a man who also exhibited Y chromosome deletions then this trait will be passed down. These individuals are thereby "Y-linked". Daughters are not affected and cannot be carriers due to their lack of a Y chromosome.

Other

Pre-testicular factors refer to conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including:
There is increasing evidence that the harmful products of tobacco smoking may damage the testicles and kill sperm, but their effect on male fertility is not clear. Some governments require manufacturers to put warnings on packets. Smoking tobacco increases intake of cadmium, because the tobacco plant absorbs the metal. Cadmium, being chemically similar to zinc, may replace zinc in the DNA polymerase, which plays a critical role in sperm production. Zinc replaced by cadmium in DNA polymerase can be particularly damaging to the testes.

DNA damage

Common inherited variants in genes that encode enzymes employed in DNA mismatch repair are associated with increased risk of sperm DNA damage and male infertility. As men age there is a consistent decline in semen quality, and this decline appears to be due to DNA damage. The damage manifests by DNA fragmentation and by the increased susceptibility to denaturation upon exposure to heat or acid, the features characteristic of apoptosis of somatic cells. These findings suggest that DNA damage is an important factor in male infertility.

Epigenetic

An increasing amount of recent evidence has been recorded documenting abnormal sperm DNA methylation in association with abnormal semen parameters and male infertility. Until recently, scientists have thought that epigenetic markers only affect the individual and are not passed down due to not changing the DNA. New studies suggest environmental factors that changed an individual's epigenetic markers can be seen in their grandchildren, one such study demonstrating this through rats and fertility disruptors. Another study bred rats exposed to an endocrine disruptor, observing effects up to generation F5 including decreased sperm motility and decreased sperm count. These studies suggest that environmental factors that influence fertility can be felt for generations even without changing the DNA.

Post-testicular causes

Post-testicular factors decrease male fertility due to conditions that affect the male genital system after testicular sperm production and include defects of the genital tract as well as problems in ejaculation:
The diagnosis of infertility begins with a medical history and physical exam by a physician, physician assistant, or nurse practitioner. Typically two separate semen analyses will be required. The provider may order blood tests to look for hormone imbalances, medical conditions, or genetic issues.