Male infertility

Infertility affects about 15% of couples and is due to a male factor alone in 20% and a combined male and female factor in 30 to 40%.

World Health Organization estimates between 60 and 80 million couples are affected. 

The population in different regions have varying amounts of infertility.

In 25% of couples no clear cause of infertility can be identified.

Male infertility refers to a sexually mature male’s inability to impregnate a fertile female. 

It accounts for 40–50% of infertility. 

It affects approximately 7% of all men. 

Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.

There is a decrease in sperm concentration as men age.

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 > 80 years 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: generally male infertility ceases above age 65-66.

Factors relating to male infertility: 

Immune infertility

Antisperm antibodies (ASA) have been considered as infertility cause in around 10–30% of infertile couples.

Antisperm antibody production is directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, impair fertilization, influence on the implantation process, and impaired growth and development of the embryo. 

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.

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

Klinefelter syndrome is one of most commonly known causes of infertility, 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. 

Resulting in males having smaller testes, reducing the amount of testosterone and sperm production.

Males with this syndrome carry an extra X chromosome (XXY), 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. 

Testosterone concentrations in the seminiferous tubules are 20- to 100-fold greater than circulating levels and are required to mediate spermatogenesis.

The reduction of testosterone in the male body normally results in an overall decrease in the production of viable sperm for these individuals thereby forcing them to turn to fertility treatments to father children.

Y chromosomal infertility is a direct cause of male infertility due to its effects on sperm production, occurring in approximately one in 2000 males.

Y chromosomal infertility affected men show no symptoms, although they may have smaller testes. 

Y chromosomal infertility may be associated With azoospermia (no sperm production), oligozoospermia (small number of sperm production), or they may produce abnormally shaped sperm (teratozoospermia).

Y chromosomal infertility occurs during the development of gametes in the male: affected males have genetic deletions in the Y chromosome. 

These deletions affect protein production that is vital for spermatogenesis. 

Idiopathic oligospermia, or unexplained sperm deficiencies, account for 30% of male infertility.

Pre-testicular factors are conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including:

Varicocele is a condition of swollen testicle veins, which is 

present in 15% of normal men and in about 40% of infertile men.

It is present in up to 35% of cases of primary infertility and 69–81% of secondary infertility.

Obesity increases the risk of hypogonadotropic hypogonadism.

Men with celiac disease may have reversible infertility. 

In men, celiac disease can reduce semen quality and cause immature secondary sex characteristics, hypogonadism and hyperprolactinemia which causes impotence and loss of libido.

When evaluating  infertility it would best include assessment for underlying celiac disease, both in men and women.

Strenuous bicycle riding, horseback riding are associated with male infertility.

Medications that affect spermatogenesis such as chemotherapy, fluoxetine, anabolic steroids, cimetidine, spironolactone, and those that decrease FSH levels such as phenytoin, and those that decrease sperm motility such as sulfasalazine and nitrofurantoin.

Tobacco smoking may damage the testicles and kill sperm,

but their effect on male fertility is not clear.

Smoking tobacco increases intake of cadmium, which is chemically similar to zinc, and may replace zinc in the DNA polymerase, which plays a critical role in sperm production. 

Inherited variants in genes that encode enzymes employed in DNA mismatch repair are associated with increased risk of sperm DNA damage and male infertility.

Aging  is associated with a decline in semen quality, and this decline appears to be due to DNA damage.

DNA fragmentation and increased susceptibility to denaturation upon exposure to heat or acid are characteristic of apoptosis of somatic cells: DNA damage is an important factor in male infertility.

Environmental factors that change an individual’s epigenetic markers can be seen in their grandchildren, suggesting that environmental factors that influence fertility can be felt for generations even without changing the DNA.

Post-testicular factors that can 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:

Vas deferens obstruction

Lack of Vas deferens, often related to genetic markers for cystic fibrosis

Infection-prostatitis, male accessory gland infection

Retrograde ejaculation

Ejaculatory duct obstruction



Diagnostic evaluation: 

Medical history and physical exam.

Typically two separate semen analyses will be required. 

Medical history includes: prior testicular or penile insults such as torsion, cryptorchidism, trauma, infections including mumps orchitis, epididymitis. environmental factors like excessive heat, radiation, medications, drug use with anabolic steroids, alcohol, smoking, sexual habits, frequency and timing of intercourse, use of lubricants, and each partner’s previous fertility experiences are important.

History of loss of libido and headaches or visual disturbances may indicate a pituitary tumor.

The past medical or surgical history may reveal thyroid or liver disease diabetic neuropathy related retrograde ejaculation, radical pelvic or retroperitoneal surgery, absent seminal emission secondary to sympathetic nerve injury, or hernia repair with damage to the vas deferens or testicular blood supply.

A family history may reveal genetic problems.

An examination of the penis, scrotum, testicles, vas deferens, spermatic cords, ejaculatory ducts, urethra, urinary bladder, anus and rectum is performed.

A measure of testicular volume, is associated with both sperm and hormonal parameters.

Semen sampling:

The optimal sexual abstinence for semen sample obtaining is of 2–7 days. 

The first way to obtain the semen sample is through masturbation.

Two different samples have to be analyzed with an interval between them of seven days to three months, as sperm production is a cyclic process. 

The sample should never be obtained through coitus interruptus for several reasons:

Part of ejaculate could be lost.

Bacterial contamination could happen.

The acid vaginal pH could be deleterious for sperm motility.

Semen analysis:

The volume of the semen sample must be more than 1,5 ml.

The approximate number of total sperm cells, sperm motility/forward progression, and % of sperm with normal morphology are measured. 

Hyperspermia has a high volume more than 6 ml.

Hypospermia has a low volume less than 0,5 ml.

Semen deficiencies are labeled as follows:

Oligospermia or oligozoospermia – decreased number of spermatozoa in semen

Aspermia – complete lack of semen

Hypospermia – reduced seminal volume

Azoospermia – absence of sperm cells in semen

Teratospermia – increase in sperm with abnormal morphology

Asthenozoospermia – reduced sperm motility

Necrozoospermia – all sperm in the ejaculate are dead

Leucospermia – a high level of white blood cells in semen

Normozoospermia or normospermia – normal values of all ejaculate parameters and is unexplained Infertility.

Teratoasthenozoospermia, which is reduced sperm morphology and motility. 

Low sperm counts are often associated with decreased sperm motility and increased abnormal sperm morphology.

Common hormonal testing includes determination of FSH and testosterone levels. 

Genetic causes of infertility: Klinefelter syndrome, a Y chromosome microdeletion, or cystic fibrosis can be detected.

Scrotal ultrasonography may detect signs of testicular dysgenesis, (which is often related to an impaired spermatogenesis and to a higher risk of testicular cancer), testicular lesions suggestive of malignancy, 

decreased testicular vascularization characteristic of testicular torsion, hyperemia observed in epididymo-orchitis or in some malignant conditions such as lymphoma and leukemia.

Doppler ultrasonography useful in assessing venous reflux in case of a varicocele.

Dilation of the head or tail of the epididymis is suggestive of obstruction or inflammation of the male reproductive tract, and abnormalities in the texture of the epididymis are associated with abnormalities in sperm parameters.

Scrotal and transrectal ultrasonography (TRUS) can detect uni- or bilateral congenital absence of the vas deferens, which may be associated with abnormalities or agenesis of the epididymis, seminal vesicles or kidneys, and indicate the need for testicular sperm extraction.

TRUS helps assess azoospermia caused by obstruction, and detecting distal congenital absence of bilateral vas deferens or anomalies related to obstruction of the ejaculatory duct, such as abnormalities within the duct itself, a median cyst of the prostate or an impairment of the seminal vesicles to become enlarged or emptied.

Prevention of male infertility:

Avoiding smoking as it damages sperm DNA

Avoiding heavy marijuana and alcohol use.

Avoiding excessive heat to the testes.

Maintaining optimal frequency of coital activity.

Sperm counts can be depressed by daily coital activity and sperm motility may be depressed by coital activity that takes place too infrequently with abstinence, 10–14 days or more.

Wearing a protective cup and jockstrap to protect the testicles, in any sport such as baseball, football, cricket, lacrosse, hockey, softball, paintball, rodeo, motorcross, wrestling, soccer, karate or other martial arts or any sport where a ball, foot, arm, knee or bat can come into contact with the groin.

Diet: Healthy diets rich in such nutrients as omega-3 fatty acids, some antioxidants and vitamins, and low in saturated fatty acids (SFAs) and trans-fatty acids (TFAs) are inversely associated with low semen quality parameters. 

Fish, shellfish and seafood, poultry, cereals, vegetables and fruits, and low-fat dairy products have been positively related to sperm quality. 

Diets rich in processed meat, soy foods, potatoes, full-fat dairy products, coffee, alcohol and sugar-sweetened beverages and sweets have been inversely associated with the quality of semen in some studies. 

Studies relating male nutrient or food intake and fecundability suggest that diets rich in red meat, processed meat, tea and caffeine are associated with a lower rate of fecundability. 


Testicular-based male infertility tends to be resistant to medication. 

Usual approaches include using the sperm for intrauterine insemination (IUI), in vitro fertilization (IVF), or IVF with intracytoplasmatic sperm injection (ICSI). 

With IVF-ICSI even with a few sperm pregnancies can be achieved.

Obstructive causes of post-testicular infertility can be fixed with either surgery or IVF-ICSI. 

Surgery may play a role with varicocoelectomy, vasectomy reversal, dand sperm retrieval.

Ejaculation abnormalities, may be treatable by medication, or by IUI therapy or IVF.

Vitamin E helps counter oxidative stress that may be present and is associated with sperm DNA damage and reduced sperm motility.

The sperm count may be improved with a hormone/antioxidant combination therapy.

Giving oral antioxidants to men in couples undergoing in vitro fertilisation for male factor or unexplained subfertility may lead to an increase in the live birth rate but overall the risk of adverse effects is unclear.[54]

Administration of luteinizing hormone (LH), or human chorionic gonadotropin, and follicle-stimulating hormone (FSH) is very effective in the treatment of male infertility due to hypogonadotropic hypogonadism.

Exogenous testosterone therapy is ineffective in benefiting men with low sperm count, because very high local levels of testosterone in the testes are required and exogenous testosterone therapy cannot achieve these required high local concentrations.

 Exogenous androgen therapy can actually impair or abolish male fertility by suppressing gonadotropin secretion from the pituitary gland, as seen in users of androgens/anabolic steroids, who often have partially or completely suppressed sperm production.

The suppression of gonadotropin levels results in decreased testicular androgen production with diminished local concentrations in the testes.

FSH is independently critical for spermatogenesis, but LH has little role in male fertility outside of inducing gonadal testosterone production.

Estrogen, at some concentration, has been found to be essential for male fertility/spermatogenesis.

Estrogen levels that are too high can impair male fertility by suppressing gonadotropin secretion and thereby diminishing intratesticular androgen levels.

Clomiphene citrate and aromatase inhibitors such as testolactone or anastrozole have shown effectiveness in benefiting spermatogenesis.

Low-dose estrogen and testosterone combination therapy may improve sperm count and motility in some men, including in men with severe oligospermia.

A study was done in 1992 with men who had never experienced infertility showed that the amount of sperm in semen had declined by 1% per year since 1938: other more recent studies confirm the decline in sperm count, sperm count, motility, morphology and seminal volume.

Other research has confirmed the decline in sperm count and also seminal volume: this has been a worldwide phenomenon.

Some factors may include exposure to high temperatures:  A 1 degree increase in temperature will reduce 14% of spermatogenesis.

There are a variety of social stigmas that surround male infertility throughout the world. 

This decline in male fertility: Proposed explanations include lifestyle factors, such as diet, and environmental endocrine disruptors, such as those found in plastics.

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