Sperm dysfunction

Sperm dysfunctions include defects in sperm production and emission. Diagnosis of sperm dysfunction is based on sperm analysis and genetic testing. The most effective treatment for sperm dysfunction is artificial insemination by intracytoplasmic sperm injection.

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Causes sperm dysfunction

Spermatogenesis occurs continuously. Each germ cell requires approximately 72-74 days to fully mature. Spermatogenesis occurs most efficiently at a temperature of 34 C°. Within the vas deferens, Sertoli cells regulate maturation, and Leydig cells produce the necessary testosterone. Normally, fructose is produced in the seminal vesicles and secreted through the vas deferens. Sperm disorders may result from inadequate sperm quantity: too little (oligospermia) or no sperm (azoospermia) or defects in sperm quality: abnormal motility or abnormal sperm structure.

Spermatogenesis may be impaired by high temperature, urinary tract disorders, endocrine disorders or genetic defects; by taking medications or toxins, resulting in inadequate quantity or defects in sperm quality. Causes of decreased sperm emission (obstructive azoospermia) include retrograde ejaculation into the bladder in diabetes mellitus, neurological dysfunction, retroperitoneal dissection (eg, in Hodgkin's lymphoma) and prostatectomy. Other causes include obstruction of the vas deferens, congenital bilateral absence of the vas deferens or epididymis. Many infertile men have mutations in genes at the level of cystic fibrosis transmembrane conductance regulators (CFTR, cystic fibrosis), and most men with symptomatic cystic fibrosis have congenital bilateral absence of the vas deferens.

Men with Y-chromosome microdeletion may develop oligospermia by various mechanisms, depending on the specific deletion. Another rare mechanism of infertility is the destruction or inactivation of sperm by sperm antibodies, which are usually produced in men.

Causes of decreased spermatogenesis

Causes of sperm dysfunction	Examples
Endocrine disorders	Hypothalamic-pituitary-gonadal regulation disorders Adrenal disorders Hyperprolactinemia Hypogonadism Hypothyroidism
Genetic disorders	Gonadal dysgenesis Klinefelter syndrome Microdeletion of sections of the Y chromosome (in 10-15% of men with spermatogenesis disorders) Mutations in genes at the level of cystic fibrosis transmembrane conductance regulators (CFTR, cystic fibrosis)
Urogenital tract disorders	Cryptorchidism Infections Injuries Orchitis after mumps Testicular atrophy Varicocele
The influence of high temperatures	Exposure to extreme temperatures within the last 3 months Fever
Substances	Anabolic steroid Diethylstilbestrol Ethanol Regional drugs, such as opioids (hypnotics) Toxins

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Diagnostics sperm dysfunction

In case of infertile marriage, it is always necessary to conduct an examination to detect sperm disorders in the man. The medical history of the disease is studied, the patient is examined to identify potential causes (for example, disorders of the genitourinary tract). The normal volume of each testicle is 20-25 ml. It is necessary to perform a spermogram.

In cases of oligospermia or azoospermia, genetic testing should be performed, including standard karyotyping, PCR of labeled chromosome regions (to detect Y-chromosome microdeletions), and evaluation for CFTR (cystic fibrosis) gene mutations. The female partner of a man with a CFTR gene mutation should also be tested to exclude CF carrier status before sperm is used for reproduction.

Before the semen analysis, the man is asked to abstain from ejaculation for 2-3 days. Since the amount of sperm varies, more than two samples obtained more than 1 week apart are necessary for a complete analysis; each sperm sample is obtained by masturbation into a glass container, preferably in a laboratory. If this method is difficult, the man can collect the sperm at home in a condom. The condom should be free of lubricants and chemicals. The ejaculate is examined after keeping the sperm at room temperature for 20-30 minutes. The following parameters are assessed: volume (normally 2-6 ml), viscosity (normally begins to liquefy within 30 minutes; completely liquefies within 1 hour), appearance and microscopic examination are carried out (normally opaque, creamy, contains 1-3 leukocytes in the field of view at high magnification).

Measure pH (normal 7–8); count sperm (normal >20 million/ml); determine motility after 1 and 3 h (normal motility >50%); calculate the percentage of sperm with normal morphology (normal >14%, according to strict WHO criteria used since 1999); determine the presence of fructose (indicates proper functioning of at least one vas deferens). Additional computerized methods of determining sperm motility (e.g., linear sperm velocity) are available, but their correlation with fertility is unclear.

If a man does not have hypogonadism or congenital bilateral absence of the vas deferens, and the volume of ejaculate is less than 1 ml, then urine is taken for the purpose of testing to determine sperm after ejaculation. A disproportionately large number of sperm in the urine relative to their number in the semen suggests retrograde ejaculation.

If specialized sperm tests, available in some infertility centers, do not explain the cause of infertility in both partners, then the question of the possibility of artificial insemination and embryo transfer into the uterus is decided.

A test is performed to detect sperm antibodies, as well as a hypoosmotic swelling test to measure the structural integrity of the sperm plasma membranes. A sperm binding test to the zona pellucida and a sperm penetration test are also performed to determine the ability of sperm to fertilize an egg in vitro.

If necessary, testicular biopsy is performed to differentiate between obstructive and non-obstructive azoospermia.

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Treatment sperm dysfunction

Treatment of sperm dysfunction includes therapy for urogenital tract disorders. Men with ejaculate sperm counts of 10-20 million/ml and no endocrine disorders are given clomiphene citrate (25-50 mg orally once a day for 25 days a month for 3-4 months). Clomiphene (an antiestrogen) can stimulate sperm production and increase sperm count. However, whether it improves sperm motility or morphology is unclear; increased fertility has not been confirmed.

If the sperm count is less than 10 million/ml or clomiphene is ineffective with normal sperm motility, the most effective treatment is artificial insemination with a single injection of sperm into one egg (called intracytoplasmic sperm injection). An alternative method is sometimes intrauterine insemination using washed sperm samples if ovulation occurs. Pregnancy usually occurs in the 6th treatment cycle, if the method is effective.

Reduced sperm count and viability do not exclude pregnancy. In such cases, fertility can be increased by ovarian hyperstimulation in women with the simultaneous use of artificial insemination or other methods of reproductive technology (e.g., artificial insemination, intracytoplasmic sperm injection).

If the male partner does not produce sufficient fertile sperm, then insemination using donor sperm may be considered. The risk of developing AIDS and other sexually transmitted diseases is minimized by freezing donor sperm for more than 6 months, after which donors are re-tested for infections before the insemination procedure.