Male azoospermia, what is it and what to do?

Azoospermia refers to the absence of sperm in the ejaculate, which means that no sperm is present in the analyzed seminal fluid.

It is a very difficult diagnosis to accept especially for the male partner who realizes that he is the cause of the couple’s infertility.

The good news is that most men with azoospermia will still be able to have children.

Azoospermia may be due to inadequate hormonal stimulation, impaired spermatogenesis, or obstruction of the vas deferens. In most cases, evaluation of physical and laboratory information, including semen volume, testicular volume, presence of bilateral vas deferens, and serum FSH level, will aid in differentiation of azoospermia types .

Some men with azoospermia actually have small amounts of sperm in their semen, but there are so few of them that they may miss routine tests.

When a male fertility expert (an andrologist who specializes in male fertility) is consulted following a diagnosis of azoospermia, they will perform more detailed tests with specific diagnostic tools. If sperm are found in the semen using these techniques, the condition is called cryptozoospermia . This distinction is very important because it shows that the man is producing sperm and this radically changes his fertility prognosis.

If a spermiogram results in azoospermia, it must necessarily be repeated.
Even some men with normal fertility, for various reasons, can have semen without sperm during the year. Repeating the exam a few weeks or months later may indeed show the presence of sperm.

There are some specific illnesses or exposures that can cause temporary azoospermia : a bad flu or other illness accompanied by a high fever . Frequent use of the hot tub or testosterone therapy can also cause reversible azoospermia .

Prestiticular causes   are endocrine (hormonal) abnormalities that negatively affect spermatogenesis. Testicular or non-obstructive causes involve intrinsic disturbances of spermatogenesis within the testicles. Post testicular or obstructive causes of azoospermia include obstruction of the ductal system anywhere in the male reproductive tract.

Obstructive azoospermia: Sperm are normally produced inside the testicle, but there is a blockage or obstruction in the pathways that allow semen to flow to the outside world.

Non-obstructive azoospermia : the tubules are patent, but there is a problem in the production of sperm: either they are not produced or there is a very low level of sperm. This level is often so low that sperm never make it all the way out of the testicle and can only be found inside the testicle during surgery.

Pretesticular and post-testicular abnormalities that cause azoospermia are often treatable , which may facilitate restoration of fertility potential. In contrast, testicular disorders are usually irreversible, and success rates for surgeries associated with intrinsic testicular abnormalities are significantly lower.

The causes of azoospermia

To understand the causes and treatments of azoospermia, we must first look at the functioning of the male reproductive organs. Understanding how they work under “normal” conditions allows us to understand what can go wrong.

The testicles are the male reproductive organs and are made up of millions of microscopic tubules called seminiferous tubules.

Sperm cells are produced within the walls of these tubules in a process called spermatogenesis which takes about 72 days. The large, round immature germ cells divide and transform into spermatids with heads and tails.

This process is under the hormonal control of the hypothalamus and pituitary glands in the brain. These glands produce hormones which cause the testicle to produce testosterone and sperm.

The sperms are then released into the hollow canal of the seminiferous tubule and make their way to the epididymis, the organ where they are stored and matured.

The epididymis lies above and behind the testicle and continues into the vas deferens.   This duct is the small tube that the surgeon cuts when performing a vasectomy. The vessel flows from inside the scrotum up the body, then behind the bladder and meets with the seminal vesicle. They join together to form the ejaculatory duct which runs through the prostate.

The prostate and seminal vesicles produce most of the fluid that makes up the ejaculate. This fluid settles in the back of the urethra (urinary channel) during an ejaculation.

The causes of presticular azoospermia

Presticular causes are generally linked to pathological endocrine conditions.

• • Hypogonadotropic hypogonadism: May be caused by Kallmann syndrome, pituitary trauma, pituitary tumors, and anabolic steroid use. Hypogonadotropic hypogonadism is a rare cause of congenital or acquired male infertility.
  • Hyperprolactinaemia  is a form of hypogonadotropic hypogonadism caused by excessive prolactin secretion. Hyperprolactinemia suppresses both FSH and LH and can be caused by drugs, concomitant medical conditions, tricyclic antidepressants, some antihypertensives, stress, or pituitary tumors (macroadenoma or microadenoma); the cause may also be idiopathic. The most common drugs that induce hyperprolactinaemia are phenothiazines, imipramine, methyldopa, and reserpine. The most common causes of hyperprolactinaemia are prolactin-producing microadenomas and prolactin-producing macroadenomas. Symptoms of prolactinomas include infertility, decreased sex drive, galactorrhea, headache, fatigue, and erectile dysfunction.
  • Androgen insensitivity syndrome: Occurs in about 1 in 60,000 births. More than 300 mutations have been identified in the androgen receptor gene located on the X chromosome (Xq11-q12) . Because many mutations exist, the syndrome is clinically variable and ranges from phenotypic females (complete androgen insensitivity) to normally virilized but sterile males (partial and minimal androgen insensitivity). Depending on the intensity of the defect, serum testosterone levels can be low, normal or high.

The causes of obstructive azoospermia

They can be genetic, congenital or acquired.

• Vasectomy : The most common cause of obstructive azoospermia, this surgical procedure cuts off the spermatic ducts to stop the flow of sperm.
• Infections : Obstructive azoospermia can be caused by infections of the testicles, prostate, or reproductive tract. These are infections such as epididymitis, orchitis, prostatitis or sexually transmitted diseases such as chlamydia . These can cause a blockage in the small tubules of the epididymis or ejaculatory duct.
• Congenital conditions : Some men are born without a portion of the vas deferens. Other men are born with a cyst in the prostate that blocks the ejaculatory ducts.
• Surgical complications : Surgical procedures performed on the urogenital organs can cause scarring which causes blockage of the ducts. This is more common in pediatric patients because the reproductive tract in children is very small.

The causes of non-obstructive azoospermia

The causes of testicular or non-obstructive azoospermia concern intrinsic disturbances of spermatogenesis. Nonobstructive azoospermia can be caused by varicocele-induced testicular damage, undescended testicles (cryptorchidism), testicular torsion, mumps orchitis, gonadotoxic effects of drugs, genetic abnormalities, and idiopathic causes.

• Genetic causes : These include chromosomal abnormalities (aneuploidies or translocations) The most common chromosomal problem causing azoospermia in men is a situation where there is an extra X chromosome. This condition is called Klinefelter syndrome (the male with this syndrome has an extra X chromosome). Another genetic cause of azoospermia is a deletion of certain genes on the Y chromosome.  Genetic causes of azoospermia are not reversible, but most men with genetic problems still produce small quantities of sperm inside the testicles which can be taken with a testicular biopsy and used in an assisted reproduction treatment (via ICSI)
• Varicocele : it is a  reversible cause that manifests itself with varicose veins around the testicle. This condition is the most common cause of male infertility and is easily fixed. Most males with varicoceles experience only a slight decrease in sperm count, but in some cases the varicocele causes azoospermia.
• Maturation arrest: In this situation there is a problem in the development of the sperms. This developmental arrest can occur early or late in the sperm maturation process.
• Del Castillo syndrome (or sertoli cell alone or germ cell aplasia). It is a condition in which the germ cells from which the sperm are derived are missing. Even in this apparently dramatic situation, in 15-20% of men with this syndrome it is possible to find sperm in the testicle to be able to perform an ICSI. One of the most important things that have been learned about the testicle in the last 20 years is that sperm production in an abnormal situation is not homogeneous, which means that it is not the same or constant in all areas of the testicle. Thus, while one area might have tubules that exhibit no germ cells, another area might have some germ cells and some mature sperm cells.
  Special microsurgical sperm extraction techniques have been developed (such as MICROTESE) which allow the surgeon to examine the inside of the testicles, and extract the sperm.
• Testicular cancer: Sometimes the first sign of testicular cancer or other cancers of the reproductive system is azoospermia or a very low sperm count. For this reason, in the case of azoospermia it is always important to analyze the patient well: by detecting the tumor in advance, a patient’s life could be saved.
• Cryptorchidism : it is the most common genital malformation: it is seen in 2.7% of newborns and up to 0.8% of 1-year-old children. Early treatment can potentially minimize the risk of infertility, and success depends on the initial position of the testicle.
• Testicular torsion : Occurs in about 1 in 4,000 males before the age of 25. Treatment consists of immediate manual detorsion followed by surgery.
• Mumps orchids
• Medical Treatments:    Chemotherapy and radiation therapy used to treat cancer are two types of medical treatments that can cause temporary azoospermia. Most men undergoing azoospermia treatment will resume sperm production within two years of therapy, depending on the type of treatment they received.
• Prescription drugs: Major causes of drug-related nonobstructive azoospermia include testosterone and other anabolic steroids. These can cause infertility and are a very common and usually reversible cause of azoospermia.