Azoospermia

What is Azoospermia?

Male factors play a key role in cases of infertility among couples. Around 15% of the total population experience infertility issues, with a significant part of male infertility being the condition known as azoospermia. This is a severe form of male infertility, characterized by the complete absence of sperm in two separate semen samples. There are also cases of aspermia, which means the total lack of ejaculation. About 1% of all men and between 10 and 15% of all infertile men have azoospermia, often as a result of untreatable testicular disorders.

Azoospermia can be split into three categories based on whether it is caused by issues before the testicle (pre-testicular), within the testicle (testicular), or after the testicle (post-testicular) (see Table 1 for Classification According to Causes). It can also be classified into obstructive azoospermia (OA – blockage in the ducts or vas deferens) and nonobstructive azoospermia (NOA). It’s important to recognize the difference between OA and NOA, which is primary testicular failure. Thanks to advancements in assisted reproductive technologies, several fertility treatments are available for couples struggling to conceive due to male infertility, including azoospermia.

About 40% of men with azoospermia have OA, which can be caused by a variety of things. Causes include congenital bilateral absence of the vas deferens, blockage of ejaculatory and epididymal ducts, atresia of the seminal vesicles, various infections of the genitourinary tract causing blockage, or pelvic and inguinal procedures leading to complete blockage such as a bilateral vasectomy. For men with OA, the production of sperm is often normal. As such, treatment options often involve surgery to remove the blockage and other assisted reproductive techniques.

The more common type of azoospermia is NOA, which affects about 60% of men with azoospermia. NOA usually occurs due to severe defects in sperm production, commonly resulting from primary testicular failure or dysfunction. This can result from dysfunction of important hormonal glands such as the pituitary or hypothalamus. For most cases of NOA, the cause is often unknown. However, NOA (primary testicular failure) can often be treated using advanced assisted reproductive techniques.

In severe cases of sperm production failure, testicular biopsies often show some areas of normal sperm production. These sperm can be collected using techniques such as Testicular Sperm Extraction (TESE) or Testicular Sperm Aspiration (TESA) and used in advanced reproductive techniques like Intracytoplasmic Sperm Injection (ICSI). Sperm retrieved this way and used for IVF with ICSI generally results in healthy offspring.

Diagnosing and providing care to infertile men struggling with sperm production failure present a significant challenge for healthcare professionals. Diagnostic tools used for patients with azoospermia may include hormonal assessment, biomarkers in semen, ultrasonography, testicular biopsy, and vasography. Transrectal ultrasound is generally the best method for diagnosing blockage in the distal male reproductive system.

What Causes Azoospermia?

In male fertility issues, there are two types: obstructive azoospermia (OA) where men typically produce normal sperm, and non-obstructive azoospermia (NOA) where the cause is often unknown.

NOA can come about due to many factors, such as:

– Use of muscle building steroids
– Immunity to male hormones
– Cancer treatment (chemotherapy)
– Being born without germ cells (a condition called Sertoli cell-only syndrome)
– Exposure to dangerous metals
– Overproduction of prolactin (a hormone)
– Underactive sexual glands, like in Kallmann syndrome
– Problems in sperm production due to chromosome abnormalities like in Klinefelter syndrome or certain genetic issues on the Y chromosome
– Infections like mumps and orchitis (an inflammation of the testes)
– Radiation therapy

Keep in mind, there’s an unsuccessful experiment with a compound called epsilon aminocaproic acid to protect sperm DNA from radiation damage, but it’s not approved for use yet.

Other causes of NOA include halt in sperm maturity, twisting of the spermatic cord in the testes (testicular torsion), testosterone supplement therapy, change in the position or direction of a genetic region affecting sperm production (azoospermia factor), undescended testes (cryptorchidism), and enlarged veins in the scrotum (varicoceles).

Causes of male infertility can be sorted into three categories:

– Pre-testicular Causes: These usually relate to hormonal irregularities involving the brain (specifically the hypothalamus), pituitary gland, and male sexual glands (testes). Treating these issues typically improves fertility outcomes.
– Testicular Causes: These often involve problems with sperm production. Unfortunately, treatment doesn’t often improve fertility because these disorders are usually irreversible.
– Post-Testicular Causes: These involve any blockages in the male reproductive tract that prevent sperm from being ejaculated. Treatment usually improves fertility in these cases.

Risk Factors and Frequency for Azoospermia

Infertility affects nearly 15% of all couples. Azoospermia, a condition occurring in men that is characterized by the absence of sperm in semen, impacts around 1% of the male population and accounts for 10% to 15% of male infertility cases. In the United States, there are estimated to be roughly 600,000 men of reproductive age with azoospermia, most of who are categorized with Non-obstructive Azoospermia (NOA).

Men with azoospermia have a higher risk of developing cancer compared to other men. Research indicates that 5% to 8% of men with testicular cancer will be diagnosed with azoospermia. However, it’s important to remember that actual numbers may be higher, as infertility is not a regularly reported disease and is often managed privately in doctor’s offices. Additionally, in developing countries where advanced treatment may be too expensive or unavailable, cases go unreported.

Signs and Symptoms of Azoospermia

Patients with azoospermia, a condition characterized by the absence of sperm in semen, required a careful and detailed evaluation. It starts with a thorough review of the patient’s medical, sexual, and surgical history. This includes collecting information about any genital injuries, drug allergies, medications taken (such as hormones, steroids, testosterone supplements, toxins), and any chemotherapy, pesticide, or radiation exposure. It’s crucial to also inquire about past genitourinary infections and sexually transmitted diseases.

A physical examination is another essential step. It should be carried out with the patient either lying down or standing up, and ideally in a room with a temperature between 96.8 °F to 100.4 °F. The doctor should look for varicocele, a swelling of the veins that drain the testicle, and evaluate the development of secondary sexual traits. The patient’s body, armpit, and pubic hair growth may be reduced if androgen levels are low. The doctor should also check thyroid gland by palpitation, listen to the patient’s heart and lungs, and conduct breast and abdominal examinations.

The examination of the male genitalia is of utmost importance. The doctor needs to palpate the testicles and note their length, width, and volume. Size reduction can be associated with impaired sperm production. Normal testicular size usually is 20 cc or more, and length is typically 4 cm. However, the “normal” length varies depending on racial background.

• Generally, a normal length is 31 mm for whites and 34 mm for blacks.
• Patients with obstructive azoospermia usually have normal hormonal profiles and testicular size.
• However, small or atrophied testicles, alongside high levels of FSH hormone, usually suggest primary testicular failure, and these patients often have worse fertility outcomes. In some cases, intracytoplasmic sperm injection (ICSI) might still be possible.

The doctor should also feel and check the consistency of the vas deferens and epididymis, the tubes that transport sperm. If one or both vas deferens are absent, it’s often due to a mutation in the cystic fibrosis gene. Lastly, a digital rectal examination helps rule out any masses and assess the size and consistency of the prostate gland. The doctor might be able to feel prominent seminal vesicles in cases of ejaculatory duct obstruction.

Testing for Azoospermia

If you’re a man having trouble with fertility, there are a number of tests and procedures doctors use to try to identify the problem. Here’s a quick summary of what these tests might involve.

First up, is a semen analysis. For accurate results, you’ll be asked to abstain from sexual activity for three days before each of two different tests. If these tests show no sperm, this could mean there’s either a problem with sperm production, or a blockage in the path between the testes and the seminal vesicles. If there’s less semen than expected, this could indicate ejaculation issues, or a blockage in the ejaculatory duct. In these cases, post-ejaculation urine will also be tested.

If your sperm count is very low or non-existent, you might be asked to have a hormonal evaluation. This is to check for imbalances in hormones like testosterone that can impact sperm production. If your testicles are a normal size but your sperm count is low, an overactive or underactive thyroid gland could be the cause.

Imaging tests like scrotal ultrasound can help to identify any physical issues that could be stopping the production or movement of sperm. They can show up things like varicoceles (enlarged veins in the scrotum), cysts, or any masses which might not be noticeable through other methods. These tests can also help your doctor to determine if the issue is obstruction (a blocked pathway) or Non-Obstructive Azoospermia (an issue with sperm production).

Your doctor may also recommend genetic testing if there’s a chance a genetic disorder could be causing your fertility issues. The most common genetic cause of male infertility is Klinefelter’s syndrome which is found in about 3% of all infertile men. This disorder can cause a wide range of symptoms, including a small penis, enlarged breast tissue, and trouble with movement and coordination. Other genetic conditions your doctor might check for include Kallmann’s syndrome, and cystic fibrosis.

Lastly, if all other tests fail to determine the cause of low sperm production, you may need to have a testicular biopsy. This is generally only done as a last resort. The biopsy can provide a definitive diagnosis by showing the cells inside your testicles up close.

Infertility can be a difficult, confusing issue but the good news is, there are many tests and treatments available. By working with your doctor to understand the underlying cause, you can hopefully find a solution that allows you to have children.

Treatment Options for Azoospermia

Infertile couples have numerous options to have their own biological children thanks to advancements in reproductive techniques.

There are two types of azoospermia – obstructive and non-obstructive.

Obstructive Azoospermia (OA):

The main goal in managing OA is to fix the obstruction site using surgery, such as vasoepididymostomy and vasovasostomy. An alternative treatment is Assisted Reproductive Techniques, which are valuable for patients born without a vas deferens, since surgical reconstruction can’t be done in these cases. For obstructions in the ducts used to eliminate semen, surgical correction is performed to restore their function.

When surgical repair isn’t an option, the use of sperm retrieval for assisted reproduction is an excellent alternative with a nearly 100% success rate. In these cases, sperm is collected and may also be frozen for future use.

In cases where surgery doesn’t yield successful results, sperm collected during the procedure can be stored for future use. There are a variety of surgeries that can be performed, including surgeries done through small incisions near the groin or with the assistance of laparoscopic or robotic techniques.

Non-obstructive Azoospermia (NOA):

Advanced assisted reproductive techniques are usually required for patients with NOA. Microscopic Testicular Sperm Extraction (Micro-TESE), a procedure where sperm are obtained directly from the testicular tissue, and Intra-Cytoplasmic Sperm Injection (ICSI) where a single sperm is injected directly into an egg, can be beneficial for these patients.

For some men, the absence of sperm in their semen can be a side effect of testosterone supplementation therapy. In these cases, simply stopping the hormonal treatment and waiting can result in the recovery of sperm production within two years.

In order to stimulate sperm production in cases of hypothalamic hypogonadism or pre-testicular azoospermia (conditions causing low testosterone levels), doctors might prescribe hormone drugs. However, the use of hormone therapy remains contentious, and some experts do not recommend its routine use. In particular, men with NOA and primary hypogonadism (where the body produces little or no sex hormones) usually have to rely on techniques like Micro-TESE and ICSI.

Just like with OA, people with NOA have a chance of developing other health problems including tumors and an elevated risk of developing malignancies in the future. About 30% of men with NOA also have low testosterone levels.

However, certain conditions might make attempts at sperm retrieval impossible, such as specific genetic disorders which lead to zero sperm retrieval rates. But even in adverse situations, there’s still a chance of at least a 24% success rate for sperm retrieval with Micro-TESE.

What else can Azoospermia be?

When a patient is diagnosed with azoospermia, which means they are producing no sperm, there are several conditions the doctor needs to consider that might be causing it:

• Missing one or both vas deferens from birth (CUAVD or CBAVD), which are the tubes that carry sperm from the testicles
• Congenital adrenal hyperplasia, a group of genetic disorders affecting the adrenal glands
• An enlarged vein in the scrotum present from birth (congenital varicocele)
• Cryptorchidism, a condition where one or both of the testes fail to descend
• Blockage or cysts in the tubes that carry sperm during ejaculation (ejaculatory ducts)
• Inflammation of the tube at the back of the testicle that stores and carries sperm (epididymitis) or inflammation of the prostate gland (prostatitis)
• Male sexual function disorders
• Having too much of the hormone prolactin in the blood (hyperprolactinemia)
• A condition where the body doesn’t produce enough sex hormones (hypogonadotropic hypogonadism)
• Kallmann syndrome, a genetic condition characterized by delayed or absent puberty and an impaired sense of smell
• Long-term use of testosterone supplements
• Side effects of certain medications, like tamsulosin
• Mumps infections that involve the testicles (mumps orchitis)
• Tumors in the pituitary gland, which regulates hormone production
• Surgery to remove both testicles (bilateral orchiectomy)
• Having had a vasectomy
• Having had a surgery to remove part of the prostate gland (post-TURP)
• Retrograde ejaculation, a condition where semen enters the bladder instead of exiting through the penis during orgasm
• Sperm-containing cysts in the epididymis (spermatoceles)
• Using testosterone supplements or having testosterone replacement therapy

What to expect with Azoospermia

The outcome of azoospermia, or the absence of sperm in semen, depends mainly on what is causing it. Two common causes include obstructions, referred to as OA, and non-obstructive reasons, known as NOA.

OA is often caused by issues like missing or blocked vas deferens, the tubes that carry sperm, which can usually be corrected with surgery. These scenarios typically have a positive outcome, and individuals with OA often achieve successful conception through surgical treatments or assisted reproductive techniques.

On the other hand, NOA usually occurs due to problems within the testicles, and it presents a tougher scenario. While procedures like testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) can allow for conception, their success isn’t guaranteed and in some instances, treatment might not be possible at all if the sperm production is too disrupted.

Therefore, accurate diagnosis, appropriate treatment plans, and continuous support are all important factors in affecting the outcome. This highlights the importance of a thorough and personalized approach to managing azoospermia.

Possible Complications When Diagnosed with Azoospermia

If a man is unable to produce sperm, a condition known as azoospermia, it can lead to a variety of complications. These complications can also occur from any surgical treatment that might be used to address the condition.

Here are some of the complications:

• Blood clot formation (hematoma) due to surgery
• Infection
• Scarring of the testes (parenchymal fibrosis)
• Shrinkage of the testes (testicular atrophy)

Not having sperm can also cause significant emotional distress, which can negatively affect a person’s mental health and can strain personal relationships. Men who pursue fertility treatments in an attempt to conceive often face financial stress, along with additional emotional strain. Dealing with infertility and facing potential societal judgment about male reproductive health can add to the difficulties and complications for men with azoospermia.

Preventing Azoospermia

Preventing and managing the condition known as azoospermia involves two main elements: deterrence and patient education. What this means is, firstly, making people aware of certain lifestyle choices that can potentially cause azoospermia. For example, smoking, drinking a lot of alcohol, taking testosterone supplements, and being exposed to environmental toxins can all contribute to this condition.

The second part, patient education, is about teaching people the importance of leading a healthy lifestyle to benefit their reproductive well-being. A balanced diet and stress management are key aspects of a healthy lifestyle. It also involves helping individuals understand the different causes and types of azoospermia. This information allows them to make informed decisions about their own reproductive health.

Proper counselling, testing, and treatment can offer most men – including those with azoospermia – the chance to father children biologically. By spreading awareness and providing complete information, healthcare professionals can help prevent risky behaviours and equip patients to understand and manage azoospermia. This ultimately encourages their active participation in managing and preserving their reproductive health.