Azoospermia: When Your Sperm Count Is Zero

Causes, diagnosis, and treatment

Azoospermia is a condition where there are no sperm found in the ejaculate (or semen) after orgasm. Affecting about 1 in 100 of the general population—but up to 1 in 10 of men with fertility problems—azoospermia is an uncommon but severe form of male infertility. The best course of treatment depends on the specific cause of the azoospermia, along with the fertility potential of the female partner.

You might assume that men with azoospermia can’t have genetic children, but this isn’t necessarily so. With the help of assisted reproductive technology, and sometimes with the help of surgery, some men with azoospermia can have genetic offspring.

This is not, however, always possible. In these situations, using a sperm donor, embryo donor, or pursuing adoption or a childfree life are alternatives.

Sperm production to ejaculation
Illustration by JR Bee, Verywell

Sperm Production

To understand azoospermia, having at least a basic understanding of how sperm are produced and get into the ejaculate can help.

Sperm cells begin their journey in the testicles, which are held slightly outside of the body in the scrotum. The testicles are slightly outside of the body because sperm are sensitive to heat. A man’s body temperature is too high for sperm cells to survive.

The sperm cells don’t just float around in a pool of fluids in the testicles, but instead, they develop inside a system of tiny tubes known as the seminiferous tubules.

Sperm cells also don’t just start in their tadpole-like form, with a head and a tail. They begin as tiny round cells. Only when exposed to reproductive hormones like testosterone, FSH (follicle stimulating hormone), and LH (luteinizing hormone) do they mature and develop into the sperm cells you're more familiar with. These hormones are controlled and produced by the pituitary gland and the testicles.

After the sperm cells get to a certain level of maturity in the seminiferous tubules, they move into the epididymis, a long, coiled tubal area. They continue to develop further here for several weeks.

After the epididymis, the sperm cells move into the vas deferens. (The vas deferens is what’s cut during a vasectomy.)

After the vas deferens, the sperm travel in the seminal vesicle, also known as the seminal gland. Here, the majority of the fluid that makes up semen is produced. This fluid nourishes the sperm cells. The next stop is the prostate gland, where prostate fluids are added to the overall semen mix.

The prostate gland is the last stop sperm make on their journey before they move into the urethra during ejaculation. The urethra travels from the bladder, through the prostate gland, and eventually through the penis.

Just below the prostate gland sit two pea-sized glands known as the bulbourethral gland, or Cowper's Gland. While sperm don’t directly travel through these glands, before ejaculation, the glands release a fluid that neutralizes any acidity in the urethra left from previous urination.

What keeps urine from ejecting through the urethra during ejaculation? The muscles around the “neck” of the bladder tighten when a man has an erection. This keeps the urine from leaving the bladder during male arousal.

Types

There are two ways to talk about azoospermia: in terms of at what point in the reproductive cycle things go wrong, or regarding whether it’s caused by a blockage or not. There’s a debate over which classification system is better.

If talking about where in the reproductive cycle things go wrong, azoospermia can be broken down into three categories: pre-testicular, testicular, and post-testicular.

Pre-testicular azoospermia is when the issue is primarily hormonal problems related to the pituitary gland or hypothalamus. This is sometimes called secondary testicular failure. The endocrine glands in the brain are not producing the right cocktail of chemicals to trigger healthy sperm development.

Testicular azoospermia is when the problem is primarily within the testes themselves. In this case, the testes may not be producing testosterone, or the testes may not be responding to hormones being released by other endocrine glands. Another possibility is that something may be wrong with the cellular development of sperm. An example of testicular azoospermia would be in a case of primary testicular failure.

Post-testicular azoospermia is when the problem is primarily a blockage or ejaculation dysfunction—for example, retrograde ejaculation (when semen and sperm fall back into the bladder instead of going out the urethra during ejaculation) or a blockage (or absence) of the vas deferens or epididymis. 

The most common way to talk about azoospermia is in reference to whether it’s caused by blockage or not. Your doctor may tell you that you have obstructive azoospermia or nonobstructive azoospermia.

Obstructive azoospermia is when the sperm can’t get into the semen or ejaculate due to a blockage or issue with ejaculation. Nonobstructive azoospermia is when the cause is primarily hormonal or an issue with the sperm development.

Symptoms

Azoospermia itself—a lack of sperm in the semen—doesn’t have any specific symptoms.

Couples trying to conceive will experience infertility if the male partner has a zero sperm count. A couple is said to be dealing with infertility if they don't get pregnant after one year of unprotected intercourse. Infertility is frequently the only sign that something is wrong.

With that said, some causes of azoospermia can lead to noticeable signs and symptoms.

Signs or symptoms that may indicate you’re at risk for azoospermia include:

  • Low ejaculate volume or “dry” orgasm (no or little semen)
  • Cloudy urine after sex
  • Painful urination
  • Pelvic pain
  • Swollen testicles
  • Small or undescended testicles
  • Smaller than normal penis
  • Delayed or abnormal puberty
  • Difficulty with erections or ejaculation
  • Low sex drive
  • Reduced male hair growth
  • Enlarged breasts
  • Muscle loss

It is possible to have none of these symptoms, however, and still have azoospermia.

Obstructive Azoospermia Causes

Obstructive azoospermia may be caused by:

  • a congenital anomaly.
  • infection or inflammation of the reproductive tract.
  • previous trauma or injury (including surgical).
  • retrograde ejaculation (even though technically there is no blockage involved in this situation).

Congenital Source

There are some genetic causes or congenital anomalies that can lead to obstructive azoospermia. Some men are born with a blockage in the epididymis or ejaculatory duct, while others may be missing the vas deferens on one or both sides of the reproductive tract. The causes of these anomalies are not always known.

Men without a vas deferens on both sides are said to have a congenital bilateral absence of the vas deferens, or CBAVD. Bilateral absence of the vas deferens is associated with the cystic fibrosis gene (CFTR).

Three out of four men with bilateral absence of the vas deferens have genetic mutations in CFTR gene.

While almost all men with cystic fibrosis will be missing the vas deferens, not all men who are missing the vas deferens have cystic fibrosis. For those with mutations on the cystic fibrosis gene, but not the full disease, they may have mild breathing or digestive problems. Others will be carriers of the CFTR gene, meaning they are at risk for passing on full cystic fibrosis to a child if their female partner also carries the gene. 

For men who are missing the vas deferens on both sides, have mutations on the CFTR gene, but don’t have full-blown cystic fibrosis, they are said to have atypical cystic fibrosis.

Because of the risk of passing on this potentially life-threatening genetic disorder, genetic testing in both the male and female partner is recommended if azoospermia is caused by the absence of the vas deferens. Cystic fibrosis is a recessive disorder, meaning that for a child to inherit the disease, both parents need to be carriers.

(More about what happens if both the male and female partner are carriers in the treatment section of this article below.)

Infection or Inflammation of the Male Reproductive Tract

Blockage of the epididymis or ejaculatory duct can be caused by infection or inflammation. Infection of the epididymis is known as epididymitis.

A possible cause of these infections is an untreated sexually transmitted infection. Note that the blockage can still be present even after an infection has been treated. This is because scar tissue may be formed during the active inflammation stage of infection. The antibiotics will get rid of the infection but won't fix the scar.

If you have a history of sexually transmitted disease, tell your doctor, even if you think that was “in the past.”

Non-sexually transmitted infections can also lead to inflammation, scar tissue, and blockage. For example, childhood mumps can cause viral orchitis, which is inflammation of one or both testicles. This infection in childhood can lead to permanent scarring, which later in life may mean infertility due to azoospermia.

Previous Trauma and/or Surgical Causes

Previous trauma to the male reproductive tract can cause damage, scar tissue, and blockage to the vas deferens, epididymis, or ejaculatory duct.

Sometimes, surgery in the general area—but not specifically on—the male reproductive tract can lead to unintentional scaring or injury. For example, surgery to treat an inguinal hernia can lead (in rare cases) to injury to the testes or vas deferens.

A previous vasectomy—a form of permanent birth control where the vas deferens are cut or blocked intentionally—is a possible cause of azoospermia. While this is the goal of vasectomy surgery, some men decide in the future to have the vasectomy reversed.

Retrograde Ejaculation

Retrograde ejaculation is when semen (and sperm) move backward into the bladder during ejaculation, instead of moving forward out the urethra. This can lead to both low semen volume (the amount of ejaculate) and low to zero sperm count, depending on the severity.

Technically, there’s no blockage in retrograde ejaculation. Still, it’s frequently placed in the category of “obstructive” azoospermia. Instead, the ejaculation process itself isn’t functioning properly. The good news is that this is an easier problem to treat (usually) than other causes of obstructive azoospermia. 

Nonobstructive Azoospermia Causes

Nonobstructive azoospermia may be caused by:

  • a genetic or chromosomal anomaly.
  • damage to the testes from radiation, chemotherapy, or other toxin exposure.
  • hormonal imbalances.
  • side effects of medications or hormonal supplements.
  • a varicocele.

Genetic and Chromosomal Anomalies

Nonobstructive azoospermia can be traced to a genetic or chromosomal cause up to a quarter of the time. The specific gene involved cannot always be traced, and there is still a lot we don’t understand and know about genetic causes of infertility.

Three known genetic or chromosomal causes of nonobstructive azoospermia include Y-chromosomal microdeletions, Klinefelter syndrome, and Kallmann syndrome.

You may be familiar with the idea that two X chromosomes indicate a female genotype, while XY indicates a male genotype.

With Y-chromosomal microdeletions, the Y chromosome is missing some genes. This can cause male infertility and lead to low (or absent) sperm counts. Many men have no other signs or symptoms, while others might have small or undescended testes.

Klinefelter syndrome is when instead of presenting with XY sex chromosomes, a person presents with XXY. While some men with Klinefelter syndrome will have physical and cognitive symptoms that lead to diagnosis during puberty or in young adulthood, other men have mild or almost no symptoms and go undiagnosed until they have fertility problems.

Kallmann syndrome is a genetic condition associated with ANOS1 gene, located on the X-chromosome. Men with Kallmann’s syndrome may not go through normal puberty, have a reduced sense of smell (or no sense of smell), and often are infertile. Kallmann’s syndrome is a possible cause hypogonadotropic hypogonadism, which is discussed further below.

Radiation, Chemotherapy, or Toxin Exposure

Exposure to toxic elements can lead to temporary or even permanent azoospermia. If radiation therapy has been used directly on the male reproductive organs during cancer treatment, azoospermia may result.

Chemotherapy often leads to azoospermia during treatment, but whether azoospermia will continue after treatment is unpredictable. Fertility may return quickly after cancer treatment in some. In other cases, sperm production will return after a few years. In others, it may take up to 10 years to return. Less commonly, sperm production may never return.

Whenever possible, before you start cancer treatment, talk to your doctor about cryopreservation of sperm.

Toxic chemical exposure at work can also lead to male infertility and nonobstructive azoospermia. Exposure to certain pesticides or heavy metals can lead to male infertility. 

Hormonal Imbalance

The pituitary gland, hypothalamus, and testes work together in creating the hormone signals and chemicals required for sperm production. Abnormalities in hormone production, levels, or interactions can lead to infertility, including nonobstructive azoospermia.

There are many possible causes of hormone imbalance, anything from inheritable or genetic conditions, to acquired hormonal problems, to lifestyle-based triggers. Sometimes, the exact cause is not identified.

Hypogonadotropic hypogonadism is when there is a problem with the pituitary gland or hypothalamus in the brain. This may be present from birth or may arise later in life. Possible causes include genetic conditions, radiation exposure, medication side effects or drug abuse, excessive exercise, or unknown causes. 

Primary testicular failure is when a hormone imbalance is linked to issues with the testes and may lead to inadequate production of testosterone and poor or absent sperm development, despite hormone support from the pituitary and hypothalamus. 

Secondary testicular failure is when the hormone breakdown occurs in the pituitary gland or hypothalamus, while the testicles may be functioning properly.

Medication Side Effects

Some medications can cause azoospermia.

The most common cause of azoospermia due to medication side effects is from testosterone supplementation. Anabolic steroid use in athletes can also cause azoospermia, as well as chemotherapy drugs.

Some drugs that cause azoospermia will have this impact only temporarily, while in other cases, long-term azoospermia can occur.

Other medications that may lead to non-obstructive azoospermia include:

  • Colchicine (used to treat gout)
  • Chlorambucil (cancer medication)
  • Cyclophosphamide (cancer medication)
  • Procarbazine hydrochloride (treatment for Hodgkin’s disease)
  • Vinblastine sulfate (cancer medication)
  • Everolimus (cancer drug and also used to prevent organ reject after transplants)
  • Sirolimus (used to prevent organ reject after transplant)

Varicocele

A varicocele is an enlarged vein in the scrotum or testicle. This enlarged vein causes blood to pool in the area, which increases the heat of the testicles and may also cause swelling, testicle shrinkage, and discomfort. Varicoceles are a common cause of male infertility.

Most of the time, varicoceles lead to lower sperm counts. However, between 4 and 13 percent of men with a varicocele will have severe low sperm count or even azoospermia.

Diagnosis and Testing

Semen analysis is the only way to know if your sperm count is abnormal or zero. If your first semen analysis comes back with zero sperm, your doctor will have you repeat the test a few months later.

Azoospermia is diagnosed after two separate semen analyses are completed, and no sperm are found in the semen samples.

After azoospermia is diagnosed, the next step is to attempt to identity the cause of the problem. Your treatment plan will be based on whatever is the suspected cause for the zero sperm count.

Further testing may include...

  • Taking a detailed medical history (that includes reporting any serious childhood illness (like mumps) or previous sexually transmitted infections)
  • Physical exam of the testicles
  • Blood work, specifically to measure FSH and testosterone levels, and possibility also prolactin or estrogen levels
  • Karyotype testing and (maybe) genetic testing for specific inheritable diseases
  • Transrectal ultrasound (TRUS) to look for blockages or abnormalities of the male reproductive tract
  • Testicular biopsy (in some cases)

A proper evaluation won’t necessarily include all of the above tests. More invasive testing (like a testicular biopsy) shouldn’t be used if other tests have already diagnosed the likely cause.

A full fertility evaluation of the female partner is also needed, as that will affect which treatment path is best for the couple. Genetic testing and counseling may also be recommended for both partners. 

Treatment

Fertility treatment will depend on the specific kind of azoospermia and the cause of the problem. Also, the female partner’s fertility situation will also determine treatment choices.

Treatment of Any Lingering Infections of Inflammation

If an active infection is present, this should be treated before any other treatments are considered.

While some men will be suffering from symptoms of an infection (like painful urination), up to one in four men have no symptoms of an infection. Still, even without noticeable symptoms, the infection can be negatively affecting their fertility and causing permanent damage to the reproductive tract.

Surgical Repair

In some cases of obstructive azoospermia, blockages and severed (or missed) connections can be repaired with microsurgical treatment. Surgical treatment may also be used to remove or treat a varicocele, and may also be used to treat retrograde ejaculation.

When surgery can correct obstructive azoospermia, natural conception may be possible. Surgical treatments don’t correct the problem overnight, however. A semen analysis will be ordered three to six months post-surgery.

If sperm levels are normal, and there are no fertility problems in the female partner, the couple may be able to try to conceive naturally. If sperm levels are still abnormal after surgery, other options can be considered. 

Medication or Hormonal Support

In some cases, azoospermia can be treated with medication. For example, retrograde ejaculation can sometimes be treated with medications, which can then enable natural conception.

Hormones or hormonal drugs used to treat male fertility may include Clomid, Letrozole, FSH injections, or hCG injections.

Hormone treatment can be used to stimulate sperm development in some azoospermic men. In some cases, the hormonal support will get sperm cells back into the semen. In other cases, it will allow enough sperm development so that healthy sperm cells can be extracted from the testicular via a testicular biopsy.  

Sperm Extraction From Post-Ejaculate Urine

In cases of retrograde ejaculation, if treating the retrograde ejaculation itself isn’t possible, your doctor can retrieve sperm from post-ejaculate urine. Then, depending on the amount of sperm available and any female fertility issues, either proceed with intrauterine insemination (IUI) or IVF treatment.

Lifestyle Change or Discontinuation of Medications

If a particular medication is linked to azoospermia, discontinuation of that medication or waiting until treatment completes is the first course of action.

For example, chemotherapy may cause azoospermia, but after cancer treatment, sperm may return months (or years) later. Or, if testosterone supplements are causing azoospermia, discontinuing testosterone may be recommended.

Never discontinue any medications or supplements without talking to your doctor first.

If exposure to toxic chemicals or excessive heat at work is suspected as a cause of azoospermia, changing your job may be recommended (if possible.) Sometimes, long-term exposure to toxins will cause permanent damage. In other cases, sperm development may return or at least improve and thereby improve the odds of success in combination with other fertility treatments. 

Testicular Sperm Extraction With IVF and ICSI

Testicular sperm extraction, or TESE, may be used to extract sperm cells directly from the testes. You will receive sedation or general anesthesia before the procedure. The doctor will make a small incision in the scrotum and extract tissue from your testes. That tissue will be examined for sperm cells and, if not being used right away, cryopreserved.

TESE can be used when obstructive azoospermia is blocking sperm cells from getting into the ejaculate. TESE may also be used in cases of nonobstructive azoospermia to look for some usable, mature sperm cells that may be being produced, but not enough to get into the semen.

Sperm cells extracted via TESE can only be used with IVF and ICSI. ICSI—which stands for intracytoplasmic sperm injection—is when a single sperm cell is directly injected into an egg. If successful fertilization takes place (which is not guaranteed, even if the sperm cell was forced into the egg!), then the resulting embryo is transferred to the woman’s uterus.

With IVF-ICSI and TESE, there is an increased risk of passing along infertility to a male child. This is something to discuss with your doctor.

PGD and Genetic Counseling

Genetic counseling is frequently recommended if there is any possibility that the azoospermia is linked to a congenital condition. It’s also recommended if IVF with ICSI is being used.

Some conditions can only be passed on if both genetic parents are carriers. This is why both partners may be tested, and not just the man.

If you discover you are at risk for passing on an inheritable disease, a possible option is to add PGD to IVF treatment. PGD stands for preimplantation genetic diagnosis. PGD allows doctors to screen embryos for some genetic conditions. Then, the healthier embryos can be transferred.

PGD is not foolproof and can’t check for all possible genetic diseases. The procedure also has some risks. But, it can be a possible solution for couples wanting to have children with their own eggs and sperm, despite the increased risk for passing along a disease.

Sperm Donor With IUI or IVF

Another possible fertility treatment option for men with azoospermia is to use a sperm donor. A sperm donor may be chosen because getting sperm isn’t an option (for example, testicular sperm extraction is not always successful or possible), or this can be a first-line choice after diagnosis because other treatment options are too expensive.

Some men choose to go with a sperm donor because they don’t want to risk passing along male infertility to their child (a possibility in some cases).

With a sperm donor, either IUI (insemination) or IVF will be used. This depends on the female partner’s fertility. 

Embryo Donor

Another possible option is using an embryo donor. The donated embryo would be transferred to the woman’s uterus (or a surrogate.) If you choose to use an embryo donor, neither intended parent would be genetically related to the child.

Alternative Options

Additional options for men with azoospermia include considering adoption, foster parenting, or living a childfree life.

Coping

Receiving a diagnosis of azoospermia can be very emotionally difficult. When this diagnosis also comes with additional news—like the diagnosis of a genetic condition or the risk of passing on an inheritable disease to your future children—it can be even more distressing.

Seeking out counseling with a therapist familiar with fertility issues is highly recommended. A therapist can help you cope with the diagnosis, and also help you consider your family building options for the future.

If you decide to use a sperm or embryo donor, your fertility clinic will likely require you to talk to a counselor first anyway.

Azoospermia can also come with increased risks of general health problems, including an increased risk of death. It’s not only about your fertility.

Some men may feel ashamed or embarrassed about their condition, and therefore not tell their primary care provider about their male infertility diagnosis. However, because of the increased risk of overall health problems, it is important to be honest with your doctor and let them know.

A Word From Verywell

Azoospermia is a severe cause of male infertility, but there are possible treatment options. Some men may still be able to have a genetic child after a diagnosis of azoospermia, while others may need to consider using a sperm donor or looking at adoption, foster parenting, or living a childfree life.

Coping with the diagnosis and navigating your family building options can be overwhelming. Seek support from both a professional counselor and your family and friends. You don’t need to go through this alone.

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Article Sources

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