What Are the Causes of Azoospermia?

By (embryologist), (gynecologist), (embryologist) and (fertility counselor).
Last Update: 07/01/2020

Azoospermia or zero sperm count can be caused by abnormalities in the male reproductive system at any of its levels: pre-testicular, testicular, and post-testicular. Throughout this article, you will find a guide to the leading causes of obstructive and secretory azoospermia.

Pre-testicular causes

In this case, the reason for azoospermia is due to endocrine abnormalities, that is, it is caused by irregularities in the levels of the hormones that are in charge of regulating sperm production (spermatogenesis). Thus, this would be a case of secretory azoospermia.

The following are some of the main endocrine disorders that can lead to azoospermia:

Hypogonadotropic hypogonadism (HH)
It is caused by a deficiency in the hormones released by the pituitary gland, which are responsible for sperm production in the testicles. The main hormones are FSH (follicle-stimulating) and LH (luteinizing). HH can be due to genetic abnormalities such as Kallmann syndrome, tumors, trauma, pharmacological treatments, anabolic steroid use, etc.
An excessive increase of prolactin hormone release that blocks the GnRH hormone (gonadotropin-releasing hormone), which function is to release FSH and LH. It might be caused by antihypertensive drug consumption, stress, tumors, antidepressants, etc.
Androgen insensitivity syndrome (AIS)
Due to genetic mutations that cause androgen resistance, which causes failure to develop the secondary male sexual characteristics (virilization) properly. Depending on the level of severity, the testosterone levels might be too low, hindering or preventing spermatogenesis, amongst other potential consequences.

Patients with secretory azoospermia due to a pre-testicular cause are likely to have a diminished testicular size, lack sperm production in the testes, and have too low FSH levels in general, except in the cases where it is due to AIS. In this case, even though LH levels are too elevated, FSH and testosterone levels tend to be normal or slightly elevated.

Testicular causes

The absence of sperm cells in the ejaculate is due to problems in the testicles, which hinder spermatogenesis, thereby leading to errors or even blockages in sperm production.

The most common testicular disorders are:

  • Varicocele: dilation of the spermatic veins.
  • Cryptorchidism: the testicle fails to descend from the inguinal canal to the scrotum.
  • Orchitis: inflammation of the testis due to an infection, as in the case of mumps.
  • Genetic abnormalities
  • Testicular torsion
  • Trauma
  • Continued exposure to heat in the testicles
  • These patients have secretory or non-obstructive azoospermia as well. However, the clinical picture is different than when the cause is pre-testicular: they have a reduced testicular volume (due to absent sperm production process), but their FSH levels are elevated.

    FSH, responsible for stimulating the testicles so they produce spermatozoa, increases its levels as well. The rationale for this is that, since the testicles do not respond to the stimulus, the organism sends higher amounts of FSH in order to cause the testicles to work.

    Post-testicular causes

    When azoospermia is due to post-testicular causes, it is a case of obstructive azoospermia. The testes are able to produce sperms correctly, but there is some kind of blockage in the seminal ducts (vasa deferentia, epididymis, or urethra), which are responsible of transporting sperm during ejaculation.

    Potential causes include:

    • Absent vasa deferentia: a birth defect that prevents the sperm from being released to the exterior, especially if it is bilateral. It is a common symptom in Cystic Fibrosis (CF) patients.
    • Blocked ejaculatory ducts, epididymis or urethra: It can occur involuntarily (trauma, surgery, diseases...) or voluntarily, as in the case of men who undergo vasectomy.

    Patients have a normal testicular size and FSH levels are normal, too.

    Obstructive azoospermia is less severe than secretory azoospermia as regards the chances of conceiving. In this case, the man is able to conceive, either naturally after a surgical procedure that allows the ducts to be unblocked, or by retrieving the sperm directly from the testis and using them in a fertility treatment.

    Assisted procreation, as any other medical treatment, requires that you rely on the professionalism of the doctors and staff of the clinic you choose. Obviously, each clinic is different. Get now your Fertility Report, which will select several clinics for you out of the pool of clinics that meet our strict quality criteria. Moreover, it will offer you a comparison between the fees and conditions each clinic offers in order for you to make a well informed choice.

    FAQs from users

    Can stress lead to azoospermia?

    By Estefanía Rodríguez Ferradas M.D., M.Sc., Ph.D. (gynecologist).

    Azoospermia means zero sperm count and there are different causes that can contribute to this sperm alteration. Among them you'll find pretesticular factors, that is, the problem is not directly linked to the testicle itself but to something that happens in the male hormonal axis, in the regulation of sperm production and which leads to their not being produced.

    To be more specific, stress can have a negative effect on hormone production, such as an increase in prolactin, a hormone produced at a cerebral level in the pituitary gland and which influences the production of the GnRH hormone at a hypothalamic level, also in the brain. If prolactin increases due to stress or other factors, the production of GnRH is inhibited, the production of FSH and LH is reduced and the testicle may stop producing sperm and testosterone.
    Read more

    Is varicocele a cause of male infertility?

    By Victoria Moliner BSc, MSc (embryologist).

    Yes, varicocele can be a cause of male infertility. This pathology can present in different degrees of affection. Therefore, its harmful effect on male fertility (mainly causes seminal and hormonal alterations) can be from mild to severe.

    Is varicocele a cause of male infertility?

    By Victoria Moliner BSc, MSc (embryologist).

    Yes, varicocele can lead to infertility in males. This condition has various levels of severity (from mild to severe), each one directly proportional to the degree of infertility. It can cause sperm disorders and hormone imbalances.

    When azoospermia is due to hormone imbalances, is it always secretory?

    By Andrea Rodrigo B.Sc., M.Sc. (embryologist).

    Yes, when a man's sperm count is zero is due to hormonal problems, it is always a case of secretory azoospermia. The fact that hormones fail to regulate this function prevents or makes spermatogenesis more complicated.

    Can bike riding cause azoospermia of testicular origin?

    By Andrea Rodrigo B.Sc., M.Sc. (embryologist).

    Prolonged bike riding does not cause azoospermia, as long as you sit correctly while riding it. Moreover, you can use certain systems to protect your testicles.

    Misusing the bicycle on a regular basis can increase the temperature of your scrotum, preventing sperm production and diminishing sperm quality.

    It should be noted that too much vigorous exercise can affect sperm production aside from other body functions.

    Can azoospermia be cured?

    By Andrea Rodrigo B.Sc., M.Sc. (embryologist).

    Yes, azoospermia can be temporary, in which case we can talk about reversible or treatable azoospermia. That means that, even though it is not so common, a man can have azoospermia for a limited time period, for example, due to stress or any other exceptional situation. Sometimes, after some time, these males can recover sperm production and they can be detected after analyzing the ejaculated semen.
    Read more

    Suggested for you

    Azoospermia is an abnormality that can be diagnosed using a semen analysis (SA). Continue reading here: How Is Azoospermia Diagnosed?

    To learn more about the treatment options you have at your disposal in order to have children with azoospermia, read: How to Conceive with Azoospermia.

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Berookhim BM, Schlegel PN. Azoospermia due to spermatogenic failure. Urol Clin North Am. 2014 Feb;41(1):97-113.

Cocuzza M, Alvarenga C, Pagani R. The epidemiology and etiology of azoospermia. Clinics (Sao Paulo). 2013;68 Suppl 1:15-26.

Ramasamy R, Lipshultz LI. Cystic fibrosis transmembrane regulator mutation and congenital bilateral absence of the vas deferens: a bad combination for successful intracytoplasmic sperm injection outcomes. Fertil Steril. 2014 May;101(5):1246.

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FAQs from users: 'Can stress lead to azoospermia?', 'Is varicocele a cause of male infertility?', 'Is varicocele a cause of male infertility?', 'When azoospermia is due to hormone imbalances, is it always secretory?', 'Can bike riding cause azoospermia of testicular origin?' and 'Can azoospermia be cured?'.

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Authors and contributors

 Andrea Rodrigo
Andrea Rodrigo
B.Sc., M.Sc.
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia. Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia along with the Valencian Infertility Institute (IVI). Postgraduate course in Medical Genetics. More information about Andrea Rodrigo
 Estefanía  Rodríguez Ferradas
Estefanía Rodríguez Ferradas
M.D., M.Sc., Ph.D.
Dr. Estefanía Rodríguez Ferradas has a degree in medicine from the University of Navarra and a PhD from the University of the Basque Country. She is also an expert in Reproduction and Medical Genetics. More information about Estefanía Rodríguez Ferradas
Licence number: 202007777
 Victoria Moliner
Victoria Moliner
BSc, MSc
Degree in Biochemistry and Biomedical Sciences from the University of Valencia (UV). Master's Degree in Biotechnology of Human Assisted Reproduction from the UV and the Valencian Infertility Institute (IVI). Presently, she works as a Research Biologist. More information about Victoria Moliner
Adapted into english by:
 Sandra Fernández
Sandra Fernández
B.A., M.A.
Fertility Counselor
Bachelor of Arts in Translation and Interpreting (English, Spanish, Catalan, German) from the University of Valencia (UV) and Heriot-Watt University, Riccarton Campus (Edinburgh, UK). Postgraduate Course in Legal Translation from the University of Valencia. Specialist in Medical Translation, with several years of experience in the field of Assisted Reproduction. More information about Sandra Fernández

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