What Is Secretory or Non-Obstructive Azoospermia?

By (embryologist), (embryologist), (gynecologist) and (invitra staff).
Last Update: 10/02/2023

Secretory or non-obstructive azoospermia occurs when the cause of lacking sperm in the ejaculated semen is due to spermatogenic failure.

It is considered a severe sperm disorder, although it can be cured in certain cases with the adequate treatment. For this reason, we can say that secretory azoospermia can be reversed in certain cases, allowing the affected male to have a baby.

This type of azoospermia is also known as excretory azoospermia or non-obstructive azoospermia (ANO).

Why does secretory azoospermia occur?

Unfortunately, secretory azoospermia is more common than obstructive azoospermia. On average, it is diagnosed in 70 percent of azoospermic males.

The testicles of men with secretory azoospermia do not produce sperm. This lack of sperm production can be due to problems in the testicles or alterations in the hypothalamic–pituitary–adrenal axis, causing hormonal imbalances.

Furthermore, secretory azoospermia can be congenital (from birth) or acquired, that is, as a consequence of a particular alteration.

Possible causes of secretory azoospermia

The main reasons why a man may develop secretory azoospermia include the following:

  • Problems during embryo development: during fetal formation, alterations like bilateral cryptorchidism, absent testicular development or testicular development failure, etc. can occur.
  • Hormonal imbalances: irregularities in hormone levels can affect spermatogenesis negatively, since it is regulated by hormones, including GnRH, FSH, and LH.
  • Genetic disorders: abnormalities in the genes involved in the development of male gonads causing pathologies such as the Klinefelter syndrome (karyotype 47XXY), Y chromosome microdeletion (loss of genetic material involved in spermatogenesis), etc.
  • Testicular problems: including increased temperature, trauma, or infections.
  • Childhood diseases: such as mumps or meningitis.
  • Chemotherapy or radiotherapy: These treatments can cause untreatable azoospermia. For this reason, oncologists should inform patients, before starting any of these treatments, on their options for preserving their fertility. Sperm freezing is a simple procedure: a series of sperm samples are collected through masturbation before getting started with chemotherapy or radiotherapy, and they are cryopreserved for later use.
  • Toxic substances and drug abuse: The presence of toxic substances or the use of anabolic steroids, as well as other drugs to treat baldness or other pathologies can affect sperm production. In most cases, it is reversible and, after a few months without using these substances, the testes can recover their function and produce sperm again.

You may also enjoy some further information reading this: What Are the Causes of Azoospermia?

Treatment of secretory azoospermia

As explained above, some cases of secretory azoospermia can be cured. Treating the causal agent and/or applying the adequate treatment can make the testis work again and produce sperm.

For instance, when the cause is a temporary exposure to a toxic substance such as anabolic asteroids, quitting using them can be the definitive solution. In such case, it is called temporary, treatable or reversible azoospermia.

Another example of treatable secretory azoospermia is when the cause are hormonal imbalances. A hormone-replacement therapy can activate spermatogenesis again. For example, if it is caused by poor FSH levels, administering this hormone externally can solve the problem.

Is pregnancy possible with secretory azoospermia?

Whenever sperm production is recovered, achieving pregnancy naturally will be possible.

However, it is possible that sperm quality is insufficient, leading the man affected to need a fertility treatment, like conventional in vitro fertilization (IVF), sperm microinjection (ICSI) with sperm collected via testicular biopsy, etc.

In the worst-case scenario, including men with severe, untreatable secretory azoospermia, the only option is using donor sperm to have a baby. Get more info: What Is Sperm Donation?

If you need to undergo IVF to become a mother, we recommend that you generate your Fertility Report now. In 3 simple steps, it will show you a list of clinics that fit your preferences and meet our strict quality criteria. Moreover, you will receive a report via email with useful tips to visit a fertility clinic for the first time.

FAQs from users

Is there treatment for secretory azoospermia with prolactin and elevated gonadotropins?

By Rut Gómez de Segura M.D. (gynecologist).

Azoospermia is the absence of sperm in the ejaculate. We say it is secretory, when such absence is due to a lack of sperm production in the testicles (spermatogenesis). This sperm alteration may be reversible or irreversible.

When we find a patient with a secretory azoospermia the first thing we must do is complete the diagnosis with genetic tests, analytical, testicular ultrasound and assessment by a urologist.

In the case of patients with hyperprolactinemia, magnetic resonance imaging of the sella turcica should be requested to rule out possible hyperprolactinoma. Depending on the outcome, it could be treated with surgery if necessary or with bromocriptine.

The main gonadotropins are FSH (follicle-stimulating hormone) and LH (luteinizing hormone). An increase in gonadotropins of 2-3 times their value in any azoospermia is a poor prognostic factor indicating that the germinal epithelium is not functioning.

Reversible azoospermia is most often due to medication (antiandrogen or anabolic). In these cases it is indicated to suspend such medication and wait at least 3-6 months to see if spermatogenesis is restored.

Secretory azoospermia of unknown origin are the most frequent and do not usually remit, so they are not treated.

Can secretory azoospermia be cured when it is due to chemotherapy?

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

Unfortunately, it cannot, although it depends on the dosage administered. Broadly speaking, cancer treatments affect sperm production function in the testicles permanently.

How is secretory azoospermia diagnosed?

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

When a semen analysis confirms the total absence of sperm in the semen, the next step is to perform a thorough physical exploration of the testicles. It will allow the specialist to determine if there is sperm production or not. Moreover, a male hormone check will be done to assess the activity of the testicles.

Even though these tests can indicate secretory azoospermia, only a testicular biopsy or epididymal sperm aspiration can help to determine whether there is sperm production.

Suggested for you

The second type of azoospermia that we can be diagnosed with is called obstructive azoospermia, which is less severe than the secretory type. Click here to read more: What Is Obstructive Azoospermia?

In any case, to delve deeper into the different reproductive options available for a man with azoospermia, click here: How to Achieve a Pregnancy with Azoospermia.

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References

Arafat M, Har-Vardi I, Harlev A, Levitas E, Zeadna A, Abofoul-Azab M, Dyomin V, Sheffield VC, Lunenfeld E, Huleihel M, Parvari R. Mutation in TDRD9 causes non-obstructive azoospermia in infertile men. J Med Genet. 2017 Sep;54(9):633-639 (View)

Bernie AM, Mata DA, Ramasamy R, Schlegel PN. Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: a systematic review and meta-analysis. Fertil Steril. 2015 Nov;104(5):1099-103.e1-3 (View)

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

Esteves SC. Clinical management of infertile men with nonobstructive azoospermia. Asian J Androl. 2015 May-Jun;17(3):459-70 (View)

Esteves SC, Miyaoka R, Roque M, Agarwal A. Outcome of varicocele repair in men with nonobstructive azoospermia: systematic review and meta-analysis. Asian J Androl. 2016 Mar-Apr;18(2):246-53 (View)

FAQs from users: 'Is there treatment for secretory azoospermia with prolactin and elevated gonadotropins?', 'Can secretory azoospermia be cured when it is due to chemotherapy?' and 'How is secretory azoospermia diagnosed?'.

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Authors and contributors

 Andrea Rodrigo
Andrea Rodrigo
B.Sc., M.Sc.
Embryologist
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
 Marta Barranquero Gómez
Marta Barranquero Gómez
B.Sc., M.Sc.
Embryologist
Graduated in Biochemistry and Biomedical Sciences by the University of Valencia (UV) and specialized in Assisted Reproduction by the University of Alcalá de Henares (UAH) in collaboration with Ginefiv and in Clinical Genetics by the University of Alcalá de Henares (UAH). More information about Marta Barranquero Gómez
License: 3316-CV
 Rut Gómez de Segura
Rut Gómez de Segura
M.D.
Gynecologist
Graduation in Medicine and Surgery from the University of Alcalá de Henares. Specialization in Obstetrics and Gynecology at the Hospital Costa del Sol in Marbella. Dr Rut Gómez de Segura currently works as medical director in the fertility center ProcreaTec in Madrid. More information about Rut Gómez de Segura
Licence number: 28/2908776
Adapted into english by:
 Romina Packan
Romina Packan
inviTRA Staff
Editor and translator for the English and German edition of inviTRA. More information about Romina Packan

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