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What is Non-Obstructive Azoospermia (NOA)

  

What is Azoospermia?

Azoospermia is the condition where there is no sperm in the ejaculate and affects around 1% of the population and 10% of infertile men[1]. This is not to be confused with aspermia, where there is no ejaculate. Men with azoospermia usually have normal ejaculate volume, so microscopic analysis of the fluid is required to make the diagnosis. Azoospermia is divided into two categories: obstructive azoospermia (OA), where sperm is blocked from reaching the ejaculate, and the more severe form, non-obstructive azoospermia (NOA) where there is an issue with sperm production. Azoospermia is diagnosed after microscopic analysis of two properly collected specimens.  If sperm are not initially seen, the samples are concentrated in a centrifuge and the fluid is re-examined under a microscope. When no sperm are found, azoospermia is confirmed.

What is Non-Obstructive Azoospermia?

Non obstructive azoospermia (NOA) results when there is a problem with sperm production. Sperm production, also called spermatogenesis, takes place in the testicles. Many men with NOA have testicles that are smaller than average. This is because the majority of testis volume is dedicated to sperm production. Therefore, if sperm production is impaired, testicle size is less.

What Causes Non-Obstructive Azoospermia?

There are many causes of NOA. The most common identifiable causes are genetic, hormonal, or medication induced. Genetic causes include: Klinefelter syndrome (an extra x chromosome) and microdeletions of the Y chromosome. These genetic causes are routinely tested for in men diagnosed with NOA. There are many other genetic factors that contribute to NOA, however they are much less common and not easily tested. Additionally, there are likely many other genetic causes that have yet to be discovered. Hormonal causes of NOA include disruption of the gonadotropins LH and FSH from the pituitary. LH and FHS stimulate the testicle to make testosterone and sperm, respectively. Disorders affecting LH and FSH may impact one or both hormones. One well described condition is Kallmann syndrome, where affected individuals do not make the gonadotropins LH or FSH and may lack a sense of smell.  Lastly, testosterone replacement can shut down sperm production because it stops the pituitary from making LH and FSH.

How is Non-Obstructive Azoospermia Treated?

Treatment of NOA depends on the cause. If the cause appears to be testosterone use, the testosterone should be immediately stopped under the supervision of a physician. Medications, such as hCG, clomiphene citrate and anastrozole may be indicated. Fortunately, the majority of men will recover sperm production, assuming they made sperm before using testosterone[2]. Patients with disorders of gonadotropin release may similarly begin producing sperm with the aid of medications such as hCG and rFSH.  Unfortunately, men with Y chromosome microdeletions in the AZFa or AZFb region do not make sperm. Lastly, patients with idiopathic NOA, Klinefelter’s syndrome or microdeletions in the AZFc region of the Y chromosome may benefit from testicular sperm extraction in combination with intracytoplasmic sperm extraction.

What is Testicular Sperm Extraction?

Testicular sperm extraction is a procedure to recover sperm from the testis. The preferred method of sperm extraction requires the assistance of an operating microscope.  Unlike the sperm seen moving in the ejaculate, testicular sperm does not move, and therefore requires assisted reproductive techniques (ART/IVF/ICSI) to fertilize the egg. Testicular sperm cannot be used for natural conception or intrauterine insemination (IUI). Men with NOA have around a 50% chance of having sperm identified in a microscope assisted testicular sperm extraction (mTESE)[3].

Can Men With NOA Still be Fathers?

Before the development of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ISCI), a technique where a single sperm is injected into a single egg, and mTESE, men with NOA were incapable of having a child of their own. Now, thanks to these technologies, many men with NOA have a chance to be fathers!

 

  1. Jarow, J.P., M.A. Espeland, and L.I. Lipshultz, Evaluation of the azoospermic patient. J Urol, 1989. 142(1): p. 62-5.
  2. McBride, J.A. and R.M. Coward, Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use. Asian J Androl, 2016. 18(3): p. 373-80.
  3. Punjani, N., C. Kang, and P.N. Schlegel, Two Decades from the Introduction of Microdissection Testicular Sperm Extraction: How This Surgical Technique Has Improved the Management of NOA. J Clin Med, 2021. 10(7).

 

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