NOA represents a failure of spermatogenesis within the testis and, from a management standpoint, is due to either a lack of appropriate stimulation by gonadotropins or an intrinsic testicular impairment. The former category of patients has hypogonadotropic hypogonadism and benefits from specific hormonal therapy. These men show a remarkable recovery of spermatogenic function with exogenously administered gonadotropins or gonadotropin-releasing hormone. This category of patients also includes some individuals whose spermatogenic potential has been suppressed by excess androgens or steroids, and they also benefit from medical management. The other, larger category of non-obstructive azoospermia consists of men with an intrinsic testicular impairment where empirical medical therapy yields little benefit.

Non-obstructive azoospermia is generally considered a non-medically manageable cause of male infertility. These patients, who constitute up to 10% of all infertile men, have abnormal spermatogenesis as the cause of their azoospermia. The establishment of in vitro fertilization using intracytoplasmic sperm injection (ICSI) as a standard treatment modality has resulted in a number of these men successfully fathering a child through surgically retrieved sperm from the testis. The challenge, however, is to improve their spermatogenic function to enable the appearance of sperm in their ejaculate or to improve the chances of a successful retrieval from the testis for ICSI.

The initial evaluation of this condition aims at resolving the following issues: 

  1. confirming azoospermia, 
  2. differentiating obstructive from non-obstructive etiology, 
  3. assessing for the presence of reversible factors and 
  4. evaluating for the presence of genetic abnormalities. 

An elevated follicle-stimulating hormone (FSH) level or an absence of normal spermatogenesis by testicular histology in the presence of azoospermia is generally considered sufficient evidence of a non-obstructive etiology. 

The most common reversible factors that need to be ruled out include recent exogenous hormone administration, severe febrile illnesses, chemotherapy/radiation or prolonged antibiotic use.

Hormone analysis forms the cornerstone of the further evaluation and management of NOA and serves two important functions. The first function is to identify a distinct subset of men who have hypogonadotropism (low FSH), in which azoospermia results from an inadequate stimulation of the testis by gonadotropins. The inherent spermatogenic potential of the testis may be partially recoverable, and the management and prognosis of infertility in these men differ from all other subsets. The second function is to predict the success of medical therapy and of surgical sperm retrieval. Based on these initial hormone studies, the two broad categories are hypogonadotropic hypogonadism and hypergonadotropic hypogonadism or eugonadism (Tab. 1 in picture gallery). There is considerable overlap in the hormone statuses of men who do not have hypogonadotropism, with similar etiologies producing a spectrum of hormonal changes. The American Urological Association recommends an estimation of serum FSH and testosterone as the initial hormonal assessment. However, endocrine abnormalities are a rare cause of male infertility and account for less than 3% of all cases. Additional hormone analysis, including luteinizing hormone (LH), estradiol and prolactin evaluations, is performed based on the likelihood of their abnormality and potential impact on management.

Associated disease


  • infertility

Risk factors

The main problem is that in ejaculate, there are no sperms which could fertilize an egg spontaneously. The only option is chirurgical extraction of sperm from testicles (MESA, TESE, micro TESE) with intracytoplasmatic sperm injection (ICSI). If the extraction methods fails to obtain any sperm, use of donor spermatozoa should be considered.

Non-obstructive azoospermia cannot be prevented, but clinicians should be attentive to the concomitant presence of infertility in the patient’s male relatives (as a result of chromosomal abnormalities, genetic conditions, etc.).

In many cases, men with non-obstructive azoospermia typically have small-volume testes and elevated FSH. The finding of atrophic testes and elevated FSH levels indicates germ cell failure. Patients with normal sperm production typically have FSH values in the lower end of the normal range, and levels above this should raise suspicion of a defect in spermatogenesis. In addition, patients with unilateral testicular disease may have elevated FSH levels. A diagnostic testicular biopsy is not indicated in patients with elevated FSH levels. Instead, patients with non-obstructive azoospermia due to a primary testicular defect and not to a hormonal deficiency should be offered genetic testing, consisting of a karyotype and a Y-chromosome microdeletion analysis. If abnormalities are found, a couple should be offered genetic counseling prior to proceeding with assisted reproductive techniques.

Does not exist.


Among men with NOA, gonadotropin therapy for hypogonadotropic hypogonadism is the only specific indication that has universally shown an improvement in semen analysis and pregnancy rates. Gonadotropins (hCG and rFSH) in combination constitute a standard therapy, with GnRH therapy reserved for non-responders. The medical management of other forms of NOA remains empirical. Drug therapy with aromatase inhibitors and gonadotropins shows potential promise in improving outcomes in men requiring surgical sperm retrieval, but there is lack of level I clinical evidence for this indication.

Surgical therapy

There is no sugical therapy for this condition.

Assisted reproduction offers men to undergo surgical sperm extraction. For sperm extraction, these four techniques are used: testicular sperm aspiration, testicular sperm extraction, fine needle aspiration mapping and microdissection testicular sperm extraction. The establishment of in vitro fertilization using intracytoplasmic sperm injection (ICSI) as a standard treatment modality has resulted in a number of these men successfully fathering a child through surgically retrieved sperm from the testis. However, in case of genetically determined NOA, PGD/PGS of early embryos is recommended.

Even with surgery, there is still the possibility that no sperm may be obtained. Then, the fertilization with donated sperm should be considered.

Find more about related issues


Focus Issue on Male Infertility ―by Kobayashi et al. licensed under CC BY 3.0
Pathway of the Sperm Cell ―sourced from Wikispaces licensed under CC BY- SA 3.0
Creative Commons License
Except where otherwise noted, content on this site is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License, involving multiple copyrights under different terms listed in the Sources section.