Typically, follicle-stimulating hormone (FSH) levels are low (hypogonadotropic) commensurate with inadequate stimulation of the testes to produce sperm.

Mast cells releasing inflammatory mediators appear to directly suppress sperm motility in a potentially reversible manner, and may be a common pathophysiological mechanism for many causes leading to inflammation.

[8] Genetic factors can cause pretesticular, testicular, and post-testicular azoospermia (or oligospermia) and include the following situations:[9] The frequency of chromosomal abnormalities is inversely proportional to the semen count, thus males with azoospermia are at risk to have a 10–15% (other sources citing 15–20% incidence[10]) abnormalities on karyotyping versus about <1 % in the fertile male population.

A section of the long arm of the Y chromosome has been termed Azoospermia Factor (AZF) at Yq11 and subdivided into AZFa, AZFb, AZFc and possibly more subsections.

[citation needed] Post-testicular azoospermia can be seen with certain point mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene commonly associated with congenital vas deferens abnormalities.

Absent or reduced expression of BRD7 protein was observed in the testes of azoospermia patients exhibiting spermatogenesis arrest.

[11] Homozygous knockout mice [BRD7(-/-)] are infertile and have higher levels of apoptosis and DNA damage in their germline cells.

[12] Four genes involved in DNA double-strand break repair and chromosome synapsis (TEX11, TEX15, MLH1 and MLH3) have key roles in genomic integrity, meiotic recombination and gametogenesis.

Single nucleotide polymorphisms in two of these genes (TEX11 and MLH3) were found to be associated with male infertility involving azoospermy or oligospermia.

It is established on the basis of two semen analysis evaluations done at separate occasions (when the seminal specimen after centrifugation shows no sperm under the microscope) and requires a further work-up.

[3] Congenital absence of the vas deferens may be detectable on physical examination and can be confirmed by a transrectal ultrasound (TRUS).

Transrectal ultrasound can also assess azoospermia caused by obstruction, or anomalies related to obstruction of the ejaculatory duct, such as abnormalities within the duct itself, a median cyst of the prostate (indicating a need for cyst aspiration), or an impairment of the seminal vesicles to become enlarged or emptied.

[15] Retrograde ejaculation is diagnosed by examining a post-ejaculatory urine for presence of sperm after making it alkaline and centrifuging it.

[3] On the other hand, "In azoospermic men with a normal ejaculate volume, FSH serum level greater than two times the upper limit of the normal range is reliably diagnostic of dysfunctional spermatogenesis and, when found, a diagnostic testicular biopsy is usually unnecessary, although no consensus exists in this matter.

[19] Seminal plasma proteins TEX101 and ECM1 were recently proposed for the differential diagnosis of azoospermia forms and subtypes, and for prediction of TESE outcome.

IVF-ICSI allows for pregnancy in couples where the man has irreversible testicular azoospermia as long as it is possible to recover sperm material from the testes.