Azoospermia is the medical condition of a man whose semen contains no sperm. It is associated with male infertility, but many forms are amenable to medical treatment. In humans, azoospermia affects about 1% of the male population and may be seen in up to 20% of male infertility situations in Canada.
In a non-pathological context, azoospermia is also the intended result of a vasectomy.
Classification
Azoospermia can be classified into three major types. Pretesticular azoospermia is seen in about 2% of azoospermia. Testicular azoospermia is a kind of non-obstructive azoospermia.
Generally, men with unexplained hypergonadotropic azoospermia need to undergo a chromosomal evaluation.
Post-testicular
In post-testicular azoospermia, sperm are produced but not ejaculated, a condition that affects 7–51% of azoospermic men. Other obstructions can be congenital (for example, agenesis of the vas deferens as seen in certain cases of cystic fibrosis) or acquired, such as ejaculatory duct obstruction for instance by infection.
Ejaculatory disorders include retrograde ejaculation and anejaculation; in these conditions sperm are produced but not expelled.
Unknown
Idiopathic azoospermia is where there is no known cause of the condition. It may be a result of multiple risk factors, such as age and weight. For example, a review in 2013 came to the result that oligospermia and azoospermia are significantly associated with being overweight (odds ratio 1.1), obese (odds ratio 1.3) and morbidly obese (odds ratio 2.0), but the cause of this is unknown. The review found no significant relation between oligospermia and being underweight.) abnormalities on karyotyping versus about <1 % in the fertile male population. Homozygous knockout mice [BRD7(-/-)] are infertile and have higher levels of apoptosis and DNA damage in their germline cells.
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. Polymorphisms in these genes were tested for associations with male infertility. Single-nucleotide polymorphisms in two of these genes (TEX11 and MLH3) were found to be associated with male infertility involving azoospermy or oligospermia.
Diagnosis
thumb|Algorithms for the workup of the infertile male. Algorithm to be considered on initial assessment (top). Algorithm for the management of the patient presenting with azoospermia (bottom).
Azoospermia is usually detected in the course of an infertility investigation. It is established based on two semen analysis evaluations done on separate occasions (when the seminal specimen, after centrifugation, shows no sperm under the microscope) and requires further work-up.
The investigation includes a history, a physical examination including a thorough evaluation of the scrotum and testes, laboratory tests, and possibly imaging. History includes the general health, sexual health, past fertility, libido, and sexual activity. Past exposure to several agents needs to be queried including medical agents like hormone/steroid therapy, SSRIs, antibiotics, 5-ASA inhibitors (sulfasalazine), alpha-blockers, 5-alpha-reductase inhibitors, chemotherapeutic agents, pesticides, recreational drugs (marijuana, alcohol), and heat exposure of the testes. A history of surgical procedures of the genital system needs to be elicited. The family history needs to be assessed to look for genetic abnormalities.
Retrograde ejaculation is diagnosed by examining a post-ejaculatory urine for the presence of sperm after making it alkaline and centrifuging it. Extremely high levels of FSH (>45 ID/mL) have been correlated with successful microdissection testicular sperm extraction.
Serum inhibin-B weakly indicates presence of sperm cells in the testes, raising chances for successfully achieving pregnancy through testicular sperm extraction (TESE), although the association is not very substantial, having a sensitivity of 0.65 (95% confidence interval [CI]: 0.56–0.74) and a specificity of 0.83 (CI: 0.64–0.93) for prediction the presence of sperm in the testes in non-obstructive azoospermia.
Seminal plasma proteins TEX101 and ECM1 were recently proposed for the differential diagnosis of azoospermia forms and subtypes, and for the prediction of TESE outcome. Mount Sinai Hospital, Canada, started a clinical trial to test this hypothesis in 2016.
Primary hypopituitarism may be linked to a genetic cause. So, a genetic evaluation may be done for men with azoospermia as a result. Pregnancies have been achieved in situations where azoospermia was associated with cryptorchidism and sperm were obtained by testicular sperm extraction (TESE).
In men with post-testicular azoospermia, different approaches are available. For obstructive azoospermia, IVF-ICSI or surgery can be used, and individual factors are considered for the choice of treatment.