Azoospermia in these patients could be a result of Y chromosome microdeletions, cancer of the testicles or damage to the pituitary gland or hypothalamus, which regulate sperm production.

[3] However, if azoospermia is related to a disorder of sexual development, such as Klinefelter syndrome, TESE is not used clinically; as of 2016, this was in the research phase.

[5] Obstructive azoospermia can be caused in a variety of ways: TESE can also be used as a fertility preservation option for patients undergoing gender reassignment surgery and who cannot ejaculate sperm.

[10] Incisions are then made through the outer covering of the testis to retrieve biopsies of seminiferous tubules, which are the structures that contain sperm.

[8] When compared with FNA of the testis, conventional TESE is 2-fold more effective at identifying sperm in men with non-obstructive azoospermia.

[12] This can cause side-effects including muscle weakness, decreased sexual function, anxiety, leading to sleep deficiency.

The use of the surgical microscope allows for small specific incisions to retrieve seminiferous tubules and evade damaging blood vessels by avoiding regions with no vasculature.

[3][10] If TESE needs to be repeated due to insufficient sperm recovery, patients are usually advised to wait 6–12 months in order to allow adequate healing of the testis before further surgery.