What is the diagnostic workup for azoospermia (absence of sperm in the semen)?

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From the Guidelines

Azoospermia workup should begin with a thorough history and physical examination, followed by at least two semen analyses to confirm the absence of sperm, as recommended by the most recent guidelines 1. The initial step in evaluating azoospermia is to confirm the absence of sperm through semen analysis. According to the 2024 AUA/ASRM guideline 1, if a semen analysis shows azoospermia, the laboratory should then centrifuge the ejaculate and re-suspend the pellet in a small volume of seminal plasma and examine under wet mount microscopy for the presence of rare sperm.

Key Components of Azoospermia Workup

  • Initial laboratory testing should include serum FSH, LH, total testosterone, and prolactin to distinguish between obstructive and non-obstructive causes, as these hormone levels can indicate the underlying cause of azoospermia 1.
  • Genetic testing is essential, including karyotype analysis to detect chromosomal abnormalities like Klinefelter syndrome, which is a common cause of non-obstructive azoospermia 1.
  • Y-chromosome microdeletion testing should also be performed to identify genetic causes, as microdeletions in the AZF region can lead to impaired spermatogenesis 1.
  • Scrotal ultrasound should be performed to evaluate testicular size and structure, while transrectal ultrasound can identify ejaculatory duct obstruction or seminal vesicle abnormalities, which can cause obstructive azoospermia 1.

Diagnostic Approach

The diagnostic approach to azoospermia should be tailored to the individual patient, taking into account their medical history, physical examination, and laboratory results. For men with suspected obstructive azoospermia and normal hormone levels, testicular biopsy may be necessary to confirm normal spermatogenesis 1. In contrast, if non-obstructive azoospermia is suspected, microdissection testicular sperm extraction (microTESE) may be performed to retrieve sperm for assisted reproductive techniques 1.

Importance of Genetic Testing

Genetic testing, including karyotype analysis and Y-chromosome microdeletion testing, is crucial in the evaluation of azoospermia, as it can identify underlying genetic causes and guide treatment options. Karyotype testing should be performed on all males with severe oligozoospermia (<5 × 10^6/ml) or non-obstructive azoospermia prior to any therapeutic procedure, as recommended by the 2017 Human Reproduction Update guideline 1. Similarly, Y-chromosome microdeletion testing should be performed on all males with severe oligozoospermia or non-obstructive azoospermia to identify genetic causes and guide treatment options 1.

From the Research

Azoospermia Workup

Azoospermia is a condition where a man has no sperm in his ejaculate, and it can be classified into two main categories: obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) 2. The workup for azoospermia typically involves a combination of medical history, physical examination, laboratory testing, genetic testing, and imaging studies.

Diagnosis

The diagnosis of azoospermia involves:

  • A thorough medical history and physical examination to identify any underlying medical conditions or physical abnormalities that may be contributing to the condition 3, 4, 5
  • Semen analysis to confirm the absence of sperm in the ejaculate
  • Hormonal assessment, including follicle-stimulating hormone (FSH) levels, to help differentiate between OA and NOA 2, 3
  • Genetic testing, such as karyotype analysis, Y chromosome microdeletion, or specific genetic testing for hypogonadotropic hypogonadism, to identify any underlying genetic conditions 2, 3, 4
  • Imaging studies, such as ultrasound or MRI, to evaluate the reproductive tract and identify any obstructions or abnormalities 2, 3

Management

The management of azoospermia depends on the underlying cause and may involve:

  • Microsurgical reconstruction, such as vasovasostomy or vasoepididymostomy, to repair any obstructions in the reproductive tract 2
  • Microdissection testicular sperm extraction with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for men with NOA 2, 3
  • Medical management, such as hormone replacement therapy, for men with underlying medical conditions or hormonal imbalances 2, 3
  • Genetic counseling and testing for men with NOA to identify any underlying genetic conditions and to discuss the risks and benefits of using assisted reproductive technologies 4

Key Considerations

  • A coordinated effort involving reproductive urologists/andrologists, geneticists, pathologists, and embryologists is essential for the optimal management of men with azoospermia 3
  • A thorough understanding of the disease etiology is necessary for optimal management of patients with azoospermia 6
  • Men with azoospermia should be offered genetic counseling before their spermatozoa are used for assisted reproductive techniques 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Review of Azoospermia.

Spermatogenesis, 2014

Research

Differential Diagnosis of Azoospermia in Men with Infertility.

Journal of clinical medicine, 2021

Research

Update in the evaluation of the azoospermic male.

Clinics (Sao Paulo, Brazil), 2013

Research

Evaluation of the azoospermic male.

Asian journal of andrology, 2012

Research

The epidemiology and etiology of azoospermia.

Clinics (Sao Paulo, Brazil), 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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