Role of Testicular Biopsy in Male Infertility

Definition and Overview

Indications

1. Azoospermia - the primary indication. Biopsy differentiates between:
   • Obstructive azoospermia (OA) - sperm production is normal but outflow is blocked
   • Non-obstructive azoospermia (NOA) - primary failure of spermatogenesis
2. Severe oligospermia - occasionally indicated when sperm counts alternate with azoospermia (cryptozoospermia)
3. Sperm retrieval for ART (TESE/ICSI) - therapeutic biopsy to harvest sperm for use with assisted reproductive technology
4. Screening for intratubular germ cell neoplasia - historically proposed in high-risk infertile men (those with a contralateral germ cell tumor have ~5% risk of in situ neoplasia), though cancer risk in infertile men overall remains low

Diagnostic Value

Types of Biopsy

1. Open (incisional) biopsy - a 1 cm scrotal incision followed by a 0.5 cm incision into the tunica albuginea; seminiferous tubules extrude and are excised. Yields the most tissue; done under local or general anesthesia.
2. Fine-needle aspiration (FNA) - uses an 18-25 gauge needle introduced percutaneously; cytological analysis correlates well with open biopsy histology. Sufficient for obstructive azoospermia sperm retrieval.
3. Percutaneous biopsy gun - a 14-gauge biopsy gun is used; yields more tissue than FNA.
4. Multisite FNA mapping - systematic sampling from multiple locations allows spatial mapping of spermatogenesis within the testis, useful in NOA where spermatogenesis may be focal/heterogeneous.

Therapeutic Role - Sperm Retrieval

• TESE (Testicular Sperm Extraction) - open biopsy to extract sperm for IVF/ICSI. Sperm retrieval fails in 25-50% of men with spermatogenic failure (NOA).
• Micro-TESE (Microsurgical TESE) - the preferred technique in NOA, using an operating microscope to identify tubules with highest likelihood of containing sperm. Patients often proceed with micro-TESE even with unfavorable diagnostic biopsy results.
• Sperm cryopreservation - retrieved sperm can be frozen for future ART cycles.

Laterality

• Unilateral biopsy is generally sufficient.
• Bilateral biopsy is warranted when testes are asymmetric in size, which may indicate a unilateral failing testis paired with a normal but obstructed contralateral testis.

Technical Precautions

• Biopsy instruments should enter the testis anteromedially or anterolaterally to avoid injury to the main blood supply, which enters posteriorly.
• The subtunical vessels are end arteries; disruption causes ischemia and permanent loss of spermatogenesis in that region.
• After puberty, testicular trauma from biopsy may rarely induce antisperm antibodies, contributing to immunologic infertility.

Relationship to Other Investigations

• FSH levels - elevated FSH indicates primary testicular failure
• Semen analysis - WHO reference limits (sperm concentration >/= 15 million/mL, etc.)
• Vasogram - if biopsy shows normal spermatogenesis in an azoospermic man, contrast injection into the vas delineates the site of obstruction
• Y chromosome microdeletion testing - indicated in NOA or severe oligozoospermia (<5 million/mL) before ART, as deletions can be transmitted to male offspring

Summary

• Smith and Tanagho's General Urology, 19th Ed., p. 729-730
• Harrison's Principles of Internal Medicine, 22nd Ed.
• Hinman's Atlas of Urologic Surgery