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Y Chromosome Microdeletion Molecular Analysis for Male Infertility

Y microdeletion, male infertility, genetic, GYMDG

Test Codes

EPIC: LAB6808

Department

Cytogenetics

Specimen Collection Criteria

Collect: One Lavender-top EDTA tube. (Minimum: 3.0 mL)

Gently invert tube to mix specimen.

Physician Office/Draw Specimen Preparation

Do not freeze specimen. Maintain peripheral blood at room temperature (20-26°C or 68-78.8°F) prior to courier pickup. For delays in transport (greater than 24 hours from the time of collection), refrigerate (2-8°C or 36-46°F) the specimen.

Preparation for Courier Transport

Transport: 5-7 mL peripheral blood at room temperature (20-26°C or 68-78.8°F). (Minimum: 3.0 mL)

Rejection Criteria

• Improperly labeled specimens.
• Frozen specimens.
• Cracked or compromised specimen tubes.
• Specimens received greater than 72 hours past the time of collection.
• This test will only be performed once in a lifetime for a patient.

In-Lab Processing

Specimens are processed immediately upon delivery to the Cytogenetics Laboratory.

Storage

Specimen Stability for Testing:

Room Temperature (20-26°C or 68-78.8°F): 24 hours 
Refrigerated (2-8°C or 36-46°F): 72 hours
Frozen (-20°C/-4°F or below): Unacceptable

Specimen Storage in Department Prior to Disposal:

Extracted DNA is stored for one year.

Laboratory

Royal Oak Cytogenetics Laboratory

Performed

Monday – Friday.
Results available in 14 days.
Additional time may be needed for reflex testing of abnormal results. 

Reference Range

Positive or negative for Y chromosome microdeletion with identification of specific region(s) deleted. An interpretative report will be provided.

Test Methodology

Multiplex Polymerase Chain Reaction (PCR).

Interpretation

The analytical sensitivity/specificity of this test is ~99%. A positive result identifies the cause of azoospermia/oligospermia. A negative result greatly reduces the possibility of Y chromosome microdeletion as the cause of azoospermia or oligospermia. Limitations of the test include an inability to molecularly delineate breakpoints in positive cases, failure to identify mutations in specific genes within the interrogated regions, a rare diagnostic error caused by primer site mutations, and the inability to detect other genetic causes of infertility.

Clinical Utility

Infertility affects 10% of couples of reproductive age. Male factor infertility accounts for half of these cases. Microdeletions of the Y chromosome are identified in 1/2000-3000 males, and are suspected in otherwise healthy males with azoospermia or oligozoospermia and/or abnormal sperm morphology/ motility for whom other causes of infertility have been eliminated. Cytogenetic testing reveals chromosome abnormalities (such as Klinefelter syndrome) in 5%-10% of these men. Molecular testing reveals microdeletions involving the long arm of the Y chromosome in another 5%-13% of these males. Microdeletions of the Y chromosome are found in approximately 35% of men with idiopathic azoospermia, 20-25% of men with severe oligospermia, and overall in approximately 7% of all infertile men. Y chromosome microdeletions are detected utilizing a multiplex PCR format that utilizes 20 primer pairs that amplify nonpolymorphic sequence-tagged sites (STS) along the long arm of the Y chromosome (designated as regions AZFa, AZFb, and AZFc). Y chromosome deletions in these regions that are amplified by these primer sets have been associated with male infertility. In addition, one primer pair amplifies a region of the SRY gene on the short arm of the Y chromosome that permits identification of XX males arising from a translocation involving the X and Y chromosomes. Amplification of a unique DNA locus in both male and female genomes (ZFX/ZFY) serves as a control in this assay. This test should detect over 90% of all deletions in the AZF regions analyzed. Identification of Y chromosome microdeletions are important for medical management utilizing assisted reproductive technologies in couples experiencing infertility.

Reference

1. Stahl PJ et al (2010): A decade of experience emphasizes that testing for Y microdeletions is essential in American men with azoospermia and severe oligospermia, Fertility and Sterility 94(5): 1753-1756.
2. Sthal PJ and Schlegel PN (2012): Genetic evaluation of the azoospermic or severely oliospermic male. Curr Opin Obstet Gynecol 24: 221-228.
3. Kent-First M et al (1999): Defining regions of the Y chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome microdeletion detection. Mol Reprod and Development 53: 27-41.

CPT Codes

81403

Contacts

Last Updated

12/30/2022