Y Chromosome Microdeletions, Molecular Detection
Evaluating men with azoospermia, severe oligozoospermia, or otherwise unexplained male factor infertility
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Tests for the presence of microdeletions in the AZFa, AZFb, and AZFc regions of the Y chromosome.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Yq microdeletions involving some, or all, of the azoospermic factor (AZF) region are the most frequently identified cause of spermatogenic failure in chromosomally normal men with nonobstructive azoospermia (3%-15%) or severe oligospermia (6%-10%). Among unselected infertile males, the overall frequency of Yq microdeletions is approximately 3%. The relative frequency of Yq microdeletions makes the evaluation for them an important aspect of the diagnostic work up in infertile males, especially those with azoospermia or severe oligospermia.
Most cases of Yq microdeletions occurs de novo, and due to the consequential infertile phenotype, they are typically not transmitted. However, in cases where assisted reproductive technology (example: testicular sperm extraction: TESE followed by intracytoplasmic sperm injection: ICSI) is used to achieve viable pregnancy, all male offspring born to a microdeletion carrier will carry the deletion and may be infertile.
Men testing positive for 1 or more microdeletions who are enrolled in an in vitro fertilization treatment program may wish to consider alternative options to intracytoplasmic sperm injection (eg, donor sperm) and consultation with an experienced reproductive endocrinologist and medical geneticist is recommended.
Most Y microdeletions are the result of homologous recombination between repeated sequence blocks. Testing for deletions involves investigating for the presence or absence of markers located within non-polymorphic regions of the AZF region.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay will not detect all of the causes of infertility or azoospermia. Therefore, the absence of a detectable microdeletion(s) does not rule out the presence of other genetic or nongenetic factors that may be the cause of clinical findings.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
In rare cases, DNA alterations of undetermined significance may be identified.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
A genetic consultation is recommended for all patients undergoing this testing. Additional consultation with a reproductive endocrinologist/urologist to discuss reproductive options is recommended when a deletion is detected.
Validation studies done at the Mayo Clinic on a series of known fertile and infertile specimens provided the following results. Of 111 DNA specimens from known fertile men, 110 gave unequivocal negative results demonstrating clinical specificity of 99%. A series of 19 specimens from females (negative controls) were all negative, as expected. In a small series of specimens from 4 men being treated for male factor infertility, no deletions were found (which may be expected given a reported prevalence of 7% for microdeletions in unselected male infertility patients). Seven specimens were mailed in from outside laboratories (3 of which were sent as part of an external quality assessment scheme organized by the European Academy of Andrology) with known deletions in either AZFa, AZFb, or AZFc. Using our assay, all were diagnosed correctly to give an analytical sensitivity of 100%.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Stahl PJ, Masson P, Mielnik A, et al: A decade of experience emphasizes that testing for Y microdeletions is essential in American men with azoospermia and severe oligozoospermia. Fertil Steril 2010 Oct;94(5):1753-1756; Epub 2009 Nov 5
2. Shalender B: Approach to the infertile man. J Clin Endo Metab 2007 June 92(6):1995-2004
3. Ferlin A, Arredi B, Speltra E, et al: Molecular and clinical characterization of Y chromosome microdeletions in infertile men: A 10-year experience in Italy. J Clin Endo Metab 2007 Mar;92(3):762-770