Y Chromosome Microdeletions

Last Literature Review: June 2026 Last Update:
  • Use to determine the cause of infertility in men with nonobstructive azoospermia or moderate or severe oligospermia
  • Aids in predicting effectiveness of assisted reproductive technologies in men with specific Y chromosome microdeletions

Infertility affects 10-15% of couples of reproductive age, with male-factor infertility accounting for one-half of cases. Y chromosome microdeletions are typically characterized by azoospermia (the absence of sperm), severe to moderate oligospermia, or abnormal sperm morphology/motility, depending on the size and location of the deletion. The European Association of Urology recommends Y chromosome microdeletion testing in men with infertility who have azoospermia or a sperm concentration <1 million/ml and consideration for Y chromosome microdeletion testing in men with infertility who have a sperm concentration of <5 million/ml.  Identification of deleted azoospermia factor (AZF) region has implications for assisted reproductive technologies. Men with an AZFc deletion have a positive prognosis for finding sperm sufficient for assisted reproduction. However, assisted reproductive techniques are contraindicated for men carrying AZFa, AZFb, AZFbc or AZFabc microdeletions, which are classically associated with spermatogenic failure. When assisted reproduction is successful, Y chromosome microdeletions are transmitted to all male offspring, giving them a high risk for infertility. Female offspring will have no increased risk for infertility. , 

Genetics

Variants

Microdeletions involve one or more of three AZF regions. Among individuals with Y chromosome microdeletions, the frequency of each deletion type is :

  • AZFa: 5% of cases
  • AZFb: 10% of cases
  • AZFc: 70% of cases
  • AZFbc: 13% of cases
  • AZFabc: 2% of cases

Etiology

The prevalence of Y chromosome deletions and microdeletions is approximately 1/2,000-3,000 male individuals. 

Inheritance

Y-linked

Penetrance

Approaches 100% in male individuals; variable expression may result in intrafamilial variation of fertility in men with an identical microdeletion

Test Interpretation

Sensitivity/Specificity

  • Clinical sensitivity: Approximately 5-10% for men with nonobstructive azoospermia or severe oligospermia 
  • Analytic sensitivity/specificity: 99%

Results

ResultDeletion DetectedClinical Significance
PositiveAZFa deletionSpermatogenic failure/SCOS resulting in azoospermia
AZFb deletionAzoospermia/spermatogenetic arrest
AZFbc deletionSCOS/spermatogenic arrest
AZFc deletion

Variable phenotype ranging from mild oligospermia to azoospermia and SCOS

Male individuals with an AZFc microdeletion have a high likelihood of finding sperm sufficient for successful ICSI for assisted reproduction

AZFabc deletionSCOS associated with azoospermia
NegativeLack of detection of an AZF microdeletionGreatly reduced possibility of a Y chromosome deletion as the cause of azoospermia or oligospermia
ICSI, intracytoplasmic sperm injection; SCOS, Sertoli cell-only syndrome 

Limitations

  • Diagnostic errors can occur due to rare sequence variations.
  • Breakpoints of identified microdeletions will not be determined.
  • Variants within individual genes included in the AZF regions will not be detected.
  • Male infertility due to causes other than the Y chromosome microdeletions tested will not be detected.
  • Partial deletions may not be detected.

References