Uncovering the Association Between Complete AZFc Microduplications and Spermatogenic Ability: The First Reported...

Area of Science:

• Human Genetics
• Reproductive Urology
• Male Infertility

Background:

• Spermatogenic failure is a complex condition with various genetic underpinnings.
• The AZFc region on the Y-chromosome is crucial for male fertility, and its deletions are well-documented causes of impaired sperm production.
• Microduplications within the AZFc region are less understood but represent a potential cause of male infertility.

Purpose of the Study:

• To characterize the clinical and reproductive profiles of men with complete AZFc microduplications.
• To determine the prevalence of complete AZFc microduplications among men undergoing fertility evaluation.

Main Methods:

• A cohort of 3000 men evaluated for reproductive urology issues between 2012-2020 was analyzed.
• High-resolution Y-chromosome microarray testing was performed on 104 men.
• Clinical, surgical, reproductive histories, semen parameters, hormonal levels, and fertility treatment responses were recorded for identified cases.

Main Results:

• Five men (0.2% of the total cohort, 4.8% of those tested with microarray, 21% of those with AZFc abnormalities) were found to have complete AZFc microduplications.
• Associated conditions included undescended testicles and autoimmune processes in some individuals.
• Semen analysis revealed azoospermia in one man, severe oligospermia in others, with variable total motile sperm counts (TMSC). One man showed improved sperm parameters and fathered a spontaneous pregnancy after treatment.

Conclusions:

• Complete AZFc microduplications are an uncommon but significant cause of male spermatogenic failure.
• These microduplications result in a heterogeneous clinical presentation and variable reproductive potential.
• Management strategies for men with complete AZFc microduplications should be individualized based on their specific characteristics and reproductive goals.