Nam, C

Abstract Introduction While microdeletions in the azoospermia factor (AZF) regions of the Y chromosome are a well-recognized cause of genetic male infertility, reproductive outcomes and broader health profiles among affected men remain poorly characterized. Objective We explore the distribution of AZF deletion subtypes and evaluate comorbidities and fertility management patterns in this unique population. Methods We performed a multi-institutional retrospective cohort study of men diagnosed with AZF deletions following evaluation by a reproductive urologist and genetic testing. The primary exposure variable was the AZF subtype (AZFa, AZFb, AZFc, or multilocus [e.g., AZFabc]).Clinical data were extracted to assess the presence of comorbidities, including hypertension, diabetes mellitus, hyperlipidemia, liver disease, and cardiac disease. Descriptive statistics were used to characterize the distribution of AZF subtypes, comorbidity profile, and outcomes of sperm retrieval procedures within our cohort. Results Among 40 men with confirmed AZF microdeletions across three academic centers, four patients with SRY translocations were excluded. Of the remaining 36, AZFc was the most common subtype (75%), followed by multilocus (16.6%), AZFa (5.5%), and AZFb (2.7%). The median age was 32.8 years (IQR: 29.2–33.6) and median BMI was 28.6 kg/m2 (IQR: 25.6–32.8). Comorbid conditions were identified in 8% of the cohort, with hyperlipidemia (13.9%), hypertension (11%), and diabetes (11%) most commonly reported. Sperm retrieval was attempted in 31% (n=11) of patients, exclusively among those with AZFc (n=10) andAZFb (n=1) deletions. Microscopic testicular sperm extraction (mTESE) was the predominant technique (91%). Sperm was successfully retrieved in 46% of these cases, all within the AZFc subgroup. Conclusions This study advances limited literature on AZF microdeletions by characterizing systemic health profiles and post-diagnosis infertility management. Our results support a broad phenotype associated with genetic causes of male infertility. In this cohort of men with YCMD, AZFc was the most prevalent subtype. Compared to national estimates for similarly aged men, our findings suggest that men with YCMD may have a distinct comorbidity profile compared to the general population, with an elevated prevalence of metabolic disease. Our findings reinforce male infertility as a heterogeneous condition that may serve as an early marker for broader metabolic disease. In addition, nearly all patients who underwent sperm retrieval were within the AZFc group. Fertility management trends favored mTESE, with moderate success rates in sperm retrieval, particularly among AZFc patients. Our results highlight provider preferences in surgical fertility management in patients withYCMD. Our findings underscore the need for a holistic approach to men with YCMD, addressing both surgical fertility management and systemic health risks. Clear patient counseling on sperm retrieval success rates and early identification of comorbidities may redefine outcomes for this unique population. Our results support a broad phenotype associated with genetic causes of male infertility. Disclosure No