Naval Medical Center San Diego, Department of Urology
Introduction: Current AUA/EUA guidelines recommend obtaining Yq microdeletion analysis, karyotype, and genetic counseling in men with non-obstructive azoospermia or severe oligospermia ( <5 mil/mL). A recent retrospective cohort study suggests that Yq microdeletions are primarily found at a sperm concentration < 0.5 mil/mL and that by lowering the concentration threshold for genetic testing, specificity could be increased and relative financial cost decreased without adversely affecting the sensitivity. Studies have shown that FSH is the best predictor of non-obstructive azoospermia (NOA) in combination with testicular volume as well as a significant predictor of microdeletion presence. We hypothesized that the combination of sperm concentration and FSH would better predict the presence of chromosome abnormalities in infertile men. Methods: A retrospective cohort study was conducted with subjects who were referred to a military tertiary Urology clinic between 2010 to 2020 and who underwent an infertility evaluation to include genetic testing, hormone profile, and at least one semen analysis. Sperm density and FSH were analyzed as independent predictors of chromosomal abnormalities using logistic regression. Receiver operating characteristics were generated for each independent variable that achieved significance in regression. Results: 356 patients met inclusion criteria. Over the ten-year period, the prevalence of Y-chromosome microdeletions and karyotype abnormalities was 3.3% (n=12) and 8.4% (n=30), respectively. The ability to predict chromosomal abnormality based on logistic regression was statistically significant for each independent variable. The area under the curve for sperm concentration and FSH was found to be statistically better in combination than concentration alone (0.71 vs 0.66, p=0.033). The best balance of sensitivity and specificity (i.e. for a diagnostic test) for concentration and FSH were found at cut-points of <0.215 mil/mL and >8.345 mIU/mL, respectively. To optimize performance as a screening test and maintain sensitivity >90%, the cut points for concentration and FSH were <1 mil/mL and >2.74 mIU/mL, respectively. There was no difference in sensitivity for concentration between 2-7 mil/mL and no abnormalities were found if concentration exceeded 7 mil/mL. Conclusions: Our military single-institution ten-year cohort, exemplifies the potential improvement in patient selection and results that can be achieved if the sperm concentration is lowered from the current cutoff as well as possible addition of FSH to algorithm. SOURCE OF Funding: None
.jpeg.jpg "Colin A. McLain, MD photo")