(255) Operating Characteristics of Sperm Concentration and FSH for Predicting Chromosomal Abnormalities

Abstract

Abstract Introduction Microdeletions of the Y-chromosome (Yq) and karyotype abnormalities are frequent causes of male factor infertility. 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 NOA in combination with testicular volume as well as a significant predictor of microdeletion presence. Identification of Yq microdeletions and karyotype abnormalities have implications when counseling patients (and their partners) about the likelihood of retrieving sperm and need for further genetic counseling. Objective 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 (karyotype, Y-chromosome analysis), hormone profile (FSH), 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 A total of 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 8.345 mIU/mL, respectively. To optimize performance as a screening test and maintain sensitivity >90%, the cut points for concentration and FSH were 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; thus a cutoff of 7 mil/mL would capture 100% of all chromosome abnormalities. Conclusions Based on receiver operating characteristics, lowering the threshold for chromosomal analysis to a sperm concentration of <1 mil/mL maintains acceptable performance as a screening test for genetic abnormality, with resulting cost savings expected. Incorporating FSH into this decision appears to improve both sensitivity and specificity in prediction of chromosomal abnormalities. 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 Disclosure No