Algorithms for Predicting the Probability of Azoospermia from Follicle Stimulating Hormone: Design and Multi-Institutional External Validation.

PURPOSE: To predict the probability of azoospermia without a semen analysis in men presenting with infertility by developing an azoospermia prediction model. MATERIALS AND METHODS: Two predictive algorithms were generated, one with follicle stimulating hormone (FSH) as the only input and another logistic regression (LR) model with additional clinical inputs of age, luteinizing hormone, total testosterone, and bilateral testis volume. Men presenting between 01/2016 and 03/2020 with semen analyses, testicular ochiodemetry, and serum gonadotropin measurements collected within 120 days were included. An azoospermia prediction model was developed with multi-institutional two-fold external validation from tertiary urologic infertility clinics in Chicago, Miami, and Milan. RESULTS: Total 3,497 participants were included (n=Miami 946, Milan 1,955, Chicago 596). Incidence of azoospermia in Miami, Milan, and Chicago was 13.8%, 23.8%, and 32.0%, respectively. Predictive algorithms were generated with Miami data. On Milan external validation, the LR and quadratic FSH models both demonstrated good discrimination with areas under the receiver-operating-characteristic (ROC) curve (AUC) of 0.79 and 0.78, respectively. Data from Chicago performed with AUCs of 0.71 for the FSH only model and 0.72 for LR. Correlation between the quadratic FSH model and LR model was 0.95 with Milan and 0.92 with Chicago data. CONCLUSIONS: We present and validate algorithms to predict the probability of azoospermia. The ability to predict the probability of azoospermia without a semen analysis is useful when there are logistical hurdles in obtaining a semen analysis or for reevaluation prior to surgical sperm extraction.

Diagnostic Properties of Total and Free Prostate-Specific Antigen to Predict Overall and Clinically Significant Prostate Cancer Among Men With Low Testosterone and Prior Negative Biopsy.

OBJECTIVE: To evaluate whether total serum PSA, free-PSA ratio and PSA density have similar diagnostic properties for detecting prostate cancer (PCa) and clinically-significant (cs) PCa in men with normal testosterone compared to men with low testosterone with a prior negative biopsy. METHODS: We conducted a retrospective analysis of 3295 men undergoing a 2-year prostate biopsy following a negative prestudy biopsy in the placebo arm of the Reduction by Dutasteride of PCa Events (REDUCE) study. Men were divided in 2 groups based on testosterone level < or ≥300 ng/dL. Diagnostic properties of total serum PSA, free-PSA ratio, and PSA density to predict PCa and csPCa, defined as Gleason score ≥7, were determined for several thresholds and plotted as receiver operator characteristic curves. RESULTS: A total of 603 men (18.3%) had low testosterone. The prevalence of PCa and csPCa was 92 (15.3%) and 27 (4.5%), respectively, for low testosterone men compared to 458 (17.0%) and 138 (5.1%), correspondingly, for normal testosterone men. Total PSA, free-PSA ratio and PSA density showed similar sensitivity, specificity, and accuracy to predict PCa and csPCa among low testosterone men compared to normal testosterone men. CONCLUSION: Among subjects in a clinical trial with a prior negative biopsy, total PSA, free-PSA ratio and PSA density have comparable diagnostic characteristics for PCa screening in low and normal testosterone men.

Proposed Key Characteristics of Male Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Evidence in Human Health Hazard Assessments.

BACKGROUND: Assessing chemicals for their potential to cause male reproductive toxicity involves the evaluation of evidence obtained from experimental, epidemiological, and mechanistic studies. Although mechanistic evidence plays an important role in hazard identification and evidence integration, the process of identifying, screening and analyzing mechanistic studies and outcomes is a challenging exercise due to the diversity of research models and methods and the variety of known and proposed pathways for chemical-induced toxicity. Ten key characteristics of carcinogens provide a valuable tool for organizing and assessing chemical-specific data by potential mechanisms for cancer-causing agents. However, such an approach has not yet been developed for noncancer adverse outcomes. OBJECTIVES: The objective in this study was to identify a set of key characteristics that are frequently exhibited by exogenous agents that cause male reproductive toxicity and that could be applied for identifying, organizing, and summarizing mechanistic evidence related to this outcome. DISCUSSION: The identification of eight key characteristics of male reproductive toxicants was based on a survey of known male reproductive toxicants and established mechanisms and pathways of toxicity. The eight key characteristics can provide a basis for the systematic, transparent, and objective organization of mechanistic evidence relevant to chemical-induced effects on the male reproductive system. https://doi.org/10.1289/EHP5045.

Microsurgical varicocele ligation: surgical methodology and associated outcomes.

The impact of clinical varicoceles on semen parameters and male infertility has long been established. In the era of assisted reproduction, clinical discussion has questioned the role of varicocelectomy, offering the potential to bypass, rather than treat, varicocele-associated male infertility. However, current literature supports improved semen parameters and reproductive outcomes following repair. This article presents the stepwise operative approaches to microsurgical varicocelectomy and discusses the recent publications on outcomes.