Artificial Intelligence Based Machine Learning Models Predict Sperm Parameter Upgrading after Varicocele Repair: A Multi-Institutional Analysis

Purpose: Varicocele repair is recommended in the presence of a clinical varicocele together with at least one abnormal semen parameter, and male infertility. Unfortunately, up to 50% of men who meet criteria for repair will not see meaningful benefit in outcomes despite successful treatment. We developed an artificial intelligence (AI) model to predict which men with varicocele will benefit from treatment. Materials and Methods: We identified men with infertility, clinical varicocele, and at least one abnormal semen parameter from two large urology centers in North America (Miami and Toronto) between 2006 and 2020. We collected pre and postoperative clinical and hormonal data following treatment. Clinical upgrading was defined as an increase in sperm concentration that would allow a couple to access previously unavailable reproductive options. The tiers used for upgrading were: 1-5 million/mL (ICSI/IVF), 5-15 million/mL (IUI) and >15 million/mL (natural conception). Thus moving from ICSI/IVF to IUI, or from IUI to natural conception, would be considered an upgrade. AI models were trained and tested using R to predict which patients were likely to upgrade after surgery. The model sorted men into categories that defined how likely they were to upgrade after surgery (likely, equivocal, and unlikely). Results: Data from 240 men were included from both centers. A total of 45.6% of men experienced an upgrade in sperm concentration following surgery, 48.1% did not change, and 6.3% downgraded. The data from Miami were used to create a random forest model for predicting upgrade in sperm concentration. On external validation using Toronto data, the model accurately predicted upgrade in 87% of men deemed likely to improve, and in 49% and 36% of men who were equivocal and unlikely to improve, respectively. Overall, the personalized prediction for patients in the validation cohort was accurate (AUC 0.72). Conclusions: A machine learning model performed well in predicting clinically meaningful post-varicocelectomy sperm parameters using pre-operative hormonal, clinical, and semen analysis data. To our knowledge, this is the first prediction model to show the utility of hormonal data, as well as the first to use machine learning models to predict clinically meaningful upgrading. This model will be published online as a clinical calculator that can be used in the preoperative counseling of patients.