P–016 Using artificial intelligence to predict semen upgrading after microsurgical varicocele repair

Study question Can we use artificial intelligence models to predict semen upgrading after microsurgical varicocele repair? Summary answer A machine learning model performed well in predicting clinically meaningful post-varicocelectomy semen upgrade using pre-operative hormonal, clinical, and semen analysis data. What is known already 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 surgery. Nomograms exist to help predict success, but these are based out of single-center databases, do not incorporate hormonal data, and are rarely designed to predict pre-defined, clinically meaningful improvements in semen parameters. Study design, size, duration Data were collected from an international, multi-center retrospective cohort. A total of 240 men were identified. Data from 160 men from Miami, USA and 80 men from Toronto, Canada were included. Data was collected from 2006 to 2020. Participants/materials, setting, methods We collected pre and postoperative clinical data following varicocele surgery. Clinical upgrading was defined as an increase in sperm concentration that would allow a couple to access new reproductive technologies/techniques. The tiers used for upgrading were 0–1million/cc (Intracytoplasmic Sperm Injection), 1–5 million (In Vitro Fertilization), 5–15 million (Intrauterine Insemination), and >15 million (Natural conception). Artificial intelligence models were trained and tested using R to predict which patients upgraded after surgery. Main results and the role of chance 51% of men underwent bilateral varicocele repair. The majority of men had grade 2 varicocele on the left, and (when present) a grade 1 varicocele on the right. Overall, 47% of men experienced an upgrade following varicocele surgery, 47% did not change, and 6% downgraded. The data from Miami were used to create a random forest model for predicting clinically significant upgrade in sperm concentration. The most informative model parameters were preoperative FSH, sperm concentration, and surgical laterality. The model identified three clinical categories: men with unfavorable, intermediate, and favorable features to predict varicocele upgrade. On external validation using data from Toronto, the model accurately predicted upgrade in 87% of men with favorable features, and in 49% and 36% of men with intermediate and unfavorable features, respectively. Overall, the model performed well on external validation with an AUC of 0.72 and good calibration. Calibration plots, using cross-validation, define how well the predicted probabilities match the actual probability of sperm concentration upgrade. The random forest model was run twelve times. All model characteristics are the mean of ten model runs with the highest and lowest performing runs removed. The model was translated to an online calculator that can be used by clinicians. Limitations, reasons for caution One limitation to our study is that we were not able to predict total motile sperm count (TMSC), which has been shown to perform slightly better than concentration at predicting assisted reproduction outcomes. By focusing on clinically significant upgrading, this difference should be minimized. Wider implications of the findings: Predicting the chances of clinically significant semen upgrading after varicocele repair is essential for patients and clinicians to understand. Several men undergo surgery with no subsequent benefit, which may lead to a delay in definitive treatment with IVF/IUI. Understanding their chances will help couples make better informed decisions moving forward. Trial registration number Not applicable

P–078 Prognostic factors for male fertility recovery after microsurgical varicocelectomy

Study question What clinical and laboratory parameters are reliable predictors of spontaneous pregnancy (SP) after microsurgical varicocelectomy in men from infertile couples? Summary answer Predictors of SP after microsurgical varicocele repair are the male age, baseline total sperm motility, and postoperative increase level of TPMSC. What is known already Varicocele is the most common correctable cause of male subfertility. According to the recent meta-analyses and studies, microsurgical varicocelectomy is the “golden standard” method for varicocele repair. However, it is still unclear why at least one-third of subfertile men do not experience improvement in semen parameters and more than half of them do not report fertility recovery after varicocelectomy. There is no consensus so far on the factors affecting the efficacy of varicocele repair in men from infertile couples. Study design, size, duration This retrospective study comprises 93 men from infertile couples, with palpable varicocele, astheno-/oligozoospermia, and who underwent microsurgical subinguinal or inguinal varicocelectomy from September 2015 to May 2019. Participants/materials, setting, methods The changes in semen analysis were assessed (in 3–6 months after surgery) according to WHO–2010, spontaneous pregnancy (SP) rates after surgery also were considered. A stepwise discriminant analysis was performed to identify predictors of SP after varicocelectomy. An increase in TPMSC by at least 12.5 million was defined as a significant effect (SE) of varicocelectomy (reference values for the total number and progressive sperm motility according to WHO–2010: 39 million x 0.32 (32%) progressively motile). Main results and the role of chance Almost all semen parameters (except for semen volume) changed positively after surgery. Sperm concentration increased from 62 mln/ml (17–107) to 85 mln/ml (39–134) p < 0.001, TPMSC increased by an average of 27 mln (2.8 times; p < 0.001). SE was observed in 52% of cases (n = 48), a slight favorable effect in 21% (n = 20), and no effect in 27% (n = 25). 29 patients (31%) reported SP within a year after varicocele repair. 83% of patients (24 from 29) who reported pregnancy after varicocelectomy showed SE. According to the stepwise discriminant analysis, significant predictors of pregnancy after varicocelectomy were the male age (coefficient of the canonical discriminant function = –0.16), the initial total sperm motility (0.02), and the postoperative increase of TPMSC (0.01). Wilks’ lambda was 0.67 and canonical correlation 0.57. The predictive ability of the prognostic model (discriminant function) with these three predictors was 84%, specificity 87%, and sensitivity 76%. The function real predictive accuracy for SP was 70% (21 correct out of 30 predicted). Limitations, reasons for caution The small sample size and the inability to obtain accurate data on the health condition of female partners were the main limitations of the study. Nevertheless, the findings are statistically significant, which suggests that they can be extrapolated to the general sample of subfertile men with clinical varicocele. Wider implications of the findings: The proposed algorithm (function) for the prediction of SP showed satisfied predictive accuracy, and after its external validation can be recommended in 3–6 months after varicocele repair to decide whether it is advisable to expect an SP within a year or to include an infertile couple in ART programs immediately. Trial registration number Not applicable

Subinguinal Cremasteric Disruption and Venous Ligation for Varicocele Repair

Aim: To evaluate the outcome of subinguinal cremasteric disruption and venous ligation for the treatment of varicocele with regard to improvement in semen parameters, recurrence hydrocele formation and testicular atrophy. Methods: The clinical study was carried out from July 2016 to June 2019. Fifty-nine patients were included in the study. Varicocele repair was done as a day case surgery under local anesthesia using cremasteric disruption and venous ligation technique. The treatment outcomes studied were improvement in semen parameters and complications like recurrence, hydrocele formation and testicular atrophy. Results: Seventy-four varicocelectomies were done in fifty-nine patients. Semen parameters improved in those nineteen patients who had abnormal semen parameters before surgery and nine out of these nineteen (47.36%) got their semen count normal after varicocele repair. There were five recurrences (6.75%). No hydrocele formation or testicular atrophy occurred during one year of follow up. Conclusion: Day case varicocelectomy by subinguinal cremasteric disruption and venous ligation is a simple, economical choice with minimal morbidity and comparable outcomes. Keywords: Varicocele, Subinguinal cremasteric disruption and venous ligation, complication