Testicular index: clinical, applicable tool to predict pregnancy in men with idiopathic infertility under FSH treatment

Purpose Follicle-stimulating hormone (FSH) therapy improves spermatogenesis, sperm quality, and reproductive outcomes. However, variability in patients' response and limited data on pregnancy rate complicate its extensive application in male idiopathic infertility. The aim of the study was to identify predictors of FSH efficacy in male idiopathic infertility in terms of pregnancy. Design A retrospective, observational study was conducted at two Italian clinics from 2019 to 2024, enrolling men with idiopathic infertility, serum FSH < 8 IU/L, treated with FSH. Data were collected at baseline (V0) and at the final follow-up visit (V1) when FSH treatment was discontinued. Different, putative "testicular indexes" (TI) were calculated. Pregnancy rate was defined at ultrasound confirmation of fetus heartbeat. Results A total of 84 achieved pregnancy (19%) on 443 patients were recorded. One TI ((FSH + Total testosterone)/bi-testicular volume) was directly related to V0-semen parameters. Significant improvements in sperm concentration (p < 0.001), count (p < 0.001) and motility (p = 0.003) were observed following FSH treatment regardless of pregnancy achievement. Men who achieved pregnancy had lower baseline TI (p = 0.001), larger testicular volume (p = 0.001), and lower FSH concentrations (p = 0.001). Multivariate analysis identified patients' age (B=-0.14, standard error (SE) = 0.05, p = 0.014) and TI (B=-1.51, SE = 0.62, p = 0.015) as significant predictors of pregnancy success. Conclusions This real-life study identified a novel TI that predicts response to exogenous FSH stimulation. TI assesses the interstitial compartment function (indicated by testosterone concentrations), spermatogenic potential (FSH concentrations), and target tissue amount (testicular volume). Low baseline TI correlates with a higher likelihood of achieving pregnancy through exogenous FSH stimulation.