Refining the Clinical Utility of the Testicular Index for Pregnancy Prediction in FSH-Treated Idiopathic Male Infertility

ABSTRACT Background and aim: Follicle-stimulating hormone (FSH) therapy is widely used for idiopathic male infertility (IMI), but high inter-individual variability in treat-ment efficacy complicates its management. The aim of this study was to refine the clinical utility of a multiparametric Testicular Index (TI) to predict pregnancy achievement in men with IMI undergoing empirical FSH therapy. Materials and methods: A retrospective, observational, real-world study was con-ducted at the University Hospital of Modena, Italy, enrolling 228 infertile couples whose male partners were treated with FSH for IMI. Clinical, seminal, and endo-crine data were collected at baseline (V0) and post-treatment (V1). Patients were al-so stratified according to the APHRODITE criteria. The TI was calculated as (FSH + Total testosterone) / Bi-testicular volume. The primary clinical outcome was the achievement of a clinical pregnancy. Results: A total of 68 clinical pregnancies (29.8%) were recorded following an av-erage treatment duration of 8.7 ± 5.0 months. Significant improvements in sperm concentration, total sperm number, and motility parameters were observed follow-ing FSH administration. Men whose partners achieved pregnancy were significantly younger (36.2 ± 4.7 vs 38.6 ± 6.4 years; p = 0.007), possessed larger baseline bi-testicular volumes (p = 0.003), and exhibited lower baseline FSH (p = 0.020) and TI values (p = 0.002). Multivariable logistic regression identified male age (OR 1.148, p = 0.011), bi-testicular volume (OR 1.091, p = 0.043), and the baseline TI (OR 0.334, p = 0.001) as independent predictors of pregnancy success. Furthermore, the TI demonstrated significant discriminative ability within APHRODITE Group 3 (AUC 0.673), unmasking potential responders within borderline-hypogonadal phe-notypes. Conclusions: This real-world study confirms the TI as a reliable clinical tool that synthesizes endocrine drive and morphological reserve. A lower baseline TI corre-lates with a higher probability of achieving pregnancy through exogenous FSH stimulation. Integrating the TI within structured phenotypic frameworks, such as APHRODITE, facilitates patient selection and supports phenotype-driven therapeu-tic strategies for male factor infertility.