Testis stimulation with follicle-stimulating hormone (FSH) is one of the empirical treatments proposed for male idiopathic infertility, although reliable markers to predict its efficacy are still lacking. This study aimed to identify parameters able to predict FSH efficacy in terms of pregnancy achievement. A real-world study was conducted, enrolling idiopathic infertile men treated with FSH 150IU three times weekly. Patients were treated until pregnancy achievement or for a maximum of two years and two visits were considered: V0 (baseline) and V1 (end of FSH treatment). Primary endpoints were the V1-V0 percentage change in sperm concentration, total sperm count, and total motile sperm number. In total, 48 pregnancies were recorded (27.7%) among 173 men (age 37.9 ± 6.2 years). All three endpoints increased after FSH administration, and only the V1-V0 percentage of sperm concentration significantly predicted pregnancy (p = 0.007). A V1-V0 sperm concentration of 30.8% predicted pregnancy, and the sperm concentration V1-V0 percentage (Y) required to obtain a pregnancy was predicted according to its baseline values (x): Y = 9.8433x2 − 203.67x + 958.29. A higher number of pregnancies was reached in men with baseline sperm concentration below 7.3 million/mL. Thus, the percentage of sperm concentration increasing after FSH administration could predict the treatment efficacy in terms of pregnancy. At the dosage used, the efficacy was significantly higher in patients with a starting sperm concentration < 7.3 mill/mL. Mathematical analyses identified a function able to predict the sperm concentration increase required to obtain a pregnancy in relation to the baseline sperm number.
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