Semen Analysis in Men with Testicular Cancer: Insights from a Large Fertility Preservation Cohort Toward Personalized Fertility Assessment

Background/Objectives: Testicular cancer accounts for approximately 1% of all male malignancies, with an incidence ranging from 1 to 10 per 100,000 men and it predominantly affects young individuals, with nearly 60% of cases diagnosed between 15 and 35 years of age. In recent decades, the incidence of testicular cancer has markedly increased, paralleling a global rise in male infertility rates. Although chemotherapy is known to adversely affect fertility, the extent to which the tumor itself and its different histological subtypes impact semen quality remains incompletely understood. The aim of this study was to evaluate semen parameters in men diagnosed with testicular cancer prior to oncological treatment and to assess the possible association between tumor histology and semen quality. Methods: This retrospective study included data from 284 men diagnosed with testicular cancer who underwent semen cryopreservation prior to surgery, chemotherapy, or radiotherapy. Data were collected between January 2016 and June 2022 at the Maternal and Child Department of the University of Naples Federico II. Histopathological classification was available for 278 patients and revealed the following distribution: 59% (165/278) classic seminoma, 14.7% (41/278) seminomatous mixed germ cell tumors, 13.3% (37/278) non-seminomatous mixed germ cell tumors, and 12.6% (35/278) non-seminomatous germ cell tumors. Results: No significant association was observed between tumor histology and abnormal semen parameters. According to World Health Organization (WHO) reference values, semen parameters in patients with testicular cancer were predominantly distributed between the 5th and 25th percentiles. Microscopic semen analysis revealed significantly lower sperm concentration, total motility, and normal morphology in cancer patients (p < 0.001; p < 0.001; and p < 0.002, respectively). Logistic regression analysis showed a significant association between age and testicular cancer risk (p < 0.001), with a negative coefficient indicating that the likelihood of developing the disease decreases with increasing age. Additionally, patients with seminoma were significantly older than those with non-seminomatous tumors: on average, 4.07 years older than those with pure non-seminoma (p = 0.007) and 5.60 years older than those with mixed non-seminoma (p < 0.001). No statistically significant age differences were observed among non-seminomatous subtypes. Conclusions: These findings underscore the importance of systematic semen evaluation in young men diagnosed with testicular cancer and highlight the critical role of fertility preservation strategies in the comprehensive management of these patients.