Semen Quality in Patients with Hematological Malignancies: A Retrospective Monocentric Study in the Perspective of Personalized Oncofertility Medicine

<b>Background/Objectives:</b> The hypothalamic-pituitary-testis axis is known to be dysregulated in patients with hematological malignancies. However, data on the association between the type of hematological malignancies and semen quality are discordant. In the era of personalized medicine, identifying disease-specific patterns of reproductive impairment is crucial to optimize fertility preservation strategies. While patients with leukemia often show a clear deterioration in semen quality, studies on Hodgkin and non-Hodgkin lymphomas have shown that spermatogenesis is not always compromised. Indeed, some patients may present normospermia before treatment. This study aimed to assess semen parameters in males affected by hematological malignancies compared with a non-cancer population and to explore implications for individualized fertility preservation counseling. <b>Methods:</b> We performed a retrospective monocentric study including all patients affected by hematological malignancies who underwent fertility preservation at the Maternal and Child Department, Gynecology and Obstetrics, Oncofertility Unit, Federico II of Naples, from January 2017 through December 2024. In total, 247 patients with hematological malignancies and 63 non-cancer males undergoing in vitro fertilization for female tubal factor, selected as a control group, were included in the analysis. Sperm parameters (semen volume, sperm concentration, motility, and morphology) were first compared between the hematological malignancy group and the control group, and then among hematological malignancies classified as Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and leukemia (L). <b>Results:</b> Overall, according to World Health Organization (WHO, 2021) criteria, semen parameters of patients with hematological malignancies were at the 25th percentile, except for motility, which was below the 5th percentile. Significant differences were observed in sperm concentration/mL, total sperm number, and percentage of total sperm motility between the hematological malignancy group and the control group (<i>p</i> = 0.0004; <i>p</i> = 0.0003; <i>p</i> < 0.0001). Based on disease classification, 158 patients had Hodgkin lymphoma, 54 had non-Hodgkin lymphoma, and 35 had leukemia. Significant differences in concentration/mL and total sperm number were found between the Hodgkin lymphoma group and the control group (<i>p</i> = 0.003; <i>p</i> = 0.001). The percentage of total sperm motility was significantly decreased in all subtypes of hematological malignancies compared with controls, especially in the leukemia group (HL <i>p</i> = 0.001; NHL <i>p</i> = 0.004; L <i>p</i> < 0.001). <b>Conclusions:</b> These findings highlight significant impairment of semen quality, particularly motility, reinforcing the role of personalized medicine in tailoring fertility preservation strategies according to malignancy subtype and baseline reproductive risk.