Effect of tyrosine kinase inhibitors on sperm parameter and pituitary gonadal axis in males with chronic myeloid leukemia: a prospective cohort study

As the survival of patients with Chronic Myeloid Leukemia (CML) on tyrosine kinase inhibitors (TKIs) is comparable to healthy counterparts, it is now being treated as a chronic disease. Hence, there is significant concern of the effect of TKI on fertility and pregnancy outcomes. While the teratogenic effects of TKIs are well established, data on their impact on male fertility remain limited. With a growing number of CML patients of reproductive age being diagnosed annually, understanding the effect of Imatinib on male fertility is crucial. To study the effect of Imatinib (TKI) on the Pituitary gonadal axis and sperm parameters in CML patients, as there is limited data in this area. A prospective cohort study (Oct 2018-Jan 2021) included 30 male CML-CP patients (18-60 years). Patients were excluded if they had known dysfunction of the pituitary-gonadal axis, structural abnormalities of the gonads, or a history of prior sterilizing treatments. After receiving imatinib treatment for 3 months, out of these 30 patients, sperm concentration declined in 22 (73.3%), though only 5 (22.7%) had oligospermia (<15 million/ml), and none had severe oligospermia (<5 million/ml). Among these 5 patients, 4 were aged ≤35 years, while 1 was older than 35 years. Progressive motility decreased in 11 patients, with 6 (54.5%) dropping below the reference range (<32%), potentially causing infertility. Vitality decreased in 13 patients. Out of these, in 10 patients, vitality dropped below the reference range (<58%). Normal sperm morphology declined in 16 patients, but in only 2 patients it fell below 4%. Post-Imatinib treatment, two patients had elevated FSH, while LH and testosterone levels remained normal in all. Although there was a mild decrease in mean values of post-imatinib samples, there was no statistically significant decrease in mean FSH (<i>p</i>-value = 0.106), LH (<i>p</i>-value = 0.080), or testosterone levels (<i>p</i> = 0.313). Mean sperm concentration reduced after imatinib treatment, though it was not significant (<i>p</i>-value = 0.080). Mean progressive motility increased, but the change was not significant (<i>p</i> = 0.059). Mean sperm vitality increased, but it was not significant (<i>p</i>-value = 0.264). Also, there was no significant correlation found between hormonal changes and sperm parameters. Imatinib therapy was associated with a decline in sperm concentration, progressive motility, vitality, and normal morphology in some patients; however, no statistically significant changes were observed in mean hormonal or semen parameters. Patients planning families should nonetheless be counselled regarding the potential impact of TKIs on sperm quality. While sperm cryopreservation is not routinely recommended, its role in selected patients warrants evaluation in larger and long-term studies.