Hydroxyurea treatment is not significantly associated with reduced spermatogonial numbers in patients with sickle cell disease

Hydroxyurea (HU) is considered a first-line therapy for patients with sickle cell disease (SCD). In cases of inadequate response to HU therapy, patients may receive conditioning therapy prior to haematopoietic stem cell transplantation, which can lead to depletion of the number of spermatogonia. Therefore, in pre-pubertal boys, fertility is preserved through cryopreservation of testicular tissue, although this is an experimental method. Analysis of this tissue showed a considerable loss of spermatogonia, leading to the hypothesis that HU therapy may reduce the spermatogonial number. However, evidence remains limited and conflicting. Therefore, this study aims to investigate the relationship between HU exposure and the spermatogonial number in boys with SCD. The number of spermatogonia per round seminiferous tubule (S/T) and the percentage of tubules containing spermatogonia were determined in cryopreserved testicular tissue from 27 HU-treated patients with SCD. Linear regression analyses were performed to assess their association with HU exposure. Spermatogonia were present in most boys with SCD, although in severely reduced numbers. S/T Z-scores and the percentage of tubules containing spermatogonia were not significantly associated with age at HU initiation, duration of HU exposure, or HU dose. In conclusion, in this cohort, no statistically significant association was observed between HU treatment and reduced spermatogonial numbers in patients with SCD.