Impact of Hydroxyurea on follicle density in patients with sickle cell disease

• No association between Hydroxyurea treatment and decreased follicle density in sickle cell patients.

• Fertility preservation is not necessary prior to HU treatment

The impact of hydroxyurea (HU) on the ovarian reserve of female patients with sickle cell disease (SCD) remains poorly elucidated. Only direct histological analysis of ovarian follicle density can effectively evaluate HU's effect on ovarian reserve. By analyzing digitized slides of ovarian tissue from girls and young women with SCD who underwent ovarian tissue cryopreservation (OTC) before hematological stem cell transplantation (HSCT), we meticulously counted follicles and categorized them based on their growth stage. We then calculated the densities of different follicle types and assessed their correlation with patient characteristics, clinical manifestations, and treatments extracted from medical records. Seventy-six SCD patients participated in the study, with a median age at OTC of 10.2 years (interquartile range [IQR] 7.5, 14.6), and 50 (65.8%) were prepubertal. Of these, 35 patients (46.1%) had received HU, with a median daily dosage of 23.0 mg/kg (IQR 20.0, 25.0) and median exposure time of 44 months (IQR 24.0, 54.0). Primordial follicle density was comparable between the HU and non-HU groups (5.8 follicles/mm2 [IQR 1.0, 13.3] versus 4.2 follicles/mm2 [IQR 1.1, 14.4], respectively; P = .95). However, in the HU group, after adjusting for age, the density of growing follicles was marginally lower compared to the non-HU group (P = .09). Notably, other parameters such as vaso-occlusive crisis did not affect follicular density. In conclusion, exposure to hydroxyurea did not demonstrate a reduction in ovarian reserve in girls/women with SCD. Therefore, fertility preservation measures before initiating HU treatment do not seem necessary.