Ovarian Follicle Density in Female Sickle Cell Disease Patients Unaffected by Hydroxyurea Exposure

Research into ovarian follicular density in younger female sickle cell disease patients finds no effect from exposure to hydroxyurea.

Research on ovarian follicle density in young females with sickle cell disease (SCD) who had an ovarian tissue cryopreservation (OTC) found that hydroxyurea (HU) exposure did not appear to reduce cortical follicle density.

The study was conducted to assess the effects of HU exposure on gonadotoxicity. The research was led by Tamara Diesch, MD, from the Department of Pediatric Hematology/Oncology at the University Children's Hospital of Basel in Switzerland.

The trial data was presented at the American Society of Hematology (ASH) Annual Meeting and Exposition.

“Little is known about gonadotoxicity in women with SCD who are taking HU,” Diesch and colleagues wrote. “The purpose of the study was to assess the impact of HU exposure and vaso-occlusive crisis on ovarian follicle density in young females with SCD who had an ovarian tissue cryopreservation (OTC) before hematological stem cell transplantation (HSCT), as fertility preservation measure.”

Background

The trial investigators recruited 88 female SCD patients with HbSS who had undergone an OTC prior to hematological stem cell transplantation (HSCT) at Avicenne Hospital in France between April of 1998 and November of 2020. Median age of the female patients was 9.92 years, with 65% of them being prepubertal by the time of the OTC.

The investigators evaluated a fragment of ovarian tissue histologically, with follicles counted and classified by growing stage.

They also calculated follicular density, with medical data related to  vaso-occlusive crisis (VOC) presence, applied HU dosage, applied transfusion units, total HU exposure in months, and pubertal development all being assessed through medical records.

Findings

The study concluded that HU exposure did not seem lead to cortical follicle density reduction for younger female SCD patients, noting that density was similar in the HU group compared to the non-HU exposure arm [median 5.97 follicle/mm2 (IQR 1.19-13.70 follicles/mm2) compared to 5.59 follicle/mm2 (1.65-12.79/mm2), P=0.614].

The research team noted that there was no correlation found between applied transfusion units and follicle density (P = 0.45).

“Hydroxyurea exposure does not appear to reduce cortical follicle density in females with SCD,” they wrote. “For the first time our study could show an influence of VOC on ovarian follicle density possibly related to reduced blood flow.”

The study, “Impact of Hydroxyurea and Vaso-Occlusive Crisis on Ovarian Follicle Density in Girls and Young Females with Sickle Cell Disease,” was presented at ASH 2022.