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. 2024 Oct 8;8(19):5227-5235.
doi: 10.1182/bloodadvances.2023011536.

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

Tamara Diesch-Furlanetto  1 , Carlos Sanchez  2 , Andrew Atkinson  2 , Corinne Pondarré  3 , Nathalie Dhedin  4 , Bénédicte Neven  5 , Cécile Arnaud  3 , Annie Kamdem  3 , France Pirenne  6 , Gilles Lenaour  7 , Isabelle Brocheriou  7 , Benoit Terris  8 , Françoise Bernaudin  3 , Jean-Hugues Dalle  9   10 , Catherine Poirot  4   11
Affiliations

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

Tamara Diesch-Furlanetto et al. Blood Adv. .

Abstract

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, 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 patients with SCD 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 per mm2 [IQR, 1.0-13.3] vs 4.2 follicles per 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 than that in the non-HU group (P = .09). Notably, other parameters such as vaso-occlusive crisis did not affect follicular density. In conclusion, exposure to HU did not demonstrate a reduction in ovarian reserve in girls or women with SCD. Therefore, fertility preservation measures before initiating HU treatment do not seem necessary.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Correlation between HU dose, HU exposure, and follicle density. (A) Follicle density in correlation with HU and age (years). (B) Follicle density according to HU exposure (months). (C) Follicle density according to HU dose (mg/kg).
Figure 2.
Figure 2.
Correlation between VOC, transfusion, and follicle density. (A) Correlation between the presence of VOC and primordial follicle density. (B) Correlation between the number of VOC and primordial follicle density. (C) Correlation between primordial follicle density and administered transfusion doses.
See this image and copyright information in PMC

Comment in

  • Hydroxyurea and follicle density in sickle cell.
    Creary S, Kebodeaux C, Nahata L. Creary S, et al. Blood Adv. 2024 Oct 8;8(19):5225-5226. doi: 10.1182/bloodadvances.2024013815. Blood Adv. 2024. PMID: 39378027 Free PMC article. No abstract available.

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