Hydroxyurea does not affect ovarian reserve of girls, young women with sickle cell disease
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Key takeaways:
- Use of hydroxyurea did not reduce ovarian reserve among girls and young women with sickle cell disease.
- Fertility preservation procedures prior to treatment may not be necessary.
Hydroxyurea did not affect ovarian reserve among girls and young women with sickle cell disease, according to results published in Blood Advances.
The findings — which contradict a long-held consensus — showed patients who received hydroxyurea had similar ovarian follicle densities as those who did not.
“There is no need for fertility preservation in females before starting hydroxyurea treatment,” researcher Tamara Diesch-Furlanetto, MD, deputy head of the department of oncology/hematology at University Children’s Hospital Basel in Switzerland, told Healio. “A higher prescription rate of hydroxyurea will improve the quality of life for patients with sickle cell disease, as hydroxyurea does not adversely affect ovarian reserve.”
Background and methods
Roughly 300,000 people are born with sickle cell disease worldwide every year, including about 100,000 in the U.S., according to study background.
Hydroxyurea, the only disease-modifying therapy approved for sickle cell treatment prior to 2017, can reduce vaso-occlusive crises (VOC) by more than 40%..
“Hydroxyurea is a crucial medication for managing sickle cell disease, offering benefits such as reduced painful crises, decreased acute complications, improved hemoglobin levels, prevention of organ damage and enhanced quality of life,” Diesch-Furlanetto said. “However, it is also known for its teratogenic effects and potential side effects, including bone marrow suppression, gastrointestinal issues and hair loss. Concerning fertility, gonadotoxicity in females remains insufficiently researched. Due to these considerations, some patients may choose to avoid taking the drug.”
Prior studies examined the impact of hydroxyurea on ovarian reserve by evaluating changes in serum anti-Müllerian hormone (AMH) levels. Results showed patients treated with hydroxyurea had significantly lower AMH levels, and researchers concluded those low levels suggested diminished ovarian reserve.
“We had the opportunity to investigate ovarian tissue directly to assess the real impact of hydroxyurea on ovarian reserve,” Diesch-Furlanetto said.
Diesch-Furlanetto and colleagues conducted a retrospective study using ovarian tissue samples collected between April 1998 and November 2020.
The analysis included 76 girls and young women (median age, 10.2 years; 65.8% prepubertal) from four centers in France who underwent ovarian tissue cryopreservation prior to hematopoietic stem cell transplantation. Slightly less than half (46%) received hydroxyurea.
Median age was significantly higher in the hydroxyurea cohort than the non-hydroxyurea group (12.2 years vs. 9.6 years).
The effect of hydroxyurea on ovarian reserve — or primordial follicle density — served as the primary endpoint. Correlation of ovarian reserve with VOC and age, the correlation between severe VOCs and primordial follicle density, and hydroxyurea’s effect on growing follicle density served as secondary endpoints.
Results and next steps
Results showed no significant difference in median ovarian reserve between the hydroxyurea and non-hydroxyurea groups (5.8 follicles/mm2 vs. 4.2 follicles/mm2).
“We anticipated a decrease in ovarian reserve among those receiving hydroxyurea treatment,” Diesch-Furlanetto said. “Therefore, our findings came as a surprise.”
After adjusting for age, the hydroxyurea cohort exhibited a slightly lower density of growing follicles (0.2 follicles/mm2 vs. 0.5 follicles/mm2), but the difference did not reach statistical significance.
“We hypothesize that a low AMH level reflects altered function of growing follicles and not a quantitative decline in their number,” Diesch-Furlanetto and colleagues wrote.
The majority (80%) of patients in the cohort had a history of severe VOC.
Researchers did not observe an association between ovarian reserve and incidence of VOC among pre- or postpubertal girls, nor did they observe an association between primordial follicle density and transfusion doses prior to ovarian tissue cryopreservation.
Researchers acknowledged study limitation, including lack of AMH data at the time of ovarian tissue cryopreservation.
“Consequently, the value of AMH level as a marker of ovarian reserve is still unclear,” they wrote.
Prospective studies are needed to further investigate the effects of hydroxyurea on fertility, they added.
“It is crucial to conduct further research with longer follow-up periods,” Diesch-Furlanetto told Healio. “Additionally, investigating the impact of reduced-intensity conditioning on ovarian reserve is also essential.”
For more information:
Tamara Diesch-Furlanetto, MD, can be reached at tamara.diesch-furlanetto@ukbb.ch.
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