Hydroxyurea found not to reduce ovarian reserve in SCD patients
Measures to preserve fertility may not be needed before taking hydroxyurea
Hydroxyurea does not reduce ovarian reserve, or the quantity and quality of eggs in the ovaries, in girls and young women with sickle cell disease (SCD), according to a direct analysis of ovarian tissue.
These findings suggest measures to preserve fertility may be unnecessary before hydroxyurea treatment.
“This is the first time we can say … that hydroxyurea doesn’t impact ovarian reserve,” Tamara Diesch-Furlanetto, MD, of the University Children’s Hospital Basel, in Switzerland, and the study’s lead author, said in a press release. “Individuals living with SCD should still consider preserving ovarian tissue … but it’s not obligatory if they are just being treated with hydroxyurea.”
The analysis was published in the journal Blood Advances as a study, titled “Impact of Hydroxyurea on follicle density in patients with sickle cell disease.”
In SCD, an abnormal form of hemoglobin, the oxygen-carrying protein inside red blood cells, clumps together and deforms cells into a sickle-like shape. Such sickled cells are destroyed, leading to anemia, and can become lodged in blood vessels, blocking blood flow and triggering painful vaso-occlusive crises, or VOCs.
Hydroxyurea used to reduce frequency of vaso-occlusive crises
Hydroxyurea, an oral medication introduced in the 1990s, is used to reduce VOC frequency, other disease complications, and the need for blood transfusions. It works by increasing the levels of fetal hemoglobin, a version of hemoglobin produced during fetal development that is more effective at transporting oxygen than its adult counterpart.
However, the treatment has long been associated with fertility problems in both men and women. Previous studies have shown hydroxyurea reduces a marker for growing ovarian follicles, which are tiny sacs containing a single oocyte, or an immature ovum or egg cell. Moreover, as the therapy can also cause fetal harm, contraception during treatment is recommended.
“Many female patients with SCD avoid hydroxyurea due to concerns about fertility,” Diesch-Furlanetto said.
To directly assess the impact of hydroxyurea on ovarian function, the team examined ovarian tissue from 76 girls and young women with SCD who underwent ovarian tissue cryopreservation (OTC) to preserve fertility before receiving a hematological stem cell transplant (HSCT).
In advance of an HSCT, patients must undergo bone marrow conditioning to eliminate the faulty blood stem cells and allow the transplanted healthy stem cells to survive and grow. The side effects of such a conditioning regimen can increase the risk of infertility.
Of the 76 patients, the median age at OTC was 10.2 years, and 50 (65.8%) had yet to reach puberty. Before OTC, 35 patients (46.1%) had received hydroxyurea, with a median daily dosage of 23 mg/kg and a median exposure time of 44 months, close to four years.
To determine ovarian reserve, or how many follicles are left in the ovaries, the team measured the density of primordial follicles, the most immature form of ovarian follicles present at birth, and categorized them based on their growth stage.
No significant difference found in primordial follicle density between patients
The analysis revealed that the primordial follicle density, measured in follicles per square millimeter under a microscope, was comparable between patients who had been exposed to hydroxyurea and those who had not (5.8 vs. 4.2). The results remained the same after adjusting for age or dividing the patients into pre- and postpubertal groups.
After age adjustments, however, the density of growing follicles in their primary stage was marginally, but not significantly, lower in those treated with hydroxyurea.
The researchers noted these findings may explain lower marker levels for growing follicles associated with hydroxyurea. They hypothesized these lower levels reflect altered function in growing follicles due to hydroxyurea but “not a quantitative decline in their number.”
While most patients (80%) had a history of severe VOCs, the number of VOCs did not affect follicular density, nor did the blood transfusion doses before OTC.
Women “should be more confident in hydroxyurea as a therapy,” Diesch-Furlanetto said. “It reduces VOC and hospitalization rates, increasing their quality of life, and, according to the data from this study, doesn’t impact fertility.”
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