Common sickle cell drug does not affect ovarian reserve

Hydroxyurea, a common sickle cell treatment has no significant effect on ovarian reserve.

Sickle cell disease, a common genetic blood disorder, impacts around 300,000 newborns globally each year. Over the past four decades, advances in treatment, particularly the introduction of hydroxyurea in the mid-1990s, have substantially improved patient outcomes by reducing the frequency of vaso-occlusive crises and acute chest syndrome episodes. However, there have been concerns about the drug's potential side effects, particularly its impact on fertility resulting from reduced ovarian reserve.

Dr Tamara Diesch-Furlanetto, lead author of the research published in Blood Advances and deputy head of the department of oncology and hematology at University Children's Hospital Basel, Switzerland, explained: 'Many female patients with sickle cell disease avoid hydroxyurea due to concerns about fertility. However, they should be more confident in hydroxyurea as a therapy. It reduces vaso-occlusive crisis and hospitalization rates, increasing their quality of life, and, according to the data from this study, doesn’t impact fertility.'

Ovarian reserve is crucial for fertility as it refers to the number of primordial follicles in the ovaries, and is established before birth and declines with age. Therefore, understanding hydroxyurea's impact on ovarian reserve is vital for planning the long-term reproductive health of women receiving this treatment.

The study examined ovarian tissue samples from 76 girls and women with sickle cell disease who had undergone ovarian tissue cryopreservation before hematopoietic stem cell transplantation. Researchers found a trend showing a reducing in the density of primordial follicles between the 35 patients who had been treated with hydroxyurea and those who had not, but this was not significant. This indicates that hydroxyurea does not negatively affect ovarian reserve, alleviating concerns about its use in young female patients.

Previous studies found that patients treated with hydroxyurea had significantly lower anti-Müllerian hormone (AMH) levels, and researchers concluded those low levels suggested diminished ovarian reserve. However, these findings support the broader use of hydroxyurea in managing sickle cell disease without compromising future fertility, offering significant relief to patients and healthcare providers alike.

Dr Diesch-Furlanetto added: 'We hypothesise that a low AMH level reflects altered function of growing follicles and not a quantitative decline in their number.'

The study acknowledged limitations, including lack of AMH data at the time of ovarian tissue cryopreservation. Prospective studies are needed to further investigate the effects of hydroxyurea on fertility, including the value of AMH levels.