Hydroxyurea Therapy Impacts Fertility in Sickle Cell Disease Patients, suggests study

Sickle cell disease (SCD) is a genetic disorder characterized by abnormal hemoglobin, leading to various complications, including pain, anemia, and organ damage. Hydroxyurea is widely used to manage SCD, as it reduces the frequency of pain episodes and other complications. Despite its benefits, concerns about the long-term effects of hydroxyurea on fertility have persisted. Observational studies have suggested adverse effects on sperm counts and ovarian reserves, prompting a systematic review and meta-analysis to quantify these impacts.

A systematic literature review identified articles published from inception to July 2023 in PubMed and EMBASE databases, focusing on fertility outcomes in SCD patients receiving hydroxyurea therapy. The review included studies of patients aged 6 years and older with the hemoglobin SS genotype of SCD. Outcomes measured included ejaculate volume, sperm concentration, total sperm count, sperm morphology, and motility in males, and anti-Müllerian hormone (AMH) levels and ovarian reserves in females.

The review identified 160 potentially relevant articles, with 34 full texts reviewed, and 8 studies included in the meta-analysis. These comprised four cohort studies for males (205 patients) and four cohort studies for females (149 patients).

Male Fertility Outcomes:

• Hydroxyurea did not significantly affect ejaculate volume (P = .71), initial sperm motility (P = .33), or sperm morphology (P = .95).

• Significant reduction in sperm concentration during treatment (mean difference [MD], –15.48 million/mL [95% CI, –20.69 to –10.26]; P < .001) and after cessation (MD, –20.09 million/mL [95% CI, –38.78 to –1.40]; P = .04).

• Significant reduction in total sperm count during treatment (MD, –105.87 million [95% CI, –140.61 to –71.13]; P < .001) and after cessation (MD, –53.05 million [95% CI, –104.96 to –1.14]; P = .05).

Female Fertility Outcomes:

• Women on hydroxyurea had significantly lower AMH levels than age-matched controls (odds ratio [OR], 2.6 [95% CI, 1.1 – 6.5]; P = .02).

• Pooled mean AMH values were 1.83 (95% CI, 1.42 - 2.56), below the normal range for the cohort's mean age.

• Approximately 72.2% showed normal ovarian reserves during and after treatment (95% CI, 42 - 89%), while 18.8% experienced diminished reserves (95% CI, 11 - 43%).

These findings highlight the significant impact of hydroxyurea on fertility in both male and female SCD patients. Given the adverse effects on sperm counts and ovarian reserves, fertility preservation counseling should be provided to patients before initiating hydroxyurea therapy.

Hydroxyurea therapy significantly impacts fertility in patients with SCD, affecting sperm concentration and total sperm count in men, and AMH levels and ovarian reserves in women. Increased knowledge and further research on fertility recovery post-therapy are urgently needed.

Reference:

Sewaralthahab S, Alsubki LA, Alhrabi MS, Alsultan A. Effects of hydroxyurea on fertility in male and female sickle cell disease patients. A systemic review and meta-analysis. PLoS One. 2024;19(6):e0304241. Published 2024 Jun 7. doi:10.1371/journal.pone.0304241