Abstract
Abstract 242
Hydroxyurea (HU) has proved its efficacy in reducing vaso-occlusive events in patients with SCD and increasing life expectancy. However, effects on fertility in adult males represent a major issue for acceptance and adherence, as HU has been reported to impair spermatogenesis through direct cytotoxic effects and hypogonadism. There are only limited data in the literature in this field and mainly retrospective.
49 adult patients aged 20–52 years with homozygous SCD eligible for first line HU treatment were enrolled after informed consent between June 2010 and April 2012 in this prospective study: HYDREP.The main objective was to compare at Day 0 and 180 of HU treatment the semen parameters according to the WHO (1999) criteria(volume, sperm concentration, viability, forward motility and morphology ). Vaso-occlusive events and other complications, number of transfusions during the 6 months preceding and following HU initiation were recorded. Hematological, biochemical, hormonal parameters, HU dosage were recorded at Day 0, Day 90 and 180. HU was begun at 15mg/Kg dose (Platt *) and modulated following haematological tolerance and renal function.
Preliminary results concern the 24/49 patients, who complete the 6 months protocol.
| BEFORE HU - N = 49 | AT 6 MONTHS HU – N=24 | |
|---|---|---|
| Sperm concentration (Million/ml) | 99 +/− 138 | 24 +/− 56 (p = 0,01) |
| Normal >20 | 14/49 <20 | 10/24<20 |
| Azoospermia | 4 | |
| Forward mobility (%) (Normal ≥ 50%) | 36.9 +/− 14.3 | 24.8 +/− 18.9 (p = 0.007) |
| Vitality(%) (Normal ≥ 60%) | 55 +/− 13.7 | 44.5 +/− 20.4 (p = 0.02) |
| Viability and morphology (Normal ≥ 30%) | 12.9 +/− 11 | 6.4 +/− 3.5 |
| BEFORE HU - N = 49 | AT 6 MONTHS HU – N=24 | |
|---|---|---|
| Sperm concentration (Million/ml) | 99 +/− 138 | 24 +/− 56 (p = 0,01) |
| Normal >20 | 14/49 <20 | 10/24<20 |
| Azoospermia | 4 | |
| Forward mobility (%) (Normal ≥ 50%) | 36.9 +/− 14.3 | 24.8 +/− 18.9 (p = 0.007) |
| Vitality(%) (Normal ≥ 60%) | 55 +/− 13.7 | 44.5 +/− 20.4 (p = 0.02) |
| Viability and morphology (Normal ≥ 30%) | 12.9 +/− 11 | 6.4 +/− 3.5 |
A statistically significant impairment in all sperm parameters was observed, after a 6 months HU therapy, with great variations between individuals, which are to be explained by complementary tests. These preliminary deleterious findings must be interpreted with caution as in our experience 1) spermatogenesis may recover after drug withdrawal 2) Repeated vaso-occlusive events are also potentially deleterious on fertility (Berthaut **)and 3)this study must be completed with a survey on effective fertility seen in men treated with HU. Thus, regarding to the great benefit offered by HU on prognosis allowing a real “life project” in young symptomatic adults with SCD, it is worth providing each patient of the most accurate information on fertility as an essential prerequisite for their adhesion to HU treatment.
Sperm cryopreservation is advised before beginning a treatment with HU. Prospective follow up studies of HU male cohort regarding fertility are warranted. Health education has a major role to play to increase HU compliance especially in view of these results.
No relevant conflicts of interest to declare.
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