Reproductive function and sperm parameters in men with sickle cell disease: a systematic review

Systematic review finds SCD impairs sperm parameters, and both hydroxyurea and stem cell transplant make it worse

Journal: Asian Journal of Andrology | Published: 2025-05-30 | Type: Systematic Review | PMID: 40443128 Authors: Leblanc C et al. — Reproductive Biology/CECOS, Tenon Hospital, AP-HP/Sorbonne University, Paris; with internal medicine and obstetrics co-authors from the same center Funding/COI: Not listed

Summary

Men with sickle cell disease (SCD) show consistently impaired sperm parameters across most studies reviewed — a consequence of hemolytic anemia, vaso-occlusive crises, and the downstream organ damage they cause. The complication is that the two main treatments — hydroxyurea (HU) for symptom management and hematopoietic stem cell transplantation (HSCT) for cure — both carry gonadotoxic effects. For HSCT, conditioning regimens can permanently ablate spermatogenesis. This review draws a practical conclusion: fertility preservation needs to happen before treatment, not after.

Claims

• Men with SCD frequently exhibit impaired sperm parameters (specific pooled effect sizes are not reported — the abstract notes findings are consistent across most studies)
• Hydroxyurea, the standard disease-modifying agent, negatively impacts male reproductive function; reversibility of these effects on sperm parameters "remains hypothetical"
• HSCT conditioning regimens are described as "highly gonadotoxic" and capable of permanently altering spermatogenesis
• Immature testicular tissue (ITT) freezing is flagged as an option for prepubertal boys before HSCT, though the review explicitly notes this technique remains experimental

Study Quality

This is a PRISMA-compliant systematic review, which means the search and inclusion methodology are at least structurally sound. The authors acknowledge upfront that "literature assessing the impact of SCD and its treatments on male reproductive functions remains limited and lacks robust evidence" — a candid admission that limits what can be concluded. Without a meta-analytic component, the review cannot pool effect sizes or weight studies by quality, making it largely a narrative synthesis. The extent to which individual studies controlled for confounders (age, SCD genotype severity, duration of HU treatment, prior gonadotoxic exposure) is not described in the abstract.

Red Flags

• No quantitative synthesis — no pooled sperm parameter data, no effect sizes, no confidence intervals
• Funding and conflicts of interest are not disclosed, which is a basic reporting failure for a 2025 systematic review
• All authors are from a single institution; no statement on whether independent reviewers assessed study quality
• "Reversibility remains hypothetical" for HU effects is a significant evidentiary gap left unresolved
• The recommendation around ITT freezing is acknowledged as experimental, but the boundary between review findings and clinical opinion is blurry in the abstract

Strengths

• Follows PRISMA reporting guidelines
• Covers both the disease mechanism and treatment effects in an underserved population — SCD-specific male fertility literature is genuinely sparse
• Authors are candid about the weakness of the underlying evidence base rather than overstating conclusions
• Addresses a clinically meaningful window: the interval before treatment initiation where fertility preservation is still possible

Verdict

This review maps a real clinical problem in a population that gets little dedicated fertility research, and it's honest that the evidence base is thin. The value is consolidation, not revelation — if you work with SCD patients or study gonadotoxicity, it's a useful map of what's known and what isn't. As a standalone piece of science, the lack of meta-analysis, no disclosed funding, and no quantified effect sizes mean you should treat its conclusions as directional rather than definitive. The takeaway that HSCT conditioning can permanently sterilize and that fertility preservation should precede treatment is not new — but having it documented in a PRISMA review for this specific population has some utility.