Sickle Cell Disease and Male Infertility: Pathophysiological Mechanisms, Clinical Manifestations, and Fertility Preservation Strategies—A Narrative Review

TL;DR

This review explores how sickle cell disease affects male fertility, the underlying mechanisms, and options for preserving fertility in affected men.

Contribution

The paper provides a comprehensive narrative review on the pathophysiology and fertility preservation strategies for male infertility in sickle cell disease.

Findings

Recurrent vaso-occlusion and chronic hypoxia can damage the seminiferous epithelium and impair Leydig cell function.

Oxidative stress and inflammation contribute to sperm DNA and membrane damage in men with SCD.

Fertility preservation methods like semen cryopreservation and TESE are recommended before treatments like hydroxyurea or transplantation.

Abstract

Sickle cell disease (SCD) is an inherited hemoglobinopathy in which hemoglobin S polymerization drives hemolysis and vaso-occlusion with progressive organ morbidity. Male reproductive impairment is increasingly recognized but remains underreported. This narrative review summarizes mechanistic pathways, clinical manifestations, and fertility preservation options relevant to men with SCD. PubMed, the Cochrane Library, and Medscape were searched through 31 December 2025 for human studies addressing endocrine changes, semen quality, priapism and erectile dysfunction, oxidative stress, and treatment-related gonadotoxicity. Evidence supports converging mechanisms: recurrent vaso-occlusion and chronic hypoxia may injure the seminiferous epithelium and impair Leydig cell steroidogenesis; oxidative stress and inflammation contribute to sperm DNA and membrane damage; and disease-modifying or curative therapies such as hydroxyurea and hematopoietic stem cell transplantation can further compromise spermatogenesis. Clinically, men with SCD may present with oligozoospermia, azoospermia, hypogonadism, and sexual dysfunction, particularly after recurrent ischemic priapism. Fertility preservation should be discussed early, ideally before prolonged hydroxyurea exposure or transplantation, and may include semen cryopreservation and testicular sperm extraction (TESE) with assisted reproduction when needed. Prospective longitudinal studies are required to define reproductive trajectories and optimize counseling and management.

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