Non-syndromic male infertility due to sperm motility disorder

Non-syndromic male infertility due to sperm motility disorder (Orphanet code 276234) is a group of rare genetic conditions in which affected males have reduced or absent sperm motility (asthenozoospermia) as the primary cause of infertility, without other associated syndromic features. Unlike syndromic forms of ciliary or flagellar dysfunction (such as primary ciliary dyskinesia), these conditions affect only the reproductive system, specifically the structure and function of the sperm flagellum, which is essential for sperm movement. Affected individuals typically produce sperm in normal or near-normal quantities, but the sperm are unable to move effectively, preventing natural fertilization. The condition is usually identified in adulthood when couples seek evaluation for difficulty conceiving. Semen analysis reveals markedly reduced progressive motility or complete immotility of spermatozoa. Ultrastructural examination of sperm may show defects in the axoneme, fibrous sheath, mitochondrial sheath, or other flagellar components. Multiple genes have been implicated, including DNAH1, DNAH17, CFAP43, CFAP44, CFAP69, CFAP251, QRICH2, TTC21A, TTC29, FSIP2, AK7, ARMC2, and others, with most following autosomal recessive inheritance. Some cases involve multiple morphological abnormalities of the sperm flagella (MMAF), a well-characterized phenotypic subgroup. There is currently no curative treatment that restores normal sperm motility. However, assisted reproductive technologies (ART), particularly intracytoplasmic sperm injection (ICSI), offer affected men the possibility of biological fatherhood by directly injecting a single sperm into an oocyte, bypassing the need for sperm motility. Genetic counseling is recommended for affected individuals and their families to discuss inheritance risks and reproductive options.

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