Genetic basis of acephalic spermatozoa syndrome, and intracytoplasmic sperm injection outcomes in infertile men: a systematic scoping review

J Assist Reprod Genet. 2021 Mar;38(3):573-586. doi: 10.1007/s10815-020-02008-w. Epub 2021 Jan 15.


Purpose: Acephalic spermatozoa syndrome (ASS) is known as a severe type of teratozoospermia, defined as semen composed of mostly headless spermatozoa that affect male fertility. In this regard, this systematic review aimed to discuss gene variants associated with acephalic spermatozoa phenotype as well as the clinical outcomes of intracytoplasmic sperm injection (ICSI) treatment for the acephalic spermatozoa-associated male infertility.

Methods: A systematic search was performed on PubMed, Embase, Scopus, and Ovid databases until May 17, 2020. This systematic scoping review was reported in terms of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) statement.

Results: Twenty articles were included in this systematic review. Whole-exome and Sanger sequencing have helped in the identification of variants in SUN5, PMFBP1, BRDT, TSGA10, DNAH6, HOOK1, and CEP112 genes as possible causes of this phenotype in humans. The results of the ICSI are conflicting due to both positive and negative reports of ICSI outcomes.

Conclusion: ASS has a genetic origin, and several genetic alterations related to the pathogenesis of this anomaly have been recently identified. Notably, only SUN5 and PMFBP1 mutations are well-known to be implicated in ASS. Accordingly, more functional studies are needed to confirm the pathogenicity of other variants. ICSI could provide a promising treatment for acephalic spermatozoa-associated male infertility. Besides the importance of sperm head-tail junction integrity, some other factors, whether within the sperm cell or female factors, may be involved in the ICSI outcome.

Keywords: Acephalic spermatozoa syndrome (ASS); Headless spermatozoa; Intracytoplasmic sperm injection (ICSI); PMFBP1; SUN5; Whole-exome sequencing (WES).

Publication types

  • Systematic Review

MeSH terms

  • Humans
  • Infertility, Male / etiology
  • Infertility, Male / pathology*
  • Male
  • Membrane Proteins / genetics*
  • Mutation*
  • Phenotype
  • Sperm Injections, Intracytoplasmic / methods*
  • Spermatozoa / abnormalities*
  • Syndrome


  • Membrane Proteins