Researchers at the University of California, Davis have discovered a sequence variation of the gene that encodes beta-defensin 126 (DEFB126), a highly-expressed sperm coating protein that is important for efficient sperm movement and immunologic protection of sperm in the female reproductive tract. As they report in the journal of Science Translational Medicine, the specific sequence variation is very common in the human population, results in altered chemical composition of the sperm surface, reduces sperm penetration through mucus, and lowers male fertility. They show that the DEFB126 genotype and its consequences on the sperm surface coat are potentially superior indicators of sperm dysfunction and male subfertility than conventional semen analysis. They demonstrate in other studies that DEFB126 can be added to the surface of deficient sperm, restoring the sperm to full function. 

From these discoveries it is clear that the risk of infertility can be determined as simply as obtaining and analyzing a biological sample, such as saliva, blood or semen. Methods of detection include a broad range of common biological laboratory techniques, including but not limited to, DNA amplification reactions, hybridization, DNA sequencing, restriction fragment length polymorphism, fluorescence resonance energy transfer, and usage of lectins, antibodies, ELISA, immunoprecipitation, Western blot, and protein array. The presence of the sequence variation, and the consequent absence of DEFB126 on the sperm surface indicates an increased risk or probability of infertility.  By determining DEFB126 status early in an infertility evaluation, clinicians could, when appropriate, justify rapid progression to directed interventions such as intrauterine insemination (IUI) and in vitro fertilization (IVF), thus saving couples the time and expense of a protracted workup. 

As a treatment option, men deficient in DEFB126 could benefit from treatment of their sperm with a synthetic DEFB126 peptide in a clinical laboratory, potentially increasing the potential for success with either cervical artificial insemination or IUI. Alternatively, exogenous DEFB126 peptide could be concentrated in a vaginal gel or foam that would be applied prior to copulation. DEFB126 would be adsorbed to the surface of deficient sperm as they moved through the gel and into the cervix.