Summary sentence: Total fertilization failure and lower fertilization rates are functionally associated with reduced/absent expression of gACE in the sperm of these patients; thus gACE may be used as a marker to diagnose fertilization failure. Keywords: total fertilization failure; lower fertilization rates; germinal angiotensin-converting enzyme; conventional in-vitro fertilization; sperm.

In conventional in-vitro fertilization (IVF), complete failure of fertilization occurs in 5-15% of treatments. Although the causes may be unclear, sperm defects appear to be the major contributor. However, a convincing test is not yet available that can predict the risk of fertilization failure. In this study, we found that germinal angiotensin-converting enzyme (gACE, also named testicular ACE (tACE)) was undetectable in sperm from patients who had total fertilization failure (TFF) and lower fertilization rates (LFR) by IVF with western blot and indirect immunofluorescence analyses. Additionally, almost all of the patients who were devoid of gACE on sperm (23/25) presented with TT genotype of the single nucleotide polymorphism (SNP), rs4316 of ACE. Together, our results indicate that absence of gACE expression is responsible for TFF and LFR by IVF. The rs4316 polymorphism of ACE might be associated with the infertility in those patients. It is concluded that sperm lacking gACE may be recognized prior to commencing IVF and the patients may be directed instead to consider intracytoplasmic sperm injection (ICSI).