Mouse group X sPLA2 (mGX) is an acrosomal protein playing an important role in fertilization and controlling acrosome reaction (AR) occurring during capacitation. We demonstrated previously that sperm from mGX knock-out mice had a severely impaired fertilization potential in vitro. We also showed that treatment of wild-type sperm with recombinant mGX during capacitation improved fertilization outcome. This interesting property suggests that sPLA2s could be used to improve fertilization in assisted reproductive technologies (ART). However the molecular mechanism explaining the mGX-dependent enhancing effect on fertilization outcome remains unclear so far. Interestingly, like progesterone (P4), mGX is a very potent activator of AR and the role of mGX-induced AR in fertilization outcome was not evaluated so far. To assess the role of sPLA2-induced AR in IVF, we first tested the potency of 9 mouse and 2 human sPLA2s and P4 to trigger AR of mouse sperm. We then tested the ability of 6 of these molecules (mouse Group IIA, mouse Group IID, mouse Group X, human Group V, human Group X and P4) to improve the yield of 2-cell embryos obtained by IVF in mouse. We showed that in the mouse neither P4 nor any of the other sPLA2s tested were able to mimic the IVF improvement produced by mGX-treatment. These results demonstrate that sPLA2s are not commutable in the context of mouse sperm fertility, indicating that their utilisation in other species, is subjected to the identification of probably unique species-specific active sPLA2.