Human leukocyte antigen-G (HLA-G) is thought to play a key role in implantation by controlling trophoblast invasion and maintaining a local immunosuppressive state. The secretion of soluble HLA-G antigens (sHLA-G) by early embryos seems necessary for a successful implantation and could be a marker of increased pregnancy rate following in vitro fertilization. We have reviewed the results obtained during the last years (from 1987 to 2005). They overall confirmed the predictive role of sHLA-G production in pregnancy outcome. Furthermore, we have examined the technical procedures utilized, with a particular attention to the monoclonal antibodies used in the enzyme-linked immunosorbent assay (ELISA) techniques. New functional roles for HLA-G molecules in pregnancy could be suggested by the relationship observed between the presence of sHLA-G antigens in follicular fluids and sHLA-G expression in the corresponding fertilized oocyte. Furthermore, since maternal mRNA is fundamental for protein production in early embryos, the biologic role of the HLA-G 14 base pair polymorphism could be explored.