The use of sHLA-G (Soluble human leukocyte antigen class G) as a tool for embryo selection

Abstract

SHLA-G, expressed and released by early embryos (48 hours), could be measured from embryo culture medium and could be a good predictor of embryo quality and a marker of implantation potential. This study aims at evaluating the efficiency of sHLA-G as an embryo quality marker and implantation potential indicator. Longitudinal study involving 97 ICSI cycles. A total of 592 were tested for the expression of sHLA-G using 50 μL droplets of culture media from day 2 embryo by an enzyme-linked immunosorbent assay (ELISA). A total of 309 embryos were transferred and they were allocated according to the groups: G1 (27 cycles; embryos expressing sHLA-G), G2 (11 cycles; embryos without sHLA-G expression), G3 (53 cycles; embryos with and without sHLA-G expression), G4 (6 cycles; a mix of embryos: positive and negative sHLA-G and also non tested embryos). All embryos were also classified according to morphological parameters: A (48 hours: 2–4 cells, 72 hours: 6–8 cells with <10% fragmentation), B, C and D (fragmentation: 10–20%, 21–30% and >30%, respectively). The embryos selected for transfer were preferably those that expressed sHLA-G if there was at least one excellent or good morphology embryo (A and B). Statistical analyses was performed using the Chi-square test and the One-way ANOVA test with significance at P<0.05. The pregnancy rate for groups G1, G2, G3 and G4 respectively was: 37%, 27.3%, 41.5%, 16.7% and the implantation rate was 21.9%, 10.7%, 11.6% and 5.3%. The percentage of embryos with positive sHLA-G and morphology type A transferred to patients that became pregnant was higher in G1: 70.4%. No correlation between sHLA-G expression and pregnancy rates was observed. Otherwise the best results were achieved when at least one embryo A or B with sHLA-G positive was transferred. Our study did not confirm if sHLA-G could be used reliably as a solely embryo viability marker. It has been suggested that the presence of sHLA-G, in the embryo culture medium, may be originating (at least in part) from the remaining maternal protein stored by the oocytes. Hence sHLA-G would be produced prior to embryonic genome activation which then can possibly bias the test performed on the embryo culture medium. Our findings suggest that the sHLA-G measurement can be an additional tool which combined with embryo morphology can be used to select embryos with higher implantation potential. Further studies should be performed to better evaluate the role of this antigen.