Can soluble human leucocyte antigen-G predict successful pregnancy in assisted reproductive technology?

Abstract

To review the predictive value of soluble human leucocyte antigen-G (HLA-G) in embryo culture fluid for implantation, considering origin, structure, function and detection method of soluble HLA-G. Soluble HLA-G in embryo culture supernatant has been proposed as a noninvasive marker for the selection of embryos with implantation potential. Controversially, some centres detect soluble HLA-G in none of the culture supernatants of embryos that evolve towards pregnancy, whereas others report it to be mandatory. According to a recently published meta-analysis, the pooled diagnostic accuracy for predicting clinical pregnancy is low. Factors influencing soluble HLA-G results are numerous, for example, embryo culture (single or multiple, washing/denudation steps, medium, day 2 to 5 sample collection), sample preservation to prevent degradation and HLA-G immunoassays (standard, detection limit, reproducibility). Published studies are very heterogeneous. Moreover, the origin of soluble HLA-G in embryo culture fluid is unresolved. From the embryonic genome activation at day 3 onwards, the embryo should be able to produce HLA-G. Before, it is maternally derived, either from the oocyte, follicular fluid or follicular cells contaminating embryo culture. At present, no studies have been published on the relationship between pregnancy and soluble HLA-G in supernatants from individually cultured and individually transferred embryos using standardized embryo culture and soluble HLA-G immunoassay, sensitive at the picogram level. As such, it remains undetermined whether the pregnancy is induced by an HLA-G-producing embryo. Therefore, the predictive value of soluble HLA-G in embryo culture supernatant for selection of embryos with good implantation potential remains unknown.