Analysis of the cytokine spectrum of the embryonic secretome using the omics approach to improve the results of assisted reproductive technology

BACKGROUND: The developing embryo secretes a wide range of cytokines that are essential for establishing a “dialogue” between the embryo and the endometrium, as well as for autocrine effects on the embryo. Non-invasive assessment of the embryo using the study of its secretome is of great interest in reproductive medicine, as it can be used for early selection of the most viable embryos in assisted reproductive technology programs.

AIM: The aim of this study was to determine the prognostic significance of cytokine levels in media after embryo culture and their impact on endothelial function in achieving clinical pregnancy in assisted reproductive technology protocols, as well as the effect of these media on endothelial function.

METHODS: The presence of cytokines [interleukin-1b, -4, -5, -6, -8, -10, growth factors (granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor)] in embryo-conditioned culture media was determined in patients undergoing infertility treatment using assisted reproductive technology. To detect cytokine levels below the sensitivity threshold, we studied the effect of conditioned culture media on the proliferation and migration of endothelial cells.

RESULTS: The patients were divided into 2 groups: in group 1 (n = 34), no cytokines were found, whereas in group 2 (n = 14), at least one of the studied interleukins or growth factors was detected. Patients in group 2 had more oocyte-cumulus complexes, 2PN2PB zygotes, embryos on day 3 of culture, embryos of quality ≥ 6B on day 3 of culture, blastocysts, and blastocysts of quality ≥ 3BB. Additionally, the effective doses of gonadotropins per oocyte and per embryo were lower in group 2. The clinical pregnancy rate was also higher in group 2. We found no differences in endothelial cell proliferation and migration parameters.

CONCLUSION: A higher concentration of cytokines in media after embryo culture may indicate greater implantation potential; therefore, cytokine assessment in culture media could be used as an additional non-invasive method for embryo evaluation.