Is There an Effect of LeukoNorm®, an Immune Therapeutic Agent, on the Improvement of the Implantation Capacity in the Human Endometrium?

Objective: Even with artificial reproduction techniques, the implantation rates are only around 30-50% per transfer of two viable embryos. These low implantation rates are most likely due to impaired endometrial receptivity. We therefore examined the potential effects of the immune therapeutic agent LeukoNorm (R) at the molecular level, and investigated both immune cells and known implantation factors in endometrial tissue. Methods: LH (LH+7/8) dated biopsies were taken from 17 women with recurrent implantation failure prior to and after the systemic administration of LeukoNorm (R). Endometrial immune cells were examined immunohistochemically and individual implantation markers, such as immunmodulators, glucose transporters and adhesion factors, all of which are known to be dysregulated in women with implantation failure, were examined by RNAse protection assay to detect RNA expression changes. Results: Immunohistochemical analysis of CD45+ and CD 56+ cells did not show significant changes in cell numbers after LeukoNorm (R) treatment. Furthermore, the RNA expression of the examined implantation factors also did not show significant changes, but analysis demonstrated large variation coefficients of 0.84 (beta 3-integrin), 0.33 ( osteopontin), 0.64 (GLUT1), 0.5 (GLUT3), 0.66 (LIF), 0,26 (TGFb-1), 0.61 (IL-1b) and 0.5 (M-CSF). Conclusions: Looking at specific implanation markers, we were not able to demonstrate a direct impact on endometrial function by LeukoNorm (R) therapy. Nevertheless, a potential effect on other parameters cannot be excluded.