Intralipid® may represent a new hope for patients with reproductive failures and simultaneously an over-immune endometrial activation

•Intralipid® therapy (IL) has been reported to have immunosuppressive properties on NK cells.•The live birth rate recorded under IL in a cohort with implantation failures and a local over-immune activation was over 50%.•Intralipids significantly decreased the biomarkers used to diagnose the over-immune activation (CD56 cells; IL-18/TWEAK, IL-14/FN-14).•Double blind placebo versus Intralipid® studies should be conducted. Continuous failures to achieve a pregnancy despite effective embryo transfers is extremely distressing for couples. In consequence, many adjuvant therapies to IVF have been proposed to achieve an “ideal” immune environment. We here focus on Intralipid® therapy (IL) reported to have immunosuppressive properties on NK cells. 94 patients exhibited an immune profile of endometrial over-immune activation and an history of repeated implantation failures despite multiple embryos transfers (RIF). They received a slow perfusion of Intralipid®. We here report the live birth rate following the procedure at the next embryo transfer. To get new insight on its mechanism of action, a second immune profiling had been performed under Intralipid® before the embryo transfer. The live birth rate of the RIF cohort treated with Intralipid® reached 54% (51/94) at the next embryo transfer. In patients successfully pregnant under Intralipid® who benefitted of a test of sensibility before the embryo transfer, we observed a significant decrease of the three biomarkers used to diagnose the over-immune endometrial activation (CD56 cells; IL-18/TWEAK, IL-14/FN-14). Double blind placebo versus Intralipid® studies should be conducted. Intralipid® may be an option to explore in RIF patients who exhibit an over-immune activation of uNK cells.