The enunciation of the T helper 1/T helper 2 (Th1/Th2) paradigm in pregnancy has represented a major step forward in our understanding of physiological and pathologic materno-foetal relationship. However, recent developments in studies of the implantation process and in the emergence of the uterine vascular bed and its control by natural killer cells and cytokines suggest that one must go beyond this hitherto useful scheme. In this review, we replace the emergence of the paradigm in its historical context and then emphasises what it does explain and what it no longer account for. A final reappraisal of the paradigm is suggested.

Labeled problemEmbryo implantation remains the main limiting factor in assisted reproductive medicine (20% success rate).Methods of studyAn endometrial immune profiling was performed among 394 women with the previous history of repeated embryo implantation failures (RIF). The endometrial immune profile documented the ratio of IL‐15/Fn‐14 mRNA as a biomarker of uNK cell activation/maturation (together with the uNK cell count) and the IL‐18/TWEAK mRNA ratio as a biomarker of both angiogenesis and the Th1/Th2 balance. According to their profile, we recommended personalized care to counteract the documented dysregulation and assessed its effects by the live birth rate (LBR) for the next embryo transfer.ResultsEndometrial immune profiles appeared to be dysregulated in 81.7% of the RIF patients compared to control. Overactivation was diagnosed in 56.6% and low activation in 25%. The LBR among these dysregulated/treated patients at the first subsequent embryo transfer was 39.8%.ConclusionEndometrial immune profiling may improve our understanding of RIF and subsequent LBR if treated.