Cytokines, implantation and early abortion:: re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept

PROBLEM: Human in vitro fertilization (IVF) embryo transfer is accompanied by a low implantation rate even after a very successful IVF, and there are a certain number of 'idiopathic sterilities' which are due to repeated implantation failures. In the very same vein, the question of improving implantation rates is of prime importance in agricultural research to improve the management of livestock. Pre-implantation prenatal diagnosis cannot be accomplished in individuals who have a high rate of implantation failure, whether)women undergoing IVF, or animals, during genetic cloning. Implantation cytokine networks need to be known in such a perspective. METHODS: We review the evolution and theories in reproductive immunology, briefly deal with the complexity of implantation as a step by step developmental event, and then present some of our recent data in mice and human. CONCLUSIONS: We conclude that the T helper cell type 1/2 (Th1/Th2) paradigm, as useful as it has been to explain pregnancy, is no longer sufficient in view of the emerging complexity of the cytokine network at the materno-fetal interface. This is peculiarly true for implantation, which, as a step by step developmentally regulated process, involving inflammatory molecules, cannot fit into such a scheme.