The JAK-STAT Signaling Pathway: A Novel Therapeutic Target for Unexplained Recurrent Implantation Failures

Unexplained recurrent implantation failure has become a public health problem especially in the context of a high cost, demand for assisted reproductive therapy and multiple therapy failures. It is attributed to the failure of immunological tolerance between the transferred embryo and the endometrium during assisted reproductive therapy cycles. Cytokines are surrogate mediators of immunological tolerance mechanisms. Since the synergistic interaction between individual cytokines is dynamic, perturbations in the cytokine crosstalk during embryo implantation is considered a major etiology for unexplained recurrent implantation failures. Genome Wide Association Studies suggests that most cytokines initiate their actions through receptor interactions that activate the JAK-STAT signaling pathways. Aberrations in the JAK-STAT signaling pathways have as well been shown to cause perturbations in cytokine crosstalk that result in diseases. We therefore propose the JAK-STAT signaling pathway a potential therapeutic target for unexplained recurrent implantation failures. Currently, many studies have recorded potential therapies in IL-6/JAK/STAT 3 pathway to treat many diseases but limited attention has been paid to unexplained recurrent implantation failures.