title: Endometrial inflammation and effect on implantation improvement and pregnancy outcome.
abstract: Implantation failure, which is presently the major barrier in human fertility, is attributed, in many cases, to the failure of the uterus to acquire receptivity. The transition into a receptive uterus includes cellular changes in the endometrium and the modulated expression of different cytokines, growth factors, transcription factors, and prostaglandins. These molecules partake in the generation of an inflammatory response followed by the recruitment of immune cells. These cells have shown to be involved in the maternal immune tolerance toward the implanted embryo as well as in the maternal-fetus interaction during pregnancy. Most of the accumulated evidence indicates that embryo implantation is associated with an active Th1 inflammatory response while a Th2-humoral inflammation is required for pregnancy maintenance. Yet, recent findings suggest that a Th1 inflammatory response is also necessary for the acquisition of uterine receptivity. This notion was originally suggested by reports from our and other clinical centers worldwide that IVF patients with repeated implantation failure subjected to endometrial biopsy exhibit a substantial improvement in their chances to conceive. These findings, followed by the demonstration of an elevated pro-inflammatory cytokine/chemokine expression, as well as an increased abundance of immune cells, in the endometrium of these patients, raised the idea that acquisition of uterine receptivity is closely associated with an inflammatory response. This review summarizes the molecular and biochemical evidence that confirm this notion and proposes a mechanism by which injury-induced inflammation improves uterine receptivity and the subsequent pregnancy outcome.
authors.affiliation: IVF Unit, Department of Obstetrics and Gynecology, Kaplan Medical Center, Rehovot, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Granot
authors.forename: Y
authors.initials: Y
authors.lastname: Gnainsky
authors.forename: N
authors.initials: N
authors.lastname: Dekel
mesh_terms: D000818:Animals; D010064:Embryo Implantation; D020964:Embryo Loss / Q000276:immunology*; D004717:Endometrium / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D012038:Regeneration