The Relationship of Systemic TNF‐α and IFN‐γ with IVF Treatment Outcome and Peripheral Blood NK Cells

Abstract

The systemic levels of TNF-alpha and IFN-gamma have no association with implantation rate or miscarriage rate in women undergoing IVF treatment. However, high levels of TNF-alpha and IFN-gamma are associated with elevated levels of activated NK cells and this may subsequently exert a negative impact on reproduction.

Expression of natural cytotoxicity receptors and cytokine production on endometrial natural killer cells in women with recurrent pregnancy loss or implantation failure, and the expression of natural cytotoxicity receptors on peripheral blood natural killer cells in pregnant women with a history of recurrent pregnancy loss

“…On the other hand, exposure of large amounts of TNF‐α to pregnant mice causes abortion . For the systemic TNF‐α, it is reported that there are no associations between systemic TNF‐α level and reproductive outcomes, such as implantation failure and recurrent miscarriage . Taken together, uterine NK cell‐derived TNF‐α and IFN‐γ may be important for cell differentiation, angiogenesis, and vascular remodeling.…”

“…30 For the systemic TNF-α, it is reported that there are no associations between systemic TNF-α level and reproductive outcomes, such as implantation failure and recurrent miscarriage. [31][32][33] Taken together, uterine NK cell-derived TNFα and IFN-γ may be important for cell differentiation, angiogenesis, and vascular remodeling. Successful function of TNF-α and IFN-γ in pregnancy, therefore, depends on the appropriate regulation and concentration of TNF-α and IFN-γ produced by NK cells.…”

First-trimester maternal cell microRNA is a superior pregnancy marker to immunological testing for predicting adverse pregnancy outcome

“…An immunological basis for "unexplained" implantation failure, miscarriage and late term pregnancy complications/failures has been supported in numerous studies (Beer et al, 1996;Beer and Kwak, 1997;Coulam et al, 1995;Kwak et al, 1998aKwak et al, , 1998bKwak et al, , 2000Kwak-Kim et al, 2003;Ng et al, 2002;Saito et al, 2007;Steinborn et al, 2008;Thum, 2007;Winger et al, 2012). Such cases have often been associated with abnormalities in several different in vitro immune parameters: natural killer cell cytotoxicity, proportion of peripheral blood CD56+CD3− cells, and Th1:Th2 bias.…”

Peripheral Blood NK Cell Cytotoxicities are Negatively Correlated with CD8+ T Cells in Fertile Women but not in Women with a History of Recurrent Pregnancy Loss

“…In women with repeated implantation failure (RIF), increased levels of TNF-a and IFN-c are associated with elevated levels of activated NK cells, and this may subsequently exert a negative impact on reproduction. 8 NK cells are innate immune effector cells and IFN-c production of NK cells is suppressed during normal early pregnancy. 6 It has been reported that dysregulated NK cells results in implantation failure, abortion, and preeclampsia.…”