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Problem: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) represent distinct clinical conditions with established definitions, both of which have been linked to an underlying pro-inflammatory state. This study aimed to explore the levels of monocytic-myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (T Reg ) in a cohort of RPL and RIF women and their potential contribution to RPL and RIF., Method of Study: One hundred and eight non-pregnant women were evaluated: 40 RPL, 41 RIF, and 27 fertile healthy controls (HC). A multiparametric flow cytometry approach was utilized to measure and quantify the frequency of M-MDSCs and T Reg cells. Cytokine levels in plasma samples were evaluated through a multiplex assay. M-MDSCs levels were significantly higher in RPL and RIF patients compared to HC., Results: M-MDSCs levels were significantly higher in RPL (9.4% [7-11.6]) and RIF (8.1% [5.9-11.6]) patients compared to HC (6% [4.2-7.6]). An optimal cut-off of 6.1% for M-MDSCs disclosed a sensitivity of 75.6% and 89.7% and a specificity of 57.7% and 57.7% in RIF and RPL groups, respectively. A significant negative correlation was observed between M-MDSCs and T Reg (p = .002, r = -.51)., Conclusions: Our preliminary data allowed us to build a predictive model that may aid as a potential diagnostic tool in the clinic. These findings could provide a better understanding of these pathologies and a better definition of patients that could benefit from personalized treatments to promote pregnancy. Additional exploration and confirmation in distinct study groups are needed to fully assess the diagnostic capabilities of this biomarker., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This review collects and critically examines data on the levels of tumour necrosis factor-alpha (TNF-α) in lean, overweight and obese subjects, and the effects of intervention with different foods and food products containing bioactive constituents in overweight/obese individuals. We additionally explore the influence of different single nucleotide polymorphisms (SNPs) on TNF-α levels and compare the response to food products with that to some anti-obesity drugs. Our aim was to provide an overview of the variability, consistency, and magnitude of the reported effects of dietary factors on TNF-α, and to envisage the reliability of measuring changes in the levels of this cytokine as a biomarker responsive to food intervention in association with the reduction in body weight. Regarding the circulating levels of TNF-α, we report: (i) a large intra-group variability, with most coefficients of variation (CV%) values being ≥30% and, in many cases, >100%; (ii) a large between-studies variability, with baseline TNF-α values ranging from <1.0 up to several hundred pg/mL; (iii) highly variable effects of the different dietary approaches with both statistically significant and not significant decreases or increases of the protein, and the absolute effect size varying from <0.1 pg/mL up to ≈50 pg/mL. Within this scenario of variability, it was not possible to discern clear differentiating limits in TNF-α between lean, overweight, and obese individuals or a distinct downregulatory effect on this cytokine by any of the different dietary approaches reviewed, i.e., polyunsaturated fatty acids (PUFAs), Vitamin-D (VitD), mixed (micro)nutrients, (poly)phenols or other phytochemicals. Further, there was not a clear relationship between the TNF-α responses and body weight changes. We found similarities between dietary and pharmacological treatments in terms of variability and limited evidence of the TNF-α response. Different factors that contribute to this variability are discussed and some specific recommendations are proposed to reinforce the need to improve future studies looking at this cytokine as a potential biomarker of response to dietary approaches.