Recurrent implantation failure and inflammatory markers in serum and follicle fluid of women undergoing assisted reproduction

It has been shown previously that the immune system plays a role in implantation and embryo development. The objective was therefore to evaluate cytokine levels and Th1/Th2 ratio in women with recurrent implantation failure in this nested case-control study. Women with no implantation after ≥ 3 embryo transfers were included in the recurrent implantation failure group (n = 29) and were compared with women with successful pregnancy after the first embryo transfer, with an indication of male factor (n = 26). Cytokines analyzed with the Meso scale discovery (MSD) technology Proinflammatory Human Kit 1 and calculated Th1/Th2 ratios were the main outcome measures. In serum there was a difference between the recurrent implantation failure group and the control group in ratios for IFN-γ/IL-10 (p = 0.01), IL-1β/IL-10 (p = 0.04), IL-2/IL-10 (p = 0.00), TNF-α/IL-10 (p = 0.02), IFN-γ/IL-13 (p = 0.01), IL-12/IL-13 (p = 0.02), IL-2/IL-13 (p = 0.00), and TNF-α/IL-13 (p = 0.00), where the control group had higher ratios, i.e. a shift towards a Th1 pro-inflammatory profile before treatment start. In follicular fluid there were differences in ratios between IL-2/IL-10 (p = 0.02), IL-8/IL-10 (p = 0.02), TNF-α/IL-10 (p = 0.02), IFN-γ/IL-13 (p = 0.01), and TNF-α/IL-13 (p = 0.03). The recurrent implantation failure group had higher ratios except for IFN-γ/IL-13, indicating a shift towards a Th1 pro-inflammatory profile in their follicular fluid. Pro-inflammatory activity in both serum and follicle fluid differs in recurrent implantation failure patients and patients with successful assisted reproduction treatment. Women at risk of immune-related recurrent implantation failure could be identified proactively. Because it is taken at a timepoint closer to implantation, ratios in follicular fluid are specifically interesting as risk markers.