Implantation failure is considered nowadays the most important limiting factor in assisted reproduction (Cross et al., 1994). Chronic endometrium inflammation has a significant role in the etiology of implantation failure, however the specific immune cells that regulate endometrium inflammation and homeostasis upon implantation have not been elucidated (Makrigiannakis et al., 2011, Makrigiannakis et al., 2015, Makrigiannakis et al., 2019).

Recently, various immune cell types, particularly special subsets of T cells have been shown to be important for a successful pregnancy and for pregnancy loss. Forkhead box P3 (FOXP3)-expressing regulatory CD4+ T cells (Treg cells) are known for their homeostatic, regulatory and anti-inflammatory properties (Sakaguchi et al., 2008). Tregs have the ability to suppress activated T effector cells and natural killer cells, maintaining in this way immune tolerance and facilitating embryo implantation and development during pregnancy (Aluvihare et al., 2004). On the other hand, CD4+ T helper (Th) cells expressing interleukin (IL)− 17 (Th17), play a crucial role in host immunity, particularly in neutrophil-mediated host defenses (Khader et al., 2009) but their function can lead to pro-inflammatory exaggerated immune responses and chronic tissue inflammation (Nakashima et al., 2010, Wang et al., 2010). Tregs have the ability to suppress the action of Th17 effectors cells (Sakaguchi et al., 2008) and Th17 are also known to antagonize the function of Tregs; thus, the balance of Th17 to Treg is crucial in determining the type of immune response. Recent investigations regarding the role of these cells in human reproduction revealed that an appropriate balance between Treg and Th17 lymphocyte and hemostasis is required to prevent harmful responses of the immune system against the embryo (Lee et al., 2011).

Given the substantial implications that implantation failure has in assisted reproduction, better understanding of the mechanisms regulating endometrial inflammation and homeostasis is pivotal to improve success rates in women with repeated implantation failure (RIF). Studies to date, point out that there are changes in Th17/Treg cell ratio in peripheral blood of women with RIF, chronic endometritis or spontaneous abortions (Ghaebi et al., 2019, Guo et al., 2022, Jasper et al., 2006, Jiang et al., 2017, Lee et al., 2011, Sasaki et al., 2004, Wang et al., 2019). Thus, Th17 and Tregs cells are believed to play a significant role in successful pregnancy and in preventing embryo loss, however, the role of Th17 to Treg balance in the endometrium of women with repeated implantation failure has not been hitherto evaluated. In this study, to shed light on the pathogenesis of RIF, we sought to investigate the potential imbalance of endometrial Th17 and Treg ratio and its correlation with endometrial inflammation in women with RIF.