P-314 The role of macrophages in systemic and local ovarian inflammation in infertile women with endometriosis and PCOS

Abstract Study question What is the role of macrophages in the systemic and local ovarian inflammatory environment of PCOS and endometriosis patients following ovulation? Summary answer We found a distinct local ovarian inflammatory response profile following ovulation, that may be dysregulated in endometriosis, suggesting a macrophage dysregulation of inflammation in endometriosis What is known already The intra-follicular microenvironment provides the necessary supportive functions for normal oocyte development. Patients with Polycystic Ovary Syndrome (PCOS) and endometriosis represent populations, where chronic low-grade systemic inflammation may result in an altered follicular cytokine microenvironment. Recent evidence suggests that the negative effect on the oocyte microenvironment of chronic low-grade inflammation may primarily becaused by a phenotypic shift in local tissue resident macrophages. The role of macrophages in the intra-follicular microenvironment is however largely uninvestigated. Study design, size, duration Prospective cohort study including 55 infertile women aged 18-37 undergoing in vitro fertilization recruited at a hospital fertility clinic from March 2023 to December 2023. Inclusion criteria were endometriosis, PCOS, or male partner infertility (control group). Power calculations were based on expected sCD163 values. To detect a difference of 1.0 between PCOS/endometriosis patients and control group, 17 patients were needed in each group. Blood samples were collected before stimulation and on the day of aspiration. Participants/materials, setting, methods Serum and corresponding follicular fluid were analyzed for general markers of inflammation (hsCRP, IFN-γ, IL-1β, IL-6, IL-8,IL-10, TNF-α) and specific markers of macrophage activation (sCD163,sCD206, sSIRPα, sLILRB1). sCD206 and sCD163 are markers of activation mainly expressed in anti-inflammatory M2 macrophages. sSIRPa and sLILRB1 are regulatory membrane glycoproteins, that negatively control macrophage activity including phagocytosis. The outcomes were analyzed using mixed models taking into account the repeated measurements for patients and confounding. Main results and the role of chance sCD206 and sCD163 were significantly lower in follicular fluid compared to plasma following ovulation in all three groups (control, endometriosis and PCOS). The difference was less pronounced for endometriosis, which is explained by a significantly lower level of sCD206 in plasma from endometriosis patients compared to both controls and PCOS, suggesting a diminished activity of anti-inflammatory macrophages in endometriosis compared to PCOS patients or controls. sSIRPα was lower in follicular fluid compared to plasma, which similarly to sCD163 was less pronounced in endometriosis samples. sLILRB1 was non-significantly lower in both plasma and follicular samples from endometriosis patients, suggesting a generally impaired LILRB1control of the macrophage activity. In contrast, apart from a higher sSIRPα level in PCOS samples, no differences were observed between PCOS compared to controls in any markers. The general inflammatory markers TNF-α, INF-γ and CRP was significantly lower in follicular fluid compared to plasma, whereas all the interleukins (IL-1β, IL-6, IL-8, IL-10) as expected were higher in follicular fluid in all three groups. IL-6 and IL-8 were higher in follicular fluid from endometriosis patients compared to controls, a difference that was not found for PCOS patients. Limitations, reasons for caution The study population consists of infertile patients included from a single clinic, and the results may not be generalizable to other populations. The clinical impact of the findings remains to be investigated. Wider implications of the findings The description of macrophage activity contributes to our understanding of inflammatory response following ovulation. Our findings are indicative of a diminished activity of anti-inflammatory macrophages and diminished macrophage control of inflammation in endometriosis patients, suggesting a potential macrophage dysfunction in endometriosis. Trial registration number No