Immunological mechanisms of low-grade systemic inflammation and its role in endometrial dysfunction in women with polycystic ovary syndrome.

Background: Emerging evidence indicates impaired endometrial receptivity may contribute to reduced embryo implantation and poorer pregnancy outcomes in Polycystic ovary syndrome (PCOS) patients, though exact mechanisms are not yet fully elucidated. Objective: To explore the impact of low-grade systemic inflammation on endometrial dysfunction in women with PCOS, and to assess the relationship between inflammatory markers, endocrine and metabolic factors, and their link to endometrial receptivity. Methods: A retrospective analysis was conducted involving 180 infertile women with PCOS recruited from the gynecology department between January 2023 and June 2025 as the case group. The control group consisted of 180 women with regular menstrual cycles and no PCOS features, who experienced infertility due to male or tubal factors during the same period. Clinical data and metabolic/endocrine parameters, including the LH/FSH ratio, estradiol (E2), testosterone (T), and HOMA-IR, were collected. Serum levels of pro-inflammatory (IL-1β, IL-6, TNF-α) and anti-inflammatory (IL-4, IL-10) cytokines were quantified using ELISA. During the mid-luteal phase, transvaginal 3D ultrasound was used to assess endometrial thickness, pattern, and blood flow indices (VI, FI, VFI), as well as uterine artery Doppler parameters (PI, RI). Between-group differences were analyzed, along with correlations among inflammatory markers, metabolic profiles, and endometrial characteristics. Results: Compared to controls, the PCOS group had significantly higher BMI, LH/FSH ratio, T, and HOMA-IR (P<0.001). They showed increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and reduced anti-inflammatory cytokines (IL-4, IL-10) (P<0.001). Endometrial blood flow patterns were poorer, and uterine artery PI and RI were higher in the PCOS group (P<0.001), while endometrial thickness, VI, FI, and VFI did not differ significantly (P>0.05). Within PCOS group, pro-inflammatory cytokines correlated positively with BMI, LH/FSH ratio, T, HOMA-IR, and uterine artery PI and RI (r=0.44-0.58, P<0.001), whereas anti-inflammatory cytokines correlated negatively with these measures (r=-0.43 to -0.63, P<0.001). No significant correlations were observed with endometrial thickness or vascularization indices. Conclusion: Patients with PCOS exhibit state of low-grade systemic inflammation, characterized by elevated pro-inflammatory cytokines and reduced anti-inflammatory cytokines, which is closely associated with insulin resistance and hyperandrogenemia. This inflammatory state may contribute to development of endometrial dysfunction by increasing uterine artery blood flow resistance.