Endometrial Cytokines in Women with Reproductive Disorders

Abstract

The purpose of this research was to study changes in endometrial cytokine concentrations in women suffering from reproductive disorders with and without chronic endometritis (CE) to justify pathogenetic treatment. Methods and Results: The study included 100 women of reproductive age with reproductive disorders. Group 1 included 50 patients with reproductive disorders and CE; Group 2 included 50 patients with reproductive disorders and without CE. Later on, all patients were divided into the following subgroups: Sub1A (n=31), and Sub2A (n=16) with an isolated bacterial flora, Sub1B (n=19) and Sub2B (n=34) with the absence of bacterial flora. The control group consisted of 31 fertile women. Endometrial aspiration pipe biopsy was performed on days 4-9 of the menstrual cycle (middle proliferative phase) using a disposable intrauterine probe (Taizhou Kechuang Medical Apparatus Co., Ltd, China) followed by histological examination of endometrial tissue. Laboratory diagnostics for sexually transmitted infections (STIs) was performed using the bacterial culture method. For the diagnosis of viral infection (HPV, HSV, CMV), cervical samples were studied using PCR. If STIs were detected, the patients were excluded from further research. Ultrasound examination of the pelvic organs was performed using the Aloka-5500 device with a 7MHz vaginal probe in two-dimensional visualization mode. The concentration of cytokines (IL-1β, INF-γ, TNF-α, ILs-4,6,8,10) in the endometrium was determined using the Protein Contour test systems (Saint Petersburg) and Multiskan EX ELISA Analyzer (Germany). In both groups, reproductive disorders were accompanied by hypoprogesteronemia and relative hyperestrogenemia, significantly apparent in CE. We found a 3-fold increase in the level of tissue pro- and anti-inflammatory cytokines (IL-1β, IL-4,6,10, INF-γ), and a 4-fold increase in the level of TNF-α and IL-8 in Group 1, compared to the CG. In Group 2, we found a 1.4-fold increase in the levels of IL-1β and INF-γ, compared to the CG. In Sub 1a, the levels of IL-6 and IL-8 were significantly higher than in the control group. In Sub1A, the isolated bacterial flora caused a cytokine inflammatory response characterized by a significant increase in the concentration of INF-γ and TNF-α, compared to Sub2A and Sub2B (P<0.05). In Sub1A, we found a tendency towards a decrease in the tissue levels of IL-4 compared to Sub1B and Sub2B; the IL-10 level was significantly lower than in Sub2B (P=0.0009) Conclusion: The results obtained in the present study showed the peculiarities of changes in cytokines at the level of endometrial tissue both in chronic inflammation of the endometrium and in its absence in women with reproductive disorders. The severity of the immune response is significantly higher in patients with CE, with the most significant change in the role of IL-10.