Abstract

Abstract Study question Is there an association between endometriosis and uterine natural killer cells? Summary answer Decreasing level of uterine natural killer cells had positively associated with Endometriosis and Adenomyosis. What is known already Uterine natural killer cells (uNK) represent the predominant lymphocyte population within the decidua during implantation and in the initial stages of pregnancy. Dysregulation of uNK function has been associated with reproductive challenges, including recurrent miscarriage (RM) or recurrent implantation failure (RIF). This suggests an underlying disruption in immune activity during implantation. Endometriosis is a chronic and inflammatory disorder that usually affects the pelvic cavity and can cause severe pain during menstruation. However, there are paucity studies focus on the role of uNK in endometriosis and adenomyosis. The aim of this study was to identify the association between endometriosis and uNK. Study design, size, duration In this Prospective cohort study, 60 participants were recruited from May 2023 to January 2024 at the outpatient department of Obstetrics and Gynecology in Chang Gung Memorial Hospital, Kaohsiung Medical Center in Taiwan. The inclusion criteria were as follows: adult women of childbearing age were eligible to participate. Old age (>45 years old) patients, or patient with underlying medical disease, immune diseases and malignancy, or patient using immunosuppressant were excluded. Participants/materials, setting, methods Endometrial tissues were collected during the mid-luteal phase using an endometrial curette. The level of uNK were measured by immunohistochemistry with CD56+, and was presented in absolute number per high power filed. CD138 was also measured, and the level above 5 cell/HPF was defined as chronic endometritis. Endometriosis and adenomyosis were confirmed histologically. RM was defined as ≧2 previous miscarriages. RIF was defined as ≧2 previous failures to achieve clinical pregnancies after embryo transfer. Main results and the role of chance At least one uNK/HPF was revealed in 58 cases, 0-10uNK/HPF in 15 cases (24.5%), 11-20 uNK/HPF in 19 cases (31.6%) and above 20 uNK/HPF in 26 cases. After adjusting for covariates, patient with endometriosis and adenomyosis were positively associated with lower uNK level(low vs. high uNK(cut-off value: 20 uNK/HPF), odds ratio (OR) (95% confidence interval (CI)), 9.434 (1.101–83.33), p = 0.032; 2.000 (1.515–2.639), p = 0.015). Moreover, there are 14 patients with RM (23.3%), 26 patients with RIF (43.3%) and 7 patients with CE (11.7%). However, our study did not find significantly association between RM or RIF or CE with uNK levels. Limitations, reasons for caution Because of the single-center, Asian origin of our patients, and the sample size was relatively small. Further large-scale longitudinal studies are required to verify our findings and evaluate the underlying pathophysiology between endometriosis and uNK. Wider implications of the findings Our study highlights the significantly decreased uNK level in endometrium of women with endometriosis and adenomyosis, which may indicate some alteration in immune environment under endometriosis. Further research is warranted for understanding the immuno-modulation in endometriosis. Trial registration number not applicable

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