Characterizing the endometrial fluid cytokine profile in women with endometriosis

Purpose To compare growth factor and cytokine profiles in the endometrial secretions of patients with and without endometriosis to determine whether a particular protein profile is predictive of the disease.

Patients undergoing laparoscopic gynecologic surgery for benign indications were recruited for this prospective cohort study. Prior to surgery, endometrial fluid was aspirated and multiplex immunoassay was used to quantify 7 cytokines and growth factors. During surgery, each patient was staged according to the ASRM staging system for endometriosis. Cytokines and growth factors were evaluated using the Mann-Whitney and Kruskal-Wallis tests. Combinations of cytokines were evaluated using logistic regression analysis, and ROC curves were generated to evaluate the predictive capacity of the assay.

Endometrial secretions were analyzed from 60 patients. Nineteen had stage 3–4 endometriosis, 19 had stage 1–2 disease, and 22 had no endometriosis. There were no significant differences between controls and stage 1–2 endometriosis; however, levels of IL-1α and IL-6 were significantly increased in women with moderate-to-severe disease. A combination of IL-1α, IL-1β, and IL-6 in endometrial secretions predicts stage 3–4 endometriosis with an AUC of 0.78. A threshold value of 118 pg/mL yields a sensitivity of 75% and specificity of 70%.

Aspiration of endometrial fluid is a safe and effective approach for evaluating the endometrial profile of women with endometriosis. Women with moderate-to-severe endometriosis demonstrate a distinct cytokine profile compared to controls. A combination of IL-1α, IL-1β, and IL-6 in the endometrial secretions is predictive of stage 3–4 endometriosis, but is not predictive of minimal-to-mild disease. Similar content being viewed by others

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Acknowledgments We would like to thank the physicians of the Reproductive Endocrinology and Minimally Invasive Gynecologic surgery divisions at the Cleveland Clinic for facilitating the involvement of their patients in this study. In particular, we would like to acknowledge Drs. Mark Dassel, Tommaso Falcone, Jeffrey Goldberg, Rosanne Kho, and Julierut Tantibhedyangkul. Additionally, we would like to acknowledge the Clinical and Translational Science Collaborative (CTSC) Bioanalyte Core of the Case Western Reserve University for their role in processing data samples. Funding Funding for this work was provided by a grant from the Cleveland Clinic Research Program Committee (#274). Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of interest. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material Supplemental Figure 1 (download PDF ) Mean cytokine and growth factor levels by endometriosis stage and cycle phase. P-values shown are for univariate analysis with Mann-Whitney test. Error bars represent standard error of the mean. Asterisk denotes statistically significant difference in luteal-phase and follicular-phase cytokine levels after adjustment for false discovery. (PDF 230 kb) ESM 1 (download DOCX ) (DOCX 16 kb) Rights and permissions About this article Cite this article Llarena, N.C., Richards, E.G., Priyadarshini, A. et al. Characterizing the endometrial fluid cytokine profile in women with endometriosis. J Assist Reprod Genet 37, 2999–3006 (2020). https://doi.org/10.1007/s10815-020-01989-y Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10815-020-01989-y