Characterizing the endometrial fluid cytokine profile in women with endometriosis
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REPRODUCTIVE PHYSIOLOGY AND DISEASE
Characterizing the endometrial fluid cytokine profile in women with endometriosis Natalia C. Llarena 1 & Elliott G. Richards 1 Rebecca L. Flyckt 1,3
&
Anju Priyadarshini 1 & David Fletcher 2 & Tracey Bonfield 2 &
Received: 27 July 2020 / Accepted: 20 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Methods 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. Results 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, IL1β, 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%. Conclusion 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. Keywords Endometriosis . Endometrium . Cytokines . Endometrial fluid profiling
Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s10815-02001989-y. * Rebecca L. Flyckt [email protected] Natalia C. Llarena [email protected]
1
Division of Reproductive Endocrinology and Infertility, Women’s Health Institute, Cleveland Clinic, Desk A81, 9500 Euclid Avenue, Cleveland, OH 44195, USA
2
Department of Genetics and Genome Sciences, Department of Pediatrics and National Center of Regenerative Medicine, Case Western Reserve University, Biomedical Research Building #822, 10900 Euclid Ave, Cleveland, OH 44106, USA
3
Present address: Division of Reproductive Endocrinology and Infertility, University Hospitals, Cleveland Medical Center, 1000 Auburn Drive, Suite 310, Beachwood, OH 44122, USA
Elliott G. Richards [email protected] Anju
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