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Characterizing the endometrial fluid cytokine profile in women with endometriosis

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

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, 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%.

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.

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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).

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Author notes

  1. Rebecca L. Flyckt

    Present address: Division of Reproductive Endocrinology and Infertility, University Hospitals, Cleveland Medical Center, 1000 Auburn Drive, Suite 310, Beachwood, OH, 44122, USA

Authors and Affiliations

  1. Division of Reproductive Endocrinology and Infertility, Women’s Health Institute, Cleveland Clinic, Desk A81, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Natalia C. Llarena, Elliott G. Richards, Anju Priyadarshini & Rebecca L. Flyckt

  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

    David Fletcher & Tracey Bonfield

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Correspondence to Rebecca L. Flyckt.

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Supplemental Figure 1

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)

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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

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  • DOI: https://doi.org/10.1007/s10815-020-01989-y

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