Abstract

To determine if a modification of the cytokine profile occurs in the follicular fluid (FF) of women with endometriosis undergoing in vitro fertilization (IVF), we performed a prospective observational study from January 2018 to February 2019. In total, 87 women undergoing IVF were included: 43 for severe endometriosis-related infertility and 40 controls with other causes of infertility. The cytokine profile of the FF was determined by multiplex fluorescent-bead-based technology allowing the measurement of 59 cytokines. Monocyte Chemoattractant Protein 1 (MCP-1) was the only variable retained in the multivariate analysis. We identified two subgroups of patients in the endometriosis group: MCP-1-low group (n = 23), which had FF MCP-1 levels comparable to the control group, and MCP-1-high (n = 20), which had significantly higher FF levels. Only patients in the MCP-1-high group had a significantly altered cytokine profile in the FF, and had a significantly higher serum estradiol level (p = 0.002) and a significantly lower number of oocytes recovered (p = 0.01) compared to the MCP-1-low and the control group. Our study has shown an alteration of the oocyte microenvironment in women with endometriosis associated with high follicular fluid levels of MCP-1, allowing the identification of a subgroup of endometriosis patients with a potentially worse prognosis.

Highlights

  • Endometriosis is a chronic disease affecting 10% of women of reproductive age [1]

  • Hauzman et al showed that implantation rates were significantly lower in recipients without evidence of endometriosis who received oocyte donation from women with endometriosis compared to recipients with endometriosis who received oocytes from women without endometriosis [5]

  • After Benjamini-Hochberg correction, the concentrations of 11 cytokines (the same ones found to be different between the two groups barring osteocalcin, as well as Granulocyte-Colony Stimulating Factor (GCSF), soluble Tumor Necrosis Factor Receptor type 1, and B-cell Activating Factor (BAFF)) were found significantly higher in the follicular fluid (FF) of Monocyte Chemoattractant Protein 1 (MCP-1)-high patients compared to MCP-1-low patients

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Summary

Introduction

Endometriosis is a chronic disease affecting 10% of women of reproductive age [1]. Women with endometriosis often present with dysmenorrhea and pelvic pain, dyspareunia, and in 25% of cases, infertility [2,3]. Different biological signatures have been assessed in order to better understand the pathophysiology behind the endometriosis-related infertility, using proteomics [15], metabolomics [16,17,18,19,20], and the analysis of the cytokine profile [21,22,23,24,25]. Such studies have been scarce and have yielded disparate results. The aim of our study was to compare the cytokine profiles of the FF in patients undergoing in vitro fertilization (IVF) for isolated forms of severe endometriosis to those of patients free from endometriosis, and to evaluate the potential impact of the disease on the oocyte microenvironment

Study Participants
Embryo Culture and FF Samples
Quantification of Cytokines and other Inflammation-Aassociated Ffactors
Statistical Analysis
Cytokine Analysis
DViascruiasbsiloens
Summary of Evidence
Biological Rationale
Strength and Limitations
Findings
Conclusions

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