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Inflammatory cytokines IL-6, IL-10, IL-13, TNF-α and peritoneal fluid flora were associated with infertility in patients with endometriosis Original paper

Researched by:

  • Kimberly Eyer ID
    Kimberly Eyer

    User avatarKimberly Eyer, a Registered Nurse with 30 years of nursing experience across diverse settings, including Home Health, ICU, Operating Room Nursing, and Research. Her roles have encompassed Operating Room Nurse, RN First Assistant, and Acting Director of a Same Day Surgery Center. Her specialty areas include Adult Cardiac Surgery, Congenital Cardiac Surgery, Vascular Surgery, and Neurosurgery.

May 19, 2025

  • Women’s Health
    Women’s Health

    Women’s health, a vital aspect of medical science, encompasses various conditions unique to women’s physiological makeup. Historically, women were often excluded from clinical research, leading to a gap in understanding the intricacies of women’s health needs. However, recent advancements have highlighted the significant role that the microbiome plays in these conditions, offering new insights and potential therapies. MicrobiomeSignatures.com is at the forefront of exploring the microbiome signature of each of these conditions to unravel the etiology of these diseases and develop targeted microbiome therapies.

  • Endometriosis
    Endometriosis

    Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.

Researched by:

  • Kimberly Eyer ID
    Kimberly Eyer

    User avatarKimberly Eyer, a Registered Nurse with 30 years of nursing experience across diverse settings, including Home Health, ICU, Operating Room Nursing, and Research. Her roles have encompassed Operating Room Nurse, RN First Assistant, and Acting Director of a Same Day Surgery Center. Her specialty areas include Adult Cardiac Surgery, Congenital Cardiac Surgery, Vascular Surgery, and Neurosurgery.

Last Updated: 2018

Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.

Karen Pendergrass

Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.

What Was Studied?

This study investigated the association of inflammatory cytokines and peritoneal fluid flora with infertility in endometriosis patients. Researchers aimed to explore the correlations between elevated inflammatory markers—IL-6, IL-10, IL-13, and TNF-α—and changes in microbial communities within the peritoneal fluid of women suffering from endometriosis-related infertility. Using Ion Torrent PGM platform sequencing, the microbial composition of the peritoneal fluid was mapped, while ELISA assays were employed to quantify cytokine levels. Logistic regression analysis was conducted to determine the relationship between inflammatory factors and infertility severity.

Who Was Studied?

The study included 55 women diagnosed with endometriosis and infertility and a control group of 30 women without endometriosis or infertility. All participants were treated at a gynecology clinic between June 2014 and July 2017. Peritoneal fluid samples were collected laparoscopically from the vesicouterine and rectovaginal pouches. Women receiving hormonal therapy or antibiotics within two months of surgery were excluded to avoid confounding microbial and inflammatory responses. This patient population allowed for a focused analysis of microbial and cytokine-driven inflammation linked to infertility in endometriosis.

What Were the Most Important Findings?

The study found that endometriosis patients with infertility exhibited significantly higher levels of IL-6, IL-10, IL-13, and TNF-α in peritoneal fluid compared to controls (p <0.05). White blood cell counts, including monocytes, neutrophils, eosinophils, and basophils, were also elevated in the peritoneal fluid of endometriosis patients, supporting the inflammatory hypothesis of disease pathogenesis. Analysis of peritoneal fluid microbiota revealed a predominance of Proteobacteria and Firmicutes, with secondary representation from Actinobacteria, Bacteroidetes, Fusobacterium, and Tenericutes. However, there were no significant differences in the abundance of these phyla between endometriosis patients and controls, suggesting that bacteria themselves are not the primary drivers of infertility in endometriosis. Instead, the study highlighted the role of inflammatory cytokines as critical mediators of infertility. Logistic regression analysis confirmed that IL-6, IL-10, IL-13, and TNF-α were significantly correlated with infertility severity in endometriosis patients, suggesting these cytokines may serve as diagnostic biomarkers for assessing infertility risk. Receiver Operating Characteristic (ROC) analysis showed that IL-6 and TNF-α had the highest diagnostic sensitivity, with AUC values of 0.893 for both, indicating their strong predictive value for identifying infertility risk in endometriosis.

ParameterFindings in Endometriosis Patients with Infertility
Inflammatory CytokinesElevated levels of IL-6, IL-10, IL-13, and TNF-α in peritoneal fluid (p <0.05).
Immune Cell CountsIncreased monocytes, neutrophils, eosinophils, and basophils in peritoneal fluid.
Peritoneal Fluid MicrobiotaDominated by Proteobacteria and Firmicutes, with secondary presence of Actinobacteria, Bacteroidetes, Fusobacterium, and Tenericutes.
Microbial ShiftsNo significant differences in bacterial phyla between endometriosis patients and controls.
Diagnostic BiomarkersIL-6 and TNF-α showed the highest diagnostic sensitivity for infertility with AUC values of 0.893.
Inflammatory ImplicationsCytokines linked to immune activation, peritoneal inflammation, and possible inhibition of sperm motility.
Therapeutic PotentialAnti-inflammatory strategies targeting IL-6 and TNF-α could improve fertility outcomes in endometriosis patients.

What Are the Greatest Implications of This Study?

This study underscores the critical role of inflammatory cytokines in endometriosis-associated infertility, particularly IL-6, IL-10, IL-13, and TNF-α. These cytokines appear to contribute to peritoneal inflammation, immune cell activation, and possibly sperm motility inhibition, collectively reducing fertility. Although peritoneal fluid microbiota did not significantly differ between endometriosis and control groups, the elevated cytokine levels suggest that microbial translocation and immune responses within the peritoneal cavity may exacerbate inflammation. These findings highlight IL-6 and TNF-α as potential biomarkers for diagnosing infertility in endometriosis patients and suggest that anti-inflammatory therapies targeting these cytokines could improve fertility outcomes. Additionally, the study indicates that monitoring cytokine levels in peritoneal fluid could serve as a non-invasive diagnostic tool for assessing infertility risk in endometriosis, offering a novel approach to reproductive management in affected women.

Endometriosis

Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.

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