Infections and the Reproductive Microbiome Chronic Endometritis

Chronic endometritis and altered embryo implantation: a unified pathophysiological theory from a literature systematic review

Buzzaccarini G, Vitagliano A, Andrisani A, Santarsiero CM, Cicinelli R, Nardelli C, Ambrosini G, Cicinelli E

Published December 2020 Journal of assisted reproduction and genetics
DOI 10.1007/s10815-020-01955-8 PMID 33025403 PMC PMC7714873

RRM Academy Synopsis

Chronic endometritis may disrupt embryo implantation in several ways

A 2020 systematic review of 15 original studies proposes that chronic endometritis may disrupt embryo implantation in several linked ways. Infection is the main trigger. The authors propose that inflammation then alters immune cells, blood vessels, contractions, and hormone response.

Key Findings

  • From 419 records, 41 full-text articles were assessed. Of these, 26 were excluded and 15 original articles were included.
  • Moreno 2018 reported streptococci as the most abundant bacteria in chronic endometritis samples (47%), with enterococci at 15%.
  • Pinto 2015 reported retrograde uterine contractions around ovulation occurring 3.3 times less often in women with chronic endometritis than in women without it.
  • Carvalho 2013 reported that vascular changes were associated with chronic endometritis in 85.7% of cases.
  • Matteo 2009 found lower percentages of uterine natural killer cells (CD56+ CD16- and CD56bright CD16-) in secretory-phase endometrium with chronic endometritis.

Interpretation

The review brings together 15 original studies into one proposed pathway. Several studied infertile women, and most compared the lining with and without chronic endometritis. In the authors' model, infection sets off a cytokine and white blood cell pattern. The pattern turns the immune tolerance implantation needs into an immune reaction. Vessel changes reduce what the authors call endometrial flow reserve, and altered uterine wave propagation could affect embryo contact. Chronic endometritis also slows decidua maturation by reducing estrogen and progesterone action, the authors write. Most studies were case-control, cohort, or retrospective, and the authors note that various biases could arise from these designs.

RRM Context

The authors cite 40.7 to 55.7% of women with unexplained infertility having chronic endometritis. Treatment of the infection can restore the lining and reproductive function, they write. A treatable cause in the lining shows how unexplained infertility can be undiagnosed. Restorative reproductive medicine looks for why implantation fails. IVF places an embryo into that lining without asking.

Abstract

Purpose

Chronic endometritis (CE) is a frequent hysteroscopic and histological finding which affects embryo transfer implantation during IVF-ICSI cycles. In particular, CE impairs proper decidualization and, subsequently, implantation. Although this correlation has been clearly clarified, a pathophysiological explanation assembling all the studies performed has not been elucidated yet. For this reason, we have structured a systematic review considering all the original articles that evaluated a pathological element involved in CE and implantation impairment.

Methods

The authors searched electronic databases and, after screening, collected 15 original articles. These were fully scanned and used to create a summary pathway.

Results

CE is primarily caused by infections, which lead to a specific cytokine and leukocyte pattern in order to prepare the uterus to fight the noxa. In particular, the immunosuppression requested for a proper semi-allogenic embryo transfer implantation is converted into an immunoreaction, which hampers correct embryo implantation. Moreover, endometrial vascularization is affected and both irregular vessel density and luminal thickening and thrombosis reduce what we have first identified as endometrial flow reserve. Finally, incorrect uterine wave propagation could affect embryo contact with decidua.

Conclusion

This is the first summary of evidence on CE pathophysiology and its relationship with infertility. Understanding the CE pathophysiology could improve our knowledge in embryo transfer success.

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Topics

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Related research

Infections and the Reproductive Microbiome › Chronic Endometritis › Endometritis and Reproductive Outcomes · Infertility › Uterine Factor › Endometrial Receptivity · Genetics and Immunology › Reproductive Immunology › Inflammation and Reproduction
Giovanni Buzzaccarini, Amerigo Vitagliano, Alessandra Andrisani, Carla Mariaflavia Santarsiero, Rossana Cicinelli, Claudia Nardelli, Ettore Cicinelli
G Buzzaccarini, A Vitagliano, A Andrisani, C Santarsiero, R Cicinelli, C Nardelli, E Cicinelli
PMID 33025403 33025403 DOI 10.1007/s10815-020-01955-8 10.1007/s10815-020-01955-8 Buzzaccarini et al. 2020, Buzzaccarini 2020