Diagnosing chronic endometritis: when simplification fails to clarify

Abstract

Reproductive immunology has grown in importance in recent years and has even developed into a discipline of its own within the field of reproductive medicine. Many aspects of reproductive failure such as repeated implantation failure or recurrent miscarriages are, meanwhile, seen as a consequence of aberrant expression of immunological factors. This is reflected by the increasing number of tests for assessing and quantifying different immune cell types as well as by a wide range of immune therapies offered to a clientele consisting of desperate patients requesting additional 'IVF tools': first, what is still usually disregarded is the enormous plasticity and fluctuation of most immune cells in the genital tract; second, their still poorly characterized functions in the endometrial cycle: further, their partially unknown role in embryo implantation and in establishing a pregnancy; and third, the fact that one of the fundamental hypotheses of reproductive immunology-of note-the Medawar concept or 'Medawar's Paradox' of semi-allogeneic graft embryo, is partially based on an erroneous assumption, i.e. the immunologic rejection and tolerance of an embryo. In the present opinion article, we comment on the diagnostic procedures and therapy approaches for chronic endometritis within the scope of reproductive medicine.

Keywords: CD138+; chronic endometritis; overdiagnosis; plasma cell; reproductive immunology.

Figure 1.

Simplified illustration of postulated mechanisms how chronic endometritis (CE) might impact female fertility (modified from Buzzaccarini et al., 2020). Reported pathophysiological effects of CE on immune cells and gene expression. contradictory results (marked by asterisks) were reported for IGFBP-1 (up- and downregulated and BAX (unaffected, respectively upregulated). BAX, Bcl-2-associated X protein; BCL2, B-cell lymphoma 2; CASP8, Caspase-8; CCL, Chemokine (C-C motif) ligands; CXCL, chemokine (C-X-C motif) ligand; EGFR, epidermal growth factor receptor; IGF-1, insulin-like growth factor 1; IGFBP-1, insulin-like growth factor-binding protein 1; IL, interleukin; MΦ, macrophages; LC3, microtubule-associated proteins 1A/1B light chain 3B; LPS, lipopolysaccharides; mTORC1, mTOR Complex 1; ${\mathrm{O}}_2^{-}$, superoxide; PC, plasma cells; TIMP-1, TIMP metallopeptidase inhibitor 1; TGF β, transforming growth factor beta; uNK, uterine natural killer cells; Th, T helper cells; TLR, Toll-like receptors.