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

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.

Antibiotic therapy for chronic endometritis and its reproductive implications: a step forward, with some uncertainties

“…Third, Song et al (3) found a low percentage of women with CE signs at hysteroscopy in the treatment arm (25/59, 42.4%). Previous studies found a significant correlation between the disappearance of CE signs at hysteroscopy and improvement of the patients' reproductive outcome (5). In this respect, the number of women in whom a relation between disappearance of hysteroscopic signs and enhancement of fertility could be evaluated was too small for significant results (3) enrolled patients with heterogeneous characteristics (i.e., suffering from infertility, repeated implantation failure, recurrent miscarriage, abnormal uterine bleeding, or cervical incompetence), potentially leading to miscellaneous estimates of the reproductive outcomes.…”

“…During the last 2 decades, there has been growing interest in the study of endometrial pathologies and their reproductive implications. Chronic endometritis (CE), defined as the abnormal invasion of plasma cells within the endometrial stroma, has been one of the most investigated conditions (1)(2)(3)(4)(5).…”

Induction of the epithelial-mesenchymal transition in the endometrium by chronic endometritis in infertile patients

“…In addition, a large number of patients with implantation failure were potentially included in the patients treated with IVF [ 43 , 44 ]. Since it has been reported that CE is related to implantation failure [ 45 , 46 ], and because we hypothesized that the occurrence of EMT was related to implantation failure, IVF patients were targeted in the present study. However, the occurrence of the EMT may differ from that in patients who are not infertile.…”

Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art

“…Irregular bleeding, pelvic pain, or dyspareunia can be symptoms of CE; however, in most cases, patients with a CE remain asymptomatic. CE could further negatively impact reproduction by altering uterine contractility, vascularization, decidualization, and autophagy [ 86 ]. Still, the cut-off level of CD138 + PC within the endometrium remains unclear.…”

“…While Kitaya et al found no difference in identifying CE during the menstrual cycle [ 88 ], some studies showed a higher prevalence of CE in the proliferative phase compared to the secretory phase [ 89 , 90 , 91 ]. The underlying pathophysiological mechanism is likely to be an inflammatory reaction, which leads to an altered cytokine secretion [ 86 , 92 ]. CD68 + macrophages, CD83 + DC, CD8 + T cells, FOXp3 + Tregs [ 93 ], as well as uNK have shown to be elevated in CE [ 26 ].…”