Chronic endometritis can be described in one word – inflammation.

Signs of any inflammatory process described before our era are:

redness
edema
pain
local temperature rise
dysfunction
Experts consider chronic endometritis as a persistent inflammation of the uterine mucosa, characterized by superficial endometrial edema, high stromal cell density, dissociated maturation between the epithelium and stroma, and infiltration of endometrial stromal plasma cells.

Until 10 years ago, gynecologists were not wary of chronic endometritis. The problem is that patients may not be aware of the pathology for years, which does not manifest itself in any way.

According to the literature – 25% of cases of chronic endometritis are asymptomatic!

Even in the presence of complaints, clinical symptoms are nonspecific (Romeroetal., 2004), similar to other diseases.

Therefore, chronic endometritis in gynecology was not given much importance. He was treated as a kind of ghost diagnosis.

Reproductologists were the first to talk about the importance of diagnosing chronic endometritis.

The diagnosis was found to be closely related to:

idiopathic infertility – infertility of uncertain origin (Cicinellietal., 2018; Liuetal., 2018),
recurrent miscarriages (Kitaya, 2011; McQueenetal., 2005; Zolghadri et al., 2011)
repeated implantation failures (RIF) – two or more negative attempts to transfer good quality embryos – blastocyst (Bouetetal., 2016; Cicinellietal., 2005; Johnston-MacAnannyetal., 2011; Songetal., 2018; Tersoglioetal., 2015; Jan et al. , 2014).
The presence of chronic provokes changes in the contractile capacity of the uterus. This affects fertility and promotes pain during menstruation and pelvic pain (Coughlanetal., 2014).

According to statistics, 56.8% of patients with infertility (Cicinellietal., 2015) are diagnosed with chronic endometritis.

Moreover, the prevalence of pathology in these women is twice as high as in fertile women (Liuetal., 2018; level of evidence 2b) and higher than the population average (Puenteetal., 2020).

We emphasize that in women with endometrial polyps, the prevalence of chronic endometritis increases significantly (Pereletal., 2019; level of evidence 2b).

Women of childbearing age with chronic endometritis have a 60% higher risk of future infertility (Wiesenfeldetal., 2012; level of evidence 2b).

Logically, the question arises: should all patients be examined for chronic endometritis?

Definitely need to be examined for chronic endometritis:

all women with infertility
all women with suspected endometrial polyps
women with pelvic pain
patients with miscarriage in early pregnancy.
Causes of chronic endometritis

Infectious factor
Chronic endometritis is associated with qualitative and quantitative changes in the endometrial microbiome: the abnormal reproduction of various types of microorganisms, mainly gram-negative and intracellular bacteria (eg Enterococcus faecalis, mycoplasma, ureaplasma, chlamydia, and Streptococcus).

Evidence of the infectious origin of chronic endometritis is the effectiveness of antibiotics in this pathology.

Immune factor
Scientists consider infection only a trigger of a complex sequence.

Microbial infection of the endometrium or dysbiosis leads to abnormal expression of pro-inflammatory molecules and causes unusual local immune responses. Such immune responses distort the microenvironment in the endometrium, cause the migration of circulating B cells into the endometrial stroma and the deposition of these lymphocytes in the lumen of the glands. In addition, the proportion of accumulated B cells can differentiate into stromal plasma cells (plasma cells) (ESPC). All this affects the contractility of the uterus and disrupts endometrial function.

Kushnir and others. In 2016, he proved that chronic endometritis does not have a significant autoimmune component. These results need further confirmation. However, the hypothesis of an autoimmune-controlled inflammatory response is currently not supported.

Infections are considered the main immune trigger for chronic endometritis.

Implantation is the result of a subtle “molecular dialogue” between the blastocyst and the endometrium. Various signaling pathways are involved in this unique biological chain. Labile balance can be disturbed by both embryonic and endometrial factors.

Adequate endometrium is essential for successful implantation!

Chronic endometritis suppresses the ability of the endometrium to reach receptivity and ensure successful implantation.

Diagnosis

Biopsy with histological conclusion
Diagnosis on office hysteroscopy
Today, the gold standard diagnosis is histological confirmation of the presence of plasma cells. However, the histologist may have difficulty visualizing plasma cells due to endometrial infiltration by mononuclear cells, stromal cell proliferation, the presence of fibroblasts, or decidual transformation of the endometrium during the luteal phase. Therefore, in recent years it is recommended to conduct immunohistochemical studies to determine

 

Diagnostic criteria for chronic endometritis at fluid hysteroscopy: (A) strawberry aspect: large areas of hyperemic endometrium flushed with white central points; (B) focal hyperemia: small areas of hyperemic endometrium; (C) hemorrhagic spots: focal red areas with sharp and irregular borders possibly in continuity with capillary; (D, E) focal or diffuse micropolyps: small intrauterine new growths <1 mm in size with a distinct connective-vascular axis, distributed on focal areas (D) or on all of the endometrial surface (E); (F) thick and pale appearance of the endometrium in the follicular phase owing to stromal edema (a normal finding during the secretory phase).

Treatment

Positive news: in the vast majority of cases, chronic endometritis is successfully treated with courses of antibiotics when taken orally.

Often, especially in cases of ineffectiveness of standard treatment regimens, we use in combination with antibiotics alternative treatments:

Intrauterine administration of autologous plasma – PRP-therapy
Successful Implantation and Live Birth Following Autologous Platelet-rich Plasma Treatment for a Patient with Recurrent Implantation Failure and Chronic Endometritis SFAKIANOUDIS K. Et al. in vivo 33: 515-521 (2019)

Intrauterine administration of antibiotics
SFAKIANOUDIS K. Et al. Effective treatment of chronic endometritis through a novel approach of intrauterine antibiotic infusion: a case series BMC Women’s Health volume 18, Article number: 197 (2018)

Diagnostic hysteroscopy and endometrial biopsy can cause positive effects. On the one hand, hysteroscopy can physically remove bacterial biofilms involved in the pathophysiology of chronic endometritis. On the other hand, endometrial biopsy and minor trauma (scratching) with subsequent recovery process promote the secretion of cytokines and growth factors in the endometrium.

To confirm this, we have research from the University of Leicester, which conducted a review of 2,062 case studies. Four of them were randomized. According to the results, endometrial injury caused 70% of pregnancies compared to cycles completed without intervention, in cases of repeated implantation failures (Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis Neelam Potdar 1, Tarek Gelbaya, Luciano G Nardo 2012 Dec; 25 (6): 561-71.doi: 10.1016 / j.rbmo.2012.08.005)

indifferent current.
Conclusions

Chronic endometritis adversely affects the receptivity of the endometrium. The use of antibiotic therapy significantly improves reproductive outcomes
After diagnosis and treatment of chronic endometritis, there is an improvement in the results of in vitro fertilization in patients with repeated implantation failures (RIF)
Office hysteroscopy can be used to diagnose chronic endometritis
At Damia Medical Center, we, doctors, perform office hysteroscopy for all patients with infertility.

In addition, we are well aware of and use evidence-based protocols for the treatment of chronic endometritis. In combination with systemic agents, we widely use additional alternative methods of treatment of this pathology – in particular the use of enriched platelet plasma (PRP therapy), the use of indifferent current generated by Zimmer MedizinSysteme for anti-inflammatory purposes.

The experience of conducting hysteroscopies, both classical and office, allowed to start an author’s course for doctors of Ukraine and CIS “The Art of Hysteroscopy”.

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