Chronic Endometritis in Repeated miscarriage and Repeated implantation failure

05/02/2023ABOUBAKR ELNASHAR

Chronic Endometritis

in Repeated miscarriage

and Repeated implantation

failure

Prof. Aboubakr Elnashar

Benha university, Egypt


CONTENTS1.Definitions2.Clinical significance3.Prevalence4.Causes5.Clinical picture6.Diagnosis7.TreatmentConclusion 7


1. DEFINITIONCE:Chronic inflammation of the endometrial lining

(Romero et al, 2004). Persistent inflammation of the endometrium that is

characterized by the presence of plasma cells (Johnston-MacAnanny, 2010).


RM:3 or more consecutive failed pregnancies

(RCOG, 2011)2 or more

(ASRM, 2008) Causes:

uterine abnormalitiesAntiphospholipid antibody syndromeendocrine disorders. parental chromosomal imbalances/translocations

50% unexplained(Stephenson,1996).


RIFFailure to conceive following

2 or 3 ET cycles, or Cumulative transfer of 10 good quality embryos

(El-Toukhy and Taranissi, 2006).Causes:

EmbryonicMaternal:

uterine anatomic abnormalitiesthrombophilia,

non-receptive endometrium immunological (Salim et al., 2002).

Idiopathic


Recently, there has been increasing interest in the role of CE in RM and RIFLimited publicationsThe impact of CE on reproductive capacity:

controversial


2. CLINICAL IMPLICATION1. Infertility:

CE: RM: 42.9% to 56%.RIF: 30.3% to 66% Infertile women: 2.8-9%

(Kasius et al, 2011, Viana et al, 2015) suggesting: Correlation between CE and RM or RIF rather than

infertility {create a suboptimal IU environmenthamper endometrial receptivity}

±cause infertility{endometrium is characterized by an abnormal

pattern of lymphocyte: an aberrant endometrial microenvironment }

(Matteo et al., 2009).


2. In RM: CE is a frequent finding (42.9% to 56%).Antibiotic tt: significantly higher rate of successful

pregnancies compared with women who were not treated or with persistent disease

(Cicinelli et al., 2014).


3. In RIF:CE was identified in 30.3% to 66% Women diagnosed with CE had lower IR (11.5%)

after IVF (Quaas and Dokras, 2008).


MechanismAltered endometrial receptivity by

1. Abnormal infiltration of plasma cells2. Secretion of IgM, IgG, and IgA antibodies

(Kasius et al, 2011).3. Alteration in:

Endometrial cytokine production[Maybin et al, 2011],

Secretion of paracrine factors[Matteo et al, 2009, Di Pietro et al, 2013].

Endometrial expression of genes (Johnston-MacAnanny, 2010).

4. Delay differentiation of the EM in the mid-secretory phase (out-of-phase morphology)

[Mishra et al, 2008].


3. PREVALENCEHighly variable RM: 42.9% to 56%.RIF: 30.3% to 66%

(Johnston-MacAnanny et al, 2010; Cicinelli et al, 2015) 1. Small sizes of some studies2. Difference in:

1. Ethnicities2. Definitions of RM and RIF3. Techniques used for diagnosis.4. Histologic definition of CE


4. CAUSESInfectious agents: (Cicinelli et al, 2014).

GonorrheaChlamydiamycoplasma,ureaplasma, Escherichia coli, Streptococcus spp., Staphylococcus spp.,Enterococcus faecalis, Yeast, and Tuberculosis (Romero et al, 2004).

CE can result from retained tissue:incomplete pregnancy loss or retained placental tissue (Haggerty et al, 2005).


5. CLINICAL PICTUREUsually asymptomaticCan present with Chronic pelvic painDyspareuniaAbnormal uterine bleeding Persistent vaginal discharge

(Romero et al, 2004).


6. DIAGNOSISDifferent methodsHistology

H&E IHC

HysteroscopyCulture


1. Histologic diagnosis using H&EGold standard for the diagnosis

(Kasius et al.,2011) Time-consuming and difficult.Low diagnostic rate (<10%)

[Kasius et al, 2011, McQueen et al, 2014] ±miss the diagnosis.

{normal presence of leukocytes in the endometrium especially before menstruation}

[Kasius et al, 2012]. ± over diagnosis

{Plasma cells can appear morphologically similar to other stromal cells and leukocytes} (Greenwood, Moran, 1981).


For diagnosis:one plasma cell in the endometrial stroma

(Johnston-MacAnanny et al 2011, Kasius et al, 2011; McQueen et al, 2014).At least 5 plasma cells

(Bayer-Garner et al, 2004).


Chronic endometritis on endometrial biopsy. Plasma cells identified by morphology using H&E staining.


2. Immunohistochemistry (IHC) with CD138 (syndecan-1)

Chronic endometritis on endometrial biopsy. Plasma cells identified in brown by immunohistochemical CD138 staining.


Higher sensitivity 56%, as compared to a 13%for H&E staining

[McQueen et al, 2015].

(Miguel et al, 2011)More accurate:

(Bayer-Garner et al, 2001). Reducing false-negative diagnosis

(McQueen et al.2014)Not yet recommended in daily clinical practiceNot widely used for the diagnosis of CE

IHC H&E100% 75% Sensitivity100% 65% Specificity


3. Office Hysteroscopy In the follicular phase (between D6 and 12) of the

menstrual cycle.Diagnosis:

1. Mucosal edema,2. Focal or diffuse endometrial hyperemia,3. Micropolyps (<1 mm) (Cicinelli et al, 2005).


Micropolyps identified in 50%-54% of patients with a histologically

confirmed CE (Cicinelli et al, 2005; Bouet et al, 2016)

{inflammatory microenvironment}.Biopsy:

1. Higher density of B cells and plasma cells2. Lower density of natural killer cells(Kitaya et al, 2012).

This explains decreased endometrial receptivity in CE: RM and RIF


Chronic endometritis: ‘‘strawberry aspect.’’Large area of hyperemic endometrium flushed with white central points


Sensitivity:40% (Bouet et al, 2016).much greater sens

Specificity80%(Bakas et al, 2014; Bouet et al, 2016)

dependent on the clinician's experienceAccuracy

93.4%[Cicinelli et al, 2008,2010].

Normal hysteroscopyrelatively accurate predictor of successful pregnancy after ART [Cicinelli et al , 2015].


4. Culture:Positive in 75% of histologically confirmed CECommon bacteria:

Escherichia coli, Enterococcus faecalis Streptococcus agalactiae: 77.5%Mycoplasmae/Ureaplasma: 25%Chlamydia: 13% (Cicinelli et al, 2014).

Often a causal organism cannot be identified. CE have no correlation with

Bacterial colonization of the EM orClinical presentation of PID

[Korrn et al, 1995; Andrews et al, 2005].


The recent view that Uterine cavity is normally not sterilePresence of micro-organisms does not mean

inflammation(Cowling et al., 1992; Eckert et al.,2003).

It is not just the presence of infectious agent within the internal genital tract

The most critical issue that determines the pathology interactions between:

infectious agents and endometrial environment

(Eckert et al.,2003)


7. TREATMENTRegimen:Ofloxacin: 400 mg daily for 2w ORDoxycycline: 100 mg twice daily for 2 w

Histological cure: 70-95%

Persistent CE:Ciprofloxacin: 500mg and

Metronidazole: 500 mg twice daily for 2 w


LBR in RM with CEAfter tt Before tt56% 7% McQueen et al. 2014

LBR in RIF with CEAfter tt Before tt60.8% 13.3% Cicinelli et al, 2015

Results of treatment


CONCLUSIONS1. Definition:

Persistent inflammation of the endometriumcharacterized by the presence of plasma cells

2. Clinical implicationCorrelation between CE and RM or RIF 3. Prevalence Highly variable RM: 42.9% to 56%.RIF: 30.3% to 66%

4. Clinical pictureUsually asymptomatic


5. Diagnosis:1. Conventional H&E2. IHC3. Office hysteroscopy 4. Culture

6. Treatment: Ofloxacin or Doxycycline for 2w


You can get this lecture from:1.My scientific page on Face book:

Aboubakr Elnashar Lectures. https://www.facebook.com/groups/227744884091351/

2.Slide share web site

3. [email protected]

4.My clinic: Althwara st, Mansura, Egypt

Health & Medicine

Chronic Endometritis in Repeated miscarriage and Repeated implantation failure