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05/02/2023ABOUBAKR ELNASHAR
Chronic Endometritis
in Repeated miscarriage
and Repeated implantation
failure
Prof. Aboubakr Elnashar
Benha university, Egypt
05/02/2023ABOUBAKR ELNASHAR
CONTENTS1.Definitions2.Clinical significance3.Prevalence4.Causes5.Clinical picture6.Diagnosis7.TreatmentConclusion 7
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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).
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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).
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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
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Recently, there has been increasing interest in the role of CE in RM and RIFLimited publicationsThe impact of CE on reproductive capacity:
controversial
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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).
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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).
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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).
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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].
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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
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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).
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5. CLINICAL PICTUREUsually asymptomaticCan present with Chronic pelvic painDyspareuniaAbnormal uterine bleeding Persistent vaginal discharge
(Romero et al, 2004).
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6. DIAGNOSISDifferent methodsHistology
H&E IHC
HysteroscopyCulture
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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).
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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).
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Chronic endometritis on endometrial biopsy. Plasma cells identified by morphology using H&E staining.
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2. Immunohistochemistry (IHC) with CD138 (syndecan-1)
Chronic endometritis on endometrial biopsy. Plasma cells identified in brown by immunohistochemical CD138 staining.
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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
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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).
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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
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Chronic endometritis: ‘‘strawberry aspect.’’Large area of hyperemic endometrium flushed with white central points
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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].
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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].
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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)
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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
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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
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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
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5. Diagnosis:1. Conventional H&E2. IHC3. Office hysteroscopy 4. Culture
6. Treatment: Ofloxacin or Doxycycline for 2w
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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
4.My clinic: Althwara st, Mansura, Egypt