Chronic Endometritis in Repeated miscarriage and Repeated implantation failure

Chronic
Endometritis
in
Repeated miscarriage
and
Repeated implantation
failure
Prof. Aboubakr
Elnashar
Benha university, Egypt4/20/2017ABOUBAKR ELNASHAR

CONTENTS
1.Definitions
2.Clinical significance
3.Prevalence
4.Causes
5.Clinical picture
6.Diagnosis
7.Treatment
Conclusion
4/20/2017ABOUBAKR ELNASHAR

1. DEFINITION
CE:
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 abnormalities
Antiphospholipid antibody syndrome
endocrine disorders.
parental chromosomal imbalances/translocations
50% unexplained
(Stephenson,1996).

RIF
Failure to conceive following
2 or 3 ET cycles, or
Cumulative transfer of 10 good quality embryos
(El-Toukhy and Taranissi, 2006).
Causes:
Embryonic
Maternal:
uterine anatomic abnormalities
thrombophilia,
non-receptive endometrium
immunological
(Salim et al., 2002).
Idiopathic

Recently, there has been increasing interest in the role
of CE in RM and RIF
Limited publications
The impact of CE on reproductive capacity:
controversial

2. CLINICAL IMPLICATION
1. 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 environment
hamper endometrial receptivity}
±cause infertility
{endometrium is characterized by an abnormal
pattern of lymphocyte: an aberrant endometrial
microenvironment }
(Matteo et al., 2009). 4/20/2017ABOUBAKR ELNASHAR

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).

Mechanism
Altered endometrial receptivity by
1. Abnormal infiltration of plasma cells
2. 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. PREVALENCE
Highly 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 studies
2. Difference in:
1. Ethnicities
2. Definitions of RM and RIF
3. Techniques used for diagnosis.
4. Histologic definition of CE

4. CAUSES
Infectious agents:
(Cicinelli et al, 2014).
Gonorrhea
Chlamydia
mycoplasma,
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 PICTURE
Usually asymptomatic
Can present with
Chronic pelvic pain
Dyspareunia
Abnormal uterine bleeding
Persistent vaginal discharge
(Romero et al, 2004).

6. DIAGNOSIS
Different methods
Histology
H&E
IHC
Hysteroscopy
Culture

1. Histologic diagnosis using H&E
Gold 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 practice
Not widely used for the diagnosis of CE
IHCH&E
100%75%Sensitivity
100%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)

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 cells
2. 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 4/20/2017ABOUBAKR ELNASHAR

Sensitivity:
40%
(Bouet et al, 2016).
much greater sens
Specificity
80%
(Bakas et al, 2014; Bouet et al, 2016)
dependent on the clinician's experience
Accuracy
93.4%
[Cicinelli et al, 2008,2010].
Normal hysteroscopy
relatively accurate predictor of successful pregnancy
after ART
[Cicinelli et al , 2015].

4. Culture:
Positive in 75% of histologically confirmed CE
Common bacteria:
Escherichia coli, Enterococcus faecalis
Streptococcus agalactiae: 77.5%
Mycoplasmae/Ureaplasma: 25%
Chlamydia: 13%
Often a causal organism cannot be identified.
CE have no correlation with
Bacterial colonization of the EM or
Clinical presentation of PID
[Korrn et al, 1995; Andrews et al, 2005].

The recent view that
Uterine cavity is normally not sterile
Presence 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. TREATMENT
Regimen:
Ofloxacin: 400 mg daily for 2w OR
Doxycycline: 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 CE
After ttBefore tt
56%7%McQueen et al. 2014
LBR in RIF with CE
After ttBefore tt
60.8%13.3%Cicinelli et al, 2015
Results of treatment

CONCLUSIONS
1. Definition:
Persistent inflammation of the endometrium
characterized by the presence of plasma cells
2. Clinical implication
Correlation between CE and RM or RIF
3. Prevalence
Highly variable
RM: 42.9% to 56%.
RIF: 30.3% to 66%
4. Clinical picture
Usually asymptomatic

5. Diagnosis:
1. Conventional H&E
2. IHC
3. 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/2277
44884091351/
2.Slide share web site
3. elnashar53@hotmail.com
4.My clinic: Althwara st, Mansura, Egypt

Chronic Endometritis in Repeated miscarriage and Repeated implantation failure

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