Chronic endometritis (CE) is a persistent inflammation of the endometrial lining characterized by the presence of plasma cells. CE has been correlated with repeated miscarriage (RM) and repeated implantation failure (RIF), with prevalence rates ranging from 42.9-56% in RM and 30.3-66% in RIF. CE is typically diagnosed through histological examination of an endometrial biopsy sample using hematoxylin and eosin staining or immunohistochemistry, though office hysteroscopy may also be used. Treatment with a 2 week course of antibiotics such as ofloxacin or doxycycline results in histological cure in 70-95% of cases and significantly improves live birth rates in

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

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

3. 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).
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4. 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).
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5. 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
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6. 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
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7. 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

8. 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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9. 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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10. 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].
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11. 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
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12. 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).
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13. 5. CLINICAL PICTURE
Usually asymptomatic
Can present with
Chronic pelvic pain
Dyspareunia
Abnormal uterine bleeding
Persistent vaginal discharge
(Romero et al, 2004).
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14. 6. DIAGNOSIS
Different methods
Histology
H&E
IHC
Hysteroscopy
Culture
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15. 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).
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16. 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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17. Chronic endometritis on endometrial biopsy.
Plasma cells identified by morphology using H&E
staining.
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18. 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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19. 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
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20. 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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21. 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
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22. Chronic endometritis: ‘‘strawberry aspect.’’
Large area of hyperemic endometrium flushed with
white central points 4/20/2017ABOUBAKR ELNASHAR

23. 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].
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24. 4. Culture:
Positive in 75% of histologically confirmed CE
Common 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 or
Clinical presentation of PID
[Korrn et al, 1995; Andrews et al, 2005].
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25. 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)
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26. 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
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27. 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
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28. 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
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29. 5. Diagnosis:
1. Conventional H&E
2. IHC
3. Office hysteroscopy
4. Culture
6. Treatment:
Ofloxacin or Doxycycline for 2w
4/20/2017ABOUBAKR ELNASHAR

30. 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
4/20/2017ABOUBAKR ELNASHAR