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Chronic
Endometritis
in
Repeated miscarriage
and
Repeated implantation
failure
Prof. Aboubakr
Elnashar
Benha university, E...
CONTENTS
1.Definitions
2.Clinical significance
3.Prevalence
4.Causes
5.Clinical picture
6.Diagnosis
7.Treatment
Conclusio...
1. DEFINITION
CE:
Chronic inflammation of the endometrial lining
(Romero et al, 2004).
Persistent inflammation of the e...
RM:
3 or more consecutive failed pregnancies
(RCOG, 2011)
2 or more
(ASRM, 2008)
 Causes:
uterine abnormalities
Antiph...
RIF
Failure to conceive following
2 or 3 ET cycles, or
Cumulative transfer of 10 good quality embryos
(El-Toukhy and T...
Recently, there has been increasing interest in the role
of CE in RM and RIF
Limited publications
The impact of CE on r...
2. CLINICAL IMPLICATION
1. Infertility:
 CE:
RM: 42.9% to 56%.
RIF: 30.3% to 66%
Infertile women: 2.8-9%
(Kasius et al, 2...
2. In RM:
CE is a frequent finding (42.9% to 56%).
Antibiotic tt: significantly higher rate of
successful pregnancies co...
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, 2...
Mechanism
Altered endometrial receptivity by
1. Abnormal infiltration of plasma cells
2. Secretion of IgM, IgG, and IgA a...
3. PREVALENCE
Highly variable
RM: 42.9% to 56%.
RIF: 30.3% to 66%
(Johnston-MacAnanny et al, 2010; Cicinelli et al, 201...
4. CAUSES
Infectious agents:
(Cicinelli et al, 2014).
Gonorrhea
Chlamydia
mycoplasma,
ureaplasma,
Escherichia coli,
Strep...
5. CLINICAL PICTURE
Usually asymptomatic
Can present with
Chronic pelvic pain
Dyspareunia
Abnormal uterine bleeding
...
6. DIAGNOSIS
Different methods
Histology
H&E
IHC
Hysteroscopy
Culture
4/20/2017ABOUBAKR ELNASHAR
1. Histologic diagnosis using H&E
Gold standard for the diagnosis
(Kasius et al.,2011)
Time-consuming and difficult.
Lo...
For diagnosis:
one plasma cell in the endometrial stroma
(Johnston-MacAnanny et al 2011, Kasius et al, 2011; McQueen et ...
Chronic endometritis on endometrial biopsy.
Plasma cells identified by morphology using H&E
staining.
4/20/2017ABOUBAKR E...
2. Immunohistochemistry (IHC)
with CD138 (syndecan-1)
Chronic endometritis on endometrial biopsy.
Plasma cells identified...
Higher sensitivity
56%, as compared to a 13%for H&E staining
[McQueen et al, 2015].
(Miguel et al, 2011)
More accurate:...
3. Office Hysteroscopy
In the follicular phase (between D6 and 12) of the
menstrual cycle.
Diagnosis:
1. Mucosal edema,
...
Micropolyps
 identified in 50%-54% of patients with a
histologically confirmed CE
(Cicinelli et al, 2005; Bouet et al, 2...
Chronic endometritis: ‘‘strawberry aspect.’’
Large area of hyperemic endometrium flushed with
white central points 4/20/2...
Sensitivity:
40%
(Bouet et al, 2016).
much greater sens
Specificity
80%
(Bakas et al, 2014; Bouet et al, 2016)
dependent...
4. Culture:
Positive in 75% of histologically confirmed CE
Common bacteria:
Escherichia coli, Enterococcus faecalis
Stre...
The recent view that
Uterine cavity is normally not sterile
Presence of micro-organisms does not mean
inflammation
(Cow...
7. TREATMENT
Regimen:
Ofloxacin: 400 mg daily for 2w OR
Doxycycline: 100 mg twice daily for 2 w
Histological cure:
70-...
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 a...
CONCLUSIONS
1. Definition:
Persistent inflammation of the endometrium
characterized by the presence of plasma cells
2. Cli...
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/gro...
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Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 1 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 2 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 3 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 4 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 5 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 6 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 7 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 8 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 9 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 10 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 11 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 12 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 13 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 14 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 15 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 16 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 17 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 18 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 19 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 20 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 21 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 22 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 23 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 24 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 25 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 26 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 27 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 28 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 29 Chronic Endometritis  in   Repeated miscarriage  and  Repeated implantation failure Slide 30
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Chronic Endometritis in Repeated miscarriage and Repeated implantation failure

  1. 1. Chronic Endometritis in Repeated miscarriage and Repeated implantation failure Prof. Aboubakr Elnashar Benha university, Egypt4/20/2017ABOUBAKR ELNASHAR
  2. 2. CONTENTS 1.Definitions 2.Clinical significance 3.Prevalence 4.Causes 5.Clinical picture 6.Diagnosis 7.Treatment Conclusion 4/20/2017ABOUBAKR ELNASHAR
  3. 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). 4/20/2017ABOUBAKR ELNASHAR
  4. 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). 4/20/2017ABOUBAKR ELNASHAR
  5. 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 4/20/2017ABOUBAKR ELNASHAR
  6. 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 4/20/2017ABOUBAKR ELNASHAR
  7. 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. 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). 4/20/2017ABOUBAKR ELNASHAR
  9. 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). 4/20/2017ABOUBAKR ELNASHAR
  10. 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]. 4/20/2017ABOUBAKR ELNASHAR
  11. 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 4/20/2017ABOUBAKR ELNASHAR
  12. 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). 4/20/2017ABOUBAKR ELNASHAR
  13. 13. 5. CLINICAL PICTURE Usually asymptomatic Can present with Chronic pelvic pain Dyspareunia Abnormal uterine bleeding Persistent vaginal discharge (Romero et al, 2004). 4/20/2017ABOUBAKR ELNASHAR
  14. 14. 6. DIAGNOSIS Different methods Histology H&E IHC Hysteroscopy Culture 4/20/2017ABOUBAKR ELNASHAR
  15. 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). 4/20/2017ABOUBAKR ELNASHAR
  16. 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). 4/20/2017ABOUBAKR ELNASHAR
  17. 17. Chronic endometritis on endometrial biopsy. Plasma cells identified by morphology using H&E staining. 4/20/2017ABOUBAKR ELNASHAR
  18. 18. 2. Immunohistochemistry (IHC) with CD138 (syndecan-1) Chronic endometritis on endometrial biopsy. Plasma cells identified in brown by immunohistochemical CD138 staining. 4/20/2017ABOUBAKR ELNASHAR
  19. 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 4/20/2017ABOUBAKR ELNASHAR
  20. 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). 4/20/2017ABOUBAKR ELNASHAR
  21. 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 4/20/2017ABOUBAKR ELNASHAR
  22. 22. Chronic endometritis: ‘‘strawberry aspect.’’ Large area of hyperemic endometrium flushed with white central points 4/20/2017ABOUBAKR ELNASHAR
  23. 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]. 4/20/2017ABOUBAKR ELNASHAR
  24. 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]. 4/20/2017ABOUBAKR ELNASHAR
  25. 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) 4/20/2017ABOUBAKR ELNASHAR
  26. 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 4/20/2017ABOUBAKR ELNASHAR
  27. 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 4/20/2017ABOUBAKR ELNASHAR
  28. 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 4/20/2017ABOUBAKR ELNASHAR
  29. 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. 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
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Chronic Endometritis in Repeated miscarriage and Repeated implantation failure

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