Chronic endometritis, inflammation of the endometrial lining, may hinder fertility by disrupting the implantation process. Early diagnosis and treatment are crucial for optimizing reproductive outcomes and addressing infertility challenges.

1. Chronic
Endometritis
& Infertility
Dr Kaberi Banerjee
New Delhi

2. Chronic
Endometritis
- Definition
Chronic endometritis (CE) is a persistent inflammatory
disorder of the endometrial lining, characterized by
superficial endometrial edematous change, high
stromal cell density, dissociated maturation between
epithelium and stroma, and infiltration of endometrial
stromal plasmacytes (Buzacarini et al 2020)
Chronic endometritis (CE) is a condition involving the
breakdown of the peaceful co-existence between
microorganisms and the host immune system in the
endometrium. (Park et al, 2016)

4. Pathophysiology
Alters endometrial
receptivity
“Out-of-phase”
endometrial
morphology
Uterine
contraction
pattern changes in
CE

5. Alters
Endometrial
Receptivity
Exhibit high level of estrogen,
progesterone receptor, and Ki-67 nuclear
marker of cell proliferation, in addition to
increased expression of anti-apoptosis
genes, i.e., BCL-2, BCL-6, and BCL-XL.8
Plasma cells (PCs) and immunoglobulin
(Ig) involved in inflammatory reactions
exert a negative influence on
endometrial receptivity

6. “Out-of-phase” endometrial
morphology
• Represent proliferative changes in the
endometrium even during the secretory
phase of the menstrual cycle.

7. Uterine
contraction
pattern changes
in CE.
• During the proliferative phase -
antegrade contractions from
fundus to cervix preceded by
retrograde contractions in
periovulatory and luteal phases of
menstrual cycle (favors sperm
migration to the fallopian tubes)
• During CE - “altered peristalsis”

9. Diagnosis –
Symptoms
• Mostly asymptomatic
• Vague symptoms - pelvic
discomfort, spotting, and
leukorrhea
• No systemic inflammatory
markers - peripheral blood
leukocytosis, raised serum C-
reactive protein

10. Signs
• Implantation Failure
• Recurrant miscarraiges
(Park et al, 2016)

11. Diagnosis
• Ultrasound in Chronic
Endometritis
• Conventional Tissue Staining
• Immunohistochemical CD138
Staining
• Microbial Culture
• Hysteroscopy
• Newer Diagnostic Methods

12. Ultrasound in Chronic
Endometritis
• Persistance endometrial
focal thickening or
echogenicity
• Persistently thin
hypovascular endometrium
with an altered junctional
zone in preovulatory as
well as secretory phases

13. Conventional Tissue
Staining
• Endometrial sampling - hematoxylin and eosin
(H and E) staining
• Multiple endometrial stromal plasmacytes
(ESPCs)
• Presence of ≥ 1 plasma cells in 10 HPFs
with sensitivity - 87.5% and specificity -
64.9 % (Hirata et al 2021)
• Superficial edematous change in the
endometrium
• High-stromal cell density
• Glandular-stromal asynchrony
• Eosinophil infiltration
• CE detected more often in proliferative phase

14. Immunohistochemical
CD138 Staining of
Plasma Cells
• Histopathological evaluation using
IHC - currently most reliable and
rapid method for diagnosing CE
• CD-138 (Syndecan 1) - type I
transmembrane heparan sulfate
proteoglycan
• Antibodies (i.e., clone B-B4 and
B-A38) can selectively recognize
CD138 antigens on the PCs
• Plasma cells are identified
brown by IHC staining

15. Microbial
Culture for
Chronic
Endometritis
• Microorganisms detected frequently in
endometrium with CE –
Streptococcus, Escherichia coli,
Enterococcus, Staphylococcus,
Mycoplasma, Ureaplasma, Proteus,
Klebsiella, Gardnerella, Pseudomonas,
and yeasts
• Chlamydia trachomatis and Neisseria
gonorrhoeae - principal pathogens
responsible for acute endometritis rarely
detected in CE

16. Hysteroscopy
• Presence of local or diffuse hyperemia
• Edematous stroma
• Presence of micropolyps - small
pedunculated, vascularized
protrusions of the uterine mucosa
measuring <1 mm in size

17. Newer Diagnostic Methods
• RT-PCR
• Reference diagnostic test
• Low cost
• Less time-consuming diagnostic method
• Identify and quantify very small
amounts of bacterial DNA, irrespective
of their culturable or nonculturable
nature
• Microbiome results using next-generation
sequencing (NGS)
• Concordant with RT-PCR in 91.67% of
cases

18. Treatment
• Indication - H/o unexplained infertility, RPL,
and RIF
• Targeted antimicrobial therapy
• Empirical antimicrobial therapy –
1. Doxycycline (Preferred treatment)
200 mg per day for 14 days
Clearance of CD138 positive ESPCs in 70%
after therapy
2. Combination of ciprofloxacin and
metronidazole - Resistant to doxycycline
500 mg of each per day for 14 days)

21. Endometrial Scratching & CE Rx Options
Topical Injury –
>Decidualization -
> IR
Release of
Cytokines and
Growth Hormones
Delays earlier
maturation

22. Hysteroscopy & CE Rx Options
Physically
removing
Bacterial Biofilms
Clear adhesions
and Polyps

23. Endometrial TB
• One of the important causes of chronic endometritis
• Mycobacterium tuberculosis - highly prevalent in India
• 5–10% of infertile women - genital tuberculosis
• Endometrium - affected in 50–80% of women with
FGTB
• Pathophysiology -
• Implantation failure due to alterations in the
immune response mechanisms
• Change in the hormonal milieu
• Release of antiphospholipid antibodies.
• Chronic infection - extensive destruction of the
endometrium and myometrium resulting in
complete narrowing of uterine cavity

24. • Rx- 6-9 months of ATT

27. Endometrial
Dysbiosis
Endometrial dysbiosis can be the
cause of implantation failure (Simon
2018)
A Lactobacillus –dominant
endometrium is more receptive with
fewer miscarriages (Moreno 2016)
Optimization of endometrial
microbiota may be considered Pre -
IVF

28. Endometrial
Dysbiosis
A recent study investigated different routes of
antibiotic administration (metronidazole)
combined with prebiotic (lactoferrin) and
probiotic administration, concluded that the
combined vaginal and oral metronidazole
administration along with a vaginal probiotic
treatment could restore normal endometrial
microbiome in women with RIF (Kadogami et
al., 2020).

34. Cost Analysis – RIF Rx
PGS- 40 LASER
HATCHING- 4
ERA- 12 RX FOR CE-1

35. Conclusion
• Association of chronic endometritis with unexplained infertility,
repeated reproductive failures and recurrent miscarriages
• Should be ruled out before offering more expensive options of
treatment for RIF
• Multiple diagnostic modalities available
• Diagnosis and treatment of CE with suitable antibiotics may result
in an increase of spontaneous conceptions and reduction in
miscarriages.
• Overdiagnosis and Treatment must be avoided
• A detailed understanding of the dynamics of uterine microbiome
and the implications of its imbalance is warranted.
• The role of Probiotics in Fertility Treatment needs to be
established.