Endometritis
Synonyms and keywords: acute endometritis, chronic endometritis, postpartum endometritis, puerperal endometritis

# Overview
Endometritis is classified histopathologically into two subtypes: acute endometritis and chronic endometritis (CE).  Acute endometritis occurs following abortion, childbirth, menstruation, curettage, or IUD insertion. Symptoms of acute endometritis may include fever, pelvic pain, and vaginal discharge. On histopathology, many neutrophils are seen in the endometrial stroma in acute endometritis. Chronic endometritis may cause infertility. Chronic endometritis (CE) is mostly asymptomatic but may have vague symptoms. On histopathology, plasma cells are seen in the endometrial stroma in chronic endometritis (CE). Endometritis is mostly caused by infection and treated with antibiotics. Pyometra is a rare disorder with pus accumulation in the uterine cavity due to abnormal drainage of the uterus.

# Historical Perspective
There is limited information on the historical perspective of endometritis.

# Classification
Endometritis  may be classified according to histopathology into two subtypes:
- Acute endometritis
Following abortion, childbirth, menstruation, curettage, or IUD insertion.
The time following childbirth until about 6 weeks after childbirth is traditionally referred to as puerperium (postpartum).
- Following abortion, childbirth, menstruation, curettage, or IUD insertion.
- The time following childbirth until about 6 weeks after childbirth is traditionally referred to as puerperium (postpartum).
- Chronic endometritis (CE)
Mycobacterium tuberculosis causes a subtype of chronic endometritis (CE) (chronic granulomatous endometritis) in some developing countries.
- Mycobacterium tuberculosis causes a subtype of chronic endometritis (CE) (chronic granulomatous endometritis) in some developing countries.

## Pyometra
- Pyometra is a rare disorder with pus accumulation in the uterine cavity due to abnormal drainage of the uterus.
- Pyometra is caused by:
Atrophic cervicitis due to aging
IUD use
Malignant or benign gynecologic tumors
Radiation cervicitis
- Atrophic cervicitis due to aging
- IUD use
- Malignant or benign gynecologic tumors
- Radiation cervicitis
- Mostly seen in postmenopausal women and rarely in the premenopausal women
- The classic triad of symptoms in pyometra includes:
Lower abdominal pain
Purulent vaginal discharge
Postmenopausal bleeding
- Lower abdominal pain
- Purulent vaginal discharge
- Postmenopausal bleeding

# Pathophysiology

## Postpartum endometritis
Postpartum endometritis is caused by bacteria (vaginal microflora) ascending from the lower genital tract during labor.
- These bacteria colonize the cervix and then ascend into the lower part of the uterus and enter the amniotic fluid.
- The amniotic membranes are weakened and ruptured due to the collagenases and proteases that are produced.
Artificial or spontaneous rupture of membranes may also happen without bacterial colonization.
- In these cases bacteria may colonize the decidua and amniotic fluid.
- An amnionitis without deciduitis is caused when bacteria do not colonize the decidua. Chorioamnionitis occurs but the uterus is not infected.
- Deciduitis may result in the infection of the myometrium that may not be diagnosed initially. However, it may not lead to postpartum endometritis with antibiotic treatment after delivery.

## Chronic Endometritis
In the normal endometrium, B-cells are mostly seen in the basal layer.
- The basal layer is the layer that remains across the menstrual cycle.
- In the lymphocyte aggregates, B-cells are the central cells that are surrounded by CD8 T-cells and macrophages.
In chronic endometritis (CE):
- B-cells are seen in the endometrial functional and basal layers.
The endometrial functional layer is the layer that sheds in menstruation.
These increased numbers of B-cells in the endometrial stroma invade into the gland lumina.
- The endometrial functional layer is the layer that sheds in menstruation.
- These increased numbers of B-cells in the endometrial stroma invade into the gland lumina.
- Decreased CD16negative CD56positive/bright natural killer cells and increased T-cells in the secretory phase of the endometrium.
- Abnormal expression of some adhesion molecules and chemokines in the endometrial endothelial and epithelial cells.
CD62E, CXCL1, and CXCL13 (these are involved in B-cell extravasation and migration).
- CD62E, CXCL1, and CXCL13 (these are involved in B-cell extravasation and migration).
- IL-6 is increased in the menstrual flow.
IL-6 is a differentiation factor of mature B-cells.
- IL-6 is a differentiation factor of mature B-cells.
- Increase in IL-1b and tumor necrosis factor (TNF)-a.
TNF-a increases estrogen biosynthesis in the endometrial glandular cells. 
May be associated with endometrial micropolyposis which is seen in the hysteroscopy of patients with CE.
- TNF-a increases estrogen biosynthesis in the endometrial glandular cells. 
May be associated with endometrial micropolyposis which is seen in the hysteroscopy of patients with CE.
- May be associated with endometrial micropolyposis which is seen in the hysteroscopy of patients with CE.
- Increased immunoglobulin subclasses (IgM, IgA1, IgA2, IgG1, and IgG2), especially IgG2.
Negatively affect embryo implantation.
Rarely cause systemic inflammation or affect leukocyte counts, CRP, or cause fever.
- Negatively affect embryo implantation.
- Rarely cause systemic inflammation or affect leukocyte counts, CRP, or cause fever.
- Delayed differentiation of endometrium in the mid-secretory phase.
One-third of biopsies from infertile patients with CE have 'out-of-phase' morphology.
Pseudostratification and mitotic nuclei in the glandular and surface epithelial cells.
- One-third of biopsies from infertile patients with CE have 'out-of-phase' morphology.
- Pseudostratification and mitotic nuclei in the glandular and surface epithelial cells.
- In the secretory phase, the expression of the followings are upregulated:
Antiapoptotic genes (BCL2 and BAX)
Nuclear marker associated with proliferation (Ki-67)
Ovarian steroid receptors (estrogen receptor-a, and -b, progesterone receptor-A, and -B)
- Antiapoptotic genes (BCL2 and BAX)
- Nuclear marker associated with proliferation (Ki-67)
- Ovarian steroid receptors (estrogen receptor-a, and -b, progesterone receptor-A, and -B)
- The expression of the followings are downregulated:
Genes  associated with embryo receptivity (IL11, CCL4, IGF1, and CASP8)
Decidualization (PRL and IGFBP1)
- Genes  associated with embryo receptivity (IL11, CCL4, IGF1, and CASP8)
- Decidualization (PRL and IGFBP1)

## Histopathology
Mycobacterium tuberculosis causes a subtype of chronic endometritis (CE) (chronic granulomatous endometritis) in some developing countries.  Histopathologically, chronic granulomatous endometritis has caseating granuloma surrounded by infiltrates of lymphocytes which include endometrial stromal plasmacytes (ESPCs).

# Causes
Acute endometritis may be caused by Chlamydia trachomatis and Neisseria gonorrhea.
The rate of infections with Chlamydia trachomatis (2%7%) and Neisseria gonorrhea (0%8%) in chronic endometritis (CE) are very low. 
Mycobacterium tuberculosis causes a subtype of chronic endometritis (CE) (chronic granulomatous endometritis) in some developing countries.
The association of viral infections as causes of chronic endometritis (CE) is still unclear.

# Differentiating Endometritis from other Diseases
Puerperal endometritis must be differentiated from:
- Respiratory disorders
- Pyelonephritis
- Appendicitis
To view more differential diagnosis, click here.

# Epidemiology
Puerperal Endometritis
The prevalence of endometritis is 1% to 2% of births and 27% of cesarean births.
Chronic Endometritis
The prevalence of chronic endometritis (CE) is about 10% to 11% on biopsies performed from hysterectomies of patients with gynecologic conditions.
In a study, the prevalence of CE has been reported to be 15% in infertile women with in vitro fertilization (IVF) and 42% in women with recurrent implantation failure (RIF).
The prevalence of CE has been reported to be 57.8% in women with three or more recurrent pregnancy losses (RPLs).
In one study, the prevalence of CE has been reported to be 14% and 27% in patients with RIF or RPL, respectively.

# Risk Factors

# Screening
Routine antepartum screening for GBS infection and treatment of genital tract infections are important in preventing puerperal genital tract infection.
There is insufficient evidence to recommend routine screening for chronic endometritis (CE). However, it has been suggested that hysteroscopy may have the potential to be a screening tool for CE.

# Natural History, Complications, and Prognosis

## Natural History
Studies have suggested that patients with chronic endometritis (CE) may develop:
- Infertility
- Recurrent implantation failure (RIF)
- Recurrent pregnancy losses (RPLs)

## Complications

## Prognosis
A study showed that after antibiotic treatment of patients with CE and recurrent pregnancy losses (RPLs),  the pre-pregnancy live birth rate increased from 7% (before treatment) to 56% (after treatment).
Another study showed that after antibiotic treatment of patients with CE, the implantation rate and pregnancy rate increased from 4.9% and 7.4% (before treatment) to 18.6% and 29.3% (after treatment), respectively.

# Diagnosis

## Diagnostic Study of Choice
The histological finding of acute endometritis includes a large number of neutrophils in the endometrial stroma.
The diagnosis of chronic endometritis (CE) is made with endometrial biopsy and the histological  diagnostic criterion is plasma cells in the endometrial stroma.

## History and  Symptoms

## Physical Examination
Clinical findings found on physical examination in puerperal endometritis may include:
- Fever
- Tachycardia
- Uterine tenderness
- Pelvic pain on bimanual examination
- Lochia
- Subinvolution of uterus

## Laboratory Findings
Laboratory tests in puerperal endometritis include:
- Complete blood count with differential
- Metabolic panel
- Urine culture
- Blood culture
There is insufficient evidence that suggests obtaining endometrial or cervical cultures in puerperal endometritis due to contamination while obtaining an endometrial culture.
Laboratory findings in acute endometritis may include:
- Leukocytosis
- Elevated serum inflammatory markers
Staining used in  histological detection of chronic endometritis (CE) include:
- Hematoxylin and eosin (H&E)
- Immunohistochemical (IHC) stain that detects CD38 and CD138 plasma cell-specific surface antigens:
Confirms the presence of plasma cells in the endometrium.
IHC staining for CD138 has higher sensitivity for diagnosing CE compared to H&E staining (56% vs. 13%).
- Confirms the presence of plasma cells in the endometrium.
- IHC staining for CD138 has higher sensitivity for diagnosing CE compared to H&E staining (56% vs. 13%).

## Electrocardiogram
There are no ECG findings associated with endometritis.

## X-ray
There are no x-ray findings associated with endometritis. However, a chest x-ray should be performed if there is suspicion of a respiratory disorder.

## Echocardiography or Ultrasound
There are no echocardiography findings associated with endometritis.
Ultrasound is usually not helpful in the diagnosis of endometritis. However, an ultrasound may be helpful to rule out other disorders in postpartum patients that are nonresponsive to therapy.
Ultrasound and CT findings in postpartum endometritis may include:
- Normal uterus
- Nonspecific findings due to retained products of conception:
Intrauterine fluid (with or without internal echoes due to blood, gas, or retained products of pregnancy)
Thickened heterogeneous endometrium
- Intrauterine fluid (with or without internal echoes due to blood, gas, or retained products of pregnancy)
- Thickened heterogeneous endometrium

## CT scan
Ultrasound and CT findings in postpartum endometritis may include:
- Normal uterus
- Nonspecific findings due to retained products of conception:
Intrauterine fluid (with or without internal echoes due to blood, gas, or retained products of pregnancy)
Thickened heterogeneous endometrium
- Intrauterine fluid (with or without internal echoes due to blood, gas, or retained products of pregnancy)
- Thickened heterogeneous endometrium
Compared to ultrasound, CT scan is more helpful in identifying the inflammation of the soft tissues and pelvic abscesses.

## MRI
There are no specific MRI findings associated with endometritis. However, MRI may be helpful if there is suspicion of septic pelvic thrombophlebitis.

## Other Imaging Findings
Fluid hysteroscopy is helpful in diagnosing chronic endometritis (CE) and the findings include:
- Edema of the stroma
- Micropolyps
- Focal or diffuse hyperemia

# Treatment

## Medical Therapy

## Surgery
Surgery may be indicated if there is drainable fluid collection due to infection.

## Primary Prevention
The American College of Obstetricians and Gynecologists (ACOG) and the World Health Organization (WHO) recommend antimicrobial prophylaxis 60 minutes prior to incision of cesarean birth.
A Conchrane study showed that antimicrobial prophylaxis decreases uterine and wound infections.
Some of the measures that should be considered in order to reduce genital tract infections include:
- Routine antepartum screening and treatment of GBS and infections
- Handwashing
- Aseptic procedure
- Decrease in vaginal examinations
- Limiting use of invasive procedures
- Limiting episiotomies
- Synthetic suture use
- Decrease in cesarean births
- Rapid repair of lacerations
- Standard suture techniques
- Prophylaxis with antibiotics in anal sphincter injuries

## Secondary Prevention
There are no established measures for the secondary prevention of endometritis.