Endometritis

Endometritis is an inflammation of the endometrium, the inner layer of the uterus. The most common subtype is postpartum endometritis, resulting from the ascension of normal vaginal flora to the previously aseptic uterus. The 2nd subtype is endometritis unrelated to pregnancy, which is further subdivided into acute and chronic forms. Pelvic inflammatory disease usually precedes acute endometritis, while the chronic form is often idiopathic but may be associated with chlamydia, tuberculosis, radiation therapy, or intrauterine devices. Clinical features include fever, abdominal pain, abnormal vaginal bleeding, and vaginal discharge. Diagnosis is based on history and physical examination. Imaging is performed to exclude abscesses, septic pelvic thrombophlebitis, and retained products of conception. Management includes hydration and antibiotic therapy.

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Overview

Definition

Endometritis is an inflammation of the inner lining of the uterus, the endometrium.

Epidemiology

Postpartum endometritis:

  • Most common postpartum infection
  • Incidence: 1%–2% following spontaneous vaginal delivery
  • Incidence following C-section in women who received prophylactic antibiotics (which is standard of care even in emergent cases):
    • 7% for C-section performed after the onset of labor
    • 1.5% for C-section performed prior to the onset of labor (e.g., scheduled cases for breech presentation)
  • Incidence following C-section in women who did not receive prophylactic antibiotics:
    • 18% for C-section after the onset of labor
    • 4% for C-section prior to the onset of labor
  • Risk factors:
    • Chorioamnionitis
    • Prolonged membrane rupture
    • Prolonged labor
    • Meconium-stained amniotic fluid
    • Multiple cervical examinations
    • Invasive fetal monitoring
    • Nulliparity
    • Young maternal age
    • Obesity
    • Bacterial colonization of the lower genital tract
    • Low socioeconomic status

Endometritis unrelated to pregnancy:

  • Incidence: unknown
  • Risk factors:
    • Pelvic inflammatory disease
    • Gynecologic procedures
    • Radiation therapy
    • Intrauterine foreign bodies

Etiology

Postpartum endometritis is a polymicrobial infection involving aerobic and anaerobic organisms.

  • Aerobic organisms:
    • Streptococcus pyogenes
    • Staphylococcus aureus
    • Groups A and B streptococci
    • Enterococcus spp.
    • Escherichia coli
    • Chlamydia:
      • A cause of late-onset endometritis
      • Presents up to a week after labor
  • Anaerobic organisms:
    • Peptostreptococcus spp.
    • Bacteroides spp.
    • Clostridium spp.
    • Gardnerella vaginalis
    • Ureaplasma urealyticum

Acute endometritis unrelated to pregnancy is associated with the causative agents of pelvic inflammatory disease (PID):

  • Neisseria gonorrhoeae 
  • Chlamydia trachomatis 
  • Pathogens causing bacterial vaginosis: Peptostreptococcus spp., Bacteroides spp.
  • Enteric pathogens: E. coli, Bacteroides fragilis, group B streptococci
  • Respiratory pathogens: Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus

Chronic endometritis unrelated to pregnancy:

  • Often idiopathic
  • Associated with:
    • Radiation therapy
    • Intrauterine foreign bodies
    • Intrauterine growth (e.g., leiomyoma)
    • Slow-growing or latent infections (e.g., Chlamydia trachomatis, Mycobacterium tuberculosis)

Pathophysiology

Postpartum endometritis

  • Rupture of the amniotic sac → movement of normal vaginal flora to the uterus → colonization of the damaged uterine lining → inflammation
  • May also be caused by lochia retention

Endometritis unrelated to pregnancy

  • Ascending infection (e.g., PID, after gynecologic procedures)
  • Hematogenous spread (tuberculous endometritis)
  • Cellular damage (e.g., radiation therapy, intrauterine devices) → activation of proinflammatory pathways → chronic inflammation

Clinical Presentation

Postpartum endometritis

  • Fever
  • Midline, lower abdominal pain 
  • Foul-smelling and/or purulent lochia
  • Heavy vaginal bleeding (often caused by uterine subinvolution)
  • Uterine tenderness
  • Diarrhea (in the case of infections by group A Streptococcus)
  • Can progress to toxic shock syndrome (in the case of infections by Staphylococcus, group A Streptococcus, or Clostridium sordellii)

Endometritis unrelated to pregnancy

Acute:

  • Fever
  • Abdominal or suprapubic pain
  • Dyspareunia
  • Dysuria
  • Abnormal vaginal discharge
  • Abnormal vaginal bleeding

Chronic:

  • Often asymptomatic
  • Infertility (especially in cases with TB infection)
  • Abnormal vaginal bleeding
  • Crampy abdominal pain (associated with intrauterine devices, leiomyomas, polyps)

Diagnosis

Endometritis is a clinical diagnosis based on the patient’s medical history and physical exam.

History

  • Features of the pain (onset, location, intensity)
  • Fever
  • Risk factors

Physical exam

  • Abdominal exam: to look for abdominal tenderness and to rule out possible abdominal conditions (e.g., appendicitis, pyelonephritis)
  • Pelvic exam:
    • Uterine or adnexal tenderness
    • Cervical motion tenderness
    • Cervical discharge
    • Presence of masses

Diagnostic testing

  • CBC/DIFF shows leukocytosis.
  • Endocervical/endometrial cultures:
    • Not routinely used
    • Can be contaminated from the vaginal flora
  • Blood cultures:
    • Rarely positive
    • Used when there is a high suspicion of sepsis
  • Gram stain/acid-fast stain
  • Endometrial biopsy:
    • Necessary to confirm genital TB
    • Acute endometritis: Biopsy reveals neutrophils and microabscesses.
    • Chronic endometritis: Biopsy reveals plasma cells in endometrial stroma.
  • Ultrasonography is performed to exclude:
    • Intrauterine hematoma
    • Retained products of conception
    • Uterine abscess
  • CT is performed to exclude:
    • Ovarian vein thrombosis
    • Septic pelvic thrombophlebitis
Endometrium prior to administration of anti-tuberculosis drugs - endometritis

Tuberculosis endometritis:
Left: Endometrial tissue with granuloma and lymphocytes
Right: Histiocytes and epithelioid and Langhans multinucleated giant cells

Image: “The endometrium prior to administration of anti-tuberculosis drug” by Raditya Perdhana et al. License: CC BY 2.0, edited by Lecturio.

Management

Postpartum endometritis

  • Treatment is administered until the patient becomes afebrile for ≥ 24 hours.
  • Imaging is performed if symptoms persist for > 72 hours after antibiotic therapy.
  • Medications:
    • Amoxicillin–clavulanate
    • Clindamycin plus gentamicin in penicillin-allergic patients
    • Combination of 2nd- and 3rd-generation cephalosporins with metronidazole
  • Prophylaxis:
    • Decreases morbidity
    • Used in patients undergoing C-section
    • Medications:
      • 1st- or 2nd-generation cephalosporins
      • Cephalosporin plus azithromycin/metronidazole

Acute endometritis unrelated to pregnancy

  • Requires the same treatment as PID
  • Outpatient setting:
    • Ceftriaxone for 1 dose plus doxycycline for 2 weeks
    • Ceftriaxone + azithromycin for gonococcal infection
  • Inpatient setting:
    • Treatment is administered for 2 weeks.
    • Possible regimens:
      • Clindamycin + gentamicin 
      • Cefoxitin + doxycycline
      • Cefotetan + doxycycline
      • Consider adding metronidazole in the case of recent vaginal instrumentation.

Chronic endometritis unrelated to pregnancy

  • Unknown etiology: doxycycline
  • Infectious:
    • Doxycycline for 10–14 days
    • Azithromycin
  • Tuberculous endometritis:
    • 9–12 month therapy with a combination of antimycobacterial drugs (rifampin, isoniazid, pyrazinamide, ethambutol)
    • Radical hysterectomy
  • Intrauterine devices: removal of the device
  • Intrauterine growth: resection of the mass
  • Complications:
    • Sepsis
    • Abscess
    • Infertility
    • Septic pelvic thrombophlebitis (endovascular thrombosis in the setting of associated infection)
    • Necrotizing fasciitis (potentially life-threatening infection involving subcutaneous tissue and fascia)

Differential Diagnosis

  • Pyelonephritis: bacterial infection resulting in kidney inflammation. Patients with pyelonephritis present with fever, flank pain, nausea, vomiting, and costovertebral angle tenderness. Diagnosis is based on history, physical examination findings supported by urinalysis, and urine cultures. Pyelonephritis can be managed in the outpatient or inpatient setting depending on the presence of risk factors and the severity of the disease. Management includes the administration of analgesics, antibiotics, and antipyretics.
  • Septic pelvic thrombophlebitis: rare condition in which an infected thrombus causes venous inflammation. Septic pelvic thrombophlebitis presents with a fever that is resistant to antibiotic therapy and pelvic or lower abdominal pain that is noncolicky and constant. Diagnosis is confirmed with imaging, CT, or MRI. Management includes anticoagulation and antibiotic therapy.
  • Ovarian vein thrombosis: rare complication during the postpartum period. The right ovarian vein is more predisposed to thrombosis. Patients have nonspecific symptoms, including fever, diffuse abdominal pain, and malaise. Diagnosis is made by Doppler ultrasonography, MRI, or CT. Management includes the administration of anticoagulation and antibiotic therapy. Surgery may be performed in complicated cases.
  • Chorioamnionitis: common obstetric complication caused by a bacterial infection ascending from the lower reproductive tract and subsequent inflammation of the amnion and chorionic membranes. Risk factors include preterm or prolonged labor and premature rupture of membranes. Patients present with fever, abdominal pain, uterine tenderness, and foul-smelling vaginal discharge. Diagnosis is based on clinical findings. Management includes the administration of antibiotics and antipyretics.

References

  1. Endometritis. (2019). Medscape. Retrieved May 26, 2021, from https://emedicine.medscape.com/article/254169-overview
  2. Singhal, A., Alomari, M., Gupta, S., Almomani, S., Khazaaleh, S. (2019). Another fatality due to postpartum group A streptococcal endometritis in the modern era. Cureus 11(5):e4618. https://doi.org/10.7759/cureus.4618
  3. Agrawal, P., Garg, R. (2012). Fulminant leukemoid reaction due to postpartum Clostridium sordellii infection. Journal of global infectious diseases, 4(4):209–211. https://doi.org/10.4103/0974-777X.103899
  4. Mackeen, A. D., Packard, R. E., Ota, E., Speer, L. (2015). Antibiotic regimens for postpartum endometritis. Cochrane Database of Systematic Reviews 2015(2):CD001067. 
  5. Park, H. J., Kim, Y. S., Yoon, T. K., Lee, W. S. (2016). Chronic endometritis and infertility. Clinical and Experimental Reproductive Medicine 43:185–192. https://doi.org/10.5653/cerm.2016.43.4.185
  6. Chen, K. T. (2020). Postpartum endometritis. UpToDate. Retrieved on June 24, 2021, from https://www.uptodate.com/contents/postpartum-endometritis

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