3.1.3: Endometritis

3.1.3.1 Definition

Inflammation of the endometrium is classified into acute or chronic based on the inflammatory cellular infiltrate (neutrophilic or lymphoplasmacytic). Lymphocytes are normally present in the endometrium; the presence of plasma cells is diagnostic for chronic endometritis.⁷

3.1.3.2 Etiology

Acute endometritis is less common than chronic and is mainly caused by postpartum bacterial infections due to placental or abortive residues. It could also be associated with other urogenital inflammatory conditions caused by bacterial or viral infections.

Chronic endometritis could follow acute inflammation or happen as subtle inflammation without an initial acute stage. It occurs as part of the pelvic inflammatory disease. The most frequent causative agents are pyogenic pathogens such as streptococci, staphylococci, enterococci, and Escherichia coli, as well as bacteria such as Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma, and Ureaplasma urealyticum. Viruses such as herpes simplex virus (HSV) and cytomegalovirus (CMV) infections can cause postpartum endometritis, particularly in patients with HIV. Mechanical and chemical factors such as intrauterine devices can also cause chronic endometritis. Granulomatous endometritis is caused by tuberculosis and is usually associated with tuberculous salpingitis and peritonitis. These are usually seen in immunocompromised women.

3.1.3.3 Clinicopathological Features

• Clinical Picture

All types of acute endometritis present with fever, abdominal pain, and menstrual abnormalities. Chronic endometritis is often clinically silent. Some cases present with infertility, recurrent miscarriage, and repeated abortions. Endometrial inflammation seems to interfere with the physiological mechanisms of oocyte fertilization and embryonic implantation. Therefore, hysteroscopy should be a part of the diagnostic work-up of infertile women complaining of unexplained repeated miscarriage or repeated implantation failure.

Other symptoms include abnormal uterine bleeding (intermenstrual spotting or metrorrhagia), dysmenorrhea, dyspareunia, leucorrhea (malodorous, purulent vaginal discharge), urinary symptoms, and mild fever.

Tubercular endometritis always occurs secondary to respiratory or abdominal localization, with adnexal localization. It generally affects young women of childbearing age and is rare in menopausal women. Symptoms are variable, including changes in menstrual flow (polymenorrhea to amenorrhea) and infertility.

3.1.3.4 Diagnosis

• Imaging and Hysteroscopy

Two-dimensional transvaginal sonography (TVS) is difficult to diagnose chronic endometritis due to the absence of pathognomonic signs associated with the condition. Sonography signs include hematometra, endometrium with hyperechogenic spots, and increased endometrial thickness that mismatches the menstrual cycle phase.

A hysteroscopy, performed in the proliferative phase of the menstrual cycle, allows the identification of signs of endometrial inflammation. The pathognomonic hysteroscopic findings (Figures 3.1.6, 3.1.7, 3.1.8) include:

• Hyperemia: Accentuated vascular network, especially at the peri glandular level.
• Stromal edema: Pale and thickened endometrium
• Micropolyps: Small pedunculated, vascularized protrusions of the uterine mucosa (<1 mm) covered by endometrium and characterized by an accumulation of inflammatory cells (lymphocytes, plasma cells, and eosinophils) intermingled with normal stromal cells.

In tuberculous endometritis, suggestive diagnostic signs include the presence of a thin, uneven, and pale endometrium with irregular whitish spots scattered over the uterine walls. Intrauterine adhesions are common.

Figure 3.1.6 Hysteroscopic view of chronic endometritis in a 30-year-old infertile woman. Saline used as distension medium does not affect endometrial microcirculation, making it easier to identify the characteristic signs of chronic endometritis. Note the micropolyps, which appear as small pedunculated, vascularized protrusions (<1 mm) on the uterine mucosa (A). The close-up view clearly shows a marked accentuation of the vascular network at the level of the uterine fundus (B). To right, an overt stromal edema is evident (C), though the examination was carried out in the early proliferative phase.
Image Source: Sardo, Attilio Di Spiezio, Federica Palma, Gloria Calagna, Brunella Zizolfi, Giuseppe Bifulco, Attilio Di Spiezio Sardo, Federica Palma, Gloria Calagna, Brunella Zizolfi, and Giuseppe Bifulco. “Chronic Endometritis.” Arkhiv Patologii 62, no. 3 (June 29, 2016): 48–52. Distributed under the terms of the CC BY 3.0 license. doi.org/10.5772/63023

Figure 3.1.7 Hysteroscopic view of chronic endometritis in a 34-year-old woman with a positive anamnesis of three early spontaneous abortions (A–C). The stromal edema is clearly evident on the posterior wall (A) and micropolyps are detected on any of the uterine walls (A–C).
Image Source: Sardo, Attilio Di Spiezio, Federica Palma, Gloria Calagna, Brunella Zizolfi, Giuseppe Bifulco, Attilio Di Spiezio Sardo, Federica Palma, Gloria Calagna, Brunella Zizolfi, and Giuseppe Bifulco. “Chronic Endometritis.” Arkhiv Patologii 62, no. 3 (June 29, 2016): 48–52. Distributed under the terms of the CC BY 3.0 license. doi.org/10.5772/63023

Figure 3.1.8 Detail of micropolyps under hysteroscopic examination using a liquid distension medium: the micropolyps, which appear with a varied morphology, are scattered over the uterine wall and may often be encountered with polyps (A) and/or pseudopolyps.
Image Source: Sardo, Attilio Di Spiezio, Federica Palma, Gloria Calagna, Brunella Zizolfi, Giuseppe Bifulco, Attilio Di Spiezio Sardo, Federica Palma, Gloria Calagna, Brunella Zizolfi, and Giuseppe Bifulco. “Chronic Endometritis.” Arkhiv Patologii 62, no. 3 (June 29, 2016): 48–52. Distributed under the terms of the CC BY 3.0 license. doi.org/10.5772/63023

Other morphological features include increased B lymphocytes; normally, these are less than 1% of the leukocyte count.

Figure 3.1.9 Very high magnification micrograph of endometritis. H&E stain. Images show endometrium with abundant plasma cells (blue arrows) (diagnostic for chronic endometritis).
Image Source: Neprhon. "Endometriosis -2-cropped". (2012). Own work, licensed under the CC SA 3.0. Available from Wikimedia Commons.

3.1.3.5 Treatment

Broad-spectrum antibiotics are the first line of treatment. Doxycycline is the drug of choice, administered in doses of 100 mg every 12 hours for 14 days. Cephalosporins, macrolides, or quinolones could also be used. It is preferable that the partner also undergoes the same antibiotic treatment. An endometrial culture should be performed in case of persistent endometritis, and an appropriate antibiotic treatment must be prescribed. In cases of tuberculous endometritis, the patient should be given a specific antibiotic therapy for tuberculosis (isoniazid, ethambutol, rifampicin, and pyrazinamide for 2 months, followed by isoniazid and rifampicin for another 4 months).

Glossary Terms

Adnexal

Relating to the uterine appendages (adnexa uteri), including diseases involving the ovary, the fallopian tubes, and ligaments of the uterus (broad ligament; round ligament)

Amenorrhea

Absence of menstruation

Dysmenorrhea

Painful menstruation

Dyspareunia

Genital pain before, during, or after intercourse

Endometrium

Inner lining of the uterus, part of which builds up during the secretory phase of the menstrual cycle and then sheds with menses

Granulomatous endometrititis

A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the condition is inherited in an autosomal recessive pattern

Hematometra

Blood-filled UTERUS

Hyperechogenic spots

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Hysteroscopy

Endoscopic examination of the uterus

Immunocompromised

human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation

Leucorrhea

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Lymphocytes

Agranular leukocytes of the lymphoid stem cell line, many of which function in specific immunity

Lymphoplasmacytic

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Metrorrhagia

Excessive bleeding from the uterus not related to menstruation

Neutrophilic

Related to granulocytes that stain with a neutral dye and are the most numerous of the leukocytes; especially active against bacteria

Pelvic inflammatory disease

Spectrum of inflammation involving the female upper genital tract and the supporting tissues

Peritonititis

Inflammation of the peritoneum

Plasma cells

A type of B lymphocyte that produces antibodies, which bind to specific foreign or abnormal antigens in order to destroy them

Polymenorrhea

Variations of menstruation which may be indicative of disease

Proliferative phase

Phase of the menstrual cycle in which the endometrium proliferates

Pyogenic

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Tuberculous salpingitis

inflammation of the uterine salpinx, the trumpet-shaped fallopian tubes, usually caused by ascending infections of organisms from the lower reproductive tract. Salpingitis can lead to tubal scarring, hydrosalpinx, tubal occlusion, infertility, and ectopic pregnancy (pregnancy, ectopic)

Footnotes

7. Sardo, Attilio Di Spiezio, Federica Palma, Gloria Calagna, Brunella Zizolfi, Giuseppe Bifulco, Attilio Di Spiezio Sardo, Federica Palma, Gloria Calagna, Brunella Zizolfi, and Giuseppe Bifulco. “Chronic Endometritis.” Arkhiv Patologii 62, no. 3 (June 29, 2016): 48–52. doi.org/10.5772/63023

Image Acknowledgements

• Neprhon. "Endometriosis -2-cropped". (2012). Own work, licensed under the CC SA 3.0. Available from Wikimedia Commons.
• Sardo, Attilio Di Spiezio, Federica Palma, Gloria Calagna, Brunella Zizolfi, Giuseppe Bifulco, Attilio Di Spiezio Sardo, Federica Palma, Gloria Calagna, Brunella Zizolfi, and Giuseppe Bifulco. “Chronic Endometritis.” Arkhiv Patologii 62, no. 3 (June 29, 2016): 48–52. doi.org/10.5772/63023