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23/01/2019 Endometritis unrelated to pregnancy - UpToDate

Official reprint from UpToDate® ©2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Endometritis unrelated to pregnancy

Author: Katherine T Chen, MD, MPH

Section Editor: Robert L Barbieri, MD
Deputy Editor: Sandy J Falk, MD, FACOG

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2018. | This topic last updated: Nov 08, 2017.

INTRODUCTION — Endometritis refers to inflammation of the endometrium, the inner lining of the uterus.
Pathologists have traditionally classified endometritis as either acute or chronic. Acute endometritis is
characterized by the presence of microabscesses or neutrophils within the endometrial glands, while chronic
endometritis is distinguished by variable numbers of plasma cells within the endometrial stroma [1,2].

In the absence of a tissue sample, other factors can help distinguish between acute and chronic endometrial
inflammation. Symptoms alone are not useful since the clinical manifestations of both disorders are similar
(abnormal vaginal bleeding and pelvic pain). An exception is fever: patients with acute endometritis frequently
have fever, while it is less common in women with the chronic process. Reviewing the clinical scenario is also
helpful for determining whether endometritis is acute or chronic (table 1):

● Acute endometritis in the nonobstetric population is usually preceded by pelvic inflammatory disease
(PID) either secondary to a sexually transmitted infection or an invasive gynecologic procedure.

● Chronic endometritis in the nonobstetric population can be due to a number of processes, including
infections (eg, chlamydia, tuberculosis, other organisms related to cervicitis and PID), intrauterine foreign
bodies or growths (eg, intrauterine contraception, submucous leiomyoma, polyp), and radiation therapy.
No etiology is identifiable in approximately one-third of patients [3].

Endometritis unrelated to pregnancy will be discussed here. Endometritis in postpartum women is reviewed
separately. (See "Postpartum endometritis".)


Pelvic inflammatory disease — PID affects the upper genital tract. Most PID results from ascending
migration of pathologic lower genital tract flora to the upper genital tract. Infection may be confined to the
tubes (salpingitis) or may involve the ovaries (salpingo-oophoritis) and/or uterine cavity (endometritis). In
general, the endometrium and ovaries are less susceptible to infection than the fallopian tube. However,
either the endometrium (endometritis) or ovary (oophoritis) may occasionally be the sole focus of infection.

Epidemiology and pathogenesis — Concomitant endometritis occurs in 70 to 90 percent of

laparoscopically documented cases of salpingitis. There is no correlation between the degree of tubal
damage and the histopathologic severity of endometritis. Women with signs and symptoms of PID, but who
have no laparoscopic evidence of the disease, may have an isolated endometritis that is responsible for their
symptoms [4,5].

Endometritis is strongly associated with chlamydial colonization or infection of the cervix (see 'Chlamydia'
below) [6]. Weaker, but positive, correlations exist between endometritis and cervical gonococcal infection
and bacterial vaginosis [7-9]. Ascending infection has been suggested as an explanation for both the… 1/9
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association among cervicitis, endometritis, and salpingitis, and the overlap in symptomatology between these
infections. (See "Pelvic inflammatory disease: Pathogenesis, microbiology, and risk factors".)

Diagnosis — The diagnosis of acute endometritis is made clinically based upon criteria for the diagnosis
of acute PID. An endometrial biopsy for microbiologic and histologic studies may be helpful for the specific
diagnosis of acute endometritis, but is not necessary. (See "Endometrial sampling procedures".)

The overlap in symptoms between women with laparoscopically documented PID and those with isolated
endometritis is such that differential diagnosis by any specific clinical criterion is not possible. One large
series of 152 women with suspected PID who underwent both laparoscopy and endometrial biopsy found that
43 (28 percent) had neither endometritis nor salpingitis, 26 (17 percent) had isolated endometritis, and 83 (55
percent) had acute salpingitis [10]. Histologic endometritis was present in 85 percent of patients with
confirmed acute salpingitis. (See "Pelvic inflammatory disease: Clinical manifestations and diagnosis".)

Although vaginal white blood cells are usually present in women with histologic endometritis (sensitivity: 91
percent), many normal women will also have white blood cells noted on saline wet mount of vaginal
discharge (specificity: 26 percent) [11]. Thus, this test is useful in excluding upper tract infection in the
uncommon cases when it is negative (negative predictive value: 95 percent), and is seldom used.

Treatment — The therapy of acute endometritis related to acute PID is the same as the treatment of acute
PID. (See "Pelvic inflammatory disease: Treatment in adults and adolescents".)

Outcome — PID is associated with increased risks of infertility, ectopic pregnancy, chronic pelvic pain,
and recurrent PID. (See "Pelvic inflammatory disease: Treatment in adults and adolescents".) The presence
or absence of endometritis does not appear to be a factor for whether women with a clinical diagnosis of PID
who are treated with antibiotics subsequently achieve pregnancy [12].

Gynecologic procedures — Endometritis is an uncommon complication of transcervical diagnostic

gynecologic procedures. As an example, there were only two cases of postoperative infection in a series of
927 diagnostic and operative hysteroscopies; both infections occurred in patients undergoing hysteroscopic
myomectomy [13]. The most common pathogens are chlamydia and gonorrhea, but other cervicovaginal
organisms can be involved.

Screening for chlamydia and gonorrhea before minimally invasive procedures confined to the endometrium,
such as hysteroscopy, intrauterine contraception insertion, and endometrial biopsy, is not necessary. If
cultures are done, appropriate treatment should be administered to patients with positive results, but
prophylactic treatment in the absence of culture results, or in women with negative cultures, is not indicated

The American College of Obstetricians and Gynecologists does not recommend routine use of antibiotic
prophylaxis prior to hysteroscopy or hysteroscopic surgery, intrauterine contraception insertion, endometrial
biopsy, and endometrial ablation because of the low risk of procedure associated infection [15]. However,
prophylactic antibiotics are recommended in the following situations:

● Prior to hysterosalpingography (HSG) and sonohysterography in women with a history of pelvic infection
— If dilated tubes are noted during the procedure, doxycycline 100 mg orally twice daily can be
continued for five days to reduce the incidence of post-procedure PID. In women with no history of pelvic
infection, HSG and sonohysterography can be performed without prophylactic antibiotics. However, if the
procedure shows dilated fallopian tubes, doxycycline 100 mg twice daily for five days is suggested.
However, data supporting use of prophylactic antibiotics in women with dilated tubes undergoing HSG
are sparse [16].

● Before surgical termination of pregnancy — We suggest doxycycline 100 mg orally one hour before the
procedure and 200 mg orally after completion of the procedure. An alternate treatment option is… 2/9
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metronidazole 500 mg orally twice daily for five days. Randomized trials have consistently shown that
antibiotic prophylaxis decreases the risk of post-abortal infection [17].


Unknown etiology — Chronic endometritis is detected histologically in approximately 8 percent of

endometrial specimens [18]. There is no apparent etiology in as many as one-third of these patients, thus
making idiopathic endometritis the most common cause of chronic endometritis in women who are not
pregnant/postpartum [3].

Clinical manifestations and diagnosis — Women with symptomatic chronic endometritis usually present
with abnormal uterine bleeding, which may consist of intermenstrual bleeding, spotting, postcoital bleeding,
menorrhagia, or amenorrhea. Vague, crampy lower abdominal pain accompanies the bleeding or may occur
alone. The most common finding on physical examination is uterine tenderness or cervical motion
tenderness. However, in contrast to acute endometritis, many women have no symptoms and a completely
normal examination.

Women with abnormal vaginal bleeding often undergo an endometrial biopsy as part of their diagnostic
evaluation. In these patients, histology that reveals plasma cells in the endometrial stroma is diagnostic of
chronic endometritis, but it cannot be assumed that this is the cause of the abnormal vaginal bleeding. An
endometrial culture should be performed and may be positive for an infectious organism, despite negative
endocervical cultures. The diagnosis of chronic endometritis of unknown etiology is made if culture results
are negative, ultrasound does not reveal a submucous fibroid, and there is no history of radiation therapy or
recent intrauterine contraception (see below). Although culture results are negative, these women are more
likely to have a history of genital tract infection than women without chronic endometritis [19].

Hysteroscopy using fluid for distending the uterine cavity may be a useful and reliable technique for detecting
chronic endometritis [20,21]. When hyperemia, mucosal edema, and micropolyps were used as diagnostic
parameters, hysteroscopy showed a diagnostic accuracy of 93.4 percent. These authors found over 70
percent of chronic endometritis resulted from common bacteria and mycoplasma [22].

Treatment — Empiric antimicrobial therapy appears to improve symptoms and histology in some women
with chronic endometritis [23]. We suggest a course of doxycycline (100 mg orally twice daily for 10 to 14
days) for patients with chronic endometritis of unknown etiology [24]. The rationale is that negative cultures
may represent false negative tests for detecting chlamydia [6] or the presence of other difficult to cultivate
microbes, and doxycycline is active against some common bacteria and mycoplasma.

If the patient remains symptomatic after treatment with doxycycline and cultures are negative, the provider
should investigate other etiologies of abnormal uterine bleeding and/or abdominal pain.

If the patient is allergic to doxycycline, we suggest a five-day course of azithromycin: 500 mg orally on the
first day and then 250 mg orally on days 2 through 5. This provides coverage for chlamydia, common
bacteria, and mycoplasma.

Chlamydia — Chlamydia trachomatis is an infectious cause of chronic endometritis in the setting of PID or
cervicitis. In one study, as an example, C. trachomatis was detected using polymerase chain reaction (PCR)
or immunohistochemistry in 24 percent of endometrial tissue samples with plasma cell endometritis
compared to 4 percent of those with no evidence of plasma cell endometritis [6]. By comparison, another
study which used PCR to detect C. trachomatis in 43 specimens of histopathologically diagnosed chronic
endometritis detected C. trachomatis in only one case in which dense plasma cell infiltrates were present;
concurrent C. trachomatis infection of the cervix was documented [25].

Symptoms of chronic chlamydial endometritis (intermenstrual bleeding, dyspareunia, and pelvic pain) are
similar to those of chronic PID or chronic endometritis from other etiologies. However, the Centers for… 3/9
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Disease Control and Prevention (CDC) minimal diagnostic criteria for PID appear less sensitive for diagnosis
of chronic endometritis (sensitivity 33 percent) than for PID [26].

The recommended treatment is 10 to 14 days administration of broad spectrum antibiotics effective against
C. trachomatis and other probable pathogens. (See "Treatment of Chlamydia trachomatis infection".)

Tuberculous endometritis — Approximately one-third of the world's population is infected with

Mycobacterium tuberculosis, and it is a leading cause of infertility in endemic countries. The global incidence
of tuberculosis (TB) is growing at approximately 0.4 percent per year, and much faster in sub-Saharan Africa
and in countries of the former Soviet Union [27]. TB is a relatively common cause of upper genital tract
infection in women from Nepal and Northern India [28]. However, it is a rare cause of upper genital tract
infection in developed countries.

Epidemiology — Tuberculous endometritis most commonly occurs in young women from countries where
TB is endemic and among older women exposed to TB before the advent of effective chemoprophylaxis.
(See "Epidemiology of tuberculosis".)

Pathogenesis — Genital tract TB usually arises from hematogenous spread from a pulmonary or other
nongenital tract focus. Inoculation of the genital tract from other intraperitoneal foci or from male sexual
partners with tuberculous epididymitis is unusual. (See "Clinical manifestations, diagnosis, and treatment of
miliary tuberculosis".)

The fallopian tube and endometrium are the most frequently affected sites in the female genital tract,
although the cervix and ovary can also be involved [29]. The vagina and vulva are rarely infected. (See
"Tuberculosis: Natural history, microbiology, and pathogenesis".)

Clinical manifestations — Genital tract TB usually results from reactivation of a focus of infection which
originated at the time of initial infection; thus, clinical manifestations may not appear until 10 years after the
initial seeding of the genital tract. Infertility is the chief presenting complaint among young women with genital
tract TB [29,30]. Genital involvement without renal TB is more common in women than in men [31]. Unusual
patterns of vaginal bleeding, such as changes in menses, amenorrhea, and postmenopausal bleeding are
other common presentations of disease. Approximately 25 to 35 percent of women with pelvic TB complain of
vague, chronic lower abdominal or pelvic pain. Tuberculous peritonitis and ascites, which are usually
secondary to direct hematogenous seeding of the peritoneum, are infrequently observed.

Diagnosis — The diagnosis should be suspected in women with symptoms suggestive of TB, residence
in or travel to endemic areas, and a chest roentgenogram with evidence of healed pulmonary TB. However, a
significant number of women with pelvic TB may have a normal chest x-ray and no prior history of TB [32]. A
skin test with a purified protein derivative of tuberculin is the best way to screen for asymptomatic infection.
(See "Clinical manifestations and complications of pulmonary tuberculosis" and "Approach to diagnosis of
latent tuberculosis infection (tuberculosis screening) in adults".)

A hysterosalpingogram performed as part of an infertility evaluation may show some or all of the
characteristic changes of tuberculous infection: beading; sacculation; sinus formation; and rigid pipestem

The diagnosis should be confirmed by histologic examination of a surgical specimen (showing typical
granuloma) or by an acid-fast stain or culture of menstrual blood or tissue from an endometrial biopsy.
Menstrual fluid, which may be collected in a vaginal cup or cervical cap, is more sensitive than biopsy
specimens for the diagnosis of tuberculous endometritis [30]. Culture and histology are also more sensitive
than acid-fast stains. (See "Diagnosis of pulmonary tuberculosis in adults".)

Treatment — The treatment of genital tract TB is primarily medical and consists of combination drug
therapy for 9 to 12 months. Surgery is indicated if the symptoms or the physical examination suggest
persistence or increase in disease despite adequate therapy or if culture or biopsy results demonstrate… 4/9
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resistant organisms. Total abdominal hysterectomy and bilateral salpingo-oophorectomy is the definitive
surgical procedure for pelvic TB. However, early aggressive medical therapy may allow conservative
procedures in women who wish to attempt a future pregnancy. (See "Treatment of drug-susceptible
pulmonary tuberculosis in HIV-uninfected adults".)

Intrauterine foreign objects, intrauterine growths, and radiation therapy — The copper intrauterine
contraception induces a foreign body reaction in the endometrium; the resulting inflammatory response
prevents viable sperm from reaching the fallopian tubes [33]. This reaction subsides after removal of the
device. In addition, women with noncopper intrauterine contraception who have discomforting symptoms (eg,
irregular bleeding, crampy pain) are more likely to have histological evidence of endometritis compared to
those who are asymptomatic [34].

Intrauterine growths (eg, submucous leiomyoma or polyps) in the uterine cavity and radiation therapy can
also induce chronic endometrial inflammation [33,35]. Excision of the fibroid or polyp may lead to resolution.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected
countries and regions around the world are provided separately. (See "Society guideline links: Gynecologic
infectious diseases (non-sexually transmitted)".)


● Pathologists have traditionally classified endometritis as either acute or chronic, based upon histological
findings. Symptoms alone are not useful for distinguishing these entities since the clinical manifestations
of both disorders are similar (abnormal uterine bleeding, pelvic pain, uterine tenderness). An exception is
fever: patients with acute endometritis frequently have fever, while it is less common in women with the
chronic process. (See 'Introduction' above.)

Acute endometritis

● Acute endometritis is a common component of acute pelvic inflammatory disease (PID); it is usually
present along with acute salpingitis. (See 'Pelvic inflammatory disease' above.)

● Transcervical gynecologic procedures are an uncommon cause of acute endometritis. For this reason,
we suggest not performing tests for chlamydia and gonorrhea before minimally invasive procedures
confined to the endometrium (Grade 2C). (See 'Gynecologic procedures' above.)

● To prevent postprocedure endometritis, we recommend antibiotic prophylaxis before pregnancy

termination (Grade 1A). We suggest its use before hysterosalpingography or sonohysterography in
women with a history of pelvic infection and after these procedures in those found to have
hydrosalpinges (Grade 2C). (See 'Gynecologic procedures' above.)

Chronic endometritis

● As many as one-third of patients with chronic endometritis have no identifiable etiology; infection,
intrauterine growths/foreign bodies, and radiation therapy account for the remainder. (See 'Chronic
endometritis' above.)

● In contrast to acute endometritis, many women with chronic endometritis have no symptoms and a
completely normal examination. (See 'Clinical manifestations' above.)

● We suggest a course of doxycycline (100 mg orally twice daily for 10 days) for patients with chronic
endometritis of unknown etiology (Grade 2C). (See 'Unknown etiology' above.)

● Targeted therapy is appropriate when the cause of endometritis is known. (See 'Chronic endometritis'
above.)… 5/9
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1. Kurman, R, Mazur, M. Benign disease of the endometrium in Blaustein A, ed. Pathology of the Female
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Am J Obstet Gynecol 1972; 112:749.
4. Paavonen J, Kiviat N, Brunham RC, et al. Prevalence and manifestations of endometritis among women
with cervicitis. Am J Obstet Gynecol 1985; 152:280.
5. Wølner-Hanssen P, Mårdh PA, Svensson L, Weström L. Laparoscopy in women with chlamydial
infection and pelvic pain: a comparison of patients with and without salpingitis. Obstet Gynecol 1983;
6. Paukku M, Puolakkainen M, Paavonen T, Paavonen J. Plasma cell endometritis is associated with
Chlamydia trachomatis infection. Am J Clin Pathol 1999; 112:211.
7. Hillier SL, Kiviat NB, Hawes SE, et al. Role of bacterial vaginosis-associated microorganisms in
endometritis. Am J Obstet Gynecol 1996; 175:435.
8. Korn AP, Bolan G, Padian N, et al. Plasma cell endometritis in women with symptomatic bacterial
vaginosis. Obstet Gynecol 1995; 85:387.
9. Peipert JF, Montagno AB, Cooper AS, Sung CJ. Bacterial vaginosis as a risk factor for upper genital
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17. Sawaya GF, Grady D, Kerlikowske K, Grimes DA. Antibiotics at the time of induced abortion: the case
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18. Michels TC. Chronic endometritis. Am Fam Physician 1995; 52:217.
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21. Cicinelli E, Resta L, Nicoletti R, et al. Endometrial micropolyps at fluid hysteroscopy suggest the
existence of chronic endometritis. Hum Reprod 2005; 20:1386.
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24. Johnston-MacAnanny EB, Hartnett J, Engmann LL, et al. Chronic endometritis is a frequent finding in
women with recurrent implantation failure after in vitro fertilization. Fertil Steril 2010; 93:437.
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by polymerase chain reaction. Hum Pathol 1996; 27:1085.
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Topic 5462 Version 17.0… 7/9
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Classification of endometritis

1. Nonobstetric causes

Pelvic inflammatory disease related to sexually transmitted organisms

Pelvic inflammatory disease related to gynecologic procedures

2. Obstetric causes

Postpartum endometritis

Retained products of conception

1. Nonobstetric causes

A. Infectious
Other organisms related to cervicitis and pelvic inflammatory disease

B. Intrauterine foreign bodies or growths

Intrauterine device
Submucous leiomyoma

C. Radiation related

D. Unknown etiology

2. Obstetric causes

Retained products of conception

Graphic 61306 Version 1.0… 8/9
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Contributor Disclosures
Katherine T Chen, MD, MPH Other Financial Interest: OBG Management [Honoraria for quarterly app
review series]. Robert L Barbieri, MD Nothing to disclose Sandy J Falk, MD, FACOG Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform
to UpToDate standards of evidence.

Conflict of interest policy… 9/9