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763
MICROBIAL LANDSCAPE OF THE ENDOMETRIUM IN PATIENTS WITH
CHRONIC ENDOMETRITIS.
UDС: 575: -616.1-002: -616.3
Ikramova N.A.
Chartaeva A.E.
RIOvaBSIATM
Annotation:
The aim of the study was to investigate the microbiological features of chronic
endometritis (CE) in women of reproductive age. A total of 76 patients with histologically
confirmed CE were examined, divided into two groups according to the degree of inflammation
activity. Real-time PCR with the Femoflor-16 kit was used to analyze the endometrial
microbiota. In patients without CE, the microbiota was predominantly represented by
Lactobacillus spp. (85.0%) and Eubacterium spp. (60.0%). In moderate CE, Streptococcus spp.,
Staphylococcus spp. and Enterobacteriaceae spp. were detected more often, while associations of
Mobiluncus
spp./Corynebacterium
spp.
and
Gardnerella
vaginalis/Prevotella
bivia/Porphyromonas spp. were less common (p < 0.05).
Key words:
chronic endometritis; women of reproductive age; endometrium; microbiota;
microorganisms.
Chronic endometritis (CE) remains a pressing issue, especially among women of reproductive
age, which maintains high interest in the study of this pathology. The prevalence of CE varies
from 3% to 98% according to various studies. Modern studies focus on the study of etiology,
pathogenesis, effectiveness of antibacterial therapy and criteria for assessing treatment.
Particular attention is paid to the role of microbial associations, especially aerobic-anaerobic
ones. It has been established that associations of microorganisms are more aggressive than
monocultures. More than 20 types of opportunistic microorganisms (129 strains) were identified
in the endometrium, including obligate anaerobes (61.4%: bacteroides, eubacteria,
peptostreptococci, etc.), microaerophiles (31.8%: genital mycoplasmas and diphtheroids), and
facultative anaerobes (6.8%: group B and D streptococci, epidermal staphylococcus).
Inflammation of the endometrium often changes the composition of the cervical canal
microbiome. However, there are opinions that the microbial factor does not play a decisive role
in the development of CE, since the frequency of endometrial contamination in complex
microbiological studies is 52.7%. Nevertheless, the results of modern studies confirm the
participation of representatives of the vaginal and cervical flora in the infection of the
endometrium. At the same time, intrauterine infections caused by Neisseria gonorrhoeae or
Chlamydia trachomatis are not always associated with chronic pelvic pain in histologically
proven CE. Studies have shown ambiguous results in assessing the correspondence of cultures
from the uterine cavity, cervical canal and vagina, including differences in the type of pathogens.
This indicates a possible influence of the cervical canal microbiome on the development of
inflammatory processes in the uterine cavity in non-pregnant women. However, the isolation of
pathogens in inflammatory diseases of the pelvic organs remains a difficult task in modern
conditions.
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The aim of this study was to identify the microbiological characteristics of chronic endometriitis
in women of reproductive age.
Materials and methods of the study.
The study involved 76 women with histologically confirmed chronic endometritis (CE). The
following inclusion criteria were used: age from 18 to 45 years, presence of histologically
verified active CE, detection of an infectious pathogen or association of microorganisms from
the lesion (endometrium), as well as the absence of sexually transmitted diseases at the time of
the study.
Exclusion criteria were: use of hormonal, antibacterial or immunomodulatory drugs
(systemically or locally), postpartum or post-abortion periods. All participants provided written
informed consent, and the study protocol was approved by the local ethics committee.
The control group included 20 gynecologically healthy women who sought pregnancy planning.
Patients with CE were divided into two groups depending on the degree of activity of the
inflammatory process and the results of the morphological study of the endometrium:
• Group 1 - 36 women (47.4%) with a low degree of CE activity,
• Group 2 - 40 women (52.6%) with a moderate degree of CE activity.
The age of the participants ranged from 19 to 40 years, averaging 27.8 ± 1.07 years. The age
characteristics of the groups were comparable, with the most common age range being from 22
to 30 years.
The patients were examined using a standard method, including collection of passport data, life
and disease history, complaints, as well as a general clinical and gynecological examination.
A double-lumen catheter was used to obtain the contents of the uterine cavity, preventing
contamination of the samples with vaginal and cervical canal microflora. Real-time polymerase
chain reaction (PCR) was used to analyze the types and amounts of endometrial microbiota using
the Femoflor-16 reagent kit (NPO DNA-Technology, Moscow). DNA was extracted from 100 μl
of the sample using the Proba-GS reagent kit (NPO DNA-Technology, Moscow) according to
the instructions. Numerical data were tested for normality using the Kolmogorov-Smirnov test.
Quantitative indicators were processed statistically, the arithmetic mean (M) and its error (SE)
were calculated. The statistical significance of differences between values was determined
using Student's t-test, with the minimum acceptable significance level being p<0.05.
Results and discussion.
Among the examined patients, the largest number were office workers (44.7%) and housewives
(42.1%). Among the extragenital diseases, acute respiratory viral infections (39.5%) and urinary
tract infections (34.2%) were common. According to the anamnesis, spontaneous miscarriages,
abortions and ectopic pregnancy were recorded in 23.7%, 40.8% and 6.6% of women,
respectively. Pregnancy loss was reported by 43.4% of patients. Of the gynecological diseases,
ectopia (28.9%) and chronic cervicitis (26.3%) were most common. Inflammatory diseases of the
uterus and appendages, including complications after abortions or childbirth, were reported in
39.5% of cases.
The average duration of chronic endometritis was 3.6±0.8 years. The main complaints of patients
included lower abdominal pain (43.4%), painful menstruation (57.9%), abnormal vaginal
discharge (24.4%), painful intercourse (25.0%), irregular menstrual cycle (36.8%), cyclic and
acyclic bleeding (25.0%) and infertility (22.4%).
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Microbiological analysis of the endometrium showed different frequencies of microorganism
detection among the examined groups. In patients with a low degree of chronic endometritis
activity (group 1), Staphylococcus spp. (52.8%), Streptococcus spp. (50.0%) and the
Enterobacteriaceae family (47.2%) were most often detected. In women with a moderate degree
of activity (group 2), these microorganisms also prevailed. In this group, Staphylococcus spp.
occurred in 65.9%, Streptococcus spp. and the Enterobacteriaceae family in 62.5%. Among
women without chronic endometritis, Lactobacillus spp. (85.0%) and Eubacterium spp. (60.0%)
dominated, while Staphylococcus spp. were detected in 40.0% of cases.
Comparative analysis showed that the frequency of Staphylococcus spp. detection in patients of
groups 1 and 2 was 2 times (p<0.05) and 1.5 times (p<0.05) higher than in the control group.
Significant differences in the frequency of Streptococcus spp. between patients with chronic
endometritis and the control group were revealed: in women of group 1, the frequency of this
microorganism was 10 times higher (p<0.001), and in patients of group 2 it was 10.5 times
higher (p<0.001). Bacteria of the Enterobacteriaceae family, which includes both representatives
of normal microflora and pathogenic microorganisms, were also frequently encountered. In
groups 1, 2 and the control group, the Enterobacteriaceae family was identified in 47.2%, 62.5%
and 30.0% of cases, respectively. Compared with the control group, in patients of group 1 its
frequency was 1.6 times higher (p<0.05), and in patients of group 2 it was 2.1 times higher
(p<0.05).
When studying the endometrial biocenosis, associations of microorganisms were revealed. In the
control group, the association Ureaplasma (urealytikum+parvum) (40.0%) and Lachnobacterium
spp. + Clostridium spp. (25.0%) were frequently encountered. In patients with low CE activity
(group 1), these associations were encountered in 22.2% of cases. In women with moderate CE
activity (group 2), the association Ureaplasma (urealytikum+parvum) was recorded in 22.5% of
cases, and the association Lachnobacterium spp. + Clostridium spp. — in 15.0% of cases. Thus,
the association Ureaplasma (urealytikum+parvum) in chronic endometritis was less common
than in the control group. In patients with low and moderate activity of chronic endometritis, the
frequency of this association was lower than in the control group by 1.8 times (p<0.05),
respectively. The frequency of detection of the association Lachnobacterium spp. + Clostridium
spp. in groups 1 and 2 compared to the control group was reduced by 1.1 and 1.7 times (p<0.05).
Statistically significant differences were also observed between the control group and the group
of women with moderate activity of CE in the frequency of detection of associations Mobiluncus
spp. + Corynebacterium spp. and Gardnerella vaginalis/Prevotella bivia/Porphyromonas spp.,
where in patients of the second group the frequency was reduced by 2.0 times (p<0.05).
When compared with low CE activity, with moderate CE activity, the endometrial microbiota
was characterized by an increase in the frequency of detection of streptococci and staphylococci
by 1.2 times, as well as enterobacteria by 1.3 times. When comparing the frequency of
microorganism associations between groups 1 and 2, a statistically significant difference was
found in relation to the associations Mobiluncus spp. + Corynebacterium spp. and Gardnerella
vaginalis / Prevotella bivia / Porphyromonas spp., which were found 1.7 times less frequently
with moderate CE activity (p < 0.05). Our results again confirmed that the uterine cavity is not
sterile, which is consistent with literature data. In the endometrial microbiota of women without
chronic endometritis, normocytosis representatives prevailed, such as Lactobacillus spp. (85.0%)
and Eubacterium spp. (60.0%). Eubacterium spp. are gram-positive bacteria of the family
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Eubacteriaceae of the order Clostridiales. The genus Eubacterium is highly heterogeneous and
includes various species with different phenotypes. The literature describes that these bacteria
are found in the vagina of both healthy women and those suffering from bacterial vaginosis.
However, their role in endometrial colonization has not yet been fully determined.
Conclusions. Thus, in patients without morphological signs of chronic endometritis, lactobacilli
and eubacteria predominated in the endometrium, while in patients with CE, the endometrial
microbiota was characterized by a decrease in the frequency of detection of lactobacilli and an
increase in the frequency of detection of staphylococci, enterobacteria, and streptococci.
Literature
1.
Радзинский В.Е., Петров Ю.А., Калинина Е.А. и др. Патогенетические особенности
макротипов хронического эндометрита // Казанский медицинский журнал. 2017. Т. 98. №1.
С.27-34. DOI:10.17750/ KMJ2017-27.
2.
Яковенко Л.А. Этиологические аспекты хронического эндометрита (обзор
литературы) // International Journal of Applied and Fundamental Research. 2016. №4. С.574-
577.
3.
Casari E., Ferrario A., Morenghi E., et al. Gardnerella, Trichomonas vaginalis, Candida,
Chlamydia trachomatis, Mycoplasma hominis and Ureaplasmaure alyticum in the genital
discharge of symptomatic fertile and asymptomatic infertile women // New Microbiol. 2010. Vol.
33. №1. P.69-76.
4.
Chen C., Song X., Wei W., et al. The microbiota continuum along the female
reproductive tract and its relation to uterinerelated diseases // Nat Commun. 2017. Vol. 8. №1.
P.875. DOI: 10.1038/s41467-017-00901-0.
5.
Johnston-MacAnanny E.B., Hartnett J., Engmann L.L., Nulsen J.C., Sanders M.M.,
Benadiva C.A. Chronic endometritis is a frequent finding in women with recurrent implantation
failure after in vitro fertilization. Fertil Steril 2010; 93: 2: 437—441.
6.
McQueen D.B., Bernardi L.A., Stephenson M.D. Chronic endometritis in women with
recurrent early pregnancy loss and/or fetal demise. Fertil Steril. 2014 Apr; 101: 4: 1026—1030.
7.
Carvalho F.M., Aguiar F.N., Tomioka R., Oliveira R.M., Frantz N., Ueno J. Functional
endometrial polyps in infertile asymptomatic patients: a possible evolution of vascular changes
secondary to endometritis. Eur J Obst Gynecol Reprod Biol 2013; 170: 152—156.
8.
Ju J., Li L., Xie J., Wu Y., Wu X., Li W. Toll-like receptor-4 pathway is required for the
pathogenesis of human chronic endometritis. Exp Ther Med 2014 Dec; 8: 6: 1896—1900.
9.
Matteo M., Cicinelli E., Greco P., Massenzio F., Baldini D., Falagario T. et al. Abnormal
pattern of lymphocyte subpopulations in the endometrium of infertile women with chronic
endometritis. Am J Reprod Immunol 2009; 61: 5: 322—329.
