The Role of Secreting Function of Decidua in the Development of Complications of Gestation Process in Pregnant Women With a Past History
Of Chronic Endometritis

Тарановська, Олена Олексіївна; Ліхачов, В. К.; Dobrovolska, L. M.; Макаров, Олег Геннадійович; Shymanska, Yanina V

doi:10.36740/wlek202011115

Cited by 8 publications

(7 citation statements)

References 7 publications

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“…У ході досліджень нами виявлено суттєве пригнічення синтезу a 2 -мікроглобуліну фертильності в жінок із ХЕ [21]. За настання вагітності цей білок відіграє одну з провідних ролей у процесах інвазії трофобласту, і механізм його дії пов'язаний з активацією ряду прозапальних і протизапальних цитокінів, серед яких важливими є фактор некрозу пухлини альфа (ТNF-a), інтерферон гамма (INF-g), а також інтерлейкін 10 (IL-10) [1,16,23].…”

Section: оригінальні дослідженняunclassified

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Likhachov,

Taranovska

2023

UJPP

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The incidence of chronic endometritis is more than twice higher the prevalence of other clinical forms of intrauterine pathology, leading to infertility, unsuccessful attempts of in vitro fertilization and spontaneous abortion. There is a lack of data on the alteration of pro- and anti-inflammatory cytokine production in chronic endometritis and their role in the subsequent development of miscarriage. Purpose - to investigate the levels of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ), as well as the anti-inflammatory cytokine interleukin 10 (IL-10) in cervical mucus of women with chronic endometritis and to assess the impact of the developed comprehensive preconception treatment on normalizing cytokine disorders in these women. Materials and methods. The levels of pro-inflammatory cytokines TNF-α and INF-γ, as well as the anti-inflammatory cytokine IL-10, were determined using the enzyme-linked immunosorbent assay method in the cervical mucus of 426 women with chronic endometritis who were planning pregnancy. Among them, 168 patients (the Group I) received preconception comprehensive treatment, which included broad-spectrum antibacterial agents (azithromycin), hormonal estrogen-progestin therapy (Femoston 2/10) and L-arginine. The remaining 258 women (the Group II) did not receive treatment for chronic endometritis at the preconception stage. The control group consisted of 30 healthy individuals. Data analysis was performed using mathematical statistical methods, calculating the mean sample values (M), variance (σ) and standard errors of the mean (m). The Student’s t-test was applied, and probabilities were determined using the statistical program «STATISTICA» (StatSoft Inc., USA). Results. In the cervical mucus of women with chronic endometritis, an increase in the levels of pro-inflammatory cytokines INF-γ by 2.8 times (p<0.001) and TNF-α by 2 times (p<0.001) was detected, along with a 2-fold decrease in the concentration of the anti-inflammatory cytokine IL-10 (p<0.001). The shift in the cytokine balance towards pro-inflammatory cytokines is associated with a high frequency of miscarriage in these women. After the treatment of chronic endometritis, women had a 2.6 times lower level of INF-γ (p<0.05), a 2 times lower level of TNF-α (p<0.01), and a 1.7 times higher level of IL-10 (p<0.05) compared to untreated patients. Conclusions. Women with chronic endometritis experience a cytokine imbalance, characterized by an excessive increase in pro-inflammatory cytokines and a decrease in anti-inflammatory cytokines. Women with chronic endometritis who are planning pregnancy require comprehensive preconception treatment, which includes the administration of azithromycin, femoston 2/10 and L-arginine in addition to traditional preconception folate prophylaxis. This treatment, by promoting improved conditions for implantation, leads to a 15% increase in the pregnancy rate and a 1.9-fold reduction in the frequency of spontaneous abortion. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

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Section: оригінальні дослідженняunclassified

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Likhachov,

Taranovska

2023

UJPP

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“…A necessary prerequisite for a normal pregnancy is a complete gestational remodeling of the blood circulation, which is achieved by the invasion of cytotrophoblast cells into the walls of the spiral arteries [1][2][3][4]. As a result, the spiral arteries are transformed into uteroplacental vessels in which the endothelial and smooth muscle layers are completely replaced by endovascular trophoblasts [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…This is mainly due to the morphofunctional characteristics of the uterine mucosa resulting from prolonged persistent inflammatory processes: destruction of endometrial cells, sclerosis of the spiral arteries, luminal narrowing with restricted blood flow [14][15][16][17][18]. This is associated with disturbed secretory transformation of the endometrium during the menstrual cycle, decreased synthesis of endometrial proteins, and disturbances in the activity of the receptor apparatus of the uterine mucosa [1,[19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Changes in the Intensity of Uterine Circulation in Pregnant Women With a History of Chronic Endometritis

Likhachov,

Taranovska

2023

Neonatol. hìr. perinat. med.

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Introduction. An essential prerequisite for the normal course of pregnancy is a complete gestational remodeling of the blood circulation, when the spiral arteries are transformed into uteroplacental vessels with reduced resistance and constant blood flow. Chronic endometritis is characterized by morphofunctional changes in the mucous membrane and microcirculatory disorders in the pool of spiral arteries. If pregnancy develops with the above disease, it may lead to disruption of gestational remodeling of the spiral arteries and contribute to increased resistance to fetoplacental blood flow.Aim. To study the peculiarities of blood flow in the uterine spiral arteries and uterine arteries during pregnancy in women with a history of chronic endometritis and to evaluate the role of preconception care in the prevention of pregnancy complications.Material and Methods.303 women with chronic endometritis were followed during pregnancy. Of these, 135 received antepartum treatment (Group I), which included broad-spectrum antibiotics, hormone replacement therapy for 3 months, and L-arginine during the antepartum period and the first 17-18 weeks of pregnancy. The other 168 women received no treatment during the preconception period (Group II). A control group of 20 healthy patients without chronic pre-pregnancy endometritis was also included.Doppler ultrasound of the spiral and uterine arteries was performed at 5-6 weeks of gestation and 17-18 weeks of gestation. The systolic-to-diastolic ratio (SDR) was calculated as the ratio of the maximum systolic blood flow velocity to the end-diastolic velocity, the pulsatility index (PI) was calculated as the ratio of the difference between the maximum systolic and minimum diastolic velocities to the mean blood flow velocity, and the resistance index (RI) was calculated as the ratio of the difference between the maximum systolic and minimum diastolic velocities to the maximum systolic blood flow velocity.The obtained data were processed using the methods of mathematical statistics, calculating the mean sample values (M), variance (σ), standard error of the mean (m), applying the Student’s t-test and calculating the odds ratio using the statistical software "STATISTICA" (StatSoft Inc., USA).During the research, the principles of patient-centered care were followed in accordance with the requirements of the Tokyo Declaration of the World Medical Association, the International Recommendations of the Helsinki Declaration on Human Rights, the Convention on Human Rights and Biomedicine of the Council of Europe, the Laws of Ukraine, the Orders of the Ministry of Health of Ukraine, and the requirements of the Ethical Code of the Ukrainian physician.The paper is an excerpt from the initiative scientific research project of the Department of Obstetrics and Gynecology No. 2 at Poltava State Medical University, entitled “Optimization of approaches to the management of pregnancy in women at high risk of obstetric and perinatal pathology” (State registration number 0122U201228, duration:10.2022-09.2027).Results. In healthy women at 5-6 weeks of gestation, low resistance blood flow with low pulsatility and high diastolic component was observed in the uterine spiral arteries, as indicated by relatively low resistance indices. In Group II patients who became pregnant with chronic endometritis, an increase in SDR by 11.3% (p<0.01), PI by 36% (p<0.01) and RI by 36.2% (p<0.05) was observed in the spiral arteries at 5-6 weeks of pregnancy, as well as at 17-18 weeks, when SDR increased by 23% (p<0.001), PI by 63% (p<0.001) and RI by 47.5% (p<0.01) compared to healthy women. No significant changes in resistance indices were found in the uterine arteries. The calculated blood flow indices in the uterine spiral arteries at 5-6 weeks of gestation were significantly higher in those Group II women who developed pre-eclampsia later in pregnancy. In these patients, SDR, PI, and RI were 12.4% (p<0.05), 21.7% (p<0.05), and 17.7% (p<0.05) higher, respectively, than in group II women who did not develop pre-eclampsia during pregnancy. Furthermore, the more significant the increase in vascular resistance at the beginning of pregnancy, the more severe the pre-eclampsia. At 17-18 weeks' gestation, the increase in Doppler blood flow indices in the uterine spiral arteries was more pronounced and was accompanied by an increase in SDR, PI, and RI in the uterine arteries.In women of Group I who received pre-pregnancy treatment for chronic endometritis, both at 5-6 weeks and at 17-18 weeks of pregnancy, the values of resistance indices in the uterine spiral arteries were significantly lower than in the group of patients who did not receive such treatment. A more favorable course of pregnancy was also observed: the incidence of spontaneous abortion decreased by a factor of 2.3 (OR 5.20; 95% CI [1.75-15.42]; p <0.05), and the incidence of pre-eclampsia decreased by a factor of 1.8 (OR 2.3; 95% CI [1.25-4.31]; p <0.05). At the same time, the proportion of moderate forms of pre-eclampsia increased (85% of cases of moderate pre-eclampsia in Group I versus 73% in Group II) and the proportion of severe forms decreased (15% versus 27%). The mean duration of disease manifestation also decreased (34.3±0.4 weeks in Group I versus 29.4±0.6 weeks in Group II).Conclusions: In patients with chronic endometritis, pregnancy is associated with a high incidence of spontaneous abortion, especially in early pregnancy, and pre-eclampsia. This is accompanied by vasoconstriction and spasm of the uterine spiral arteries, as evidenced by a significant increase in the resistance indices of these vessels, which appears as early as 5-6 weeks of pregnancy and progresses to 17-18 weeks. It is more pronounced in women whose pregnancy is complicated by the development of pre-eclampsia. Preconception treatment of chronic endometritis can reduce vascular resistance in the pre-placental circulation at the stage of cytotrophoblastic transformation of the walls of the spiral arteries, which leads to a decrease in the incidence of spontaneous abortion and preeclampsia, especially its severe forms.

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“…The development of CE is associated with a number of pathological processes that significantly affect the functional state of the uterine mucosa, thereby creating unfavorable conditions for the onset of pregnancy [4,5]. These are primarily related to destructive changes in endometrial cells that occur during prolonged infl ammation [6], impaired microcirculation in the basin of the uterine spiral arteries [4], inadequate transformation of the uterine mucosa during the menstrual cycle [4][5][6][7], as well as a decrease in the synthesis of α2-microglobulin of fertility (also known as glycodelin-A) [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…In our previous studies, a decrease in the level of fer tility α2-microglobulin (glycodelin-A) was demonstrated in women with CE both in the preconception stage and during the first weeks of pregnancy [2,7]. Adequate synthesis levels create favorable conditions for implantation and embryonic development [8,9], as well as ensure adequate progression of trophoblast invasion into the uterine spiral arteries, which is a necessary step in the formation of adequate feto-maternal blood fl ow [10,11].…”

Section: Introductionmentioning

confidence: 99%

Changes in Cytokine Balance in Pregnant Women With Chronic Endometritis in the Past Medical History and Their Role in the Development of Preeclampsia

Likhachov,

Taranovska

2023

Neonatol. hìr. perinat. med.

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Few data regarding the levels of TNF-α, INF-γ and IL-10 in the cervical mucus of pregnant women with the past medicalhistory of chronic endometritis have been found. The abovementioned cytokines have the impact on the course of pregnancy as well as the processes of trophoblast invasion into the spiral arteries of the uterus. Deviations in their levels at the early stages of pregnancy may be associated with the development of preeclampsia at later stages.Purpose: to assess the levels of TNF, INF-γ and cytokine IL-10 in the cervical mucus of pregnant women with a past medicalhistory of chronic endometritis. Additionally, the study aims to determine their role in the development of preeclampsia andevaluate the eff ectiveness of comprehensive preconception treatment in preventing cytokine imbalance and the occurrence of gestational complications.Method and Materials. 135 pregnant women with the past medical history of chronic endometritis have been supervisedduring their pregnancy and received preconception treatment (Group I), as well as 168 women, whose pregnancy occurred in the presence of untreated chronic endometritis (Group II). The control group (CG) involved 20 healthy women. Preconception treatment included the administration of azithromycin, hormonal therapy with Femoston- Comb 2/10, and L-arginine aspartate in combination with folate prophylaxis. During the study, the principles of patient- centered care were followed in accordance with the requirements of the Tokyo Declaration of the World Medical Association, the International Recommendations of the Helsinki Declaration on Human Rights, the Convention on Human Rights and Biomedicine of the Council of Europe, the Laws of Ukraine, the Orders of the Ministry of Health of Ukraine and the requirements of the Ethical Code of the Ukrainian physician. The cytokine (TNF-α, INFγ, IL-10) analysis in the cervical mucus was performed at 5-, 17-18 and 32 weeks of pregnancy, using the enzyme- linked immunosorbent assay method with corresponding standard commercial reagent kits from the «Vector BEST» company. The obtained data were processed using mathematical statistical methods, calculating the mean sample values (M), variance (σ) and standard errors of the means (m). Student’s t-test was used for assessment and the likelihood ratio was calculated using the «STATISTICA» software (StatSoft Inc., USA).The paper is an excerpt from the initiative scientifi c research project of the Department of Obstetrics and Gynecology No.2 at Poltava State Medical University, entitled «Optimization of approaches to the management of pregnancy in women at high risk of obstetric and perinatal pathology» (State registration number 0122U201228, duration:10.2022-09.2027).Results. In pregnant women with a past medical history of chronic endometritis an increase in the levels of INF-γ in cervicalmucus by 2.1 times at 5-6 weeks (p<0.001), by 2.4 times at 17-18 weeks (p<0.001) and by 1.7 times at 32 weeks of pregnancy(p<0.001) compared to corresponding levels of this cytokine in healthy pregnant women, has been detected. Similarly, TNF-αwas by 4.3 times greater at 5-6 weeks of pregnancy compared to the values in the control group (p<0.001), by 3.3 times greater at 17-18 weeks of pregnancy (p<0.001) and by 4.4 times at 32 weeks of pregnancy (p<0.001). All pregnant women with a past medical history of chronic endometritis who had levels of INF-γ in the cervical mucus greater than 66.4 pg/ml and/or levels of TNF-α greater than 90.9 pg/ml at 5-6 weeks of pregnancy subsequently manifested preeclampsia (OR 2.01; 95 % CI [1.1-7.12]; p<0.05 and OR 1.8; 95 % CI [1.2-6.29]; p<0.05 respectively). The level of IL-10 in their cervical mucus was by 4 times higher than the control values at 5-6 weeks of pregnancy (p<0.0001); by 3.1 times higher at 17-18 weeks of pregnancy (p<0.0001) and by 3 times higher at 32 weeks of pregnancy (p<0.0001). This compensates for the increase in pro-infl ammatory cytokines, allowing the TNF-α/IL-10 ratio to remain at a level characteristic of healthy women throughout pregnancy. In treated women, the concentration of INF-γ is by 1.8 times lower than in untreated patients at 5-6 weeks of pregnancy (p<0.0001), by 2.1 times at 17-18 weeks of pregnancy (p<0.0001), and by 1.4 times at 32 weeks of pregnancy (p<0.0001). Similarly, TNF-α in cervical mucus was found to be lower by 3.6 times (p<0.01), 2.6 times (p<0.0001), and 4 times (p<0.001) respectively, in the specifi ed terms. This helps to avoid excessive production of the anti-infl ammatory cytokine IL-10.Conclusions. In women who got pregnant with untreated chronic endometritis, an increased production of cytokines INF-γand TNF-α at the early stages of pregnancy has been established. Comprehensive pregravidar treatment of chronic endometritis allows for the normalization of levels of anti-infl ammatory cytokines INF-γ and TNF-α at the beginning of gestation, which creates conditions for preventing the development of preeclampsia. This leads to a 1.9 times reduction in the frequency of this complication (OR 2.3; 95 % CI [1.25-4.31]; p<0.05), a 1.8 times decrease in the frequency of severe forms of preeclampsia (OR 4.64; 95 % CI [1.23-17.48]; p<0.05) and a delay in the average onset of its manifestations by 4.9 weeks (p<0.0001).

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The Role of Secreting Function of Decidua in the Development of Complications of Gestation Process in Pregnant Women With a Past History Of Chronic Endometritis

Cited by 8 publications

References 7 publications

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Changes in the Intensity of Uterine Circulation in Pregnant Women With a History of Chronic Endometritis

Changes in Cytokine Balance in Pregnant Women With Chronic Endometritis in the Past Medical History and Their Role in the Development of Preeclampsia

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