ULTRASTRUCTURAL RESEARCH OF THE ENDOMETRIUM RECEPTIVITY IN CONDITIONS OF PRE-CONCEPTIONAL PREPARATION IN REFRACTORY PREGNANCY LOSS

Background. Refractory pregnancy loss (RPL) is a multifactoral pathology in women of reproductive age which treatment represents great difficulties. Great role in RPL pathogenesis is stipulated by chronic endometritis resulting from disturbances of implantation followed by gestational sac malfunction, which is not less significant than progesterone deficiency.Objective. The aim of research was to study the dynamics of ultrastructural changes of endometric epithelial cells in the conditions of pre-conception preparation in refractory pregnancy loss.Methods. 63 samples of endometrium bioptates obtained from female patients of reproductive age with insufficient middle luteal phase of the cycle were studied. Light and electronic microscopy was used to study the morphological changes in endometric epithelial cells.Results. Pre-conceptional cyclic hormone therapy (1 mg 17-estradiol and 20 mg of didrogesteron) in comparison with monotherapy of 20 mg of didrogesteron during 3 months contributed to intracellular regeneration and restoration of secretor phenotype of endometrium epithelial cells corresponding to the status of receptivity with “opened window of implantation”.Conclusions. Cyclic hormonotherapy in combination with complex metabolic therapy as a pre-conceptional preparation contributing to pregnancy illustrates much higher effectiveness of pathogenetically proved preconceptional hormonotherapyKEY WORDS: refractory pregnancy loss, endometrium receptivity, hormone therapy, ultrastructure

Features of matrix metalloproteinases MMP2, MMP3, MMP9 genes regulatory region polymorphism in patients with uterine fbroids

Violation of the extracellular matrix components synthesis regulation contributes to the formation and growth of uterine fbroids (MM). Changes of collagen metabolism in connective tissue may be associated with polymorphism of matrix metalloproteinase (MMP) genes. Aim of the study was to analyze of the association of regulatory regions of matrix metalloproteinase genes MMP2 (rs243865), MMP3 (rs3025058), MMP9 (rs3918242) with the development of uterine myoma, its histological form, several concomitant gynecological diseases. Material and methods. The clinical study of 69 patients (23–54 years old) with uterine myoma was conducted. According to the anamnesis, 57.9 % of patients had childbirth, 46.4 % of women had an artifcial termination of pregnancy, and 15.9 % of women had endometriosis. In histological examination, in 48.14 % the nodes corresponded to the phenotype of simple fbroids with a large proportion of fbrous tissue, 51.6 % with the phenotype of proliferating fbroids. The comparison group is represented by a random population sample of women from Western Siberia. 183 women without pronounced gynecological pathologies were examined. MMP2-1306 C/T polymorphism was analyzed by TaqMan, MMP3-1171 5A/6A, MMP9-1562 C/T by restriction fragment length polymorphism method. Results. The genotype frequencies of the analyzed genes did not signifcantly differ between the groups. The complex genotype MMP2-1306CC:MMP3-11715A6A:MMP9-1562CT was decreased in women with uterine myoma relative to the persons of the comparison group. In endometriosis patients MMP9-1562CC genotype was reduced and heterozygosity was increased relative to patients without endometriosis. The frequency of MMP2-1306CC:MMP9-1562CT complex genotype is signifcantly higher in women who gave birth than in women who did not give birth. Complex genotypes differences between histological variants of uterine myoma were revealed. Conclusions. The results of the study show the signifcance of polymorphism effect of the regulatory regions of the MMP genes in the development and nature of the course of uterine myoma

CLINICAL AND HISTOLOGIC FEATURES OF UTERINE MYOMA IN REPRODUCTIVE-AGE WOMEN UNDER THE TREATMENT BY SELECTIVE PROGESTERONE RECEPTOR MODULATORS

Aim of the study was to investigate the clinical features of reproductive age women with uterine body myoma and the production of vascular endothelial growth factor (VEGF) in the dominant myoma node and perifocal myometrium under the preoperative use of ulipristal acetate (UA). Material and methods. 140 samples of 35 women surgical material were studied, VEGF content in the incubation medium of samples of myoma and myometrium was measured using enzymelinked  immunosorbent assay.Results and discussion. The treatment by UA before myoma surgery according to the standard regimen per 5 mg daily for 13 weeks deals with significantly reduced production of VEGF in the dominant myoma node compared to perifocal myometrium (p < 0.001), which is similar to patients of the control group. However, when comparing tumor nodes, a significantly lower content of VEGF was revealed in the UA-group (p = 0.026); unlike the perifocal myometrium samples. Conclusion. The use of a selective modulator of progesterone receptors downregulates the production of VEGF by the cells of the myoma nodes and doesn’t impact on the perifocal myometrium

Взаимосвязи в системе мать – плацента – ребенок при состоянии тромботической готовности и гематогенных тромбофилиях

The purpose of this study is to understand the relationships in the mother-placenta-child system in case of hematogenous thrombophilia and thrombotic state of readiness in pregnant women.Materials and methods. The research group consisted of 454 patients, was divided into two subgroups: the 1st subgroup included 225 women (pregnant and, subsequently, obstetric patients) and the 2nd subgroup included their 229 infants who were in the perinatal center of State Novosibirsk Regional Clinical Hospital. At 3–5 days of life 75 newborns from the 2nd sub-group underwent hemostatic system assessment. 42 healthy newborns from somatically healthy mothers (without thrombophilia) were included in the control group. The assessment of their hemostatic system was carried out to determine the performance of reference values.Results. The relationships between the health condition of newborns and hemostatic system disorders in mothers with thrombotic state of readiness, hematogenous thrombophilia, and morphohistological changes in the placenta were studied. The researchers analyzed labour and delivery records, pathomorphological examination of a placenta, neonatal records, and assessed the hemostatic system. A number of complications were detected during a gestational process and an early neonatal period. The correlation analysis has established a relationship in the mother – placenta – child system in a number of factors affecting children’s health outcomes. To correct above mentioned abnormalities preventive measures can be taken. They allow to avert the development of perinatal complications in case of hematogenous thrombophilia and (or) thrombotic readiness.Цель исследования – выявление взаимосвязей в системе мать – плацента – ребенок при наличии гематогенной тромбофилии и (или) состоянии тромботической готовности у женщин во время беременности.Материал и методы. В группу исследования были включены 454 пациента, распределенных на две подгруппы: 1-я – 225 женщин (беременных и в последующем рожениц) и 2-я – 229 их новорожденных, находившихся в отделениях перинатального центра ГБУЗ НСО «Государственная Новосибирская областная клиническая больница». На 3–5-е сут жизни 75 новорожденным из 2-й подгруппы проведено исследование показателей системы гемостаза. В группу контроля входили 42 здоровых новорожденных от соматически здоровых матерей (без тромбофилии). Им проведено исследование системы гемостаза для определения показателей референсных значений.Результаты. Изучены взаимосвязи между нарушениями системы гемостаза у матерей с состоянием тромботической готовности, гематогенной тромбофилией, морфогистологическими изменениями в последе и состоянием здоровья новорожденных. Проведены анализ историй родов, патоморфологического исследования последа и историй развития новорожденных, оценка системы гемостаза. Выявлен ряд осложнений в течении гестационного процесса и раннего неонатального периода. Корреляционный анализ установил наличие взаимосвязей в системе мать – плацента – ребенок по ряду факторов, влияющих на показатели состояния здоровья детей. Для коррекции указанных нарушений могут быть применены на практике профилактические мероприятия, позволяющие предупреждать развитие перинатальных осложнений при гематогенной тромбофилии и (или) тромботической готовности

Влияние раково-эмбрионального антигена на продукцию цитокинов иммунокомпетентными клетками крови у больных с опухолями молочной железы

Aim. Investigation of the influence of canceroembryonic antigen (CEA) on the immune cells in patients with breast tumors.Materials and methods. Peripheral blood of 67 patients with invasive ductal carcinoma (n = 44), fibroadenoma (n = 12) and breast pre-cancer (n = 11). In the supernatants of the blood cells cytokine production induced by CEA was determined by ELISA.Results. It was found that CEA stimulated production of IL-6, IL-8, IL-10, IL-1β, IL-1Ra, TNFα, G-CSF, GM-CSF and the protein MCP-1 by blood immune cells in patients with fibroadenoma compared with groups of patients with invasive ductal carcinoma and precancerous lesions. Stimulation index of CEA on cytokine production by immunocompetent cells in patients in these groups was lower than in groups of patients with fibroadenoma due to initially high levels of spontaneous cytokine production.Results.  In  patients  with  fibroadenoma  CEA  was  found  to  stimulate  the  production  of  IL-6,  IL-8,  IL-10,  IL-1β,  IL-1Ra,  TNFa,  G-CSF,  GM-CSF  and  MCP-1  compared  with  groups  of  patients  with  invasive ductal carcinoma and precancerous conditions. Indexes of the influence of CEA on cytokine production by immunocompetent cells in these groups was lower than in the fibroadenoma due to initially high spontaneous production of cytokines.Conclusion.  Evident  spontaneous  cytokine-producing  function  of  immunocompetent  blood  cells  was revealed in patients with invasive ductal carcinoma and precancerous conditions compared to patients with fibroadenoma.  The  differences  between  the  indices  of  CEA  influence  on  cytokine  production  in  patients with malignant, benign and precancerous conditions can serve as a basis for the development of methods of differential diagnosis of breast tumors.Цель – изучение влияния раково-эмбрионального антигена (РЭА) на иммунокомпетентные клетки крови при опухолях молочной железы.Материалы и методы. Исследована периферическая кровь 67 пациентов с инвазивным протоковым раком (n = 44), фиброаденомой (n = 12) и предраковыми состояниями молочной железы (n = 11). В супернатантах клеток крови иммуноферментным анализом определяли продукцию цитокинов, индуцированную РЭА.Результаты. Обнаружено, что у больных с фиброаденомой РЭА стимулировал выработку IL-6, IL-8, IL-10, IL-1β, IL-1Ra, TNFα, G-CSF, GM-CSF и белка MCP-1 по сравнению с группами больных с инвазивным протоковым раком и предраковыми состояниями. Индексы влияния РЭА на продукцию цитокинов иммунокомпетентными клетками в этих группах были ниже, чем при фиброаденоме вследствие изначально высокой спонтанной продукции цитокинов.Заключение. Выявлена выраженная спонтанная цитокинпродуцирующая функция иммунокомпетентных клеток крови пациентов с инвазивным протоковым раком и предраковыми состояниями по сравнению с группой пациентов с фиброаденомой. Различия в индексах влияния РЭА на продукцию цитокинов у пациентов со злокачественными, доброкачественными и предраковыми состояниями могут служить основой создания методов дифференциальной диагностики опухолей молочной железы

Enzyme immunoassay of interleukin content in tumor supernatants in patients with multiple uterine myoma

The aim of the study was to determine the effects of a mixture of polyclonal activators on the interleukin production by dominant myomatous and myometrial tissue samples under treating by ulipristal acetate (UA), a selective modulator of progesterone receptors.Цель работы — изучить эффект поликлональных активаторов на продукцию интерлейкинов и 17-ОН-прогестерона в ткани доминирующего миоматозного узла и перифокального миометрия в условиях применения улипристала ацетата (УА), селективного модулятора прогестероновых рецепторо

The relationships in the mother – placenta – child system in case of hematogenous thrombophilia and thrombotic state of readiness

The purpose of this study is to understand the relationships in the mother-placenta-child system in case of hematogenous thrombophilia and thrombotic state of readiness in pregnant women.Materials and methods. The research group consisted of 454 patients, was divided into two subgroups: the 1st subgroup included 225 women (pregnant and, subsequently, obstetric patients) and the 2nd subgroup included their 229 infants who were in the perinatal center of State Novosibirsk Regional Clinical Hospital. At 3–5 days of life 75 newborns from the 2nd sub-group underwent hemostatic system assessment. 42 healthy newborns from somatically healthy mothers (without thrombophilia) were included in the control group. The assessment of their hemostatic system was carried out to determine the performance of reference values.Results. The relationships between the health condition of newborns and hemostatic system disorders in mothers with thrombotic state of readiness, hematogenous thrombophilia, and morphohistological changes in the placenta were studied. The researchers analyzed labour and delivery records, pathomorphological examination of a placenta, neonatal records, and assessed the hemostatic system. A number of complications were detected during a gestational process and an early neonatal period. The correlation analysis has established a relationship in the mother – placenta – child system in a number of factors affecting children’s health outcomes. To correct above mentioned abnormalities preventive measures can be taken. They allow to avert the development of perinatal complications in case of hematogenous thrombophilia and (or) thrombotic readiness

Experience of using MHT combined with dipyridamole in patients in the early postmenopause

This article presents the evaluation of efficacy of low-dose dipyridamole used to prevent thrombotic complications during menopausal therapy in women in the early postmenopause

COMPARATIVE ANALYSIS OF CYTOKINE PRODUCTION BY BLOOD IMMUNOCOMPETENT CELLS AND TUMOR IN DIFFERENT AGE GROUPS OF PATIENTS WITH INVASIVE DUCTAL CARCINOMA

It is known that a relationship exists between patient’s age and pathogenesis of malignant tumors associated with ability of tumor and its microenvironment to secrete cytokines that may play an important role in carcinogenesis. The aim of present study was a comparative analysis of cytokine production by peripheral blood cells and tumor samples when exposed to polyclonal activators (PA) in patients of different age groups with invasive ductal carcinoma. Peripheral blood samples of 54 women with invasive ductal carcinoma were under study. The patients were divided into the following groups: I, 40-60 years old; II, 61 year and older. Metastases into lymph nodes were revealed at the moment of study in 13 patients (42%) from group I. By contrast, only 3 of 23 (10%) patients with metastases were revealed in group II. Fisher’s ratio test showed significant differences between occurrence of metastases in lymph nodes, and patient age (p = 0.034). In both groups of patients, there was an increase of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ra, G-CSF, GM-CSF and VEGF concentrations in tumor supernates and its microenvironment, when compared with the production of cytokines by blood cells, thus indicating to high functional activity of tumor together with its microenvironment. Effect of PA led to increase of IL-2, IL-10, IL-17, IL-1β, IL-1ra, TNFα and IFNγ concentrations in blood cells supernatant which suggested their high ability to produce cytokines. In the group of patients who were 40-60 years old, the stimulatory index of PA (SIPA) for IFNγ production was several times higher than similar index in patients aged 61 years or more. Increase of SIPA for all cytokines in blood cells supernates, in comparison to SIPA of tumor supernates, could be explained by initially high levels of spontaneous cytokine production by the tumor and its microenvironment that are able to promote tumor growth. Therefore, effect of PA upon tumor tissue was not so expressed as its effect upon immunocompetent blood cells. Both tumor and microenvironment maintained high ability of IL-18 production, thus confirming its important role in carcinogenesis. In summary, these findings suggest that circulating immunocompetent cells may serve as an additional factor providing tumor progression, due to their high ability to secrete cytokines

Experience in using dipyridamole in the group of pregnant women with a high risk of perinatal pathology

This article provides the evaluation results of the efficacy of low-dose dipyridamole (CurantylÒ) [1, 2] taken to prevent placental insufficiency in women in the group with a high risk of perinatal pathology and feto-maternal disease in past medical history. The early use of low-dose dipyridamole in high-risk groups contributes to a significant reduction in the frequency of intrauterine growth retardation, premature labour and birth of low birth-weight babies