BACKGROUND: Approximately two thirds of all implantation failures are due to impaired endometrial receptivity. The lack of implantation may be due to an implantation window failure found in approximately 25-30% of women with a history of failure to perform assisted reproductive technology protocols. The receptivity phase in such patients can be shifted in terms of timing, have a short duration, or not form. Currently, there are several commercial tests for determining endometrial receptivity based on transcriptomic data. However, these tests differ very significantly from each other in the set of genes studied, and the exact mechanism of endometrial receptivity is still not fully understood.
AIM: The aim of this study was to create and check our own test based on RNA AmpliSeq technology to assess the receptivity status of the endometrium and the implantation window.
MATERIALS AND METHODS: We previously created an RNAampliSeq panel containing 421 gens. With its use, the differential expression of these genes was analyzed in 38 endometrial samples taken in the proliferative and receptive phases.
RESULTS: The studied samples form clearly distinguishable clusters with the receptive and proliferative endometria. 271 genes from our panel are differentially expressed in different phases of the menstrual cycle.
CONCLUSIONS: We have created and tested a model that allows clearly distinguishing between the proliferative endometrium and the receptive one and identifying patients with disorders of the menstrual cycle.
Background. Deep infiltrative endometriosis (DIE) is characterized by the invasion of endometriosis lesions in tissues and organs to a depth of over 5 mm. In recent years, the proportion of infiltrative forms of endometriosis has been steadily increasing. The main clinical manifestations is chronic pelvic pain syndrome and infertility. A key element in the pathogenesis of deep infiltrative endometriosis is an ineffective inflammatory response.Objective. Evaluate the content and the role of pro- and anti-inflammatory cytokines, growth factors and chemokines in the pathogenesis of deep infiltrative endometriosis for pathogenetically grounded immunomodulatory therapy.Materials and methods. The present study included 120 women with deep infiltrative endometriosis. In the peritoneal fluid, using IFA determined the level of IL-33, and with the help of running cytofluometry format NEA has estimated the levels of IL-2, IL-6, IL-10, IP-10, MCP-1 and growth factors – FGF, TGF-β.Results. In the study of peritoneal fluid of patients with DIE was a significant decrease in the level of IL-2 and IL-10 6.7 times compared to the control group. The level of IL-6 was increased in 1.5 times, as well as the level of IL-33, and was awarded the data link cytokines with the severity of pain. DIE is characterized by increased levels of MCP-1 in 2 times and decrease in IP-10 1.3 times, as well as increased levels of FGF 1.5 times and reduced levels of TGF-β in 1.9 times in comparison with the control group.Conclusion. For effective treatment of DIE and to increase the duration of recurrence-free period actual and pathogenetically justified is the inclusion of a combined treatment of immunomodulatory therapy with recombinant IL-2 aimed at the elimination of immunological disorders in the pelvic cavity.
Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder in women of reproductive age. Further research is required to justify new directions of effective targeted therapy of this condition. Resveratrol possesses anti-inflammatory, antioxidant and antidiabetic properties. The purpose of this study was to evaluate the potential effectiveness of resveratrol in PCOS based on the created model of this disease in Wistar rats.The PCOS model was created by oral administration of letrozole to female Wistar rats.. The animals received resveratrol at a dosage of 20 mg/kg and 30 mg/kg for the next 30 days. Then ovariectomy was performed for histological confirmation of the effectiveness of resveratrol in the treatment of PCOS. Regularity of estrous cycle, animal's body mass and the level of soluble receptors for advanced glycation end products (sRAGE) in the blood of rats were also evaluated in dynamics.The study revealed that administration of resveratrol leads to dose-dependent restoration of normal morphology of ovarian tissue, normalizes regularity of estrous cycle and decreases body weight of rats with PCOS.The results obtained in rats suggest that resveratrol may be a promising agent for the treatment of PCOS in women.
BACKGROUND: The studies on how sex steroid hormones affect growth of uterine leiomyoma cells with chromosomal abnormalities is highly relevant for development of personalized tumor therapy.
AIM: To study in vitro the isolated and combined effects of estrogen and progesterone on uterine leiomyoma cells with chromosomal aberrations — deletions in 7q.
MATERIALS AND METHODS: The study was performed on 15 uterine leiomyomas, excised from 15 women of 26–44 years of age who were not treated with hormones. Uterine leiomyoma cells were cultured in hormone-free medium, in the medium supplemented with estrogen, progesterone or both hormones. The chromosome preparations were made and stained with QFH/AcD to perform conventional karyotyping and fluorescence in situ hybridization (FISH) to accurately describe chromosomal rearrangements. The frequency of uterine leiomyoma cells with chromosomal aberrations was assessed by interphase FISH.
RESULTS: Deletions in 7q were identified in 6 out of 15 karyotyped uterine leiomyomas; four of them had one clone with deletion in 7q whereas two others comprised two clones with 7q deletions of different length. The frequency of cells carrying deletions in 7q greatly varied in uterine leiomyoma samples cultured in hormone-free medium: from 3.5% to 93.6%. Exposure of cell cultures to estrogen and progesterone resulted in a fold change frequency increase in some of the uterine leiomyomas and decrease in the others. The most significant changes in the frequency of cells with deletions in 7q were registered in response to the isolated estrogen and, to a lesser extent, to progesterone exposure; less significant changes were observed after combined hormonal effect.
CONCLUSIONS: In uterine leiomyomas with deletions in 7q, the frequency of abnormal cells may either increase or decrease in response to estrogen and progesterone in vitro supplementation. The isolated effect of estrogen or progesterone on the frequency of uterine leiomyoma cells with deletion in 7q is more pronounced compared to the combined one.
Introduction: Changes in hormonal status in patients with prolonged disorders of consciousness (PDC) remain poorly understood. There are no studies devoted to the investigation of prognostic value of hormonal changes to predict the outcome which is primarily due to a relatively small number of patients, different variants of structural brain disorders in vegetative state (VS) patients, concomitant somatic pathology including typical complications. The objective: to study the correlation between outcomes in VS patients with hormonal status and the level of natriuretic peptide. Subjects and methods. 275 patients in VS were examined for the time period from 2007 to 2017. 152 patients had sequela of traumatic brain injury (TBI) and 123 patients suffered from hypoxic brain damage. All patients matched the international criteria of VS diagnosis. In all patients, blood samples were collected during the first week after admission to ICU to test hormones and natriuretic peptide levels. ACTH, cortisol, TSH, free T 3 and T 4 , STH, prolactin and natriuretic peptide were tested in the period from 2 to 4 months of staying in VS. In men, the level of total testosterone, LH and FSH was additionally tested. The obtained data were compared with VS outcome. Results. The tested hormones were stably insufficient only in few VS patients. None of the tested hormones of the hypothalamic-pituitary-adrenal axis made a reliable criterion for predicting VS outcome. The tendency of disrupted rhythm of cortisol secretion was found to be most frequent and consistent, with higher rates in the evening hours. The average value of STH was higher in men with sequela of traumatic brain injury who had recovered consciousness versus those who remained in VS. A significant decrease in testosterone levels, regardless of age, was found in the patients with TBI sequela. Mean levels of LH were higher in patients with TBI sequela and hypoxia who remained unconscious versus patients who later restored consciousness. The average level of FSH was higher in patients who had recovered consciousness compared to those who remained in chronic VS. The increased level of natriuretic peptide was observed both in patients who remained in chronic VS and in those who restored consciousness. Conclusions. When investigating levels of certain hormones, no specific endocrine background characterizing this category of patients was found. Abnormal rhythms of some hormones secretion, in particular cortisol, can be considered typical of VS patients especially patients with TBI sequela.
To analyze glucose variability and investigate its role as a predictor for preeclampsia development in pregnant women with type 1 diabetes mellitus (T1DM) with various insulin therapy regimens.A total of 200 pregnant women with T1DM were included in the study. A hundred women used continuous subcutaneous insulin infusion (CSII), and the rest of the group was administered with multiple daily insulin injections (MDI). Continuous glucose monitoring (CGM), index calculation of glucose variability (MAGE, MODD, CONGA, and CV), assessment of preeclampsia frequency and severity were conducted.The work results show the link between the severity rate of preeclampsia and the duration of T1DM as well as the level of HbA1c before and during pregnancy. The rate of preeclampsia in the group of women, using CSII comprises 26.8% of cases that appear less than in the group of those, administered with MDI that is 46.6% (χ2 = 5.45; р < .05). A negative correlation is defined between pathological glucose variability and gestational age when preeclampsia occurs. A negative correlation was also revealed between MODD, CV, and the time for the detection of preeclampsia: r = -0.30, r = -0.24, respectively. The study illustrates the correlation obtained between preeclampsia and glucose variability and the value of MAGE, MODD, CV, and SD. Preeclampsia development is affected by the duration of hyperglycemic conditions in the third trimester of pregnancy. The data in the group of women using MDI marks the early development of preeclampsia on the 33.0 [32-34] week of pregnancy compared to the group of women practicing CSII on 35.5 [33-36] week of pregnancy (Z = 5.4; p < .001). The increase of risk of preeclampsia development is proved in pregnant patients with T1DM when the hyperglycemic condition lasts more than 25% of a 24-h period according to the rate of CGM and measurements of glucose variability MODD > 1.07 and CONGA > 3.39.Comprehensive evaluation of the glycemic profile while using CGM revealed a correlation between pathological glucose variability and the frequency and severity of preeclampsia thus proving the benefits of CSII in pregnant patients with T1DM to perform glycemic targets and decrease glucose variability, which eventually led to the decrease of preeclampsia frequency in this group of women.
This review article presents modern data on the diagnosis and pathogenesis of adenomyosis, various classifications of the disease being highlighted. The role of genetic and immunological factors in the development of internal endometriosis is discussed. The results of domestic and foreign studies are presented, with the most informative non-invasive markers for the diagnosis of adenomyosis described.
Background. Endometriosis is a chronic progressive recurrent disease associated with pelvis pain, menses disorders and infertility. The prevalence of endometriosis (EGE) tends to increase steadily and reaches 15% among women of reproductive age. Endometriosis-associated pain can persist despite surgical and drug treatment of this disease, resulting in a significant decrease in the quality of life of patients. The main causes of EGE-associated pain are local inflammatory, adhesive, neuro- and angiogenic processes. Currently, the search for alternative methods of pathogenesis-based therapy of the disease is one of the priority tasks. Given its anti-inflammatory, enzymatic, antioxidant effects and anti-adhesion mechanism of action, bovhyaluronidase azoximer, an enzyme agent with hyaluronidase activity, is a promising drug in the complex therapy of EGE.
Aim. To compare bovhyaluronidase azoxymer efficacy in complex therapy of patients with EGE using dienogest (2 mg) versus monotherapy with this progestogen in real clinical practice.
Materials and methods. 149 female patients of reproductive age were enrolled in the study after surgical treatment for EGE. The patients were divided into two groups: the first group (n=94) was treated with complex therapy by dienogest (2 mg) daily within 6 months in combination with suppositories containing bovhyaluronidase azoxymer (3000 IU): 1 suppositorium once within 3 days,10 administrations; and then 1 suppositorium once in 7 days, 17 administrations, within 120 days; the second group (n=55) received monotherapy with dienogest (2 mg) daily up to 6 months. EGE-associated pelvic pain intensity, uterine bleeding severity and life quality were assessed during the study, after 30, 90, 150 and 180 days with regard to the basic values.
Results. There was a statistically significant reduction of pain intensity observed in both groups compared to the basic level, using visual analogue scale of pain (VAS), the Biberoglu and Berman scale, but there was a distinct trend towards a more significant decrease in pelvic pain score basing on VAS in patients received complex therapy versus monotherapy with dienogest 2 mg after 30 days of treatment (p=0.051). Life quality assessment of patients in both groups revealed statistically significant increase in scores for all values of the SF-36 life quality scale just after the second follow-up visit. More significant life quality improvement in patients was observed with complex therapy with regard to such descriptors of the SF-36 Questionnaire as Physical functioning, Role-physical functioning, Pain intensity (p0.05).
Conclusion. Bovhyaluronidase azoxymer in combination with dienogest (2 mg) improves the overall therapy effectiveness for EGE and is associated with more significant reduction in pelvic pain intensity, inflammatory and adhesive processes in the pelvis, and significant life quality improvement compared to monotherapy with 2 mg dienogest.
BACKGROUND: Patients with any form of diabetes during pregnancy should achieve the target (close to physiological) values of glycaemia, the main condition for a safe course and outcomes of pregnancy. To accomplish this task, effective and safe methods of insulin therapy should be selected.
AIM: To determine the glycaemic profile and pregnancy outcomes in women with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) and multiple insulin injections (MII).
METHODS: A continuous glucose monitoring (CGM) of 100 pregnant women with type 1 diabetes treated with CSII and 100 women treated with MII was conducted to assess the effectiveness of these insulin therapy regimens in achieving target blood glucose values.
RESULTS: HbA1c levels were significantly lower during the first, second, and third trimesters in patients treated with CSII than those treated with MII. Glucose variability has already improved since the second trimester of pregnancy in women treated with CSII, which was not observed in those treated with MII. The period of hyperglycaemia according to the results in pregnant women treated with CSII was 25 [13; 38] %, which was lower than those treated with MII, 41 [18; 54] %. No risk of obstetric and perinatal complications was observed with the duration of the hyperglycaemic state of 25% of the CGM time, whereas the risk of neonatal hypoglycaemia appeared with the duration of the hypoglycaemic state of a mother with type 1 diabetes of 0.2%. The relationship between glucose variability in terms of MAGE and MODD and the risk of developing macrosomia has been observed, and the dependence of glucose variability (MODD and CONGA) and the risk of neonatal hypoglycaemia and preeclampsia have also been confirmed.
CONCLUSION: Comprehensive assessment of the glycaemic profile when using CSII, confirmed the advantages of using CSII in pregnant women with type 1 diabetes to achieve the target glycaemia values, to reduce glucose variability and duration of hypoglycaemic episodes, which led to decreased frequency of obstetric and perinatal complications.
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