No 4 (2022)

Preeclampsia (PE) is a multisystem pregnancy complication that is the leading cause of maternal and perinatal morbidity and mortality. Today, a large body of data has been accumulated, suggesting that an abnormal maternal immune response in PE is manifested, among other things, as a change in the functional activity of the monocyte-macrophage system, the most important unit of innate immunity. The cause of abnormal placentation underlying PE, especially early PE, may be dysfunction of placental immune cells, namely macrophages. The macrophages are one of the main cellular constituents of the decidua, the maternal component of the placenta, and also play an important role in the development of the fetal part of the placenta, per se being one of the first immune cells of a baby. Depending on their functional state, the macrophages can either stimulate or suppress inflammation, angiogenesis, and the proliferation of neighboring cells. According to the concept of binary polarization, there are two states of macrophages: classically activated macrophages (M1) produce proinflammatory cytokines and reactive oxygen/nitrogen species. The other type of macrophages (M2)produces anti-inflammatory cytokines and is involved in the elimination of inflammation. Conclusion: Turning to the key differential markers of macrophages, this review attempts to summarize the current data on the functioning of the monocyte-macrophage system in physiological pregnancy and PE.

Periodontal diseases are among the most common in the world and are a risk factor for a large number of systemic pathological processes. These systemic conditions currently include unwanted pregnancy outcomes. This review is devoted to the analysis of the etiopathogenetic mechanisms of a relationship between periodontal diseases and unwanted pregnancy outcomes. Publications in recent years on a given topic were analyzed. Most researchers currently consider that the key factor that links periodontal diseases with systemic disease is the ability of a number of periodontal pathogenic bacteria to persist in the body, which reach distant organs and tissues, inducing a pronounced inflammatory response not only at the local, but also at the systemic level. In pregnant women, the incidence of periodontal diseases amounts to as much as 40% and is accompanied by a significant increase in that of preterm birth, premature rupture of membranes, low fetal weight, preeclampsia, and other adverse events. The basis for these impairments in the course of the gestational process is the development of inflammatory reactions that accompany periodontitis and become systemic with time. Inflammation in turn provokes birth activity. In addition, the appearance of periodontal pathogenic bacteria in the placenta and amniotic fluid was recorded in periodontitis diseases, which affects fetal development. Among the periodontal pathogens in these cases, Porphyromonas gingivalis prevails with its unique set of virulence factors, the ability to affect macrophages intracellularly and to induce the autoimmune processes accompanied by the production of specific cardiolipin antibodies. Conclusion: The investigation has found a relationship between periodontal diseases and adverse pregnancy outcomes due to the unity of a number of etiopathogenetic mechanisms. The presence of these phenomena creates a prospect for prevention of unwanted pregnancy outcomes through measures aimed at treating periodontal diseases.

Objective: To assess the morbidity, clinical course, maternal and perinatal outcomes of the new coronavirus infection COVID-19 in pregnant women in the Far Eastern and Siberian Federal Districts based on the results of2020-2021. Materials and methods: The latest information on COVID-19 in pregnant women, women in labor and women who recently gave birth was analyzed. The findings were presented by the chief obstetricians-gynecologists of the regions in the period from March 11, 2020 to December 25, 2021. Results: A total of 27,210 cases of COVID-19 in pregnant, parturient and puerperal women were registered during the 2-year pandemic. The morbidity rate in these women was 2.4 times higher compared to the general population: 18988.0vs 8019.5 per 100,000people. SARS-CoV-2 infection was asymptomatic in 24.2% of mothers; it was mild in 50.0%, moderate in 21.3%, severe in 3.7%, and extremely severe in 0.8%. Pregnant women were more often hospitalized and stayed in intensive care and anesthesiology units compared to patients in the general population (5.5% vs 1.9%, p<0.001), and invasive mechanical ventilation (IMV) was used less often (0.7% vs 1.4%, p<0.05). There were 6,416 (23.6%) patients who gave birth to 6,512 children. Preterm delivery was in 18.5% (6.1% in Russia); cesarean sections - 38.8% (30.1% in Russia); operative vaginal delivery - 0.3% (0.13% in Russia). There were 81 (0.3%) deaths among mothers with COVID-19 (2.5% of cases among the population, p<0.001). Perinatal losses were registered in 156 cases (2.4%): stillbirths - 141 (2.17%), early neonatal mortality - 15 (0.23%). COVID-19(+) was revealed in 165 (2.5%) newborns. Conclusion: The incidence of COVID-19 in pregnant women was significantly higher than in general population during the 2-year pandemic, but the disease is characterized by more frequent hospitalization to intensive care and anesthesiology units, by lower demand for IMV and lower mortality rate. The second year of the pandemic was characterized by a more unfavorable course of COVID-19 in mothers and by an increase in the severe forms of the disease and indicators of maternal and perinatal mortality. The rates of preterm delivery and cesarean section in patients with COVID-19 were higher than in the general population. The incidence of SARS- CoV-2 virus isolation in newborns decreased significantly (from 6.2 to 2.5%). Further studies in this area are necessary. The morbidity rate of COVID-19 in pregnant women in Siberia and the Far East is higher than in the general population, but the disease is characterized by a lower need for IMV and a lower mortality rate. The rates of preterm birth and cesarean section are higher in patients with COVID-19 than in the general population. Finding of the SARS-CoV-2 RNA in newborns suggests vertical transmission of the infection.

Objective: To develop the concept of preeclampsia based on the similar clinical and laboratory features of preeclampsia and insulin resistance syndrome (IRS). Materials and methods: This prospective study included 292 pregnant women retrospectively divided into four groups. Group 1 comprised 89 high-risk women with preeclampsia, Group 2 consisted of 50 women with IRS and preeclampsia, Group 3 consisted of 32 pregnant women with IRS without preeclampsia, Group 4 (control group) included 30 pregnant women with a healthy pregnancy. The examination was conducted at weeks 11-14, 18-21, and 30-34 of pregnancy and the onset of preeclampsia. Results: There was a similarity of clinical manifestations of preeclampsia and IRS in the form of arterial hypertension, proteinuria/microalbuminuria, abnormal diurnal blood pressure pattern, gestational /obstructive sleep apnea syndrome, abdominal visceral adipose tissue accumulation and insomnia. There were no significant differences in the incidence of preeclampsia at different times of its onset and severity in the high-risk group without somatic pathology (49.4%) and the group with IRS (61.0%) [x2=2.56, p=0.11]. Preeclampsia and IRS had common underlying mechanisms, characterized by an increase in pathological IR and hyperinsulinemia (HI) from the early stages of pregnancy and associated with them dyslipidemia, leptinemia, uricemia, abdominal visceral adipose tissue accumulation, inflammatory state, endothelial and hemostasis disorders, due to disruption of gestational adaptation to placental anti-insulin factors that provide stable fetal nutritional and energy supply. The time of preeclampsia onset is determined by processes associated with pathological IR, HI, and alteration in the fetal-placental unit. Conclusion: Comprehensive evaluation of pregnant women with preeclampsia and without somatic comorbidities, with preeclampsia and IRS, and with an uncomplicated pregnancy allowed for creating a scientific concept of preeclampsia development, according to which preeclampsia is considered as a separate gestational clinical and pathogenetic form of IRS, which defines the prospect of the prediction and prevention strategy as the priority directions of medical management of high-risk pregnant women.

Objective: To identify the genera of microorganisms that inhabit endometrium of healthy women and patients with recurrent pregnancy loss (RPL), as well as the genera of microorganisms causing chronic endometritis (CE). Materials and methods: The endometrial microbiome was examined in 14 women with RPL and 15 fertile healthy women by sequencing the next generation 16S rRNA gene. In addition, correlation between CE, CD138, CXCL13 markers and members of various endometrial bacterial genera was analyzed. Results: In patients of both groups, the most abundant bacterial genus in the endometrial samples was Lactobacillus (30.3% in patients with RPL, 29.3% in fertile patients). Statistically significant differences between the groups were found only for the bacterial genera Brevibacillus and Corynebacterium 1. The mean relative abundance of Brevibacillus was higher in the healthy fertile women [0.11 (0;0.3)%] than in the women with RPL [0 (0;0)% (p=0.008)]. The relative abundance of Corynebacterium 1 was 0 (0;0)% and 0.07 (0;0.13)% (p=0.002), respectively. The marker CD 138 was associated with the presence of the bacteria of genus Pseudorhodoferax. The presence of marker CXCL13 was associated with bacteria of genera Alistipes, Butyricimonas, Dialister, Leuconostoc, Neisseria, Parabacteroides, Phascolarctobacterium, Prevotella, Ruminococcaceae, Sutterella, Sphingobium, Subdoligranulum. Conclusion: Simultaneous analysis of the endometrial microbiome and CE markers can optimize preconception care in women with high perinatal risk.

Objective: To investigate the postoperative course of patients receiving exosome - extracellular microvesicles (EMV) of mesenchymal stromal cells (MSC) during a previous cesarean section and the results of subsequent delivery. Materials and methods: The study group included 60 women who received 500 pl of MSC EMV. The control group consisted of 100 patients without exosomal support. At the stage of delivery, patients were further divided into subgroup a (spontaneous delivery) and b (repeat cesarean section). Results: The study group had no septic complications, while in the control group 6% and 2% of the patients developed postpartum endometritis and lochimetra, respectively. In the study group, 5/8 (62.5%) patients had spontaneous labor, while in the control group 16/20 (80%) women underwent a repeat cesarean section. Nineteen biopsy specimens from the dissected scars were submitted for pathomorphological examination. Conclusion: Intraoperative injection of EMV was highly effective in complete scar formation compared to the control group. In 5/8 (62.5%) patients with exosomal support resulted in spontaneous delivery; in the control group, this figure was 4/20 (20%). The study showed the feasibility of using MSC EMV to reduce abdominal delivery rate in patients with post-cesarean uterine scar.

Objective: To identify immunohistochemical markers of uterine myoma recurrence. Materials and methods: The study involved 13 patients (Group 1) with newly diagnosed uterine myomas (UM) and 18 patients (Group 2) with recurrent uterine myomas (R UM). All participants underwent laparoscopic reconstructive surgery at the Department of Operative Gynecology of the V.I. Kulakov NMRC for OG&P. Myomatous tissue and nodules of patients who underwent organ-sparing surgery were submitted for pathomorphological and immunohistochemical examination. Analysis included evaluation of the expression of a proliferation marker (Ki-67), vascular endothelial growth factor (VEGF), progesterone (PgR), and estrogen (ER) receptors, p16 protooncogene, and p53 anti-oncogene. Results: VEGF expression was higher in tumor tissue compared to myometrial samples in patients in both groups. The level of Ki-67 in myomatous nodules in Group 2 patients was higher than in Group 1 (p=0.031), which may reflect the proliferative potential of the tumor most susceptible to recurrence. Higher levels of ER and PgR in the myomatous tissue of patients in Group 2 than in Group 1 probably reflect the potential for tumor growth. The expression level of p16 was higher in the myomatous nodules in patients in Group 2 (p=0.027). Apparently, changes in p53 protein expression are not the leading factor in the pathogenesis of uterine myoma, as no statistically significant differences were found in the expression of this protein between the patients of the study groups. Proteins and growth factors identified in tissue samples may be considered potential markers of the disease and its recurrence. Conclusion: High levels of Ki-67, VEGF, p16, ER, and PgR in uterine myoma nodules are pathogenetic factors of myoma recurrence. Morphological evaluation of myometrial tissues and myomatous nodules in patients undergoing surgery for uterine myoma for the first time and for recurrent myoma allows identification of molecular and biological mechanisms of uterine myoma development and recurrence.

Objective: To study clinical and morphological features of endometrial cancer in postmenopausal women with obesity (BMII≥30 kg/m2) depending on the use of menopausal hormone therapy (MHT). Materials and methods: A prospective study included 214 postmenopausal patients with verified endometrial cancer. The patients underwent surgical treatment in the Department of Gynecology of the Medical and Rehabilitation Center, Ministry of Health of Russia and in the Department of Oncogynecology in the University Clinical Hospital No. 4 of I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, in the period 2019-2021. The stage of uterine cancer was diagnosed in accordance with TNM classification (UICC, the 8th edition, 2016) and international FIGO classification (2009). Endometrial cancer (EC) was differentiated by grades: G1 - well differentiated; G2 - moderately differentiated; G3 - poorly differentiated cancer. The main group included 140postmenopausal women with BMII≥30 kg/m2; 58patients took hormonal therapy (HT). The comparison group comprised 74 women without cancer with BMI 17.6-24.9 kg/m2, including 20 patients receiving HT. All patients used estrogen/gestagen combination preparations for 12 months and longer. Results: Endometrial cancer with myometrial invasion less than 50% (Т1а according to TNM classification (UICC, the 8th edition, 2016) was found signif icantly more often in the subgroup of women with normal body weight, while later stages of EC with advanced invasion were significantly more often in the main group of women with obesity (p=0.012). Assessment of differentiation grades also demonstrated significant differences: in the comparison group the rate of well differentiated EC (G1) was significantly higher compared with the main group, where moderately differentiated EC was observed more often (p=0.001). The comparative analysis of the studied parameters in the subgroups of women who did not take HT, showed no significant differences (р=0.383; р=0.745). Conclusion: The study demonstrated that in the subgroup of patients with obesity, who used HT, the incidence of later stages of moderately and poorly differentiated (G2-G3) EC was significantly higher. The results of the study proved importance of BMI monitoring and timely correction of hormonal-metabolic disorders in menopausal women prior to HT, aimed both to reduce EC rates, and to minimize the risk of development of later stages of moderately and poorly differentitated EC.

Objective: To determine the frequency of iron deficiency in the pre-pregnancy period in Moscow residents with the previous history of early pregnancy losses. Materials and methods: The study included 98 women of reproductive age (18-39 years old) who presented to the clinic with the history of early pregnancy loss. A retrospective study was performed during six months in 2019 2020 at a multidisciplinary clinic in Moscow, Russia. The patients were evaluated for hemoglobin, serum iron and ferritin. Results: The histories of42 (42.85%) women with early pregnancy losses showed iron def iciency (according to the criteria of the WHO - ferritin 15 mcg/ml or less) and 32 (32.7%) patients had iron deficiency anemia (IDA), i.e. 2/3 of women, namely 75 (75.5%), planned their pregnancy without any iron stores in the body. The medication Ferretab comp. was chosen as an iron supplement. This medication contains 50 mg of elemental iron (152 mg of ferrous fumarate) and 500 mcg of folic acid. During three months, all women who had preconception care took one capsule a day with increased dose of ferritin to 30 mcg/ml or more; no side effects were reported. Two capsules of Ferretab comp. were taken in the morning by 41 women; 2/3 of them demonstrated the restored level of hemoglobin within 4-5 weeks, all the rest women had it within 8-9 weeks. One woman did not have any effect from taking the medication Ferretab comp.; a thorough examination revealed gastritis and colitis, and appropriate therapy was prescribed. All patients became pregnant, four of them (4.08%) had pregnancy following assisted reproductive technologies. The level of ferritin during pregnancy was not assessed, IDA was detected in four cases (4.1%). These pregnant women had bloody vaginal discharge (threatened miscarriage, placenta previa). Conclusion: Iron deficiency and IDA are common in patients with a history of early pregnancy loss. In order to restore the level of the microelement in the organism of a woman before the onset of pregnancy, it is necessary to determine the level of ferritin and hemoglobin. Ferretab comp. is a medication containing 50 mg of iron (iron fumarate) and 500 mcg of folic acid; it is released during the passage of the gastrointestinal tract, it has a minimal number of side effects, and effectively replenishes iron stores.

Background: The dualistic theory of ovarian cancer has been currently accepted. Types 1 and 2 tumors are different molecular biological masses and are not components of the same pathway of carcinogenesis. They differ in the morphological pattern, molecular prof ile, clinical course, and approaches to therapy. It is important for clinical practice to establish the true cause of cancer, as this may affect treatment policy in patients. Case report: The paper describes a clinical case of a combination of the mutations characteristic of Types 1 and 2 tumors: the patient has been found to have a combination of a germline mutation in the BRCA1 gene and a somatic mutation in the NRAS gene and the development of the tumor along the molecule cascade that is uncharacteristic for BRCA1 mutation carriers. Conclusion: The identification of the true genetic cause of the development of an ovarian tumor is emphasized to be of great importance, since this affects the treatment strategy.