No 6 (2021)

This literature review analyzes the studies published over the past 10 years on the role of the complement system in the physiological development of pregnancy. The complement system belongs to the factors of innate immunity and plays an important role in maintaining homeostasis and developing a normal pregnancy. The paper presents the currently available data on changes in complement factors from preimplantation to full term. Many authors recognize that normal pregnancy develops after the moderate activation of the system of the complement, which is accompanied by the higher expression of its regulatory proteins in both maternal blood flow and the placenta. By the end of the third trimester, there are increases in the concentration of C3, C4d, C9, sC5b-9, anaphylatoxins C3a, C4a, C5a, regulatory factor H, as well as the C4d/C4, C3a/C3 ratios. Adequate placentation is accompanied by local expression of regulatory proteins, such as DAF (CD55), CD59, and MCP (CD46), which block the formation of C3 and C5 convertases and the assembly of MAC on the cell membrane surface. In addition, the investigators studied the role of the complement system in the processes of implantation and placentation, development of fetal organs and systems, and preparation for childbirth, as well as the risk of pregnancy complications and postnatal diseases in both the mother and her baby when complementary homeostasis is disrupted. Conclusion. Clinical trials using complement biomarkers in serum, urine, and placenta have shown a direct relationship between complement system dysregulation and adverse pregnancy outcomes, such as preeclampsia, fetal growth retardation, miscarriage, and preterm birth.

The predominant role in the overall pattern of perinatal mortality is currently played by antenatal fetal death (73%), the most considerable contribution to the pattern of which is made by chronic hypoxia. The pathophysiological processes of chronic fetal hypoxia are multicomponent and have not been fully explored. Its diagnostic methods used in obstetric practice have their limitations and disadvantages; they are often set up to register secondary or indirect signs, which cannot accurately predict severe neonatal outcomes or stillbirth. The most promising areas for research can be considered methods for the early diagnosis of placental insufficiency and noninvasive techniques for the functional assessment of fetal hypoxia, which is fundamentally important for initiating its maintenance therapy. This paper considers the general issues related to the pathophysiology of chronic hypoxia in the fetus and study methods for its assessment. It describes the new criteria for Doppler study, the widely used diagnostic method, which can assess the functional state of the fetal cardiovascular system in case of cardiac sparing and brain sparing effects. There are also the results of some pilot studies concerning the determination of specific hypoxia-induced RNA of the fetus in maternal blood, which have a high potential for the clinical biomarkers of obstetric complications. Attention is paid to a study method, such as MRI, the value of which will be able to significantly increase in the coming years. MRI allows a detailed study of the anatomical features of the placenta, identifying the causes of placental insufficiency. Furthermore, diffusion-weighted MRI (DW-MRI) or diffuse-tensor imaging (DTI) can provide additional functional information about the placenta, by detecting the areas of hypoperfusion. MRI also holds great promise to assess the fetal functional state: the markers of heart failure and lung tissue maturity are only part of new noninvasive fetal state imaging techniques that have the potential for further investigation and implementation in obstetric practice. Conclusion. Doppler blood flow study remains promising in the antenatal period; at the same time, great hopes are associated with MRI of placental insufficiency and the functional assessment of the fetal state, analysis of circulating fetal nucleic acids in maternal blood as markers of obstetric or fetal pathology.

Recently, there have been more and more reports on the role of intrauterine infection (IUI) in pregnant women in the occurrence of a wide spectrum of obstetric and perinatal complications. To date, there is no generally accepted terminology for this complication. IUIshould be considered as a spectrum of infectious and inflammatory processes in various placental structures. The diagnosis of IUI during pregnancy presents significant difficulties. IUI can be verified only on the basis of placental morphological examination. In this connection, this diagnosis is made mainly retrospectively after the related complications have occurred. At the present stage, the search for non-invasive markers of subclinical IUI is being continued. Much attention is paid to the peculiarities of the course of pregnancy, ultrasound signs, and the study of immune factors. The treatment of IUI is no less difficult than its diagnosis. Recent publications on the pathogenesis, diagnosis, and treatment of IUI during pregnancy are reviewed. Conclusion. Despite the clinical significance of the problem of IUI during pregnancy, there is still no algorithm that allows for a comprehensive approach to diagnostic and therapeutic measures. The timely diagnosis and reasonable use of antimicrobial drugs can become a promising area in the package of therapeutic measures for the prevention of pregnancy complications and adverse perinatal outcomes in the presence of IUI.

Malignant neoplasms (MNs) of the reproductive system are the most common cancer localizations in the female population of the Russian Federation. Surgery is the most common treatment for genital MNs. Bilateral oophorectomy leads to surgical menopause (SM) and, as a result, contributes to family problems and limited professional activities, and has an extremely negative impact on quality of life in reproductive-aged women. SM is associated with body composition changes that are characterized by adipose tissue redistribution, increased visceral fat, and decreased muscle mass. Bilateral oophorectomy has been found to contribute to an impaired lipid profile, insulin resistance, and, as a result, a higher risk for cardiovascular disease (CVD) and diabetes mellitus (DM). The clinical manifestations of SM are highly diversified, and vasomotor symptoms (VMS) are some of the most painful ones, which affect up to 85% of women. VMSs reduce not only quality of life in patients, but also have an impact on their health. In patients with severe SM, the risk for CVD and DM has been established to increase by 50-77% and 20%, respectively; which correlates with the severity of SM. The most serious and intense manifestations of VMS are typical for patients with SM, especially for those with cancers, which extremely negatively affects their quality of life, by contributing to sleep problems, anxiety and depressive disorders. Another clinical manifestation of SM is an impaired attention and memory, which has a profoundly negative impact on quality of life in women and contributes to their limited professional activities. As many as 75% of cancer patients receiving chemotherapy or hormone therapy suffer from cognitive impairment. Conclusion. The timely and adequate comprehensive treatment aimed at correcting the early and long-term consequences of sex hormone deficiency is extremely important in patients with SM and a history of reproductive system cancers.

Aim. To provide scientific substantiation of the distinction between the notions “incomplete uterine rupture after surgery” and “dehiscence/aneurysm of the uterine scar during pregnancy and childbirth”. Materials and methods. A retrospective analysis of 112 birth histories with uterine rupture along the scar after cesarean section, 44 birth histories of patients with dehiscence/aneurysm of the uterine scar after cesarean section and myomectomy was carried out. The births took place in maternity hospitals of Moscow Department of Healthcare, clinical hospital MD Group in the period from 1999 to 2018. Results. Out of 112patients with uterine rupture along the scar after cesarean section, delivery by re-surgery was in 62 patients, spontaneous delivery was in 50. Out of 62 patients with abdominal delivery, the risk symptoms of uterine rupture were in 53, and the incipient uterine rupture was in 48 women. Out of 50patients, uterine rupture after spontaneous delivery was in 49 women in early postpartum period. Out of 112 babies, 5 were born dead, 3 - with severe asphyxia, and 6 - with moderate asphyxia. In 29patients, the total blood loss volume was more than 1000 ml. Dehiscence/aneurysm of the uterine scar had common signs: the patients had no complaints, ultrasound examination detected very thin lower uterine segment (<1 mm), pregnancy was prolonged to full-term or almost full-term pregnancy, the intraoperative scar dehiscence was seen as a translucent bulging into the gestational sac and blood loss during cesarean section was with in the typical range for the blood loss. Conclusion. The notion “dehiscence/aneurysm of the uterine scar” should be distinguished from “incomplete uterine rupture”, since the concept of commonality of these notions will justify the doctors and contribute to their incompetence. The doctors should know both the symptoms of the risk for uterine rupture and the incipient uterine rupture.

Aim. Assessment of the risk of pelvic organ prolapse in women after obstetrical traumas. Materials and methods. This was a prospective observational study. It included the women aged 45-74 years. The study was conducted in the Antenatal Clinic of Maternity hospital No. 7 in Baku. Initially, a list of all female patients (17,814) aged 45-75 years, who were assigned to the Antenatal Clinics was prepared. The research sample included consistently every 25th woman from this list. The sample size (710 women) was determined taking into account the probable prevalence of pelvic organ prolapse in women and maximum permissible sampling error (3%). The sample population was divided into groups according to the degree of prolapse, the age, number of pregnancies and childbirths in medical history, body weight and body mass index, the employment, educational level and severity of comorbidity. The differences between the groups were assessed using x2 test. Statistical data processing was carried out using qualitative data analysis method. Results. The prevalence of pelvic organ prolapse was 59.9% among all assessed women, and it was low in the group of women without obstetric traumas in history (26.5%), and in women with obstetric traumas of different degrees it was 67.2-100%. Assessment of risk factors in women showed that only a small proportion of them did not have risk factors for pelvic organ prolapse (50/710; 7%). Most of women had 2 and 3 risk factors in history (32.5 and 27.0%, respectively). Conclusion. The prevalence of pelvic organ prolapse was 59.9% and varied ranging from 26.5% (in the absence of obstetric traumas) to 100% (with third- and fourth-degree perineal tears in medical history). Among the risk factors for genital prolapse (age, dysplasia of connective tissue, burdened family history and others), obstetric traumas prevail. A combination of risk factors and obstetric traumas increase the risk of pelvic organ prolapse.

Aim. To compare blood and peritoneal fluid effector and regulatory subpopulations of innate immunity cells of women with different stages of endometriosis. Materials and methods. The study included women with stage I-II (n=12) and III-IV(n=28) endometriosis. Blood samples drawn from the study subjects before surgery and peritoneal fluid samples obtained intraoperatively were tested for mononuclear cells using flow cytometry. Results. The number of neutrophils and their ratio to lymphocytes were increased in the peripheral blood of women with endometriosis. There were no significant changes in the subpopulations of NK cells, neither between the groups of patients with endometriosis nor compared with the control group. However, patients in both groups had a pronounced decrease in the proportion of T-regulatory lymphocytes with CD4+CD25+CD127low/-phenotype (P=0.004), a decrease in the number of CD14highCD16low - classical (P=0.038) and an increase in CD14highCD16high - intermediate monocytes (P=0.028). The peritoneal fluid of patients with endometriosis was characterized by an increased proportion of cytotoxic CD3-CD56+CD16+- and regulatory CD56brigh'CD16dim-NK cells compared with control subjects. Conclusion. Changes in the ratio of blood neutrophils and lymphocytes and the ratio of monocyte subpopulations suggest the persistence of the systemic inflammatory process. The decrease in the proportion of T-regulatory cells in the peripheral blood and the increase in the proportion of cytotoxic and regulatory subpopulations of NK cells in the peritoneal fluid indicates dysregulation of immune response mechanisms contributing to the development of endometriosis.

Objective. To identify the most informative qualitative and quantitative diagnostic criteria for adenomyosis according to the data of transvaginal contrast-enhanced ultrasound (TV CEUS). Materials and methods. Forty-eight patients (a study group) with adenomyosis and 36 women (a control group) with the unchanged myometrium were examined. All the patients underwent TV CEUS using the ultrasound contrast agent (USCA) SonoVue. The investigation was conducted in the V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, in 2018-2019. Results. There were differences in the qualitative parameters of TV CEUS of the myometrium in health and adenomyosis in terms of the intensity and homogeneity of enhancement, the rate and type of contrasting, and the uniformity of USCA washout. The best diagnostic informative value indicators of adenomyosis are heterogeneous contrasting (sensitivity - 100%, specificity - 83.33%, and AUC - 0.917), uneven washout (sensitivity - 85.42%, specificity - 83.33%, and AUC - 0.844), slow accumulation (sensitivity - 81.25%, specificity - 88.89%, and AUC - 0.851), and low contrasting (sensitivity - 72.92%, specificity - 88.89%, and AUC - 0.809). There were differences between the groups in the quantitative parameters of TTR, PI, AT, AS, and DS. With a threshold value of TTP > 19.52s, sensitivity, specificity, andAUC were 87.0%, 83.3%, and 0.895, respectively; with a threshold value of PI < 36.1 dB, these were 95.7%, 83.3%, and AUC 0.941. Conclusion. TV CEUS revealed the most informative qualitative and quantitative diagnostic criteria for adenomyosis.

Objective. To develop recommendations for the choice of modern contraceptives, depending on the vaginal microbiocenosis and individual genetic characteristics. Subjects and methods. The investigation enrolled 120 women of reproductive age (18-45 years) who desired to use contraception; they were randomly divided into four equal groups: 1) 30 patients using barrier contraceptive methods; 2) 30 patients taking a monophasic combined oral estrogen-gestagenic contraceptive; 3) 30 women using a vaginal ring; 4) 30 women having a hormone-releasing intrauterine system. A clinical examination was performed 3, 6, and 9 months after starting hormonal contraceptives in order to estimate the frequency of and time to the occurrence of their adverse reactions. The composition of the vaginal microbiota was quantitatively assessed by Femoflor 16 PCR. To study gene polymorphism, DNA was isolated from peripheral blood. Results. In women using hormonal contraception, vaginal dysbiosis due the higher proportion of Gardnerella vaginalis was a significant risk factor for inflammatory diseases. Groups at risk for developing dysbiosis were determined in the examined groups using contraception. Patients with the IL4: -590 T/Tgenotype or carriers of the T allele of the IL1R1 polymorphic locus: Pst11970 C>T were shown to have a high risk for developing inflammatory diseases and to require monitoring of the vaginal microbiocenosis during hormonal contraception. Conclusion. Thus, dysbiosis is an important prognostic criterion when prescribing a contraceptive method. It is advisable to assess the vaginal biocenosis during hormonal contraception once every 12 months.

Objective. To optimize treatment and intimate hygiene for mixed and Candida vulvovaginitis in patients with persistent herpesvirus infection. Materials and methods. Eighty-three patients with mixed vulvovaginitis and 81 patients with vulvovaginal candidiasis that had developed in the presence of persistent herpesvirus infections were examined and treated. In mixed vulvovaginitis, standard local antibacterial therapy + Panavir as one suppository once daily was prescribed for 10 days. In Candida vulvovaginitis, antimycotics + Panavir as one suppository once daily was used for 10 days. At the second stage, both groups underwent comparative characterization of the feminine intimate sprays Panavir intima and Panavir Intima Normaflor used once daily for 14 days, followed by their application once every 3 days for another 2 weeks. Results. Including the antiviral drug Panavir and the spray Panavir Intimate Normaflor along with antibacterial drugs in the therapy of mixed vulvovaginitis showed a 6.4-fold reduction in disease recurrence. Incorporating the antiviral drug Panavir as suppositories along with antimycotics, as well as the spray Panavir Intima at the second stage displayed a 9.1-fold decrease in the recurring process. Conclusion. To optimize therapy for vulvovaginitis in the presence of herpesvirus infections, it is advisable to take the antiviral drug Panavir with a subsequent recommendation to use the feminine intimate sprays Panavir Intima Normaflor and Panavir Intima for mixed vulvovaginitis and candida vulvovaginitis, respectively.

Objective. To investigate the clinical and bacteriological efficacy of nifuratel in the therapy of urinary tract infections. Materials and methods. This systematic review includes all studies published in English and Russian for the period 1969-2020 that assessed the effectiveness of nifuratel in the treatment of lower urinary tract infections (LUTI) in women, including pregnant women. The review was written using the PRISMA checklist. The analysis involved randomized and nonrandomized original clinical trials (prospective controlled, prospective cohort, retrospective studies, etc.) and case series studies that included at least 10patients. Results. After searching for and excluding duplicates, 192 publications were included in the screening, of which 169 ones were excluded by reviewing the title and abstract. A total of 9 studies were obtained for qualitative synthesis, 7 of them were clinical ones that included the analysis of 442patients. Conclusion. The systematic review shows that the efficacy of nifuratel as a drug for the therapy of urinary tract infections is comparable and sometimes superior to that of other antibiotics. Nifuratel shows more pronounced therapeutic efficacy and better tolerability compared to nitrofurantoin. Today, it is impossible to consider LUTI in women in isolation and not take into account the state of biocenosis of the vagina and intestines. Nifuratel is also interesting in that it has a spectrum of activity not only with respect to the main uropathogens, but also the causative agents of individual vaginal infections and is suitable for the treatment of acute and chronic LUTI. However, there remains a need to conduct a large number of randomized controlled trials, as well as to examine the safety profile for renal failure and in the elderly.

Background. Pregnancy-associated atypical hemolytic-uremic syndrome (aHUS) is characterized by an aggressive avalanche-like course and an extremely poor prognosis with fulminant thrombotic microangiopathy (TMA), whereas targeted therapy with a complement-blocking drug is always impossible in the first 24 hours. There are very few cases of recurrent pregnancy-associated aHUS in the modern literature; in this connection it is important to display the management of patients with the second disease episode that has developed during pregnancy. In the era of eculizumab, the role of plasma exchange in verified aHUS is becoming increasingly limited. Just the same, when eculizumab is not available, plasma exchange remains the only treatment option. Case report. The paper presents the experience in successfully treating two consecutive pregnancy-associated aHUS episodes manifested after delivery in one patient, by using only plasma exchange, which showed a favorable outcome, including complete recovery of renal function. Conclusion. Different types of TMA in pregnancy are fulminant and represent a life-threatening condition for the mother. In this condition, the most urgent issue is the timely initiation of appropriate therapy. The presented observation of two aHUS episodes demonstrates difficulties in choosing a treatment policy and in making a rapid differential diagnosis, even when there is only one episode of TMA in the history. The discussion lists the recommended treatment regimens, as well as the possibility of a favorable outcome with timely initiation of plasma therapy