No 6 (2022)

Chronic endometritis (CE) is an infectious and inflammatory disease of the uterine mucosa, which leads to impaired reproductive function. The mechanism of this disorder is associated with the activation of pro-inflammatory cytokines and with a change in the ratio of immune cell populations in the endometrial mucosa. There are few studies that directly or indirectly indicate an association between the carriage of infectious viruses and the development of chronic inflammation of reproductive organs. At the same time, the role of Toll-like receptors (TLRs) that are responsible for the recognition of bacterial and viral agents on the mucosal surfaces, in the development and course of pelvic infectious and inflammatory diseases is being actively studied. The purpose of this review is to systematize the available information on the contribution of sexually transmitted viral infections to the development and course of CE and on the role of the molecular mechanisms of interaction of viral agents with TLRs. Literature was sought on January 19, 2022 to February 21, 2022, by using the scientific literature databases NCBI, PubMed, and Google Scholar (foreign sources), CyberLeninka and eLibrary (Russian sources). The review includes literature sources for the period 1986-2021. The data presented in this review cannot lead to the conclusion that viral infections of the reproductive tract play a direct role in the development of CE with the involvement of TLRs. However, the presence of reproductive tract TLR expression and its change influenced by physiological factors (a cycle phase) or infectious agents, as well as in pelvic inflammatory diseases, reflect the need for study the role of these receptors in the development and course of CE. In addition, numerous studies pointing to the modeling effect of viruses on the functional activity of TLRs generate interest, which may be the reason for viral resistance against the immune system and provoke inflammatory reactions. Conclusion: Thus, to study the role of the interaction of TLRs with viruses in the development of CE is a promising area not only for solving fundamental problems, but also for improving methods for diagnosing and treating this disease.

In the modern world, cervical diseases associated with high-risk human papillomavirus (HR-HPV) are one of the urgent problems discussed by researchers. In most HR-HPV-infected women, the virus is known to eliminate on its own within two years, and only in 10-15% papillomavirus infection becomes persistent and is able to cause cellular changes leading to the development of squamous intraepithelial lesions (SIL) and cervical cancer. Therefore, the identification of patients in the early stages of SIL development is extremely important and promising. The study of HPVL1 and E4 biomarkers is an important component in the differential diagnosis between the cytologicalfindings of atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion (HSIL) and in the sorting of women for further treatment and follow-up. Conclusion: Thus, there is a need for further investigations of these biomarkers to predict the development of cervical SIL, which will create personalized management tactics in terms of HPV biology.

Mastodynia is observed in 70% of women in the population and it occurs more frequently at the age of 30 to 50 years. We reviewed the papers published in the PubMed and RSCI database in the period from 2000 to 2022 in order to systematize the variants of the clinical course, the mechanisms of mastodynia development and individual approaches to the management tactics of patients with breast pain. Mastodynia may be associated with premenstrual syndrome, benign breast dysplasia, mastitis. The risk of breast cancer is extremely low in a situation where the only symptom is mastodynia. The examination of patients with mastodynia includes history taking, physical examination, imaging techniques aimed at identifying functional and organic disorders of the mammary gland. After appropriate clinical evaluation, most patients with breast pain respond positively to non-medication and medication treatment. The results of the clinical studies show the effectiveness of medications containing a dry extract of the fruits of Vitex agnus castus in the treatment of mastodynia in patients with diffuse benign breast dysplasia and premenstrual syndrome. Conclusion: It is necessary to conduct a thorough examination of women with mastodynia in order to exclude proliferative formations of the mammary glands and to identify the cause of breast tenderness. Mechanism-based mastodynia therapy helps to reduce episodes of pain and improve the quality of life while minimizing side effects.

Relevance: Preeclampsia is a dangerous condition that can be life threatening for the mother and baby. Globally, it is diagnosed in 10 million women annually, representing 3 to 8% of all pregnancies. Currently, there is no confirmed effective treatment for preeclampsia. In this regard, the possibility of predicting this complication is relevant. Objective: To investigate the prognostic value of matrix metalloproteases-2 and metalloproteases-9 as early markers of preeclampsia. Materials and methods: In this prospective study, 72 patients were tested for matrix metalloproteinase-2 and matrix metalloproteinase-9. Thirty-four of them (study group) subsequently developed preeclampsia during pregnancy (20 and 14 patients had moderate and severe preeclampsia, respectively); 38 patients with uncomplicated pregnancy constituted the control group. Results: In pregnant women who developed preeclampsia, matrix metalloproteinase-2 levels at 11-13 weeks' gestation were 155±73.4 ng/mL and were statistically significantly higher than in pregnant women without hypertensive disorders (75.0±32.8 ng/mL). Concentration of matrix metalloproteinase-9 in pregnant women with preeclampsia was significantly lower than in controls [749±296 ng/mL and 1667±552 ng/mL (P<0.001)]. In the first trimester, the matrix metalloproteinase-2 cut-off value to predict the development of preeclampsia was >.102 ng/mL (sensitivity, 88.24%; specificity, 82.76%). For matrix metalloproteinase-9, concentration of 4980 ng/mL in the first trimester predicts the development of preeclampsia with a sensitivity of85.29% and specificity of84.48%. Conclusion: The study identified cut-off values for matrix metalloproteases-2 and metalloproteases-9 to predict the development of preeclampsia in the first trimester.

Objective: To investigate the clinical efficacy of preconception care with exogenous melatonin for in vitro fertilization (IVF). Materials and methods: This nonrandomized controlled trial included 84 infertile women undergoing IVF and ex/eriencing slee/ disorders and elevated stress reactions. Patients in grou/ 1 (n=39) received/reconce/tion care with melatonin; women in grou/ 2 (n=45) did not receive melatonin. The effectiveness of melatonin was assessed based on the results of ovarian stimulation, com/arative evaluation of melatonin concentrations in the follicular fluid, monitoring of the culture stage, determination of the genetic status of embryos, and /regnancy rate. Results: Use of melatonin in /atients undergoing IVF /rograms was associated with a significantly higher number of oocyte-cumulus com/lexes and a higher fertilization rate. There were no statistically significant differences in melatonin levels in the follicular fluid in /atients who received and did not receive melatonin. There was an association between marginal values of melatonin levels (less than 10%o and more than 90%o) and the frequency of obtaining embryos of low mor/hological quality [risk difference, %=61.9 (15.91-74.99), /(x2)<0.009]. Melatonin administration increased the /robability of obtaining blastocysts of high mor/hological quality by 41.7% [risk difference 41.7%, /<0.001], reduced the /robability (RR=0.29 (0.09- 0.97)) of obtaining only low quality blastocysts by 3.37 times (1/0.29), reduced the risk (RR=0.52 (0.29-0.92)) of obtaining aneu/loid blastocysts by almost 2 times (1/0.52) and increased the /robability of /regnancy in the cryonreservation cycle by 2.5 times [OR=2.44 (1.17-5.11)]. Conclusion: The study findings suggest a /ositive role for exogenous melatonin administration on the clinical and biological outcomes of IVF. More studies investigating the effect of melatonin on re/roductive function are needed to form a conce/t of/reconce/tion care with melatonin su//lementation.

Objective: Assessment of the effectiveness of embyo transfer into uterine cavity at the zygote stage in patients with multiple IVF/ICSI failures in history and the absence of embryonic cleavage cultured in vitro. Materials and methods: The study included 37 patients. The mean age of patients was 38.3 (3.3) лет, and infertility duration was 6.1 (2.3) years. Idiopathic infertility was a major nosologic form of infertility. Independently of the chosen ovarian stimulation protocol and the used type of gonadotropins, the absence of embryos that could be offered for transfer and stoppage of embryonic development took place in all attempts. In 37 women in the study group, embryo transfer into the uterine cavity was performed on day 1 after transvaginal ovarian puncture, immediately after fertilization was confirmed. Results: The average number of IVF/ICSI attempts in history of the patients included in the study was 4.2 (1.6). The retrospective analysis confirmed that the parameters of early embryo development was impaired in all patients in the study group. Pregnancy rate in the group of women below 40 years was 45.0% (9/20), and 5.8% (1/17) in the group of patients of late reproductive age. Conclusion: It is supposed that in vitro embryo culture may be one of the cause of impaired embryo development and early embryonic developmental arrest. Due to this, embryo transfer strategy into the uterine cavity at zygote stage, can influence physiological preimplantation development and as a result lead to the onset of pregnancy in difficult clinical situations, when embryos stop developing. This method can be effective for the patients of young age, who mainly have euploid oocytes.

Objective: Evaluation of ephrin receptor A3 (EphA3) expression in glandular epithelial cells in uterine endometrium in women without endometrial pathology, with endometriosis and endometrial cancer (EC). Materials and methods: The study included 46 patients of reproductive age who underwent treatment in National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of Russia in the period from 2020 to 2021. The patients were divided into four groups: group 1 comprised 20 women with deep infiltrating endometriosis (DIE), group 2 comprised 21 women with peritoneal endometriosis (PE), group 3 consisted of 6 women with EC, and group 4 (control group) consisted of 9 women without endometriosis, who underwent surgery for tubal and peritoneal factors infertility, and the results of histological tests of these women showed no pathological changes in the endometrium. Additionally, the groups were divided into subgroups depending on the stage of the menstrual cycle prior to surgery. Semi-quantitative evaluation of EphA3 expression in glandular epithelial cells of uterine endometrium was performed by immunohistochemistry, using rabbit polyclonal antibodies (ab126261) and open-source image analysis software platform ImageJ. Results: Immunohistochemical examination showed that EphA3 expression in glandular epithlelial cells of normal endometrium and eutopic endometrium both in PE and DIE is significantly higher in the secretory phase versus the proliferative phase. Significantly high EphA3 expression in glandular epithelial cells of ectopic endometrium versus regular expression was detected in both phases of the cycle, in PE and DIE. There was no significant difference between EphA3 expression in glandular epithelial cells affected by endometrial cancer and in normal endometrium. Conclusion: The results of this study showed that EphA3 is overexpressed in ectopic endometrium, in PE and DIE, but not in EC.

Background: Fear of vaginal delivery is most commonly associated with uterine rupture in women with postcesarean uterine scar. The fact that the morphological competence of the scar and its ability to dehisce at the onset of labor cannot be prognostically evaluated necessitates the exchange of experience in managing vaginal delivery with uterine scar. Materials and methods: A prospective study of 41 pregnant women with a uterine scar after a single cesarean section was conducted. All the women were scheduled for vaginal delivery. Uterine scar competence was assessed clinically and ultrasonographically at the onset of labor. Results: Twenty-six women delivered vaginally; 15 were re-operated. The indications for repeat cesarean section were labor abnormalities (n=7), clinically narrow pelvis (n=4), and threat of uterine scar incompetence (n=4). Intraoperatively, the uterine scar was competent in 11 patients; there was scar incompetence, incomplete uterine rupture, and uterine scar dehiscence in 4, 2, and 2 patients, respectively. Conclusion: The causes of unsuccessful attempts at vaginal delivery after caesarean section are not always associated with scar incompetence. The scars most commonly turn out to be intraoperatively competent. It is advisable to ultrasonographically assess scar competence at the onset of labor in women planning vaginal delivery.

Relevance: Dysplasia is one of the results of the transformative effects of the human papillomavirus (HPV). Exposure to the virus more frequently leads to cervical dysplasia, and its progressive development leads to tumor progression. Monitoring and medical examination of HPV-carriers, timely selection of methods for their recovery is a reserve for reducing cervical neoplasia and cervical cancer. The probable benefit of immunomodulatory therapy as a way to reduce the risk of HPV-associated cervical lesions cannot be considered proven due to insufficient number and quality of evidence-based medicine studies. Objective: To evaluate the effect of immunomodulating medications on changes in colposcopic and cytological characteristics in HPV-associated cervical lesions. Materials and methods: This was an open multicenter randomized study conducted in 2020-2021. Five hundred women with HPV-associated cervical lesions registered electronically and monitored in women’s health clinics in 7 regions of the Russian Federation were included in the study. The research followed the multicenter comparative observational program “Evaluation of the efficacy and safety of Immunomax in the complex therapy of benign cervical dysplasia with confirmed HPV infection” which was developed in 2020-2021 in the Russian Federation (http://richt.ru/; http://greta.pro/). There were the following criteria for inclusion in the program: HPV-associated cervical diseases (ICD-10: N87.X + B97.7 CIN I-II), age from 18 to 55 years (median age 33 years). The main therapy was destructive or excisional exposure, which was prescribed to all participants of the study after signing an informed consent. Immunomax, Allokin-alfa, medications with INN inosine pranobex, which have immunotropic effects, were selected as immunomodulatory medications and were used in complex therapy. The participants of the study were randomized into groups depending on the administered immunomodulatory medications: 114 women received Immunomax, 95 women received Allokin-alfa, 154 women took INN inosine pranobex, 59 women underwent surgical treatment but they did not receive immunomodulatory therapy. Control studies confirming the effectiveness of the therapy were conducted 3 and 6months after the completion of treatment. Results: Statistical analysis of the results of the study confirmed the importance of immunomodulatory therapy in eliminating HPV and normalizing colposcopic picture. The effectiveness of combined treatment with the use of immunomodulatory medications was higher than one after destruction without administration of immunotropic medications. The study conducted 3 and 6 months after the treatment showed that frequency of elimination of highly oncogenic HPV was significantly higher in groups of patients who received surgical treatment in combination with Immunomax, Allokin-alpha, medications with INN inosine pranobex; normalization of colposcopic picture was observed in all comparison groups. Conclusion: The data obtained from 7 regions of the Russian Federation were added to a specially developed electronic register of patients with HPV-associated cervical lesions. The findings showed that surgical treatment in combination with immunomodulatory therapy resulted in a higher frequency of HPV elimination and normalization of the colposcopic picture than surgery without the use of immunomodulatory therapy.

Endometriosis is a disease in which the tissue grows, in its morphological and functional properties similarly to that of the endometrium, outside the uterine cavity. The formation of ectopic endometrial foci causes chronic pelvic pain and/or infertility. Practicing gynecologists are puzzled by the prevalence of endometriosis and the unresolved issues of its etiology, pathogenesis, diagnosis, and treatment. Patients diagnosed with endometriosis need monitoring and constant therapy even after radical treatments throughout their lives. Currently, there is no unified method for the treatment of endometriosis; each case must be considered individually, based on the characteristics of its clinical course and on the age and reproductive potential of a woman. The presented materials highlight various cases of the course of endometriosis and the treatment policy applicable to each particular patient. This clinical material is relevant for the discussion of controversial, unresolved issues of endometriosis. Conclusion: The described cases once again emphasize the need to choose surgical treatment at the right time and in full, preferably once in a lifetime. In addition, it is extremely important to choose drug for postoperative therapy, its duration in terms of preventing recurrent endometriosis.

Background: Cervical cancer occupies a leading position in the pattern of gynecological cancers. The tumor biological uniqueness during pregnancy is the combination of uncontrolled tumor growth and controlled fetoplacental unit growth in one organism. According to statistics, cancer during pregnancy is quite rare: one case per 1,000 pregnancies. Case report: The authors have presented their own experience in choosing the tactics of follow-up, treatment, and delivery in a patient with stage IV cervical cancer diagnosed in the second trimester of pregnancy. The paper shows the features of the course of the disease, the complexity of pregnancy management, including chemotherapy cycles, as well as the features of delivery and surgical treatment for cervical cancer. It is indicated that for the treatment of cancer during pregnancy, it is necessary to determine and designate the main parameters: the cancer stage, indications for treatment, disease curability, treatment regimens based on modern recommendations, and a multidisciplinary approach to choosing treatment policy. Conclusion: This clinical case clearly demonstrates the need for complex interaction in decision-making in each individual case of physicians of various specialties: a gynecological oncologist, a morphologist, a radiologist, a chemotherapist, an obstetrician, an anesthesiologist/resuscitator, a neonatologist, as well as a psychologist and a lawyer.