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Nº 5 (2024)
Reviews
Epigenetic alterations in patients with cervical intraepithelial neoplasia
Resumo
Despite numerous basic studies on the issues of malignant degeneration of precancerous diseases of the cervix and the widespread introduction of screening programs, mortality from cervical cancer continues to take the leading positions. Currently, there are no reliable prognostic criteria for malignancy of squamous cervical intraepithelial neoplasia (CIN).
The results of recent studies indicated that epigenetic regulation of gene expression plays a fundamental role in the pathogenesis of numerous malignant neoplasms including cervical cancer. The analysis of the literature data showed that squamous cell metaplasia in the cervical transformation zone is affected by cholinergic signaling. Acetylcholine and its receptors do not only regulate the processes of inflammation and proliferation of the normal cells, but they also play an important role in response to oncological processes by increasing the expression of certain receptor subunits, they inhibit apoptosis and increase the likelihood of metastasis. Thus, epigenetic modifications associated with dysplastic and metaplastic processes can serve as a powerful tool for risk stratification, prediction and treatment of cervical neoplasms caused by human papillomavirus (HPV).
Conclusion: The development of a panel of molecular predictors for accurate differential diagnosis of the degree of lesion, as well as identification of the risk group for the transition of dysplasia to cancer, will improve the examination algorithms and make it possible to timely initiate pathogenetic therapy in patients with HPV-associated cervical diseases.
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Smooth muscle tumors of the uterus: possibilities of preoperative diagnosis using imaging techniques
Resumo
The significance of preserving the reproductive potential of the female population is currently high all over the world. Uterine fibroids and leiomyosarcoma have become diagnosed more often in young patients; moreover, uterine leiomyosarcoma is characterized by an extremely aggressive course and an unfavorable prognosis. Successful preoperative diagnosis is crucial for further treatment planning. There are improvements in reconstructive plastic organ-preserving operations, at the same time minimally invasive techniques are preferred: myomectomy is more often performed through laparoscopic techniques, robot-assisted surgery, and hysteroscopic methods. In most cases, the final diagnosis is made only after surgical treatment, so the lack of morphological verification can lead to an unfavorable course of the disease.
The objective of this study is to analyze various imaging techniques, including ultrasound, magnetic resonance imaging, positron emission tomography, which are described in the scientific medical literature and devoted to modern aspects of preoperative differential diagnosis of benign and malignant smooth muscle tumors of the uterus. There are currently no clear diagnostic criteria that can improve the accuracy of preoperative diagnosis of uterine smooth muscle tumors of uncertain or obvious malignant potential.
Conclusion: Although a comprehensive approach with the use of various imaging techniques does not completely solve the issues of early diagnosis of uterine sarcoma, it makes it possible to obtain important information at the preoperative stage necessary to determine the correct management tactics for this category of patients.
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Modern problems and opportunities in the treatment of genitourinary syndrome of menopause in the context of medical science and technology development
Resumo
Genitourinary syndrome of menopause (GSM) is one of the most common complications of female reproductive aging which influences the quality of life and sexual health of most women during menopause. However, no more than 25% of women receive adequate therapy for GSM, even in developed countries. GSM is obviously a serious medical and social problem affecting a wide range of generally healthy women. The issue of finding and studying new, effective and safe, as well as patient-friendly and highly compliant methods for treating symptoms of vulvovaginal atrophy (VVA)/GSM remains extremely relevant, and its importance will only increase in the coming years, taking into account existing demographic and social trends. In addition to the objective risks associated with hormone therapy, which is the gold standard of VVA/GSM treatment, some patients do not want to use hormone-containing drugs, and some patients have contraindications for such therapy, therefore, alternative options for the treatment of GSM symptoms are necessary for them. Laser treatment may be such an option, and according to available data, laser treatment is comparable to local hormone therapy in effectiveness, and may exceed it in terms of safety.
Conclusion: Among the available laser devices used in gynecological practice, ablative and non-ablative lasers can currently be applied for correcting the symptoms of VVA/GSM, and the latter devices are rated as the safest ones. The Nd:YAG laser appears to be a very promising device that has not been sufficiently studied in terms of capabilities, limitations and methods of use in patients with symptoms of VVA/GSM; large-scale studies and observational programs are necessary to assess the effectiveness and safety of its use.
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Tissue-selective estrogen regulation capabilities in postmenopausal women
Resumo
Postmenopause is a physiological period in a woman’s life characterized by a decrease in levels of sex steroid hormones. Estrogen deficiency is associated with the development of vasomotor symptoms, genitourinary syndrome of menopause (GSM), skin and breast tissue changes, lipid and carbohydrate disorders, endothelial dysfunction, and increased cardiometabolic risks, as well as decreased bone mineral density. To date, the most effective method for correcting various symptoms of menopause is menopausal hormone therapy; one of its options that can be used in postmenopause is considered to be tibolone, a tissue–selective regulator of estrogenic activity.
The review presents the history of studying the molecule of tibolone, which is a synthetic steroid with estrogenic, progestogenic, and androgenic activity. The mechanism of action of tibolone involves the formation of three active metabolites: 3-β-hydroxytibolone and 3-α-hydroxytibolone, which are responsible for estrogenic effects of tibolone and mainly present in an inactive sulfated form, and Δ4-tibolone, which has progestogenic and androgenic activity. Tibolone use in postmenopausal women has demonstrated effective alleviation of vasomotor symptoms, GSM, increase in bone mineral density, and positive effects on the cardiovascular and central nervous systems; stimulating effect on the endometrium was absent. There is also a discussion of mechanism of tibolone impact on breast tissue. Thus, tibolone exhibits selective estrogenic activity and regulates actions in different tissues, making it a unique representative of the STEAR class.
Conclusion: Tibolone is the first representative of tissue selective regulators of estrogenic activity. The diverse hormonal effects of tibolone are due to the action of several key metabolites on various tissues. Tibolone can currently be considered as an effective therapy for many postmenopausal women. It is necessary to take into account a number of characteristics of tibolone action and determine the possibility of prescribing the therapy for a specific patient on the basis of this information.
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Original Articles
Factors of energy metabolism in fetal growth restriction
Resumo
Objective: This study aimed to was to investigate the blood plasma factors associated with energy metabolism in pregnant women with fetal growth restriction (FGR) and to evaluate their diagnostic performance.
Materials and methods: This cohort study involved 59 pregnant women. The study group (n=30) comprised patients diagnosed with FGR confirmed after childbirth. The control group (n=29) included women with normal pregnancies. The levels of energy metabolism factors (C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide (GlP), glucagon-like peptide-1 (GLP-1), glucagon, insulin, leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, and visfatin) in blood plasma were determined using a multiplex assay (10-plex Bio-Plex Pro Human Diabetes Panel test system).
Results: Analysis of maternal plasma energy metabolism factors revealed significant increases in GLP-1 and PAI-1 levels in the FGR (p=0.003 and p=0.004, respectively). Women with FGR before 37 weeks of gestation showed significant differences in leptin (p=0.05) and PAI-1 (p=0.006) levels compared with those without FGR. After 37 weeks of pregnancy, significant differences were observed in GLP-1 and glucagon levels (p=0.005 and p=0.01, respectively). This study also found that the insulin/GLP-1 ratio was significantly lower in the FGR group than in the control group (p<0.001), suggesting the development of pancreatic cell resistance to GLP-1 and a compensatory increase in its plasma levels in women with FGR. Additionally, a statistically significant direct correlation (rs=0.35, p=0.05) was observed between GLP-1 and PAI-1 (a fibrinolysis inhibitor and a pathogenetically significant factor in FGR). The combination of five factors (GLP-1, glucagon, insulin, leptin, and PAI-1) exhibited excellent diagnostic performance, with an area under the ROC curve of 0.92, a sensitivity of 96%, and a specificity of 81%.
Conclusion: The study results suggest the potential involvement of energy metabolism factors in the development of FGR and highlight prospects for further exploration. Determining the blood plasma levels of GLP-1 and PAI-1 in women with FGR could serve as new non-invasive markers for diagnosing FGR during pregnancy. Furthermore, a combination of factors (GLP-1, glucagon, insulin, leptin, and PAI-1) could identify FGR with high diagnostic accuracy.
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Difference between maternal risk factors for fetal growth restriction and small for gestational age
Resumo
Objective: This study aimed to compare the maternal gestational risks of insufficient fetal growth (IFG), including small for gestational age (SGA) and fetal growth restriction (FGR).
Materials and methods: This retrospective cohort study was conducted at Perinatal center of N.A. Semashko Republican Clinical Hospital between 2018 and 2023. The study included 611 women with IFG, including 435 with FGR and 176 with SGA. The discriminators of FGR and SGA were studied. Statistical analysis was performed using Statistica 12.0 and Microsoft Excel 2007, and CHAID analysis was conducted using the Classification Trees module.
Results: Potential causes of IFG were hypertensive disorders during pregnancy (41.74%), including preeclampsia (PE) (25.21%), severe (22.59%) or moderate (2.62%), gestational hypertension (GAH) (8.67%), chronic arterial hypertension (CAH) (7.86%), and gestational diabetes mellitus (GDM) (12.77%). The cause of IFG was unknown in 45.49% of women. FGR was more likely to be associated with PE of unknown cause (OR=1.94); SGA was associated with GDM (OR=8.76), GAH (OR=4.38), and CAH (OR=3.93). Prematurity is not obligatory for IFG (24.22%) but is typical for FGR (34.02%). Preterm delivery was associated with severe PE (OR=14.89) and CAH (OR=2.43). The rate of cesarean section for IFG was 55.16% and was associated with FGR (OR=2.95), PE or CAH in FGR, GAH (OR=12.00), and an unknown cause (OR=2.05) in SGA infants. The incidence of iatrogenic prematurity in IFG due to FGR was 86.48 %. Low birth weight (LBW) was more common in the FGR group (OR=6.38).
Conclusion: The FGR and SGA differ in terms of risk factors. The causes of IFG are associated with the risk of iatrogenic prematurity and LBW. Prevention of gestational complications of cardiometabolic origin (hypertensive disorders and GDM) is a measure for preventing IFG. The association of PE with FGR, but not with SGA, confirms the similarity of their pathogenesis and the impossibility of uniform prevention of both IFG variants.
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Prediction of neonatal complications based on quantitative proteome analysisin blood of pregnant women with fetal growth restriction
Resumo
Objective: The objective of the study was to investigate relationship between early neonatal complications and plasma proteome composition in pregnant women diagnosed with fetal growth restriction.
Materials and methods: This pilot case-control study included 40 pairs of "pregnant woman – newborn baby". Four groups were formed: Group I and group II were the main groups, group III and group IV were the comparison groups. Group I was comprised of women with early fetal growth restriction (FGR) (<32 weeks) (n=10 pairs); group II was comprised of women with late FGR (≥32 weeks) (n=10 pairs). Group III and group IV consisted of pregnant women, who delivered before and after 32 weeks (n=10 pairs/n=10 pairs) (the comparison group). Confirmation of the diagnosis of fetal growth restriction, as well as definition of normal body weight in the group of women with preterm births (before and after 32 weeks), postnatal assessment of weight and growth indicators in newborns (n=40) was performed according to the INTERGROWTH-21st centile charts that reflected the international consensus reached by the members of Neonatal Group. Quantitative analysis of 125 plasma proteins was performed using BAK 125 plasma proteomics kit (MRM Proteomics Inc., Montreal, Canada) by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Based on the support vector machine used for classification, predictive models for possible development of asphyxia and intraventricular hemorrhage in newborns were created.
Results: Based on the results of quantitative proteomic analysis of maternal plasma proteins, two prognostic models were developed. Model 1 (AUC=0.96), including the proteins α-1-acid glycoprotein 1, α-1-antichimotrypsin, α-1-β-glycoprotein, α-2-macroglobulin, antithrombin III, apolypoprotein A-IV, apolypoprotein С–II, apolypoprotein С-IV, carboanhydrase 1, CD5 antigen like protein, ceruloplasmin, clasterin, complement C3, complement component C9, complement factor H, transcortin, fibrinogen α-chain, fibrinogen β-chain, fibronectin, fibulin-1, heparin cofactor II, kallistatin, keratin, type II cytoskeletal 2 epidermal, pregnancy zone protein, prothrombin, ferotransferrin, vitamin К-depended protein S, vitamin К-depended protein Z, vitronectin as variables, with 92% sensitivity and 76% specificity will enable to detect the risks for intraventricular hemorrhage in newborns. Model 2 (AUC=0.83), including the proteins α-1-antichimotrypsin, apolypoprotein С–III, apolypoprotein D, β-2-glycoprotein 1, complement C1q subcomponent subunit C, complement component C9, kininogen-1, plasma protease C1 inhibitor, pregnancy zone protein, AMBP protein, prothrombin, vitronectin as variables with 67% sensitivity and 100% specificity, will enable to predict birth asphyxia.
Conclusion: Using the plasma proteome of pregnant women to predict the development of birth asphyxia and intraventricular hemorrhage in newborns in early neonatal period will improve the quality of medical care, as well as reduce neonatal morbidity and mortality in the group of infants with intrauterine growth restriction (IUGR).
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The influence of dysbiotic disorders and local inflammatory reactions in the reproductive tract on the development of preterm birth
Resumo
Objective: To investigate how the state of microbiocenosis and the expression profile of immune response genes in the reproductive tract of pregnant women affect the occurrence of preterm birth.
Materials and methods: This study included 228 women who were divided into groups based on gestational age at delivery. Fifty-two patients gave birth at a gestational age of 22.0–27.6 weeks, 56 at a gestational age of 28.0–31.6 weeks, 60 at a gestational age of 32.0–33.6 weeks, and 60 at a gestational age of 34.0–37.0 weeks. Each group was divided into subgroups categorized according to whether they had preterm prelabor rupture of the membranes (PPROM) or spontaneous onset of labor (SPB) without PPROM. Subgroups included women who delivered at 22.0–27.6 weeks (PPROM n=28, SPB n=24), 28.0–31.6 weeks (PPROM n=30, SPB n=26), 32.0–33.6 weeks (PPROM n=35, SPB n=25), and 34.0–37.0 weeks (PPROM n=32, SPB n=28). A total of 125 patients with PPROM and 103 with SPB without PPROM were enrolled. The control groups consisted of pregnant women with threatened preterm birth who delivered at term (n=80) and those with a normal pregnancy who delivered at 37.0–41.0 weeks (n=72). All patients were tested for vaginal microbiocenosis using the Femoflor method with determination of local inflammatory response by measuring mRNA expression levels of cytokine genes in vaginal scrapings.
Results: There were significant differences between the groups of women with preterm birth with and without PPROM and those with a normal pregnancy. The incidence of dysbiosis combined with local inflammation was higher in women with spontaneous onset of labor (p=5.02×10-15) and with PPROM (p=2.01×10-15). Normocenosis was significantly more common in women with a normal pregnancy compared to those with spontaneous onset of labor (p=3.3×10-18) and with PPROM (p=1.2×10-21).
Conclusion: Dysbiotic disorders without local inflammation are not significant prognostic factors for preterm births. To accurately predict this risk, a comprehensive assessment of microbiocenosis and local inflammation in the vagina should be performed.
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Association of COL1A1, ESR1, and VDR gene polymorphisms with the risk of pelvic floor dysfunction in postpartum women
Resumo
Objective: To investigate the influence of collagen type 1 gene polymorphisms, estrogen receptors, and vitamin D receptors on early development of pelvic floor dysfunction in postpartum women.
Materials and methods: This prospective cohort study enrolled 120 women who delivered naturally. The patients were divided into two groups. Group 1 (study group) consisted of 67 women who developed pelvic floor dysfunction, such as pelvic organ prolapse and urinary incontinence, six months postpartum. Group 2 (control group) included 53 women who did not develop pelvic floor dysfunction within six months postpartum. Molecular genetic typing and determination of COL1A1 gene polymorphisms -1997 C>A and 1546 G>T, ESR1 gene -397 T>C and -351 G>A, and VDR gene 283 A>G and 2 A>G were conducted for all women.
Results: Among patients who developed pelvic floor dysfunction after delivery, carriage of the minor allele G of the ESR1:A-351G polymorphic marker was more common than that in healthy women, where the predominant allele was ESR1:-351 A. The presence of the variant allele -397 C of the ESR1 gene in the homozygous or heterozygous state of the genotype is associated with an increased risk of developing this pathology.
Conclusion: The polymorphism of the ESR1 gene at loci -351 A>G and -397 T>C is associated with the development of pelvic organ prolapse and urinary incontinence 6 months after natural childbirth. No association was found between COL1A1 and VDR gene polymorphisms and the early development of pelvic floor dysfunction after childbirth.
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Analysis of the structure of gynecological diseases and extent of surgery in patients of different age groups supervised in the cervical and endometrial pathology office
Resumo
Objective: This study aimed to analyze the structure of gynecological diseases and the extent of surgery in patients of different age groups supervised in the cervical and endometrial pathology office.
Materials and methods: A total of 369 patients from different age groups were included in this study. Group 1 (n=290) consisted of women aged 18–44 years who received medical care in the cervical and endometrial pathology office. Group 2 (n=44) consisted of women aged 45–59 years old. Group 3 (n=30) included women aged 60–74 years old. The study analyzed the structure of gynecological pathology in these groups.
Results: The study found that CIN I was more frequently detected in women in group 2, while CIN II was most frequently detected in women in group 3. The rate of CIN III was similar in all three groups, with percentages of 14.1, 15.9, and 13.3%, respectively. In terms of surgical procedures, cervical excision (LLETZ) was performed less frequently in all age groups (group 1, 8.62%; group 2, 4.55%; and group 3, 10%) than cervical electroconization (group 1, 27.93%; group 2, 45.45%; group 3, 36.67%).
Conclusion: The findings of this study indicate that in the cervical and endometrial pathology office, the majority of patients (78.59%) were women aged 18–44 years. In 93.3–100% of cases, patients undergo tissue treatment with a solution cavitated by low-frequency ultrasound before surgical treatment. Electroconization is most commonly performed in women aged 45–59 years (45.45%) for the treatment of precancerous diseases of the cervix. Ablative treatments are predominantly used for hemostasis, and less commonly for the treatment of CIN I.
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Undifferentiated connective tissue dysplasia in women of reproductive age: cross sectional study
Resumo
Objective: The aim of the study was to identify the prevalence of undifferentiated connective tissue dysplasia (UCTD) and association with a burdened obstetric history (BOH) of miscarriage in women of reproductive age, who residents of the Minsk region (the Republic of Belarus).
Materials and methods: From March 2022 to May 2022, a cross sectional study was carried out. It included 384 women aged 22–46 years, who were admitted to healthcare facility “Maternity hospital of the Minsk region” (the Republic of Belarus) with purpose of pregravid preparation. According to the results of comprehensive evaluation, the presence of UCTD, prevalence of clinical signs of UCTD and association of UCTD with BOH were identified.
Results: Among women of reproductive age in the Minsk region, UCTD was identified in 35.7% of women (95% CI 30.9–40.7). In the group of patients with UCTD, BOH of miscarriage was 3.5 times more often – in 19/137(13,4%) women compared to women who had no UCTD – in 11/247 (4.5%); OR 3.5 [1.6; 7.5].
Conclusion: High prevalence of UCTD and association with BOH of miscarriage was identified in women of reproductive age, who are residents of the Minsk region. Based on the results of this study, formation of a comprehensive program for identifying UCTD at the stage of pregravid preparation needs to be determined.
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Damage-associated molecular patterns in patients with intramural uterine fibroids and infertility
Resumo
Objective: To investigate the levels of damage-associated molecular patterns (DAMPs) in fertile and infertile patients with uterine fibroids (UF).
Materials and methods: This single-center prospective study included 90 women. The main group comprised 60 patients with intramural UF, with 30 infertile (study group) and 30 fertile patients (comparison group). The control group consisted of 30 healthy women without uterine fibroids. The serum levels of DAMPs, including tumor necrosis factor alpha (TNF-α), protein S100, interleukin-10, glutathione, uric acid, low-density lipoprotein cholesterol (LDL-C), and fibrinogen, were measured.
Results: The data obtained indicated a significant increase in glutathione, uric acid, and LDL-C in the presence of UF, regardless of fertility, compared to the control group. More pronounced changes in parameters (increased protein levels of S100, uric acid, and LDL-C, as well as decreased glutathione levels) were observed in the presence of intramural UF and infertility compared to fertile and healthy patients. The proposed DAMPs markers (glutathione, LDL-C, S100 protein, and uric acid) can be used as diagnostic and prognostic markers of infertility in the presence of intramural UF. When threshold values are reached (glutathione less than 413 µmol/l; S100 protein more than 0.172 µg/l; uric acid more than 280.5 µmol/l; LDL-C more than 3.78 mmol/l), the relative risk of infertility increases.
Conclusion: This study significantly enhances our understanding of the pathogenesis of infertility in UF and confirms the presence of systemic metabolic disorders (oxidative-inflammatory stress) as a cofactor of infertility.
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Morphological characteristics of the endometrium in the preconception period, chorion and placenta during pregnancy resulting from in vitro fertilization in patients with chronic endometritis (secondary analysis of the results of the TULIP-2 randomized controlled trial)
Resumo
Background: Chronic endometritis (CE) is associated with unsuccessful attempts of in vitro fertilization (IVF) in 7.7–67.5% of patients.
Objective: To determine the characteristics of the morphological structure of the endometrium, chorion and placenta in patients with favourable and unfavourable pregnancy outcomes resulting from IVF with cryotransfer, after treatment of chronic endometritis in the preconception period using a complex of natural antimicrobial peptides and cytokines.
Materials and methods: A total of 600 patients with CE and infertility who underwent IVF (cryopreservation of one embryo) were selected from the electronic database. The analysis included the results of morphological examination of their endometrium, chorion and placenta after the treatment of CE in the preconception period. The patients of group I received the Superlymph drug, an antibiotic and a progestogen, patients of group II received an antibiotic and a progestogen, and then only a progestogen for up to 6 months in both groups). The morphological structure of the endometrium was assessed before and after treatment before conception, and the chorion/placenta after pregnancy.
Results: The average age of the patients was 36 (33–38) years, duration of infertility was 6.0 (4.5–7.0) and 5.5 (4.0–6.5) in groups I and II, respectively, p=0.06. The pregnancy rate as a result of cryotransfer was 57.0 versus 38.7%, respectively (RR=1.47; 95% CI: 1.24–1.75, p<0.001). Live birth rate was 45.3 and 20.7%, respectively (RR=2.19; 95% CI: 1.70–2.83, p<0.0001).
After treatment in the preconception period, the structure of the endometrium in patients in group I corresponded to the cycle phase in 85.3%, in group II – in 60.3%. After spontaneous miscarriage in the first trimester, more patients in group I than in group II had a complete gravidar transformation (RR=9.06, 95% CI: 2.35–35.0, p<0.001) with fewer signs of hematogenous infection in the chorion and its gestational immaturity. In both groups, the histological structure of the placenta after miscarriage at 120–216 weeks corresponded to the gestation period with the deposition of intercellular fibrinoid, ectasia and vascular fullness, and signs of infection. After preterm birth, the weight and thickness of the placenta were statistically significantly higher in patients in group I, however, the morphological structure differed only in a smaller number of syncytial kidneys and fibrosis of the basal plates, the remaining indicators in both groups showed that the placenta did not match the gestation period. In patients who had full-term birth, the placenta mass was comparable; as for the rest of the parameters, there was a statistically significant difference between patients of groups I and II with a decrease in the risk of defective structure in most indicators by 2 to 9 times in favour of group I. This difference determined a 2.7-fold lower risk of complications during pregnancy in patients of group I (RR=0.37, 95% CI: 0.27–0.52, p<0.001).
Conclusion: There are morphological signs of chorionic/placental inferiority in patients with CE and unsuccessful outcomes of pregnancy resulting from IVF, which determine the necessity of restoring the structure and function of the endometrium before conception. Morphological examination of the endometrium before IVF planning in patients who received a course of complex treatment, including Superlymph during preconception period, indicates a significant improvement in the structure of the endometrium compared with the control group (matching the day of the cycle, reduction of spiral artery sclerosis and periglandular fibrosis), which improves the results of IVF and pregnancy outcomes.
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Exchange of Experience
Possibilities of antibacterial therapy in patients with mixed infections of the vagina and cervix: the results of the Flora Centrum study
Resumo
Objective: To evaluate the efficacy and safety of the use of the Symprazole combined drug (ornidazole 500 mg + ciprofloxacin 500 mg) in women with mixed bacterial infections of the vagina and cervix which are caused by sensitive Gram+ and Gram- microorganisms in combination with anaerobic microorganisms in real clinical practice.
Materials and methods: The study included 40 women aged 18 to 50 years with mixed bacterial infections of the vagina and cervix confirmed by laboratory tests. The study consisted of three periods: selection of patients (initial assessment and analysis), inclusion in the study and initiation of therapy, evaluation of the effectiveness of therapy and control analyses. The schedule of patients’ visits was determined based on actual clinical practice. The participation of each patient in the study did not exceed 49 days. The total duration of the course of treatment with the Symprazole drug was determined by the researcher and ranged from 5 to 7 days: one tablet was taken twice a day.
Results: The clinical efficacy of the therapy of the above drug was 97.5%, and the microbiological efficacy was 95%. During the course of treatment, there was an improvement in clinical symptoms: the absence of discomfort, itching, burning, mucosal hyperemia, and a decrease in symptoms of dyspareunia. A fast clinical effect (complete absence of complaints after 36–72 hours) was observed in 92.7% of patients. Microbiological picture improved when laboratory parameters of vaginal microbiocenosis were normalized. After the end of the course of therapy (after 35–37 days), there was a significant decrease in the intensity of colonization by opportunistic microorganisms in the vaginal biotope of patients and there were representatives of normal biocenosis. The Symprazole drug has shown its high safety, no adverse events have been detected during its use.
Conclusion: The original combination Symprazole drug has shown its high effectiveness and rapid onset of clinical effect in the treatment of mixed bacterial infections of the vagina and cervix caused by Gram+ and Gram- microorganisms in combination with anaerobic flora.
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The variability in the clinical effects of indolcarbinol in women with mastodynia
Resumo
Objective: To present the experience of using indolcarbinol in patients with fibrocystic mastopathy.
Materials and methods: These are the results of monitoring the use of indolcarbinol for 6 months in 81 women aged 40–45 years with cyclic mastodynia accompanied by diffuse fibrocystic mastopathy (DFCM).
Results: The use of indolcarbinol for 6 months in women with cyclic mastodynia does not have a negative effect on the nature of the menstrual cycle. Its use is also accompanied by such positive trends as improvement of menstrual function, a significant decrease in the severity of dysmenorrhea as well as control of premenstrual syndrome, improvement of some ultrasound parameters characterizing adenomyosis. There is also a complete control of mastodynia, reduction or disappearance of edema and heterogeneity of the structure of the mammary glands during palpation and positive changes according to ultrasound of the mammary glands (restoration of the average echogenicity of the tissue, decrease in the diameter of the milk ducts and cysts, normalization of the severity of the connective tissue pattern, etc.).
Conclusion: The results of the observation confirmed the effectiveness and safety of indolcarbinol in women with cyclic mastodynia, which is accompanied by different variants of DFCM, both isolated and combined with uterine fibroids and adenomyosis, which can often be found in this cohort of patients.
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Guidelines for the Practitioner
Experience of laparoscopic transabdominal cerclage for correcting cervical incompetence
Resumo
Relevance: The significance and relevance of the issue of miscarriage due to cervical incompetence have been determined. According to Order 1130n and relevant clinical guidelines, the main methods for treating cervical incompetence are the combined use of progestogens in combination with obstetric pessaries or surgical correction. The article presents the experience of using laparoscopic transabdominal cerclage (LTC) in K.A. Gutkin Republican Perinatal Center, Petrozavodsk, Russia. LTC can be considered as a method of choosing the correction of cervical incompetence in patients with repeated cases of termination of pregnancy.
Case report: This is a clinical observation of a favorable termination of pregnancy after LTC in a patient with a congenital abnormality of the reproductive apparatus and habitual miscarriage due to cervical incompetence. Surgical treatment was performed at the preconception stage by applying the tape “Cervix-Set” to the uterine isthmus. The patient became pregnant after ART, cryopreservation. During pregnancy, the patient was admitted to an obstetric hospital three times as there was a threat of pregnancy termination. The length of the closed part of the cervix remained within normal values during cervicometry. The pregnant woman had a cesarean section to deliver her baby at 36 weeks 1 day gestation due to premature rupture of membranes.
Conclusion: Given the limited experience of managing patients with LTC, it is necessary to conduct further studies on the effectiveness and safety of this operation.
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Primary prevention of human papillomavirus in Russia: analysis of international experience and determination of the best strategy
Resumo
Vaccination is the only highly effective way of primary prevention of human papillomavirus (HPV) disease, which is the main cause of cervical cancer. In addition to cervical cancer, oncogenic HPV types contribute to the development of cancer of the vagina, vulva, penis and anal canal, as well as some types of cancer of the head and neck. HPV is transmitted sexually; therefore, the HPV vaccine is recommended before the start of sexual activity. Foreign experience shows that the introduction of mass HPV vaccination programs, even with a divalent vaccine, significantly reduces the incidence and mortality from cervical cancer among the vaccinated population. Vaccination course consisting of more than one dose does not provide any advantages in terms of the formation of an immune response, but it significantly increases the cost and makes the full course of vaccination more difficult. Vaccination with the Russian single-dose tetravalent vaccine will not only reduce the risks associated with cervical cancer, but it will also make a significant contribution to public healthcare. This approach will not only cover a higher share of the population, but it will also minimize the economic component of vaccination; the vaccine will be given free of charge and covered by the health insurance system. The lack of knowledge about HPV and the diseases it can cause, including cancer, among children, adolescents and adults, is a major obstacle to mass vaccination. Therefore, informing parents, children and adolescents about vaccination should become a priority task for medical professionals and specialists in the field of education. The popularization of HPV vaccination as a means of primary prevention in the media will ensure positive awareness of the population about the simple prevention of HPV-associated oncological diseases.
Conclusion: Thus, the HPV vaccination scheme with the minimum number of doses is considered to be the most effective. For the successful implementation of the HPV vaccination program in the Russian Federation, it is recommended to use the Russian tetravalent vaccine, which is already completing the last phase of trials. It is necessary to carry out mass educational work among the population in order to popularize the vaccine as a means of primary prevention of HPV-associated oncological diseases.
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Clinical Notes
Osteogenesis imperfecta and pregnancy
Resumo
Relevance: Osteogenesis imperfecta, or “brittle bone disease”, is a rare inherited disorder with a highly variable spectrum of clinical manifestations. This disease is caused by a primary defect in the protein matrix of bones and connective tissue, which causes their osteopenia. This pathology occurs at a rate of 1 case per 20,000 births among pregnant women. Modern literature describes the cases of successful delivery of women with osteogenesis imperfecta; however, all practitioners note a wide range of complications of the underlying disease during pregnancy, which in some cases require its termination.
Case report: The clinical observation presents the characteristics of the course of pregnancy in a patient with osteogenesis imperfecta and the features of ultrasound diagnosis of this pathology in the fetus.
Conclusion: The described clinical observation of the course of pregnancy in a patient with osteogenesis imperfecta may be of interest to obstetrician-gynecologists when deciding on prolongation or termination of pregnancy. This case can also be of particular relevance to specialists in ultrasound diagnosis and medical genetics when considering possible options for diagnosing the inheritance of the main pathology by the fetus.
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Early endometrial cancer in patients with congenital malformation of the genital organs
Resumo
Relevance: Double uterus in combination with early endometrial cancer is a very rare pathology which should be treated with extirpation of the uterus with appendages. However, it is possible to perform organ sparing hormonal treatment for reproductive-aged women who want to preserve fertility resulting in pregnancy and childbirth.
Case report: This article presents a clinical case of a patient with the double uterus in combination with early endometrial cancer who underwent a course of organ sparing hormonal therapy in order to achieve conception, become pregnant and give birth. A 28-year-old patient presented to the V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Moscow for a consultation and pregnancy planning. The comprehensive examination of the patient led to the diagnosis of highly differentiated stage Ia endometrial cancer of the right uterus and atypical hyperplasia of the endometrium of the left uterus. The patient refused surgical treatment; therefore, a course of organ sparing hormonal therapy was prescribed, which resulted in pregnancy and the birth of a healthy full-term girl.
Conclusion: Organ sparing hormonal therapy in reproductive-aged women with confirmed diagnosis of early endometrial cancer, as well as with malformation of the genital organs, makes it possible for women to preserve fertility, achieve pregnancy and reduce the risk of recurrence of the disease after childbirth and breastfeeding.
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