Obstetrics and Gynecology

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.

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.

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 (r_s=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.

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).

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.

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.

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.

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.

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.

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.