


Nº 12 (2024)
- Ano: 2024
- Artigos: 22
- URL: https://journals.eco-vector.com/0300-9092/issue/view/10666
Edição completa



Reviews
Intrauterine tamponade with chitosan-covered gauze for managing postpartum hemorrhage
Resumo
Severe postpartum hemorrhage is responsible for significant maternal mortality and morbidity worldwide. The traditional use of uterotonics (oxytocin, prostaglandins) and medications for maintaining coagulation (fibrinogen and tranexamic acid) is not always effective and may not be sufficient to control life-threatening postpartum hemorrhage. Severe postpartum hemorrhage leads to an increased need for blood transfusion and the use of invasive techniques such as intrauterine balloon tamponade, compression sutures and artery ligation, which are important steps in treatment. In extreme cases, hysterectomy may be required to avoid possible maternal death. Intrauterine tamponade with chitosan-covered gauze is a novel technique in the arsenal of the obstetric team, especially when resources for surgical intervention and other invasive methods may be limited.
The modified gauze was initially developed for the management of acute bleeding in military medicine. It combines the physiological anti-hemorrhagic effect of modified chitosan with compression tamponade and is used to treat acute wound bleeding. The first description of the use of gauze with chitosan in obstetrics dates back to 2012; it showed that tamponade with chitosan-covered gauze is an effective means of controlling postpartum hemorrhage that is resistant to conventional therapy. Further research has demonstrated a reduction in the rates of hysterectomy and blood transfusion. However, this technique is not sufficiently presented in the literature and is not commonly used yet.
Conclusion: Intrauterine tamponade with chitosan-covered gauze is a novel adjunctive method in the management of severe uterine hemorrhage, especially in places where resources for advanced surgical techniques and other invasive therapies may be limited. In order to put this technique into practice, it is necessary to conduct a prospective, multicenter, randomized, placebo-controlled study to determine the effectiveness of tamponade with chitosan-covered gauze in severe obstetric hemorrhage.



Impact of sperm DNA fragmentation on the outcomes of pregnancies following natural conception and assisted reproductive techniques
Resumo
The male factor can be responsible for the inability of couples to conceive a child in 50% of the cases. The standard semen analysis does not completely reflect impaired integrity of spermatozoa genetic material, which may be associated with difficulties in achieving natural conception or with poorer outcomes of IVF programs. Therefore, sperm DNA fragmentation is increasingly used by clinicians to assess male infertility, especially in couples with repeated reproductive losses.
This review presents the analysis of the results reported in the literature on the effect of sperm DNA fragmentation on the outcomes of ART programs; the relationship between DNA fragmentation parameters and early reproductive losses in couples with male factor infertility was determined. A high level of sperm DNA fragmentation has been shown to have a negative effect on the fertilizing ability of spermatozoa. Sperm DNA damage may provide a reliable biomarker of sporadic and habitual miscarriage after natural or assisted conception, as well as provide new guidelines for future approaches to fertility restoration.
Conclusion: Impaired integrity of ejaculate DNA structure has a significant impact on both the natural conception and outcomes of ART programs. In order to achieve effective outcomes of IVF cycles and reduce the risk of early reproductive losses, it is necessary to introduce sperm DNA fragmentation testing into routine practice for specific groups of couples.



Postexcision vaccination against human papillomavirus as a method of secondary prevention of cervical intraepithelial neoplasia grade 2+
Resumo
Cervical intraepithelial neoplasia (CIN) is one of the most important issues in gynecology and gynecologic oncology. Despite the efficacy of excisional treatment for CIN2+ patients, there is a risk of CIN2+ recurrence and late diagnosis of cervical cancer. The risk of developing cervical cancer after excisional treatment has been shown to triple compared to the general population. CIN2+/HSIL recurrence after excisional treatment occurs in 4.8–14.4% of cases. HPV persistence, in particular high-risk HPV (HR-HPV), is one of the main predictors of CIN2+ recurrence, regardless of the type of excisional treatment. Given the significance of HR-HPV in the development of recurrence, HPV vaccination is recommended as a method of modern prevention of HSIL recurrence. The benefit of postexcision immunization with HPV vaccine for the prevention of CIN2+, regardless of the specific HR-HPV genotype, has been demonstrated in studies published since 2011. Bivalent and quadrivalent HPV vaccines given on the day of conization or within one year after surgical excision can reduce the risk of CIN2+ recurrence by 67–85% during a follow-up period of up to 6 years. Evidence suggests that HSIL is reduced in vaccinated patients following treatment, despite the time when vaccination was initiated. It is noteworthy that the incidence of CIN2+ recurrence was reduced by 90% in patients who received 9vHPV vaccine compared to those who underwent only excision.
Conclusion: HR-HPV persistence has a prognostic value for the development of CIN2+ recurrence after excisional treatment, which explains the need for HPV testing in the follow-up dynamics. Postexcision HPV vaccination proves highly effective in reducing the risk of recurrence of CIN2+ associated with HR-HPV.



Original Articles
Pregnancy loss after intrauterine surgical treatment of twin-to-twin transfusion syndrome
Resumo
Background: The most common indication for intrauterine surgery is the fetoscopic laser coagulation (FLC) of placental anastomoses in twin-twin transfusion syndrome (TTTS). TTTS is a complication of monochorionic multiple pregnancy characterized by high perinatal and neonatal morbidity and mortality caused in most cases by preterm birth. FLC has been shown to be more beneficial than amnioreduction and is therefore the current standard of care for the treatment of TTTS. Fetoscopic coagulation is characterized by a postoperative survival rate of both fetuses of almost 90% and is associated with a high incidence of premature rupture of membranes and subsequent termination of pregnancy.
Objective: To analyze the association of preoperative cervical length shortening and its correction with termination of pregnancy in women with monochorionic twins after intrauterine TTTS surgical treatment.
Materials and methods: This was a retrospective cohort study with the analysis of postoperative termination of pregnancy and preterm labor in patients with monochorionic twins complicated by TTTS. The study included 450 pregnant women with monochorionic diamniotic twins. All of them underwent FLC for TTTS at the National Medical Research Centre for Obstetrics, Gynecology and Perinatology in Moscow from January 2013 to January 2024. Group I (n=345) consisted of patients with preoperative cervical length ≥3 cm, group II (n=104) included patients with cervical length <3 cm, one patient was excluded from the study. Depending on the methods of cervical shortening correction, group II was divided into subgroups: subgroup 1 (n=53) had pessary, subgroup 2 (n=51) had cervical cerclage. FLC was performed in 440 cases, namely, in patients with I-IV stages of TTTS. Nine pregnant women received intrauterine treatment of TTTS stage V as transabdominal cordocentesis, intrauterine transfusion of erythrocyte mass to the surviving fetus with severe anemia.
Results: No statistically significant increase in the frequency of pregnancy loss was found in patients with correction of cervical shortening. Spontaneous pregnancy loss within seven days after surgery occurred in 17 (4.9%) patients of group I and in 6 (5.8%) patients of group II. The median term of delivery was 31.8 and 32 weeks in the study groups (p=0.281 and p=0.330, respectively). In the group of patients with cervical shortening, premature rupture of membranes was statistically significantly more frequent (p<0.05), regardless of the correction method.
Conclusion: No correlation between cervical length shortening, methods of correction and adverse pregnancy outcomes was found in our study.



Prevalence of chromosomal abnormalities in fetal heart defects, congenital diaphragmatic hernia and non-immune hydrops fetalis based on molecular karyotyping data (experience of the National Center)
Resumo
The prevalence of congenital fetal malformations is about 3–4%. According to the World Health Organization, about 240,000 children with congenital malformations die each year before 28 days of life, and 170,000 die before the age of 5 years. The management of patients with malformations represents a financial and human resource challenge to the healthcare system, and a significant proportion of these patients require palliative care. Therefore, the search for the causes of congenital malformations at the antenatal stage has been a priority.
Objective: To evaluate the role of chromosomal abnormalities in the development of fetal heart defects, congenital diaphragmatic hernia, and non-immune fetal hydrops.
Materials and methods: The prospective study was conducted between 2018 and 2024 and included 155 pregnant women: 61 with fetal cardiac malformation, 57 with fetal congenital diaphragmatic hernia, and 37 with non-immune fetal hydrops. The study was carried out at the National Medical Research Centre for Obstetrics, Gynecology and Perinatology in Moscow. All patients underwent invasive prenatal diagnostic procedures at different gestational ages. Fetal DNA was examined using SNP oligonucleotide chromosome microarray analysis on CytoScan Optima microarrays (Thermo Fisher Scientific, USA).
Results: The analysis of clinical and anamnestic data of the patients from the three groups did not reveal any statistically significant differences. The analysis of pregnancy complications and outcomes showed that pregnancy in the group of patients with fetal congenital diaphragmatic hernia was more often complicated by threatened preterm labor and anemia, p<0.001 and p=0.002, respectively, while patients with non-immune fetal hydrops were significantly more likely to experience antenatal fetal death, p<0.001. The study revealed that the prevalence of chromosomal abnormalities in fetuses of pregnant women of the study groups was 19.4% (30/155), including 11.6% (18/155) of cases with pathogenic copy number variations.
Conclusion: Conventional karyotyping would classify these patients as fetuses without chromosomal abnormalities. Given these findings, chromosomal microarray analysis is recommended as a first-line test in the genetic study of fetuses with congenital malformations and non-immune fetal hydrops. Since a number of fetal malformations tend to be detected late, it is recommended to perform invasive prenatal diagnostic procedures at more than 22 weeks gestation in order to provide complete perinatal counseling to the couple and to enable the family to make a reproductive choice.



The role of vasoactive intestinal polypeptide in the development of gestational complications in women with repeat caesarean sections
Resumo
Background: Current obstetric and gynecological practice is characterized by increased caesarean section (CS) rates and CS-related prenatal and perinatal complications. The uterine scar is a potential risk factor for preterm birth, uterine rupture at the site of previous SC scar, preterm placental abruption, increased risk of placental insufficiency and other placenta-associated complications.
Objective: Given the fact that vasoactive intestinal polypeptide (VIP) plays an important role in regulation of myometrial contractility and uteroplacental blood flow, the aim of the study was to investigate correlation between VIP expression in the myometrium and prenatal complications in women with repeat CSs.
Materials and methods: The study was carried out in the Obstetric Emergency Hospital in Kursk. Complex medical examination of 21 women after repeat СS at 37–41 weeks of pregnancy was performed including general and obstetric anamnesis; obstetric examination; ultrasound and Doppler ultrasound; immunohistochemical staining of biopsy material of uterine tissues, using polyclonal antibodies that recognize VIP; pathomorphological examination of the placenta; analysis of сomplete blood count and calculation of the Garkavi index.
Results: Negative correlation was found between VIP expression in the myometrium and the concentration of leukocytes (p=0.012), and positive correlation was found between VIP expression in the myometrium and the percentage of lymphocytes and the Garkavi index (p=0.031). In women with low expression of VIP, decreased placental mass (p = 0.0009), abnormal placental function, calcium deposits, foci of fibrosis and pseudo-infarction that manifested placental insufficiency, were found.
Conclusion: Low expression of VIP in the myometrium is associated with pelvic inflammatory disease, increased concentration of leukocytes, reduced level of lymphocytes and high rate of placental insufficiency, possibly due to immunological disorders associated with VIP deficiency. High expression of VIP in the myometrium is associated with preeclampsia and is considered to be a compensatory mechanism that can improve uterine and placental blood flows.



Clinical use of expanded genetic testing in the management of couples with unexplained infertility
Resumo
Objective: To clarify the proportion of unexplained infertility within the overall structure of infertility and analyze the clinical, embryologic, and genetic characteristics of patients with unexplained infertility (UI).
Materials and methods: Patients were selected from couples referred for IVF/ICSI programs. In the retrospective phase of the study, clinical and medical history data were analyzed from 1,500 married couples who underwent 2,156 stimulated cycles from 2020 to 2022 at V.I. Kulakov NMRC for OG&P. The observation group consisted of 156 married couples diagnosed with unexplained infertility, who were referred for IVF.
Results: Of the total number of patients included in the study, 10.4% were diagnosed with unexplained infertility. The cause of infertility was established in 89.6% of the couples. Patients with UI had a longer duration of infertility (on average 4.3 (1.2) years) compared to patients with an established cause of infertility (3.2 (2.4) years), with a statistically significant difference (p<0.001, Student's t-test). Patients with UI also exhibited lower AMH levels and lower antral follicle counts compared to the control group: mean levels were 2.6 (0.46) and 13.3 (2.9), respectively, versus 3.61 (2.04) and 14.2 (4.0) (p<0.001 and p=0.004, Mann–Whitney U-test). The number of oocytes retrieved by transvaginal ovarian puncture was similar in both the groups. Comparison of the parameters of subsequent embryological stages showed that all patients with UI had significantly reduced parameters compared to those in the group with an established cause of infertility: mature oocytes were 33.3% lower, correctly fertilized oocytes were 45.5% lower, and the number of embryos (blastocysts) available for transfer was 82.2% lower. Patients with UI who did not have blastocysts retrieved on day 5 of culture underwent genetic testing, which revealed genetic variants potentially linked to IVF failure.
Conclusion: Identifying the specific genetic determinants of female infertility enables a definitive diagnosis for couples, allowing them to consider alternative ART options. It also provides an opportunity to identify molecular factors and biological pathways involved in the acquisition of oocyte competence.



Lipid profiling of follicular fluid and blood plasma as a method of predicting pregnancy in women undergoing assisted reproductive treatment
Resumo
Background: Modifications of infertility treatment protocols in assisted reproductive technology (ART) programs based on the clinical and laboratory history of couples still have limitations in predicting their effectiveness. The search for minimally invasive markers of gamete quality and markers of the effectiveness of ART treatment is a relevant area at this stage of development of reproductive medicine.
Objective: To create a model for predicting pregnancy on the basis of the lipid profile of blood plasma and follicular fluid in patients undergoing ART treatment by means of liquid chromatography and mass spectrometry.
Materials and methods: The present study analyzed the clinical and anamnestic characteristics, as well as the lipid profile, of couples undergoing infertility treatment with standard ovarian stimulation in the ART department. Follicular fluid and blood plasma sampling followed by cryopreservation was performed on the day of puncture. The lipid composition of biological fluids was studied using liquid chromatography with tandem mass spectrometry. The lipid profile of the samples underwent analysis to develop OPLS-DA models.
Results: The study revealed statistically significant differences in the composition of follicular fluid and blood plasma depending on the outcome of the treatment in patients who had assisted reproduction. ROC curve analysis of the developed models showed that the model based on plasma lipid composition was more effective than the model based on follicular fluid (AUC=0.97, AUC=0.91, respectively).
Conclusion: The data of the present study are consistent with the results of world studies and confirm the potential of using the lipid composition of follicular fluid and blood plasma as markers of the effectiveness of ART programs.



Manifestations of undifferentiated connective tissue dysplasia and prediction of recurrence after surgical correction of anterior pelvic organ prolapse in women
Resumo
Pelvic organ prolapse (POP) is a significant global health problem in women.
Objective: To examine the prevalence of clinical and phenotypic manifestations of undifferentiated connective tissue dysplasia (uCTD) in patients with anterior POP and investigate the recurrence rate after surgical treatment to develop a prognostic model for the selection of mesh or native implants.
Materials and methods: A study was conducted involving 460 patients aged 40–82 years who were diagnosed with anterior POP using the Pelvic Organ Prolapse Quantification system (POP-Q ISC, 1996). Patients were examined and underwent vaginal surgery using mesh or native implants in the gynecology department of the Research Institute of Clinical and Experimental Lymphology from 2015 to 2023. The patients were divided into two groups depending on the surgical treatment method for POP. Group 1 included 242 women aged 60 (56; 64) years, who underwent surgery using a mesh implant (transvaginal system cysto-swing, France), while Group 2 included 218 patients aged 66 (62; 68) years, who underwent surgery using native tissues.
Results: Among 328 patients in both groups, clinical manifestations of uCTD of moderate (50.87%) and severe (20.43%) grades prevailed. Pronounced manifestations of uCTD accounted for 71.3%, with no statistically significant differences in uCTD scores between groups 1 and 2. The most significant predictors of POP recurrence in patients with mesh implants, in descending order, were varicose veins (VV) and/or hemorrhoids that required surgical treatment, chronic bronchopulmonary diseases (CBPD), and vegetative-vascular dystonia (VVD). These manifestations of uCTD were also significant in group 2, with additional manifestations including hernias of various localizations, a tendency toward allergic and cold diseases, and an asthenic body type.
Conclusion: The modeling results identified three manifestations of uCTD that are universal predictors of the recurrence of anterior POP: VVD (a minor manifestation of uCTD), CBPD (a major sign of uCTD), and VV (severe manifestations of uCTD). If three additional manifestations of uCTD are identified, namely, an asthenic body type, a tendency toward allergic and cold diseases, and hernias of various localizations, it is advisable to opt for a mesh implant immediately.



Ovarian reserve and mature cystic teratomas of the ovaries in patients of reproductive age
Resumo
Background: Ovarian reserve denotes the functional potential of the ovaries, which determines the ability of the ovaries for development of healthy follicles and eggs and the adequate response to ovarian stimulation. Mature cystic teratomas account for 15–20% of all ovarian tumors. These ovarian neoplasms require timely surgical treatment, as a rule, laparoscopic surgery with organ-sparing approach, that allows to preserve reproductive function in patients.
Objective: To assess the ovarian reserve in patients of reproductive age, who have mature cystic teratomas of the ovaries before and after surgical treatment.
Materials and methods: The retrospective analysis of 267 medical histories of patients, who were admitted to the Gynecological Department of the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, with diagnosis of ovarian teratomas from 2016 to 2022. All patients underwent routine medical examination according to the standard algorithm – clinical and laboratory examination, the CA-125 and anti-Müllerian hormone (AMH) blood tests, pelvic ultrasound, and when necessary, MRI of the pelvis before and after surgery. Laparoscopic surgery was performed with maximum preservation of healthy ovarian tissue.
Results: The mean age of patients was 35.0 (6,5) years (aged 18–45 years). The age of most patients – 114/267 (43%) was 32–38 years; 19/267 (7%) were aged 18–23 years; 67/267 (25%) were aged 24–31 years, 32/267 (12%) were aged 39–42 years and 35/267(13%) were aged 43 years and over. In 259/267 (97%) of women, neoplasms were unilateral. Bilateral teratomas were in 8/267 cases (3%). The size of mature cystic teratomas ranged from 1.0 to 17.0 cm. The average antral follicle count (AFC) before surgical treatment was 4.0 (2.4) follicles; AMH level was 2.6 (2.0) ng/mL. AMH levels (р<0.001) and AFC (р<0.001) reduced 3 months after surgery. The average AMH level was 1.7 (1.5) ng/mL, and AFC was 3.0 (1.8).
Conclusion: Standard methods of surgical hemostasis are not always applicable in patients with low ovarian reserve. For this reason, it is necessary to continue searching for new methods that can minimize ovarian tissue damage with purpose of preservation of the ovarian reserve to realize reproductive function.



Predictors of spontaneous puberty and premature ovarian insufficiency in girls with Turner syndrome
Resumo
Background: Turner syndrome is one of the most common sex chromosome abnormalities associated with premature ovarian insufficiency. Phenotypic manifestations often do not correlate with the karyotype of Turner syndrome; 20% of girls exhibit timely sexual development, and 5–10% experience spontaneous menstruation. Therefore, identifying significant predictors of preserved ovarian function in this cohort of patients is essential.
Objective: To investigate the prognostic markers of spontaneous puberty and premature ovarian insufficiency in girls with Turner syndrome, focusing on age and karyotype.
Materials and methods: This retrospective study included 122 girls with Turner syndrome, aged 9–17 years, who were observed in the 2nd Gynecological Department of V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia. Patients were divided into groups based on age and karyotype variants, with subsequent rankings according to the preservation of ovarian function. Clinical and medical history data, serum hormone levels, and ultrasound findings of the gonads and mammary glands were also assessed.
Results: Spontaneous puberty was observed in 49% of the patients, with 11% experiencing menarche at a mean age of 12.62 (0.37) years; however, 41% displayed no signs of puberty. During the examination, premature ovarian insufficiency was diagnosed in 81% of the patients. No association was found between the absence of spontaneous sexual development and the set of chromosomes, including X monosomy; however, the risk of premature ovarian insufficiency was associated with ploidy of the X chromosome. The risk of detecting FSH levels greater than 25 IU/L had an inverse correlation with ovarian volume, increasing at a value of less than 1.29 cm³.
Conclusion: Despite the karyotype and characteristics of sexual development, ovarian reserve should be assessed in patients with Turner syndrome starting from prepubertal age. This assessment should consider the dynamics of blood hormone levels and ovarian volume measured using ultrasound, which serves as a valuable marker for the risk of ovarian insufficiency in this cohort of patients.



Clinical characteristics of dysmenorrhea and its association with lifestyle factors in adolescent girls
Resumo
Dysmenorrhea is the most common pathology among adolescent girls, affecting between 41.7% and 95%, depending on the diagnostic criteria and calculation method used. The multicomponent clinical manifestations, significant impact on quality of life, and potential modifiability of this condition make it not only a medical issue, but also a socially important problem.
Objective: To investigate the prevalence of dysmenorrhea among adolescent girls aged 15–19 years, as well as its symptoms, menstrual function characteristics, and impact on behavioral characteristics, physical activity, and quality of life, depending on the severity of the pain syndrome.
Materials and methods: A cross-sectional study was conducted at outpatient healthcare facilities in Arkhangelsk by surveying 585 healthy teenage girls aged 15–19 years who met the inclusion criteria, followed by a comparative statistical analysis.
Results: The prevalence of dysmenorrhea in our study was 97%. Clinical parameters of menstrual function were comparable between girls with painless and painful menstruation, suggesting that menstrual cycle characteristics alone are insufficient to fully assess dysmenorrhea. More than half of the teenage girls (52.9%) rated the severity of the pain as moderate, while approximately a quarter (24.9%) rated it as severe. Severe forms of dysmenorrhea were characterized by more widespread localization of pain. Dysmenorrhea included a wide range of “non-gynecological” symptoms, the frequency and severity of which correlated with the intensity of pain. It also had a significant negative impact on various aspects of life for the vast majority (up to 79.7%) of adolescent girls, including decreased academic performance, difficulties with homework, absenteeism, concentration problems, and limited social and physical activity. These findings are consistent with data from similar studies, and emphasize the importance of an integrated diagnostic approach for this condition.
Conclusion: The wide prevalence of dysmenorrhea and the lack of other symptoms in standard gynecological evaluations can normalize the condition and hinder a realistic assessment, potentially worsening both the medical and social prognosis. Given the specificity of the condition and the subjectivity of its clinical manifestations, careful development of objective tools for assessing the severity of dysmenorrhea is essential.



Evaluation of nicotinic acetylcholine receptor subunit expression levels for the improvement of diagnostic approaches and treatment in endometrial hyperplasia and cancer
Resumo
Objective: To determine and compare the expression levels of genes encoding nicotinic acetylcholine receptors (nAChRs) in hyperplastic and oncological endometrial processes.
Materials and methods: The study included 120 women of reproductive age divided into groups according to histological examination results: endometrial hyperplasia (EH) (n=58), endometrioid adenocarcinoma of the endometrium (n=14), and those with unchanged endometrium (n=48). The expression levels of genes encoding nAChRs (α1, α2, α3, α4, α5, α6, α7, α9, α10, β1, β2, β3, and β4) were determined by real-time reverse transcription polymerase chain reaction using specific primers for the corresponding nAChRs.
Results: Among the patients in the first group, increased expression was observed for the α1, α4, β1, and β2 subunits, with the greatest diagnostic significance attributed to the α4 subunit of the nAChRs. In the endometrium of patients in the second group, gene expression was detected for the α1, α3, and α6 subunits, with the α3 subunit of the nAChRs showing the greatest diagnostic significance. In the third group, pronounced expression was noted for the α3, α5, α6, and α7 subunits of the nAChRs.
Conclusion: The observed expression of nAChRs in EH suggests their influence on the differentiation of unchanged endometrium, potentially leading to the development of EH. The expression of these subunits in endometrial adenocarcinoma indicates that they may serve as potential predictors of endometrial neotransformation.



Differential diagnosis of early-stage ovarian cancer based on the bioinformatic analysis of the blood metabolome
Resumo
The early diagnosis of ovarian cancer (OC) represents an important step in reducing the number of fatal outcomes associated with the disease. Timely treatment initiation, minimizing the risk of recurrence and side effects of therapy, largely depend on early diagnosis.
Objective: To create stable panels of blood metabolites for differentiating healthy patients, patients with early-stage high-grade OC from other ovarian tumors.
Materials and methods. A search for markers for clustering of blood samples obtained from patients with verified stage I–II high-grade OC (n=10) and other proliferative processes (cystadenoma (n=30), endometrioid cyst (n=56), teratoma (n=21), borderline tumor (n=28), low-grade OC (n=16), stage III–IV high-grade (n=49)) and control volunteers (n=19) was performed. The study was carried out at the V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Moscow, Russia. The data were analyzed using recursive variable removal from the support vector machine and other statistical tools. There was a search for markers of malignant neoplasms (MNPs), followed by the analysis of their involvement in metabolic pathways. Models based on neural networks were built.
Results: The panels of metabolite-markers of early stages of MNPs were identified. The overlap of the obtained panels with metabolic pathway databases was studied. Artificial neural network models were developed to differentiate blood samples from I–II stage OC from controls with sensitivity and specificity of 90% and 89%, and from I–II stage OC from other ovarian neoplasms with sensitivity and specificity of 80% and 71%, respectively.
Conclusion: The introduction of post-genomic research has the potential to increase the diagnostic value of the methods used to detect ovarian MNPs at an earlier stage and also to expand the available data on the processes of carcinogenesis in the ovaries.



Features of the profile of serum autoantibodies to reproductive hormones and steroidogenic enzymes in patients with endometriosis-related infertility and infertile patients without endometriosis
Resumo
Female infertility is a pressing issue in reproductive medicine, marked by a rising number of patients and increased need for assisted reproductive technologies (ART). There is a well-established association between infertility and endometriosis, which is characterized by a diverse repertoire of autoantibodies, including those against hormones.
Objective: This study aimed to compare the profiles of autoantibodies to reproductive hormones and steroidogenic enzymes in patients with endometriosis-associated infertility and those without endometriosis.
Materials and methods: We used enzyme-linked immunosorbent assays to determine serum antibodies to steroid and gonadotropic hormones, anti-Müllerian hormone (AMH), and steroidogenic enzymes (21-hydroxylase, aromatase, and cholesterol side-chain cleavage enzyme) in patients with endometriosis-associated infertility (group 1, n=44) and those without endometriosis (group 2, n=44) prior to ART cycles.
Results: Group 1 exhibited a high detection rate of IgG antibodies to estradiol, progesterone, and aromatase (>20%), while group 2 showed a high detection rate of IgG antibodies to FSH and AMH (>30%). When comparing the two groups, IgG antibodies to estradiol were detected more frequently in group 1, whereas IgG antibodies to AMH were more prevalent in group 2. IgG antibodies to hormones and steroidogenic enzymes were detected in 9 of 10 women with reduced ovarian reserves.
Conclusion: The identified features of the autoantibody profile can improve the efficiency of diagnostics, facilitate personalized therapy prescriptions, and optimize ART programs. Prospective studies are necessary to assess the impact of autoantibodies on reproductive outcomes and explore effective immunosuppressive and immunotherapies.



Predicting response to neoadjuvant chemotherapy in cervical cancer: possibilities of radiomic analysis of MR images
Resumo
Objective: To develop and validate a radiomic model for predicting tumor response to neoadjuvant chemotherapy (NACT) in patients with locally advanced cervical cancer (LACC) based on MR imaging.
Materials and methods: A total of 182 patients aged 27 to 49 years with disease stages IB3-IIB and IIIC1 (two patients with metastatic pelvic lymph node involvement) according to FIGO 2018 were retrospectively enrolled in the study. The patients underwent treatment at the Academician Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow from 2018 to 2023. Radiomic parameters were extracted from T2-weighted (T2-WI) and diffusion-weighted (DWI) MR images. The most statistically significant characteristics were selected using LASSO (Least Absolute Shrinkage and Selection Operator) linear regression. The construction of the prediction model was based on a combination of radiomic signs and clinical data. In order to assess the prognostic effectiveness and clinical benefit of the developed model, ROC and decision curve analysis were used.
Results: Two models for predicting response to NACT were developed in the study. The first model included isolated radiomic signs and demonstrated a sensitivity of 79.6% in the main and 85.7% in the test group, specificity 80.6% and 72.1%, respectively. AUC was 0.90 in the main group and 0.83 in the validation group. In order to improve the quality of the model, clinical data (maximum linear size and degree of tumor differentiation, age of the patients, presence of metastatic lymphatic nodes) were included in the nomogram in addition to radiomic parameters. Radiomic nomogram showed sensitivity of 87.8% and 71.4%; specificity of 88.8% and 97.7% in the main and test groups, respectively. AUC was 0.96 and 0.94.
Conclusion: The constructed radiomic model is effective in predicting the therapeutic response of NACT in cervical cancer.



Mitochondrial dysfunction and embryo quality: prospects for antioxidant correction containing myo-inositol and D-chiroinositol in a 5:1 ratio, manganese and folic acid
Resumo
Objective: To evaluate the functional activity of mitochondria of cumulus cells and embryo quality in protocols of assisted reproductive technologies (ART) in reproductive-aged patients with anovulatory infertility and obesity taking myo-inositol (MI) and D-chiroinositol (DCI) complex in a 5:1 ratio in combination with manganese and folic acid.
Materials and methods: The study included 22 patients with obesity and anovulatory infertility. The patients of the main group (n=11) received one sachet of Dikirogen complex two times/day for six months before the ART protocol, the comparison group (n=11) did not receive Dikirogen. The obtained embryos were cultured in the EmbryoVisor incubator with time-lapse function. Confocal laser scanning microscopy was used to study the mitochondrial activity of cumulus cells.
Results: No statistically significant differences were found in the comparison of morphokinetic parameters of embryos, but the blastulation rate in the main group was significantly higher than in the comparison group (57.01±1.99 vs 48.19±3.13, p=0.04). The evaluation of mitochondrial networks in cumulus cells showed a significantly higher emission intensity in the main group than in the comparison group (48.28±1.14 and 42.03±1.24, p=0.002).
Conclusion: The combined therapy with antioxidants, vitamins and trace elements (2000 mg MI, 400 mg DHI, 400 μg folic acid, 10 mg manganese) administered for six months before the initiation of the ART protocol can reduce mitochondrial dysfunction of cumulus cells, decrease oxidative stress and lead to the improvement of oocyte quality.



Medicine and Law
The role of informed consent for medical intervention in the investigation of legal cases against obstetrician-gynecologists
Resumo
The article examines the patient’s informed consent for medical intervention as one of the fundamental legal principles of modern health care. The issues of providing information and obtaining patient’s informed consent for medical intervention in the routine practice of obstetrician-gynecologists are discussed. However, the proper level of information and consent for medical interventions is not always achieved and as a result, disagreements arise between patients and medical professionals, sometimes leading to the initiation of legal proceedings. Current legislation does not provide uniform requirements for the amount and format of information that an obstetrician-gynecologist must provide to a patient when performing a medical intervention. The development and adoption of universal standard forms of informed consent for medical interventions appear to be a necessary solution to this problem.
Conclusion: The development of the standard form can balance the rights of citizens to be informed when seeking medical assistance and protect doctors legally from patient claims by providing comprehensive and intelligible information. This is particularly important given that doctors may be held legally in case of violation of the informed consent rule. It should be noted that the acknowledgment of the potential risks associated with substandard medical care, as outlined in the informed consent for medical intervention, does not absolve the physician of legal responsibility.



Exchange of Experience
Efficacy and safety of mifepristone in patients with uterine fibroids
Resumo
Objective: To evaluate the efficacy and safety of Gynestril, 50 mg tablet, in patients with symptomatic uterine fibroids in routine clinical practice.
Materials and methods: This was an open, multicenter, non-interventional, prospective study conducted on the basis of seven Russian clinical centers between 2022 and 2023 in order to investigate the therapeutic efficacy and safety of Gynestril in patients with symptomatic uterine fibroids in routine clinical practice (GYNNEO). All patients (n=234) were administered the drug orally, in the form of a single tablet, once a day on days 1-3 of the menstrual cycle for a period of three months (one course of treatment). The efficacy and safety of the treatment were evaluated during the patients’ visits to the centers: before the drug was prescribed, immediately after completing the treatment with its course for three months and three months after completing the treatment. Efficacy was assessed by changes in the volume and largest linear size of the dominant myomatous node and nodes 2 and 3, which were considered to be the second and third nodes in diameter after the dominant node (provided that their initial diameter was less than 1.5 cm), uterine volume, number of visualized nodes, endometrial thickness, resistance index (RI) and blood flow velocity in the nodes, hemoglobin level, dynamics of symptom severity according to the 5-point Likert scale, etc. The incidence and characteristics of adverse and serious events were considered in the safety assessment.
Results: According to the ultrasound data, the volume of the dominant myomatous node decreased by 33% after three months of therapy with Gynestril and by 59.5% after three months of follow-up compared to baseline (pre-treatment) level. A number of other efficacy endpoints also showed positive trends during the study. They included decreases in volume of nodes 2 and 3, uterine volume, maximum linear size of the nodes, increased RI, and decreased blood flow velocity in the nodes. The severity of the symptoms associated with the disease (pain, dyspareunia, and symptoms of compression) was found to decrease with the complete elimination of moderate and severe symptoms after three months of therapy. Half of the patients had amenorrhea after the treatment and it persisted in 101/234 (43%) patients for three months after completing the treatment with Gynestril. During the study, there were 26/226 (11%) adverse events related to treatment.
Conclusion: The study demonstrates that treatment with Gynestril results in a statistically significant decrease in the volume of myomatous nodes after three months of therapy (immediately after the course) and this effect persists for three months following the completion of the course of therapy. Therapy with Gynestril controls and reduces the severity of symptoms of the disease and the amount of menstrual blood loss. The drug is generally well tolerated by patients.



Guidelines for the Practitioner
Antibacterial therapy in pelvic inflammatory diseases: current trends
Resumo
The article presents a comprehensive analysis of the scientific literature on antimicrobial therapy for pelvic inflammatory diseases (PID). This is a literature review of the data obtained from the world sources in PubMed (the National Library of Medicine), Cochrane Library, Medline, and scientific citation databases (Scopus, Web of Science) for the period from 2005 to 2024.
Sexually transmitted infections are the primary cause of PID, but recent publications point to anaerobic microorganisms as a significant etiologic factor. PID represents a significant clinical and public health issue due to its potential to cause infertility. Broad-spectrum antibiotics are the principal drugs used in the treatment of PID. Antibacterial therapy regimens for PID follow certain principles and are aimed at eliminating the main pathogens, namely Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium. The polymicrobial nature of PID is also taken into account in the current recommendations for its treatment. One antibacterial drug that meets all the principles of the prescribed therapy and is included in almost all treatment regimens for PID is doxycycline. The novel form of the well-known and widely used antibiotic, Doxycycline EXPRESS, is the bioequivalent of the original drug, doxycycline monohydrate, in the form of dispersible tablets.
Conclusion: Currently, antibiotic resistance in the treatment of women with PID remains a complex medical problem. Doxycycline has an advantage in antimicrobial activity against intracellular pathogens including Chlamydia trachomatis and Mycoplasma genitalium. Doxycycline monohydrate demonstrates improved tolerability and eliminates the development of a number of side effects associated with tetracycline-type drugs. Due to the rapid release and even distribution of the active ingredient in the blood when taking the dispersible tablet (Doxycycline EXPRESS), higher concentrations are achieved in the area of the infectious lesion that help to overcome antibiotic resistance.



Comparative pharmacoeconomic effectiveness of menopausal hormone therapy: oral versus transdermal preparations
Resumo
Objective: To evaluate the economic benefit of transdermal menopausal hormone therapy (MHT) compared to the oral treatment using the method of scientific modeling.
Materials and methods: Clinical economic modeling was used to conduct the pharmacoeconomic analysis. The results of published studies were used as sources for the effectiveness analysis. The Scottish Intercollegiate Guidelines Network (SIGN) methodology, with a minimum level of evidence of 2, was used to select studies, perform clinical and economic modeling, develop the study design, and assess the methodological quality of the studies. A pharmacoeconomic analysis was conducted to compare two regimens of menopausal hormone therapy and assess the risk of adverse complications, namely venous thromboembolism (VTE) and acute circulatory failure (ACF).
Results: The pharmacoeconomic analysis showed that the use of MHT with transdermal estradiol (Oestrogel) in continuous mode demonstrated efficiency in cost savings due to the reduction of costs for the treatment of adverse events (VTE and ACF) and their consequences; savings per one patient amount to 6,389.4 rubles per year. Savings per 1,000 women during the year will amount to 6,389,400 rubles, or 31,947,000 rubles for 5 years.
Conclusion: Transdermal MHT may prove to be cost-effective compared to oral MHT due to the reduced cost of complications associated with oral MHT. The use of the Oestrogel preparation will reduce the total cost of MHT by 11.3% compared to oral MHT.



The role and place of proper female intimate hygiene in preventing vulvovaginitis and bacterial vaginosis
Resumo
The issue of female intimate hygiene is a delicate matter that is frequently neglected in the communication between patients and primary care physicians. From a pragmatic perspective, there is an extensive range of feminine hygiene products available that women can use as part of their daily hygiene routine. However, there is a lack of research and recommendations related to the care of the female genitalia. Consequently, the present review concentrates on the issue of female hygiene, as it has been the subject of comparatively little research.
This article considers the role and place of proper intimate hygiene in the prevention of vulvovaginitis and bacterial vaginosis in women. The authors analyze the basic principles and rules of intimate hygiene that help maintain vaginal health and prevent the development of these diseases.
The relevance of the issue is due to the high prevalence of vulvovaginitis and bacterial vaginosis among women of different age groups. The authors also consider factors that contribute to vulvovaginitis and bacterial vaginosis, such as improper use of hygiene products, wearing synthetic underwear, frequent spaying, etc.
The vaginal microflora has a unique balanced environment during the reproductive period of a healthy woman’s life. This environment may change under the influence of external factors, but it returns to normal due to the mechanism of self-purification. The acid-base balance of the vaginal environment varies between 3.8 and 4.5. It can vary during the menstrual cycle, during pregnancy, and it depends on the sexual activity of the woman.
During the reproductive years, the vaginal microbiota of healthy women is characterized by the presence of various microorganisms, including aerobic and anaerobic, Gram-positive and Gram-negative bacteria. Lactobacillus spp. and Corynebacterium spp. predominate over other bacteria such as Streptococcus spp., Bacteroides spp., Staphylococcus spp. and Peptostreptococcus spp. The bacteria of the Lactobacillus spp. and Corynebacterium spp. produce lactic and acetic acid from glycogen, maintaining an acidic environment (low pH) in the vagina. This results in colonization resistance and inhibition of the multiplication of pathogenic flora in the vagina. If colonization resistance is compromised, opportunistic bacteria can cause vulvovaginitis.
The article presents the findings of the analytical study of several clinical cases on the treatment of bacterial vaginosis and vulvovaginal candidiasis and modification of intimate hygiene with the use of the Saforelle product for intimate hygiene.
Conclusion: The results showed that the use of a comprehensive approach, including antibacterial therapy and the Saforelle product for intimate hygiene, contributes to the rapid and effective elimination of symptoms of bacterial vaginosis and vulvovaginal candidiasis.


