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编号 8 (2025)
Reviews
Prevention and treatment of vitamin D deficiency during pregnancy: the position of professional medical communities
摘要
The review presents the analysis of 17 clinical recommendations and the position of 14 professional medical communities on the prevention and treatment of vitamin D deficiency in pregnant women. These recommendations are offered by the World Health Organization (WHO), the British Royal College of Obstetricians and Gynecologists (RCOG), the Institute of Obstetricians and Gynecologists of the Royal College of Physicians in Ireland, the American Pregnancy Association (APA), the American College of Obstetricians and Gynecologists (ACOG), the Society of Obstetricians and Gynecologists of Canada (SOGC), the Endocrine Society, the Royal Australian College of General Practitioners (RACGP), Health Canada, Académie de Médecine, the German Nutrition Society (Deutsche Gesellschaft für Ernährung e.V.), the Chinese Nutrition Society, the Institute of Medicine, the Russian Society of Obstetricians and Gynecologists (RSOG), the Russian Association of Endocrinologists (RAE), Health New Zealand - Te Whatu Ora and the nutrition societies of Germany, Austria, and Switzerland (D-A-CH).
Conclusion: All professional communities agree that pregnant women should receive adequate nutrition. This is best achieved by eating healthy, balanced foods, and ensuring that they get enough sunlight, which is a vital source of vitamin D. At the same time, the analysis reveals different positions among professional communities regarding vitamin D intake during pregnancy. Recommendations for vitamin D intake during pregnancy range from 200 to 4,000 IU/day. Most communities do not recommend regular prophylaxis with high doses of vitamin D for pregnant women, as the safety of this practice has not been proven. High-quality randomized controlled trials among populations with low vitamin D levels are necessary to assess the benefits of vitamin D during pregnancy, as these benefits remain uncertain and vary greatly.
5-14
Artificial intelligence technologies in gynecology
摘要
The review includes the scientific data from national and foreign studies, 90% of which were published within the last five years. Their topic is related to the testing and analysis of the effectiveness of artificial intelligence (AI) in the diagnosis, treatment and prevention of gynecological pathology. It was concluded that the effectiveness of AI algorithms in many aspects surpasses experts in the diagnosis of cervical cancer, endometrial cancer, ovarian cancer and endometriosis, namely, in evaluating the results of direct and indirect imaging. The literature data show that the integration of AI into clinical practice significantly reduces diagnostic time and is very promising. At the same time, the work of AI in assessing cytology and histology has shown contradictory results. In cervical cytology, AI has surpassed specialists, but in the case of histology of cervical cancer, the results obtained so far do not allow for AI to be fully integrated into clinical practice.
Large language models (LLM) offer significant potential for patients and doctors, with ChatGPT being a primary example. Today, the chatbot often provides correct answers to questions from patients seeking gynecological advice. However, the accuracy of its responses when the questions are more specific and detailed is still not sufficient.
The integration of professional activities with AI-based management systems may reduce the error rate in clinical practice, but their widespread implementation is still limited.
Conclusion: The review demonstrates significant progress in the application of AI in gynecology, especially in the diagnosis of cervical, endometrial, ovarian, and endometriosis cancers. AI algorithms show high effectiveness in analyzing medical images, often surpassing traditional methods in accuracy and speed. However, the use of AI faces several ethical, legal, and practical challenges, such as transparency of decisions, responsibility for mistakes, and integration into clinical practice. Despite this, the potential of AI to improve diagnosis and optimize the work of an obstetrician-gynecologist is obvious.
16-25
The use of hyaluronic acid in vulvovaginal atrophy in women after antitumor therapy
摘要
Objective: To analyze the available literature on the use of hyaluronic acid in programs of non-hormonal correction of vulvovaginal disorders associated with antitumor treatment in cancer patients.
Materials and methods: The literature search was conducted in the electronic databases, namely PubMed, Scopus, Web of Science, Cochrane Library, ScienceDirect, Embase, PsycINFO using the keywords in Russian and English. The articles were published between 1914 and 2024.
Results: The symptoms of genitourinary syndrome of menopause have a long-term negative impact on the quality of life of women who underwent antitumor treatment. Currently, it is important to develop approaches to supportive and restorative therapy for women at risk of developing genitourinary syndrome of menopause. One of the effective methods for correcting this condition in women undergoing oncological rehabilitation is the use of intravaginal preparations containing hyaluronic acid. These preparations significantly reduce the symptoms of vulvovaginal atrophy with efficacy comparable to that of topical estrogens. Besides, they have high safety and do not cause side effects.
Conclusion: The analysis of the literature showed the potential for further research into the efficacy and safety of using hyaluronic acid to correct vulvovaginal changes in cancer patients after antitumor therapy, as well as for long-term follow-up. This research could help determine whether it should be included in the standard restorative treatment for these patients. Such an approach could improve the quality of life for this patient group and address a number of psychological and socio-economic issues.
26-35
The role of lactoferrin and tyndallized Lactobacilli in the eradication of opportunistic pathogens and the restoration of vaginal eubiosis
摘要
Objective: To present the results of the use of lactoferrin and tyndallized probiotics (Lactobacillus spp.) as new strategies to fight bacterial and fungal vulvovaginal infections.
Materials and methods: The literature search was conducted in the international databases PubMed/MEDLINE, Google Scholar, Cochrane Library, and the Russian platform eLibrary using the keywords. The search depth was 10 years. The analysis included 46 publications.
Results: Lactoferrin (LF) is a biglobular protein that belongs to the transferrin family and is able to sequester iron necessary for the vital activity of bacteria. This property makes LF an effective antibacterial agent. LF has prebiotic activity and has immunotropic, anti-inflammatory and regenerative effects. Both in vitro and in vivo studies showed that tyndallized probiotic bacteria, their cell-free supernatants and purified key components obtained by heat treatment, are able to protect against pathogens, maintain the integrity of the epithelial barrier, and have an immunomodulatory effect. DuoLact is a combination of tyndallized L. casei and L. acidophilus. LF and DuoLact are part of the DERMOLIVO product line. The vaginal use of medications based on LF and tyndallized Lactobacilli has been tested in several clinical studies and has proven to be highly effective in eradicating opportunistic pathogens that cause vulvovaginal infections and in restoring vaginal eubiosis.
Conclusion: Experimental and clinical studies indicate that lactoferrin and tyndallized Lactobacilli have antibacterial and protective properties and can be used as an additional therapy for vulvovaginal infections.
37-46
Characteristics of the menstrual cycle in obese adolescent girls
摘要
Background: In recent decades, there has been a steady increase in the body mass index (BMI) among children and adolescents worldwide that reflects the growing prevalence of obesity at a young age. Excess body weight during this sensitive period of development has a significant impact on the reproductive system of adolescent girls. In this regard, early diagnosis and prevention of overweight-related disorders are of particular importance, as they help minimize potential risks and contribute to a healthy reproductive future.
Objective: To analyze the data of the foreign studies on the role of obesity in the development of menstrual cycle disorders in adolescents.
Materials and methods: This literature review analyzes studies published over the past 10 years including reviews, cohort studies and meta-analyses, on the risk factors, diagnosis, and prevention of ovarian dysfunction in obese girls. A total of 42 publications were included in the review out of 89 articles found on the issue. The search for scientific publications was conducted in databases of Elsevier, PubMed, and Web of Science using keywords related to obesity and menstrual disorders in adolescents.
Results: The analysis of literature and data of epidemiological studies has shown that high values of BMI, waist circumference and hip circumference significantly correlate with the duration, volume, and regularity of menstruation, as well as the severity of pain syndrome. Obese adolescents are more likely to suffer from oligomenorrhea, heavy menstrual bleeding, dysmenorrhea, and premenstrual disorders. These findings highlight the need for early screening of body weight and metabolic status in girls for timely prevention and correction of reproductive disorders.
Conclusion: The diagnosis of obesity in adolescents requires a comprehensive approach including the analysis of the patient’s medical history, the assessment of the diet and lifestyle, and screening for obesity, hypertension, hyperglycemia, and dyslipidemia.
48-56
A systematic review of the efficacy and safety of dydrogesterone in the treatment of menstrual disorders in young patients, including early reproductive age
摘要
Objective: To conduct a systematic review of recent publications on the mechanisms of action, clinical efficacy, and safety of dydrogesterone in patients of reproductive age, including early reproductive years.
Materials and methods: The literature search was conducted in the following databases: eLibrary, PubMed, ClinicalTrials.gov, ICTRP, Cochrane Library and Google Scholar for the period 2016-2025. A total of 927 publications were identified, resulting in the exclusion of duplicate articles (n = 95), articles that did not meet the inclusion criteria (n = 789), and those with insufficient data (n = 17). The selection was carried out according to certain criteria of relevance: clinical studies, study design, reported endpoints, dydrogesterone therapy, and patients of reproductive age and patients aged 18 years and younger, post-menarche.
Results: There was a full-text analysis of 43 articles, 12 of them met the inclusion criteria with a total number of observations of 2,817 patients. A summary of the data showed high efficacy of dydrogesterone in regulating the menstrual cycle, reducing the frequency of abnormal uterine bleeding, relieving the severity of dysmenorrhea and chronic pelvic pain in patients of the early reproductive period. The review describes pathogenetic mechanisms of action of dydrogesterone, including an immunomodulatory effect mediated by the suppression of the NF-kB/COX-2 pathway, synthesis of proinflammatory cytokines, and activation of anti-inflammatory mediators. These mechanisms help to restore endometrial receptivity, reduce the recurrence of abnormal uterine bleeding and the severity of pelvic pain.
Conclusion: This systematic review confirms the pathogenetic and clinical significance of dydrogesterone as an effective and safe therapeutic option for menstrual cycle disorders (irregular menstruation, abnormal uterine bleeding, dysmenorrhea) in patients of reproductive age, including early reproductive years. The use of dydrogesterone is characterized by good tolerability and high levels of patient satisfaction with the therapy.
57-68
Original Articles
Adaptation of the fetus to sequential cardiotocographic examinations and the development of closed loops of self-regulation
摘要
Objective: To study changes in fetal heart rate variability (HRV) during antenatal cardiotocographic (CTG) monitoring.
Materials and methods: This study included data from 13,520 CTG recordings obtained from 3,380 pregnant women. The analysis was performed using clustering methods and statistical analysis of HRV.
Results: The initial increase in HRV was identified as a response to the stimulus, whereas subsequent reductions reflected the development of self-regulatory mechanisms. Strategy-type habituation (STH) correlated with the maturity of fetal regulatory systems. In some cases, HRV reduction was associated with dysregulation and neonatal complications.
Conclusion: HRV dynamics can serve as an objective and quantitative criterion for assessing fetal physiological states and predicting potential deviations. Antenatal CTG monitoring revealed a consistent pattern of fetal HRV changes, which may indicate adaptive processes. The initial HRV increase is a response to the stimulus, whereas the subsequent reduction reflects the formation of self-regulatory mechanisms. The key parameter is STH, which enables the assessment of fetal regulatory system maturity. Furthermore, it has been established that HRV reduction under certain conditions may be linked to dysregulation and neonatal complications. The study results suggest that HRV dynamics can be utilized as a quantitative criterion for assessing fetal physiological states.
69-78
Vacuum extraction delivery: 11 years of delivery experience, maternal and fetal outcomes
摘要
The frequency of operative vaginal births using vacuum extraction delivery, also known as fetal vacuum extraction delivery (FVE), varies significantly worldwide and comprises 2.8–16.7% of the total number of births, whereas in Russia it is no more than 1.23%. Improved models of the ventouse systems, along with obvious simplicity and convenience, make the FEV method widely and safely used.
Objective: To assess the outcomes of FVE during vaginal delivery (VD) and cesarean section (CS) for mothers and their newborns.
Materials and methods: A retrospective analysis of the outcome of 387 deliveries by FVE using the KIWI vacuum system was performed on the basis of the births and newborns histories at the 2nd Maternity Department of the Novokuznetsk Perinatal Center for the period of 2013–2023. Parity, duration of labor, course of the postpartum period in women and the condition of newborns were studied.
Results: The duration of the FVE was: 5.0 (5.0; 8.0) minutes for VD and 1.0 (1.0; 2.0) minute for CS. In 85% of VD cases and in 96% of CS cases, the postpartum period passed without complications. In 58% of VD cases and in 62% CS cases, the newborns had no complications and there were no cases of severe obstetric trauma. 83% of children were extracted in satisfactory condition, in 2% of CS cases, the death of the newborn occurred. Clinically significant injuries such as subgaleal hematomas and skull fractures were not registered.
Conclusion: When used in a timely manner, taking into account contraindications, observing the conditions and impeccable technique, FVE can be considered a safe procedure both for the mother and the fetus.
80-87
Doppler evaluation of cerebral blood flow in the differential diagnosis of late-onset fetal growth restriction
摘要
Background: Late-onset fetal growth restriction (FGR) is associated with an increased risk of stillbirth and neonatal morbidity. However, the differentiation between FGR and small-for-gestational-age (SGA) fetuses in the third trimester remains challenging. Fetal Doppler assessment traditionally plays a key role and is considered to be a potential tool for risk stratification and optimization of obstetric management in cases of FGR. In recent years, there has been an active discussion about the role of cerebral blood flow in the targeted monitoring of fetal health and the improvement of perinatal outcomes.
Objective: To study the diagnostic value of Doppler ultrasound parameters characteristic of centralization of fetal cerebral blood flow after 32 weeks gestation in the differential diagnosis of late-onset FGR and SGA, as well as their association with adverse perinatal outcomes.
Materials and methods: This was a prospective study that included 140 pregnant women after 32 weeks gestation, namely 72 patients with SGA fetuses and 68 patients with late-onset FGR, selected according to the guidelines of the Russian Society of Obstetricians and Gynecologists (RSOG). All participants underwent Doppler ultrasound assessment; the cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR) were calculated. The findings of the Doppler study, performed as close to delivery as possible, were used for analysis. Changes in Doppler parameters in both groups were studied, and their correlation with perinatal outcomes was assessed using logistic regression analysis.
Results: The comparison of perinatal outcomes showed that pregnant women with late-onset FGR compared to SGA fetuses had a higher rate of preterm birth, emergency delivery by cesarean section, birth of infants with a body weight below the 3rd percentile, and need for hospitalization of newborns in the neonatal intensive care unit (NICU). The parameters of Doppler ultrasound study (umbilical artery pulsatility index (UA PI), middle cerebral artery (MCA) PI, CPR, and UCR) in the late-onset FGR group more often exceeded the standard values. The median CPR was lower (1.19 vs. 1.70; p < 0.001), and the median UCR was higher (0.84 vs. 0.59; p < 0.001) in the late-onset FGR group compared to SGA. A significant association was found between UA PI, CPR, and UCR in pregnancies with FGR and adverse perinatal outcomes, such as preterm birth (OR: 76.3, p < 0.001; 0.1, p < 0.001; 26.5, p < 0.001, respectively), emergency cesarean section due to fetal distress (OR: 4.1, p < 0.05; 0.4, p = 0.04; 4.5, p < 0.05, respectively), neonatal hospitalization in the NICU (OR: 31.9, p < 0.05; 0.1, p = 0.04; 32.8, p < 0.05, respectively), combined adverse perinatal outcome (OR: 13.3, p = 0.002; 0.2, p = 0.002; 11.2, p = 0.05, respectively); however, ROC analysis (AUC, 95% CI) of the models for predicting combined adverse perinatal outcome showed low prognostic value of these parameters. The best diagnostic accuracy was demonstrated by the gestational age-adjusted centile values of CPR and UCR [0.695 (0.604–0.777) and 0.675 (0.582-0.758)], as well as the dichotomized by a predetermined centile values of UCR < 5th centile and PCR > 95th centile [0.641 (0.547–0.727) and 0.631 (0.538–0.718)]. No data were obtained to support the greater effectiveness of CPR or UCR. At the same time, extreme values characterizing the centralization of cerebral blood flow became more obvious and clearer for interpretation in case of using UCR.
Conclusion: Doppler parameters that characterize cerebral blood flow centralization, such as UA PI, MCA PI, CPR and UCR, are not effective enough to predict combined adverse perinatal outcome and its individual components in pregnancies with SGA fetuses and FGR. Gestational age-adjusted centile (continuous) values of CPR and UCR, as well as dichotomized by a pre-established cutoff centile value of CPR (< 5th centile) and UCR (> 95th centile) are more effective in predicting adverse perinatal outcomes. Further prospective studies are required to determine whether it is possible to include these parameters in clinical practice, as well as to find new markers that can predict adverse outcomes for children with late-onset FGR.
88-98
Perinatal outcomes and characteristics of placental disorders in term pregnancies among convalescents after novel coronavirus infection (COVID-19) experienced at different gestational ages
摘要
Objective: To evaluate perinatal outcomes and the characteristics of placental disorders in term pregnancies among convalescents after COVID-19, experienced at different gestational ages.
Materials and methods: This study included 120 patients. The main group consisted of 80 women who gave birth at a gestational age of 370–416 weeks during the recovery period after COVID-19 and experienced various trimesters of pregnancy. The control group included 30 women without COVID-19 during their current pregnancy, who also gave birth at term. A retrospective analysis was conducted to assess obstetric and gynecological history, somatic pathology, course of pregnancy and childbirth, perinatal outcomes, and placental disorders.
Results: Convalescents after COVID-19, regardless of gestational age, who received low molecular weight heparin in prophylactic doses and vitamins C, E, and D in an extended regimen, exhibited favorable perinatal outcomes in term pregnancies. The most pronounced histological changes indicative of placental dysfunction were observed in cases in which COVID-19 was experienced during the second and third trimesters. In the placentas of convalescents at term, there was a statistically significant increase in the expression of the hypoxia markers HIF-1α and EPO compared to the control group. Additionally, a statistically significant increase in the apoptosis marker Caspase-3 was noted in the placentas of convalescents who experienced COVID-19 during the first and second trimesters.
Conclusion: Favorable perinatal outcomes were observed in convalescents with term pregnancies, regardless of the trimester in which the disease first manifested. However, pronounced histological and immunohistochemical changes in the placenta suggest the presence of placental insufficiency. Therefore, it is advisable to closely monitor this cohort of newborns from infancy to implement timely measures aimed at reducing the risk of potential long-term consequences.
100-108
Fetal sex as a risk factor for fetal growth restriction or small for gestational age
摘要
Objective: To evaluate the association between fetal sex and insufficient fetal growth (IFG), including fetal growth restriction (FGR) and small for gestational age (SGA).
Materials and methods: A prospective cohort study was conducted at N.A. Semashko Republican Clinical Hospital from 2018 to 2023. A total of 611 women with singleton pregnancies diagnosed with IFG were included in the study, with FGR (n = 435) and SGA (n = 176).
Results: Fetal sex in patients with IFG was associated with various factors, including parental age, age at menarche, maternal BMI, weight gain, blood pressure, hemoglobin levels, leukocyte counts, ALT and AST levels, blood creatinine, Doppler data of uteroplacental blood flow, CTG results, IFG variant (FGR or SGA), causes of IFG, prematurity, low birth weight (LBW), and the need for intensive care (IC) for the newborn. FGR, compared to SGA, was characterized by (p < 0.05–0.001) a younger age of both parents, earlier age at menarche, greater weight gain, lower systolic and diastolic blood pressure in the first trimester, lower CTG indicators, lower hemoglobin levels, but higher creatinine, ALT, and AST levels, and an earlier gestational age at delivery. Female fetuses are more commonly associated with FGR, impaired blood flow in the uterine and middle cerebral arteries, LBW, severe preeclampsia (PE), and gestational arterial hypertension as causes of IFG as well as a higher need for IC in newborns. Male fetuses are more often linked to unknown causes of IFG, chronic arterial hypertension, moderate PE, and prematurity. Decision tree analysis revealed that the IFG variant is associated with fetal sex, parental age, the cause of IFG, LBW, and the need for IC.
Conclusion: Fetal sex is interconnected with the IFG variant and numerous factors that contribute to or result from this condition. The specific nature of this relationship is influenced by the IFG variant (FGR or SGA), parental age, maternal and fetoplacental hemodynamics, and the maternal hemic, hepatic, and renal responses to pregnancy complicated by IFG. It is advisable to implement individualized centile tables adjusted for fetal sex during ultrasound monitoring.
109-122
Cytokine levels and lipid peroxidation status in the blood, follicular fluid, and saliva of infertile women and their relationship with the effectiveness of in vitro fertilization
摘要
Infertility affects approximately 17% of couples worldwide, representing approximately one-sixth of the adult population, underscoring the significance of this issue. The causes of infertility are diverse and affect human reproductive function. However, the role of immune disorders in the development of acute and chronic infectious and inflammatory diseases of the reproductive system in women has not yet been thoroughly investigated.
Objective: To determine the levels of TNF-α, interleukin-8, interleukin-10, VEGF, MCP-1, malondialdehyde, and the activity of catalase and superoxide dismutase (SOD) in the blood serum, follicular fluid, and saliva of infertile women undergoing in vitro fertilization (IVF), and to assess their impact on treatment effectiveness.
Materials and methods: This study included 32 women diagnosed with infertility who were undergoing IVF treatment. The participants were comparable in age (35.4 (4.4) years]). The study materials included blood serum, non-blood-contaminated follicular fluid samples, and saliva.
Cytokine levels (TNF-α, interleukin-8, interleukin-10, VEGF, and MCP-1) in the biological fluids were measured using enzyme immunoassays. Lipid peroxidation was assessed by measuring malondialdehyde levels and catalase and superoxide dismutase (SOD) activities.
Results: The cytokine levels in the follicular fluid were higher than those in the blood serum and saliva, regardless of IVF effectiveness. In women who successfully completed the IVF program (group 1), interleukin-8 levels increased 1.27-fold, MCP-1 levels increased 1.42-fold, and SOD activity decreased 2.54-fold in the follicular fluid. No significant differences were observed in the serum and saliva parameters.
Conclusion: The study found that follicular fluid contained the highest concentrations of cytokines, whereas TNF-α levels were nearly undetectable. In patients with favorable IVF outcomes, interleukin-8 and MCP-1 levels in the follicular fluid were higher than those in patients with negative IVF results. Distinct features of the cytokine profile were identified that may serve as potential predictors of ART program outcomes in patients diagnosed with infertility.
124-132
Optimization of art programs in women of late reproductive age by co-cultivation of oocytes with donor extracellular vesicles from follicular fluid
摘要
Background: The effectiveness of infertility treatment using assisted reproductive technologies (ART) decreases with the age of the woman due to the aging of the germ cells. It has been previously shown that co-cultivation of embryos with autologous extracellular vesicles from follicular fluid (EVFF) improves the embryological stage of treatment. However, in women of late reproductive age, biological fluids senesce and lose their effectiveness. Therefore, a hypothesis about the use of donor EVFF to improve the results of ART has been proposed.
Objective: To evaluate the effectiveness of donor EVFF in co-cultivation of embryos of women over 40 years.
Materials and methods: The study was conducted among 79 married infertile couples. Inclusion criteria: the woman's age > 40 years, normal karyotype both in a woman and a man. The patients were divided into two groups: the main group (n=40) with co-cultivation of oocytes with donor EVFF and the comparison group (n=39) with standard cultivation. Stimulation of ovarian function was performed according to the protocol with gonadotropin-releasing hormone antagonists. Transvaginal puncture was done under anesthesia. In group 1, donor EVFF were added to fertilized oocytes. The next day, they were transferred to fresh culture medium. The main evaluation parameters included: fertilization rate, blastocyst formation, and clinical pregnancy.
Results: In the group with donor EVFF, the fertilization rate was higher (84.8% vs. 70%, p=0.008), the proportion of embryo transfer cancellations was lower (22.5% vs. 46.1%, p=0.021). The frequency of pregnancy and genetically normal embryos did not statistically differ.
Conclusion: Donor EVFF improve embryological parameters but do not affect clinical outcomes in women of late reproductive age.
133-142
Exploration of the association between gonadotropin genes and their receptor gene variants and the development of polycystic ovary syndrome
摘要
Objective: To evaluate the association between gonadotropin genes and their receptor gene variants with the development of polycystic ovary syndrome (PCOS).
Materials and methods: The study included 112 women. The main group comprised 57 women with PCOS, and the control group comprised 55 women. Exploration of gene variants NM_000894.3(LHB): c. 364G>A (p. Gly122Ser), rs5030774; NM_001382289. 1(FSHB):c.236_237del(p.Val79fs), rs5030646 and NC_000011.10:g.30204981G>A, rs11031006; NM_000233.4 (LHCGR):c.537-235G>A, rs4953616; NM_000145. 4(FSHR):c.919G>A(p.Ala307Thr), rs6165 was performed using allele-specific real-time PCR method followed by statistical data processing.
Results: Our study found no association between PCOS and the variant rs5030774 in the LHB gene and the variant rs5030646 in the FSHB gene. Statistically significant differences were found between the groups under study in distribution of alleles and genotypes across the variant rs11031006 in the FSHB gene, rs4953616 in the LHCGR gene, and rs6165 in the FSHR gene. Allele frequencies of the FSHB A rs11031006 and the FSHR T rs6165 were higher in the control group (59/110 (53.6%) at p=0.008 (OR=0.485, 95% CI 0.284–0.829) and 86/110 (78.2%) at p=0.014 (OR=0.478, 95% CI 0.265–0.864), respectively, while the prevalence of the allele T rs4953616 of the LHCGR gene was higher in the group of patients with PCOS compared with the control group (87/114 (76,3%) at p=0.002 (OR=2.404, 95% CI 1.354–4.267)).
Conclusion: Exploration of polymorphic loci of gonadotropin genes and their receptor gene variants showed statistically significant association between PCOS and rs11031006 in the FSHB gene, rs4953616 in the LHCGR gene, and rs6165 in the FSHR gene.
143-149
Ovarian reserve and surgical hemostasis methods for benign ovarian tumors
摘要
The surgical strategy for benign ovarian tumors (BOTs) in women of reproductive age should focus on completely removing the pathological formation while minimizing the impact on healthy ovarian tissue to preserve the ovarian reserve. A key aspect of surgical treatment is the implementation of intraoperative hemostasis using various types of energy and hemostatic matrices.
Objective: To assess the state of ovarian reserve in reproductive-aged patients with BOT using different methods of surgical hemostasis.
Materials and methods: The study included 156 patients of reproductive age diagnosed with ovarian teratoma and/or cystadenoma who presented to the V.I. Kulakov NMRC for OG&P between 2022 and 2024. All the patients underwent surgical treatment with laparoscopic access. Two study groups were formed based on the method of surgical hemostasis: fibrin glue was used in group 1 (n=78), while bipolar coagulation was used in group 2 (n=78). Clinical and laboratory examinations were conducted for all patients, including the determination of anti-Müllerian hormone (AMH), estradiol, inhibin B, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in the blood serum on the 3rd–5th day of the menstrual cycle, as well as tumor marker levels (CA-125, CA 19-9, HE 4, CEA). Ultrasound evaluations of the pelvic organs were performed on the 5th–7th day of the menstrual cycle to assess ovarian volume, antral follicle count (AFC), and intraovarian blood flow before and after surgery.
Results: The average age of patients in group 1 was 30.0 (6.7) years, while in group 2 it was 31.0 (7.5) years. Histological examination revealed mature ovarian teratomas in 92/156 (59%) women, serous/mucinous ovarian cystadenomas in 64/156 (41%), and cystadenomas and teratomas in 6/156 (4%). Unilateral formations were observed in 130/156 (83%) patients, while bilateral cysts were present in 26/156 (17%) cases. The sizes of cystic formations ranged from 1.5 to 20.0 cm; the average tumor size in group 1 was 4.0 (3.2) cm, and in group 2 it was 5.0 (4.2) cm. The volume of the ovary with the tumor in group 1 averaged 46.6 (50.4) cm³, with an AFC of 5.0 (5.2) and a resistance index (RI) of 0.9 (0.2). In group 2, the volume of the ovary with the tumor was 45.4 (52.9) cm³, with an AFC of 4.0 (2.6) and an RI of 0.9 (0.1). In group 1, AMH before surgery averaged 2.2 (1.5) ng/ml, while in group 2 it was 2.0 (1.6) ng/ml. After surgery, the volume of the ovary in group 1 averaged 6.9 (1.3) cm³, with an AFC of 6.0 (3.0) and an RI of 0.6 (0.2); in group 2, the ovarian volume was 5.0 (1.3) cm³, with an AFC of 2.0 (2.3) and an RI of 0.9 (1.0). In group 1, AMH after surgical treatment averaged 1.7 (1.9) ng/ml, while in group 2 it was 1.2 (1.0) ng/ml.
Statistically significant differences between the groups were noted in the following parameters: AMH (p=0.017), inhibin B (p=0.008), FSH (p<0.001), ovarian volume (p=0.001), AFC (p<0.001), and RI (p<0.001).
Conclusion: In the surgical treatment of BOT, a critical issue is the maximum preservation of healthy ovarian tissue and reproductive potential of women. Assessing the ovarian reserve before and after surgical treatment allows for the identification of risk factors for its reduction and the selection of the optimal surgical hemostasis method that minimizes trauma to healthy ovarian tissue.
150-158
Exploration of protein PCP4 as a potential tumor marker in uterine leiomyoma
摘要
Objective: Evaluation of the possible role of Purkinje cell protein 4 (PCP4) as a potential tumor marker of uterine leiomyoma by measurement of antibody titer against this protein in blood serum and the applicability of this technique for evaluation of proteins as potential vaccine antigens.
Materials and methods: cDNA fragment clone was derived from PCP4 gene in leiomyoma nodule. After that the soluble PCP4-GFP chimera based on E. coli was constructed, and the recombinant protein was purified. This product was used to evaluate the upper limit of titer to detect antibodies in blood serum in patients using indirect enzyme immunoassay. Serum samples (24) were collected from donors among the patients undergoing treatment at the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, who gave informed consent to participate in the study. Four groups of patients were formed to study the immunological activity of sera against the 6His-PCP4hs-GFP protein. Group 1 was the control group and was composed of men. Group 2 consisted of women without diagnosed fibroids who had five or more successful pregnancies in history. Group 3 included women with fibroids, who also had five or more successful pregnancies in history. Group 4 included women with recurrent myomas.
Results: The pRSET-EmGFP expression vector containing the PCP4 gene and the reporter gene of the green fluorescent protein EmGFP was derived from the cDNA of the myoma nodule with a driver mutation in the MED12 gene. Human PCP4 in preparative amounts was obtained using this construct embedded in the E. coli genome, that was sufficient for analysis of its reaction with antibodies from blood serum in different groups of patients. Blood sera in the control group of men showed high immunological reactivity against the 6His-PCP4hs-GFP protein, whereas the difference between the groups of women was insignificant. Minimum difference between sera was found in groups 2 and 4. Moreover, the reaction of sera in women with recurrent fibroids was higher compared with women without fibroids, who had five or more successful pregnancies. Comparison of women in groups 3 and 4 showed statistically significant differences in the optical density values obtained in dilution of sera 1:1600, 1:3200 and 1:6400. At the same time the reaction of sera of women with recurrent fibroids was higher compared with sera of women with fibroids, who had five or more successful pregnancies.
Based on the level of activity, sera were divided into 3 categories. It was found that reaction of sera of men against the 6His-PCP4hs-GFP antigen was most pronounced. The proportion of high activity in sera was 60%. In the group of women without fibroids, who had five or more successful pregnancies, the proportion of low activity in sera was 44%, that is the maximum value of indicator compared with the other groups. The group of women with fibroids, who had five or more successful pregnancies, is characterized by the moderate level of reactivity with the 6His-PCP4hs-GFP antigen. This category accounts for 75% of sera, that is the highest value of indicator among all groups. Finally, the group of women with recurrent fibroids is characterized by equal number of sera with high and moderate activity, that shows a greater tendency for production of antibodies against PCP4/PEP19 in this group of patients compared with multiparous women.
Conclusion: For the first time, human PCP4 was in preparative amounts sufficient for analysis of its reaction with antibodies from blood serum in different groups of patients. Testing showed that most samples in all groups had significant titers of antibodies against PCP4. The activity of these antibodies varies widely both in sera of men and women. Antibodies against PCP4 are most common in women with recurrent fibroids compared with multiparous women, especially without leiomyomas. Thus, it is unlikely that PCP4 immunization сarries the risk of any pathology. The titers of antibodies to PCP4 in the general group of multiparous women were significantly lower compared with men and patients with recurrent fibroids. Therefore, using PCP4 as the basis to develop a preventive vaccine against leiomyomas is not advisable.
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Efficiency analysis of IVF programs with the use of «Ural'skaya odnoshagovaya» Ural-m-1step culture medium
摘要
The procedures of the embryological stage of in vitro fertilization (IVF) program mainly determine the effectiveness of this technology for infertility treatment. Currently, in Russia it is possible to buy culture media for IVF programs from various manufacturers.
Objective: To assess the effectiveness of IVF programs with the use of "Ural'skaya odnoshagovaya" Ural-m-1step culture medium (TU 21.20.23–001–47571069–2022), LLC "Incammedic" (Russia).
Materials and methods: Two study groups were formed: the main group, which included 240 sibling IVF and IVF/ICSI protocols, with fertilization and embryo cultivation carried out on the Ural-m-1step medium (Russia), and comparison group, which consisted of 240 sibling IVF and IVF/ICSI protocols, with fertilization and embryo cultivation performed on the Vitrolife line of media (Sweden). To stimulate ovulation in patients of both groups we used protocols with GnRH antagonists; to support the luteal phase, a micronized progesterone preparation (Iprozhin, Italfarmaco, Italy/France) was introduced at a dose of 600 mg per day in 2 doses vaginally.
In the main group, 119 embryo transfers into the uterine cavity were performed on the 5th–6th day of cultivation, whereas the comparison group included 103 embryo transfers.
Results: According to the key quality indicators adopted by the Vienna and the Maribor consensuses, the effectiveness of IVF programs using the compared media did not statistically differ, p>0.05. The percentage of fertilization, the proportion of blastocysts, the number of blastocysts of excellent quality obtained on the 5th–6th day of cultivation in IVF and IVF/ICSI cycles in the main and comparison groups also did not differ. The pregnancy/implantation rate corresponded to the target ones, according to the Vienna and the Maribor consensuses, and did not have significant differences in the main and comparison groups, both in “fresh” cycles: 57/119 (54.8%) and 47/103 (48.8%), respectively, p=0.338, and in cryoprotocols: 62/119 (58.8%) and 56/103 (59.6%), respectively, p=0.660.
Conclusion: The results of the study indicate that the outcomes of IVF programs performed with in combination with the Ural-m-1step medium (TU 21.20.23–001–47571069–2022), LLC "Incammedik" (Russia), are comparable to those using the Vitrolife media (Sweden), which proves the interchangeability of these medical products in clinical practice.
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Experience of myo-inositol use in patients with oligomenorrhea and insulin resistance
摘要
Oligomenorrhea (OM) is a menstrual disorder that can be associated with various causes including disorders of carbohydrate and fat metabolism. One of the manifestations of impaired carbohydrate metabolism is insulin resistance (IR) which leads to hyperinsulinemia. Excess insulin stimulates the adrenal glands and results in hyperandrogenism, which in turn reduces the sensitivity of estrogen-dependent ovarian receptors to insulin. This condition is further complicated by polycystic ovary syndrome.
Objective: To study the effect of administration of myo-inositol (MI) in combination with alpha-lactalbumin (α-LA) on the length of the menstrual cycle and the rate of carbohydrate metabolism in women with OM and IR.
Materials and methods: An observational study included 30 reproductive-aged patients of with OM and IR, who were administered a three-month course of treatment with the Inofert Forte complex containing MI 600 mg + α-LA + folic acid 200 mcg. The patients were evaluated for the clinical, anamnestic and anthropometric data, bioimpedance analysis of body composition, and the results of an oral glucose tolerance test (OGTT) with insulin before and after the course of therapy.
Results: After the course of treatment with a combination of MI + α-LA, the length of the menstrual cycle became normal in 13/22 (59.1%) patients and was 34.2 (1.0) days in these women. The average length of the menstrual cycle was 38.4 (1.9) days (p<0.001). A decrease in fasting glucose levels was found in 16/30 (53.3%) patients, in 20/30 (66.7%) patients after one hour and in 30/30 (100%) patients after two hours (Δ0.66±0.35, p<0.001). A decrease in fasting insulin levels was noted in 19/30 (63.3%) of the examined patients two hours after OGTT (p<0.04).
Conclusion: The addition of the complex containing MI 600 mg + α-LA + folic acid 200 mcg (Inofert Forte) to the therapy of patients with OM and IR may have a positive effect on the menstrual cycle and may improve metabolic parameters.
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Antibacterial activity of probiotic strains of lactobacilli included in the MRM Nutrition Women’s Probiotic complex (Lactobacillus plantarum LP01 and Lactobacillus PARACASEI LPC09)
摘要
Lactobacilli, recognized as probiotics, are regarded as promising instruments, both for the prevention and treatment of vaginal dysbiosis and urinary tract infection. Given the ineffectiveness of therapy and the frequent recurrence of these infections, the use of probiotics has become a progressive solution to this problem.
Objective: To evaluate the antibacterial activity of probiotic strains of lactobacilli included in the MRM Nutrition Women's Probiotic complex (Lactobacillus plantarum LP01 and Lactobacillus paracasei LPC09) against opportunistic bacteria isolated from urogenital clinical materials, and to determine the sensitivity of these lactobacilli to antibacterial drugs.
Materials and methods: Probiotic strains of Lactobacillus plantarum LP01 and Lactobacillus paracasei LPC09 were cultivated and the grown colonies were identified using the MALDI-TOF mass spectrometry method (Bruker, Germany). To study the antagonism between probiotic strains of lactobacilli and opportunistic microorganisms, a collection of 16 clinical isolates of opportunistic microorganisms was made: Escherihia coli (3), Klebsiella pneumoniae (2), Morganella morganii (1), Enterococcus faecalis (3), Enterococcus raffinosus (1), Streptococcus agalactiae (3), Staphylococcus epidermidis (1) and Candida albicans (2). To study the sensitivity of probiotic strains of lactobacilli to antimicrobial drugs, a panel for determining the sensitivity of gram-positive bacteria to antimicrobial drugs "Gram-positive AST" (AutoBio Diagnostics, China) was used.
Results: When co-cultivated with probiotic lactobacilli (Lactobacillus plantarum LP01 and Lactobacillus paracasei LPC09), a decrease in the pH of the medium was noted, and a direct antibacterial effect of these lactobacilli against all tested opportunistic microorganisms was detected. When studying antibiotic resistance, it was marked that both strains of lactobacilli were resistant to antibacterial drugs of the penicillin group, cephalosporins, and fluoroquinolones.
Conclusion: Oral administration of the MRM Nutrition Women's Probiotic complex, containing a combination of Lactobacillus plantarum LP01 and Lactobacillus paracasei LPC09, cranberry extract and D-mannose, has significant antibacterial activity against opportunistic microorganisms isolated from women’s urogenital tract. These lactobacilli strains are resistant to some antibacterial drugs widely used in clinical practice, which may be the ground for taking this probiotic drug together with prescribed antibiotics.
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Characteristics of menopausal hormone therapy use in Russia: results of a large-scale survey of peri- and postmenopausal women
摘要
Menopause is accompanied by various symptoms that can reduce the quality of life of women and have an impact on society as a whole. The identification of factors that contribute and prevent the use of menopausal hormone therapy (MHT) can provide additional opportunities and perspectives for changing attitudes towards menopause and MHT. The article was prepared by the Russian Society of Gynecological Endocrinology and Menopause (ROSGEM)
Objective: To identify and systematize the causes of the low prevalence of MHT in Russia in terms of patient perception of the problem.
Materials and methods: The study was conducted by Ipsos Comcon through an online survey of 2,536 women aged 45–59 living in Russian cities with populations over 100,000 people. Among them, 1,743 were peri- and postmenopausal women. National representative quotas were established by gender, age, and federal district. All the respondents were divided into three groups: 45–49 years old (n=890), 50–54 years old (n=835) and 55–59 years old (n=811). In addition to the main sample, the survey included 200 women who had some experience in taking MHT over the past 12 months: 100 women took herbal medicines to relieve menopausal symptoms over the past 12 months, and 100 women previously took MHT but stopped using it less than 12 months after starting therapy.
Results: The study revealed that 97.5% of women aged 45–59 years who were in the peri- and post-menopausal stages experienced at least one symptom of menopausal syndrome. The symptoms of menopause were rated as moderate or severe by 74% of patients. The women agree that their quality of life should not deteriorate during peri- and postmenopause (90%). Endocrinological (55%) and vasomotor (56%) symptoms were often the cause for seeking medical help. Among all the medical professionals, the gynecologist was the primary source of knowledge (93%) about symptoms and therapy. However, gynecologists seldom initiated active discussions about menopause with their patients. Among women who went to the doctor at least once during menopause, only 19% of women reported that the doctor was the first to initiate a conversation about menopause. Women who were aware of the appropriate treatment method perceived MHT as a therapy that totally relieves peri- and postmenopausal symptoms (49%) compared with non-hormonal therapy (36%) and combined oral contraceptives (23%). Most Russian women (67%) aged 45–59 years who associate health changes with the approach/onset of menopause and do not deny hormone therapy in the future preferred the oral route of MHT administration and only 9% of women chose the transdermal gel. The need for information about menopause and MHT was reported by about 58% of women. The recommendation to discontinue MHT in 82% of cases (among all doctors) was given by the gynecologist. The lack of a doctor’s administration is also a significant barrier to MHT: the gynecologist did not prescribe MHT to women with severe menopausal symptoms in 21% of cases. Only 10% of women had at least one/combination of several unmodifiable absolute contraindications to MHT.
Conclusion: The level of MHT use in Russia increased from 1.3% to 6.5% but it remains low compared to developed countries. It is necessary to conduct educational events for gynecologists, other doctors, as well as patients. These events should provide information about menopause, its symptoms, potential long-term health consequences and they should also discuss current ideas about the safety and benefits of MHT.
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Health Care Management
Patient satisfaction with outpatient care in the field of obstetrics and gynecology
摘要
Objective: To study patients’ satisfaction taking into account their medical and social characteristics, and to analyze the factors that influence their satisfaction.
Materials and methods: There was a special questionnaire developed that includes the medical and social characteristics of the respondents and their satisfaction with medical care. The single-stage continuous study included 400 women who visited a women’s health clinic for medical assistance. The analysis of the obtained data and the calculation of indicators were carried out using the MS Excel 2016 software program.
Results: Most patients have higher and incomplete higher education (74%). They are committed to leading a healthy lifestyle; 86.7% of women intend to have one to three children and 6% intend to have more than three children. In terms of receiving medical care in the antenatal clinic, 84.7% are satisfied with it, but 30.9% of patients consider that it is necessary to improve the material and technical support, 23.4% of women consider improving the qualifications of medical workers and the relationship with the patient, and 14.6% of them are not pleased with the comfort of staying in the antenatal clinic.
Conclusion: The high level of patient satisfaction with medical care provided in the field of obstetrics and gynecology is an important subjective assessment of the medical organization’s services by the patients. The qualifications of the doctor and the favorable conditions created in the antenatal clinic affect a woman's desire to have children.
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Guidelines for the Practitioner
A physiological approach to the interpretation of cardiotocography
摘要
In recent decades, the number of cesarean section (CS) deliveries has increased significantly worldwide. In Russia, the CS rate rose from 17.9% in 2005 to 30.3% in 2020. One of the main indications for CS is fetal distress, which requires careful monitoring of its condition. Improper or untimely interventions during childbirth can lead to complications for the mother and fetus, including irreversible damage to the central nervous system. Cardiotocography (CTG) remains the main method for monitoring fetal health, but there is often controversy among doctors about how to interpret the data. Various national and international guidelines have been developed to standardize the assessment of fetal heart rate and systematize the types of CTG. However, categorizing fetuses does not provide a personalized approach to evaluating their condition. Currently, more attention is paid to the physiological approach to CTG interpretation. This approach takes into account not only heart rate parameters, but also the adaptive capabilities of the fetus, the type of intrauterine hypoxia, the duration of pregnancy, and the individual functional reserves of the fetus under specific conditions. This method allows for a more personalized assessment of the fetal condition, which helps to make informed decisions about future delivery strategies. The introduction of a physiological approach to CTG interpretation makes it possible to reduce the frequency of neonatal hospitalizations in intensive care units, as well as to reduce the proportion of surgical deliveries.
Conclusion: The physiological approach to CTG assessment, training of medical personnel and continuous monitoring of fetal condition make it possible to optimize the management of labor, reduce the risk of complications and improve outcomes for newborns.
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Peculiarities of laboratory diagnostics of anti-MUllerian hormone levels
摘要
The assessment of a woman’s reproductive potential using the serum anti-Müllerian hormone (AMH) level remains an important clinical issue. Various laboratory techniques are used to determine the concentration of AMH. However, the results obtained from these techniques are not standardized or consistent. This can lead to different numerical values when the same sample is studied using various analytical systems.
The threshold values indicated in clinical guidelines are often provided without any information about the specific research methodology and a comment on possible differences between laboratory methods. It is important for clinicians to pay attention to the differences in results obtained using various techniques.
The review examines issues related to ovarian reserve and folliculogenesis, the chemical structure of AMH as well as the characteristics of fluctuations in its levels. It also compares modern methods for detecting AMH in blood and considers the opportunity of their practical application.
Conclusion: The absence of an international standard for measuring AMH and the presence of different immunoassay methods which are used to determine its level emphasize the need to take into consideration the analytical system factor. This factor is especially important in the development of clinical strategies and search for optimal approaches to measurement standardization.
223-228
Algorithms for prevention, diagnosis, and management of unplanned bleeding in women undergoing menopausal hormone therapy
摘要
Given the rapid growth in the number of women aged 40–60 (more than 850 million, with a forecast of over 1 billion in the coming years), the issues of effective management of patients with menopausal symptoms are becoming particularly important. In 85% of women, the cessation of menstruation is accompanied by severe psycho-vegetative, somatic, and metabolic disorders, which significantly reduce the quality of life.
In the Russian Federation, the use of menopausal hormone therapy (MHT) has increased fivefold over the past five years, reaching 6.5% among women aged 45–59 years. This reflects the active involvement of the medical community in supporting informed patient choice and ensuring the safe and clinically appropriate use of MHT. Nevertheless, the use of MHT in the Russian Federation remains lower than in a number of developed countries in Europe and North America, where it exceeds 15%.
Key limiting factors include the legal vulnerability of physicians and insufficient training in therapy individualization, particularly in managing adverse events such as unplanned uterine bleeding (UUB), which occurs in 40% of women during the first six months of therapy.
The document emphasizes the need for personalized MHT, considering age, stage of reproductive aging according to STRAW+10, clinical response, comorbidities, and the dynamic balance of benefit/risk. It presents algorithms for the diagnosis, treatment, and prevention of UUB that were developed on the basis of current scientific evidence, international and national clinical guidelines. A number of key points are based on the consensus opinion of experts, which reflects the practical significance and clinical experience in the context of a limited evidence base on certain aspects of therapy.
The algorithms include the assessment of endometrial cancer risk factors and principles of MHT adjustment in UUB; counseling and management of patients with UUB; bleeding control during cyclic MHT and continuous monophase MHT; аpproaches to the management of patients with UUB undergoing MHT with a LNG-IUS; principles of preventing UUB during MHT.
Special attention is given to step-by-step clinical actions for excluding hyperplastic and neoplastic processes, which are critical for continuing therapy. The tables serve as practical tools for education and clinical decision-making support.
Conclusion: The use of these algorithms will contribute to timely diagnosis of UUB causes, the choice of optimal management strategies, reduction in the frequency of unjustified invasive interventions and MHT discontinuation. This, in turn, can improve the quality of life of patients and achieve better medical and social outcomes.
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