Obstetrics and Gynecology

Fetal growth restriction (FGR) affects about 10% of pregnancies and it is a leading cause of stillbirth, neonatal mortality and morbidity. In addition to immediate complications, it has metabolic imprinting and affects perinatal programming.

Among the great obstetrical syndromes, FGR occupies a special place, primarily due to the lack of clinical manifestations. In this regard, modern obstetric tactics are based solely on functional methods of diagnostics of the fetal condition. The existing clinical guidelines and protocols on this issue make it much easier for clinicians to decide on an emergency delivery. At the same time, clinical situations where a balance must be achieved between prolongation of pregnancy and the risk of antenatal fetal death require close monitoring of specific anatomical zones of fetal-placental circulation, depending on the gestational age. This review presents the analysis of the national (Russian Society of Obstetricians and Gynecologists) and international (FIGO, ISUOG, SMFM, ACOG) clinical guidelines and protocols in order to form a consensus approach and, if necessary, to identify areas for further research to standardize obstetric management of pregnant women with FGR.

Conclusion: Future research should focus on determining differentiated functional diagnostic test scores based on estimated fetal weight, gestational age, patient condition, and neonatal development. Such a practical approach based on randomized trials and its implementation in clinical guidelines will reduce perinatal morbidity and mortality, as well as improve long-term outcomes in late FGR.

A search of literature sources was carried out in the PabMed/MedLine, eLibrary databases for the period 2019–2024 and a review of the endometrial microbiota in women of reproductive age without uterine pathology was conducted. Single studies of the uterine microbiome in healthy women were found. The endometrium is supposed to contain a very low microbial mass, which prevents microorganisms from being cultivated. Currently, next generation sequencing is widely used to evaluate the 16S ribosomal RNA gene sequence, that is justified by the universality of bacteria research method. However, 16S rRNA sequencing has significant limitations: firstly, the method is not applicable to viruses and fungi; secondly, the results are calculated using special algorithms, and the unit of measurement is an operational taxonomic unit, more often corresponding to the genus and not necessarily identical to the cultivated microorganism. The data on the presence and composition of the endometrial microbiota of the normal uterus are contradictory. This may be due to the lack of a single universal approach to diagnosis and there is no method for obtaining endometrial samples without contamination. Metatranscriptomic analysis of the endometrium in healthy women showed the presence of metabolically active microorganisms in normal endometrium in very low numbers without dominance of Lactobacillus.

Conclusion: Scientific findings on the microbiome of the normal endometrium continue to accumulate. There is still an unproven association of the presence and relative abundance of Lactobacillus in the endometrium with the rate of clinical pregnancy and live birth, including those after the use of assisted reproductive technologies.

Cardiovascular pathology is the leading cause of mortality in the world, and it is the number one cause of death among women. A multidisciplinary approach involving cardiologists, gynecologists and therapists is necessary to overcome this problem. This article describes the differences between chronological and biological aging, with the example of vascular aging. There are three vascular aging phenotypes: premature or early vascular aging (EVA), vascular stiffness in this phenotype is characteristic of older chronological age; normal vascular aging (NOVA), arterial stiffness parameters correspond to the chronological age of a person; and supernormal vascular aging (SUPERNOVA), this phenotype is characterized by low vascular stiffness parameters for chronological age. This concept is important since it is possible to identify people with a high-risk factor for cardiovascular disease at an early stage. The menopausal transition can have an impact on the heart and vascular health in the future. Menopausal hormone therapy (MHT) is the most effective method of correcting age-related estrogen deficiency. However, taking MHT can be limited by existing contraindications or patients’ unwillingness to take hormonal medications. The decrease in the overall risk of cardiovascular diseases and coronary heart diseases by 16% and 14%, respectively, in the Western European population was associated with the consumption of soy-rich foods. Phytoestrogens alone are obviously not able to meet all the needs during therapy. Soy isoflavones in combination with other plant extracts and micronutrients in the form of the supplement Estrovel can be considered as an alternative therapy.

Conclusion: Estrovel contains a balanced combination of bioactive components and can be used as a food supplement. This is particularly beneficial for women going through the phase of menopausal transition and in the postmenopausal period, as it can help to reduce vasomotor symptoms and prevent the development of cardiovascular pathology.

Objective: The purpose of the study was to determine the pathological features of the umbilical cord structure associated with live born small for gestational age and premature baby with prenatally diagnosed congenital heart disease (CHD).

Materials and methods: A retrospective analysis of the results of macroscopic examination of the umbilical cords was carried out in antenatally formed in the cohort with 115 cases of fetal CHD. A group of cases was divided into subgroups depending on the gestational age at delivery and baby weight at birth. Subroup 1 included 15 cases with premature and/or SGA infants; subgroup 2 consisted of 100 full-term infants with birth weight ≥ 10th percentile.

Results: Short (58.2% of cases) and lean (43.4% of cases) umbilical cord, abnormal attachment to the placenta (35.6% of cases), hypo-and hypercoiled cord (4.3% and 19.1% of cases) were most commonly observed, respectively. Pathological variants and their combinations in one umbilical cord were found in 74% and 34% of cases.

There were differences between the subgroups in the frequency of occurrence of hypercoiled and lean umbilical cord, and combined pathology, that was 46.6% versus 15%, 73.3% versus 39%, 60% versus 30% in subgroups 1 and 2, respectively, (р<0,05). At the same time, the odds ratio for the birth of premature and/or small for gestational age baby with CHD was 4.96 (95% CI 1.56–15.7), 4.3 (95% CI 1.28–14.45) and 3.5 (95% CI 1.14–10.8), respectively.

Conclusion: Postnatal assessment showed that umbilical cord pathology was in 74% of cases in babies born with congenital heart disease. Hypercoiled, lean umbilical cord and combination of umbilical cord abnormalities were significantly associated with preterm births and small for gestational age newborns. The obtained results indicate the need to expand the protocol for ultrasound assessment of the umbilical cord in cases of fetal cardiac pathology.

Objective: This study aimed to investigate the outcomes of pregnancy in relation to the quantitative and qualitative composition of cervicovaginal microbiota in early pregnancy using real-time polymerase chain reaction (RT-PCR).

Materials and methods: The study included 153 pregnant women at 7–12 weeks of gestation, with 73 experiencing a threatened miscarriage and 80 having a healthy pregnancy. The entire cohort was divided into three groups based on the outcomes. Group I (n=122) consisted of women who delivered at term, group II (n=7) included patients with preterm delivery, and group III (n=24) comprised women who experienced spontaneous miscarriage. The analysis involved laboratory investigation that quantitatively determined the DNA of opportunistic flora associated with the development of bacterial vaginosis (BV), aerobic vaginitis (AV), and candidal vulvovaginitis (CVV). Additionally, DNA from pathogens of four sexually transmitted infections (Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis) was determined. All study participants underwent diagnostic procedures in accordance with regulatory documents and received treatment in Moscow hospitals or outpatient settings, under the supervision of an obstetrician-gynecologist.

Results: Patients whose pregnancies were terminated in the first half of gestation had a higher incidence of BV (70.8%) than those who delivered at term (22.2%, p<0.05). The frequency of AV in women with spontaneous abortion was twice as high (8.3%) as that in patients who delivered at term (3.9%, p<0.05). The prevalence of VVC in the three groups was not statistically different. The presence of more than five microorganism markers involved in the development of BV, AV, and VVC, as well as opportunistic genital mycoplasmas detected in the vagina of a pregnant woman in the first trimester, was associated with the development of spontaneous miscarriage in the first trimester and preterm birth (p<0.01).

Conclusion: Laboratory evaluation of the reproductive tract using RT-PCR revealed higher detection rates of certain nosologies and syndromes in pregnant women with adverse pregnancy outcomes. The early detection of reproductive tract infections is associated with an increased risk of early pregnancy loss and preterm delivery.

Objective: The study of differential gene expression in fibroid nodules and myometrium to identify potential target genes for the development of personalized approaches to the diagnosis, prediction of the course, prevention and treatment of uterine fibroids (also known as leiomyomas).

Materials and methods: The total number of 133 tissue samples were examined, including 48 samples of myometrium and 85 samples of fibroid nodules. The material was obtained during surgical interventions. All samples of fibroid nodules were analyzed for the presence of somatic mutations in exon 2 of the MED12+ gene. In RNA samples, which were isolated from myometrial tissues and fibroid nodules using RT-PCR, gene expression analysis of the HMGA2, PAPPA1, GRPR, TYMS, PLAG1, VCAN, AVPR1A, ESR1, PLA2R1, RANKL, KLF11, KRT19, MMP11, ADAM12, MMP16, PCP4, STAB2, WIF1 genes was performed.

Results: Somatic mutations in the MED12 gene were found in 42 samples (MED 12+ fibroid nodules), and no mutations were found in 43 samples (MED12- fibroid nodules). Multiple fibroids were found in 19 patients among the studied patient sample, while fibroid nodules both MED12+ and MED12- were found in 9 patients. The results of our study showed statistically significant differences in gene expression levels between myometrium and fibroid nodules in 13 of 18 examined genes. At the same time, a number of genes demonstrated opposite changes in the transcription level compared to myometrium, depending on the presence of somatic mutation in the MED12 gene.

It has been shown that in the presence of somatic mutation in the MED12 gene, significantly increased gene expression of 7 genes – GRPR, TYMS, RANKL, MMP11, AVPR1A, PCP4 and ESR1 and significantly reduced gene expression of 2 genes – KRT19, KLF11 was in nodules compared to myometrium. There was significantly increased expression of only 2 genes – GRPR and TYMS in all fibroid nodules, whereas increased expression of the PAPPA1, VCAN, ESR1, RANKL, KRT19, MMP11, PCP4 and AVPR1A genes in MED12+ nodule phenotype was found compared to MED12- nodules.

Conclusion: The obtained data enabled to distinguish two molecular phenotypes of uterine fibroids in the examined sample – the associated and unassociated phenotype with somatic mutation in exon 2 of the MED12 gene. The expression of some genes alters in different molecular phenotypes of uterine fibroids, and statistically significant differences are found not only between each type of uterine fibroids and myometrium, but also between different molecular phenotypes of fibroids. The obtained results enable to consider some of the examined genes as potential targets to develop personalized approaches to diagnosis, prognosis of the course, prevention and treatment of uterine fibroids.

Objective: To evaluate the diagnostic characteristics of fluorescence spectroscopy using LuViva technology for diagnosing cervical intraepithelial neoplasia.

Materials and methods: This study included 156 patients. The median patient age was 32 years (Q1–Q3: 27–39 years). All patients underwent fluorescence spectroscopy and cytological examination of the cervical and cervical canal scrapings using liquid cytology. Testing for high-risk human papillomavirus (hrHPV) using real-time PCR in cervical canal discharge was performed in 138 patients (88.5%), and extended colposcopy and targeted biopsy (as indicated) were performed in 52 women.

Results: The positive predictive value of fluorescence spectroscopy for detecting cytological changes of grade ≥ASCUS was 28.7% and the negative predictive value was 88.4%. The diagnostic characteristics of the methods used were compared with those of histological examination of cervical biopsy specimens. In the presence of hrHPV (43% of patients), the odds of detecting HSIL were almost 20 times higher (odds ratio [OR]=9.96, 95% CI 1.04–384.61). The sensitivity of the cytological test for LSIL and HSIL was 35.3% and 50%, respectively, whereas the specificity was 91.4% and 93.2%, respectively. The positive predictive values of cytological examination for LSIL and HSIL were 66.7% and 57.1%, respectively, while the negative predictive values were 74.4% and 91.1%, respectively. The positive predictive values of fluorescence spectroscopy for LSIL and HSIL were 42.5% and 15%, respectively, while the negative predictive values were 100% and 83.3%, respectively.

Conclusion: Fluorescence spectroscopy has higher sensitivity than liquid cytology. The non-invasive technique of fluorescence spectroscopy can act as a triage test for patients with conflicting results of cytology and HPV testing and determines the choice between immediate colposcopy and dynamic observation.

Objective: To investigate the effect of mineral oil type on the development of human embryos during in vitro culture in the context of in vitro fertilization (IVF) programs.

Materials and methods: This study involved zygotes/sibling embryos (1198 embryos) obtained from 84 patients undergoing IVF treatment at the AltraVita Human Reproduction Clinic. After fertilization, the sibling embryos of each patient were cultured for 5–6 days in microdrops of medium, either under a layer of mineral oil or under a layer of paraffin oil. The parameters analyzed included fertilization and embryo cleavage rates, blastocyst formation rates, good-quality blastocyst formation rates, embryo implantation rates, and clinical pregnancy rates.

Results: The group of embryos cultured with paraffin oil showed a significantly higher total number of blastocysts and a higher rate of good-quality blastocyst formation compared to the group of embryos cultured under a layer of mineral oil. Fertilization and embryo cleavage rates, as well as implantation and clinical pregnancy rates, were not statistically significantly different between the two groups.

Conclusion: Coating droplets with medium using paraffin oil during in vitro embryo culture improves the efficiency of the embryological stage compared with the use of mineral oil for the same purpose.

The effective treatment and prevention of recurrence of infectious and inflammatory diseases of the cervix and vagina require careful diagnosis and therapy.

Objective: To evaluate the efficacy of peptide-protein complex containing natural peptides and cytokines in the therapy of cervicitis and vaginitis with mixed etiology.

Materials and methods: This study presents a comparative analysis of the results of therapy for 80 patients diagnosed with cervicitis, which was associated with bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and human papillomavirus (HPV). The patients were divided into two groups: group 1 (n=40) received standard therapy in combination with a complex of natural peptides and cytokines (the Superlymph drug, suppositories administered rectally at a dose of 25 IU twice a day for 20 days); group 2 (n=40) received standard therapy without peptide-protein complex. The effectiveness of the treatment was evaluated on the basis of the patient’s complaints, clinical picture of the disease and the results of laboratory tests at one and three months after the end of therapy.

Results: After one month of treatment, 2/40 (5%) patients in group 1 continued to experience pathologic discharge from the genital tract. In group 2, clinical manifestations of the disease in the form of moderate genital discharge, itching and vaginal discomfort were noted in 6/40 (15%) women. HPV DNA testing showed the absence of HPV in 57.5% of patients in group 1 and in 27.5% of women in group 2. The median viral load was calculated again: it was 3.9 lg (3.3; 4.5) in group 1 and 4.4 lg (3.8; 4.9) in group 2. After three months, no recurrence of the disease was detected in group 1; however, 4/40 (10%) women in group 2 were diagnosed with recurrent episodes of cervicitis which was associated with BV and VVC in two cases, BV in one case, and aerobic vaginitis in one case.

Conclusion: Due to the frequent recurrence of the disease resulting from inadequate efficacy of therapy, it is extremely important to prescribe treatment that targets each etiologic agent of the disease. The use of the medication based on natural peptides and cytokines showed high efficacy in the complex treatment of cervicitis and vaginitis.

The complex of antimicrobial peptides and cytokines has a positive effect on immunity, progesterone receptor expression, and angiogenesis; it also improves the rates of pregnancy and live birth in patients with infertility and chronic endometritis (CE). The question of the optimal number of treatment courses to achieve the greatest effect remains unresolved.

Objective: To compare the effectiveness of complex treatment in the preconception period of patients with infertility caused by CE in achieving spontaneous pregnancy and live birth with the use of the Superlymph drug in one and two courses.

Materials and methods: The patients of group I (n=303) received 25 IU of the Superlymph drug in one course (for 20 days), the patients of group II (n=303) received the drug in two courses with a break of 1–1.5 months; in addition, all patients received one course of antibacterial therapy and progestogen cyclically. Clinical and laboratory studies were used.

Results: During six months after treatment, pregnancy rates were 52.2% and 63.4% in groups I and II, respectively, p=0.05, with a maximum difference in the first month after the end of treatment of 15.5% vs. 31.4%, respectively, p<0.001 (OR=2.02, 95% CI 1.48–2.75), that is, it was 2-fold higher in group II compared to group I. The live birth rate was 43.2 and 57.8%, p=0.05, with a maximum difference in pregnancy in the first month after the end of treatment of 11.9% versus 28.1%, respectively, p<0.001 (OR=2.36, 95% CI 1.65–3.37). The risk of miscarriage and premature birth was two times lower with two courses of the Superlymph drug.

Conclusion: The treatment of CE using the Superlymph drug in the preconception period by two courses of 20 days with a break of 1–1.5 months increases the chances of spontaneous pregnancy by 22%, live births by 34% and helps to reduce the risk of miscarriage and preterm birth by two times compared to one course.

Urinary tract infections (UTIs) are among the most common infectious disorders. They are diagnosed in 150 million people each year and are most commonly detected in women. The incidence of UTIs during pregnancy currently ranges from 4 to 47% worldwide. Physiological changes in a woman’s body associated with pregnancy and certain risk factors contribute to the development and spread of UTIs. This review presents the scientific data on a new dosage form which is a dispersible tablet. The pharmacokinetic profile of dispersible forms increases the clinical efficacy and tolerance of the drugs thereby reducing antimicrobial resistance.

Cefixime EXPRESS refers to such drugs; it has a broad spectrum of antimicrobial activity and it affects pathogens with β-lactamase activity. Dispersible tablets have an advantage in pharmacokinetic properties, a favorable safety and efficacy profile in the treatment of uncomplicated UTIs during pregnancy. The drug is well tolerated and convenient to use for both inpatients when used in step therapy, and outpatients, namely women with UTIs; it can also be administered empirically in case of intolerance to first-line drugs.

Conclusion: Cefixime EXPRESS in the form of dispersible tablets is a promising medication for the treatment of uncomplicated UTIs during pregnancy as it shows high efficacy and safety. Administering the medication once a day is convenient and increases patient compliance.

The article presents the current data on the use of gonadotropin-releasing hormone (GnRH) agonists in the therapy of combined proliferative diseases of reproductive organs. This pathology is detected in most cases in patients aged 40–45 years. The main clinical symptoms of proliferative diseases include pain and abnormal uterine bleeding. Timely diagnosis of proliferative nosologies is very challenging due to the variety of symptoms, conflicting theories of etiopathogenesis, and difficulties in differential diagnosis. GnRH agonists completely block the synthesis of sex hormones, marked antiproliferative and antiangiogenic effects; therefore, they are the first line therapy for combined proliferative diseases demonstrating high efficacy and relative safety. The analysis of the literature showed high efficacy of the Russian drug Buserelin-depo in the treatment of combined proliferative gynecologic diseases (it is administered 3.75 mg intramuscularly, once every 28 days, during 6 months of therapy and 3 months of preoperative preparation). The use of Buserelin-depo makes it possible to reduce the size of myomatous nodes by 52% of the original volume, to control pain syndrome and abnormal uterine bleeding, to reduce the risk of recurrence of hyperplastic processes of the endometrium, and to reduce the risk of intraoperative complications. This enables the clinicians to use it widely not only in the therapy of proliferative diseases, but also in the preparation of patients with uterine fibroids and endometriosis for surgical treatment and postoperative adjuvant therapy. Its use can significantly improve the quality of life of this cohort of patients, reduce the number of radical treatment methods and improve the outcomes of organ-preserving operations.

Conclusion: GnRH agonists are the first line therapy for combined proliferative pathology of reproductive organs due to their effect on all links of pathogenesis, demonstrating high efficacy and safety. The Bucerelin-depo medication is highly effective and affordable; it has a convenient scheme of administration, which ensures high adherence to treatment; the use of algorithms for complex management is interesting and promising.

Background: Contact dermatitis of the vulva is one of the most common diagnoses in clinics dealing with vulvar pathology. Vulvar pruritis is the most frequent complaint of women visiting a gynecologist. Current causes of vulvar pruritus include not only comorbid conditions, vulvovaginal infections and diseases, but also an increase in vulvar irritants due to urbanization and aggressive intimate hygiene.

Case report: This article presents two clinical observations of patients receiving treatment for allergic dermatitis of the vulva; the women had uncompensated diabetes mellitus and took the drug empagliflozin. In the first case, a 64-year-old patient V. presented to the Department of Aesthetic Gynecology and Rehabilitation of the National Medical Research Centre for Obstetrics, Gynecology and Perinatology, with complaints of vulvar pruritus for a long time and erosions in the perineal area. After examination she was diagnosed with vulvar neurodermatitis which was caused by empagliflozin. In the second case, a 51-year-old patient R. presented to the Department of Aesthetic Gynecology and Rehabilitation of the National Medical Research Centre for Obstetrics, Gynecology and Perinatology, with complaints of itching in the vulva and anus, profuse curdy discharge from the genital tract for 6 months. She was diagnosed with vulvar neurodermatitis, recurrent candidal vulvovaginitis, exacerbation. Both patients underwent complex therapy including the use of intimate hygiene products, namely Saphorelle Gentle Cleansing gel and Saphorelle Intimate Moisturizing cream emollient. A visible clinical effect on the vulvar skin was noted after the therapy. It is recommended to continue proper intimate hygiene and perineal skin care with the Saphorelle products regularly.

Conclusion: Vulvar hygiene is based on the choice of a mild detergent capable of improving skin homeostasis from a physiologic pH value of 4.8 in the vaginal vestibule to 6–7 on the outer surface of the labia majora. The new line of the Saphorelle products supports the natural pH and microbiota of the vulva, fully complies with modern requirements for intimate hygiene of female genitalia and can also be used for vulvar diseases in the complex therapy of dermatoses and contact dermatitis according to the soak and seal method.