Obstetrics and Gynecology

Fetal growth retardation continues to be an important issue in obstetrics and neonatology due to the high level of perinatal morbidity and mortality.

The narrative review of the literature provides the information on a new paradigm in modern perinatology, namely, on the concept of placental or great obstetric syndromes, which include fetal growth retardation. The review highlights the complex process of understanding intrauterine programming, starting with the assumptions and hypotheses made by D.J. Barker. The tragic experience of the impact of famine in wartime on fetal development and morbidity in adulthood is analyzed. The concept of the thrifty phenotype as an adaptation process is presented. The concepts of possible mechanisms of intrauterine programming are discussed. The article provides the information on the concept of “The first 1000 days” (from conception to two years after birth) and developmental plasticity, which play an important role in the formation of long-term health.

The analysis of the literature showed that newborns with fetal growth retardation are at high risk of diseases in the postnatal period. This diagnosis in the patient’s history is a risk factor for the development of chronic non-communicable diseases in adulthood (hypertension, insulin resistance, type 2 diabetes, abdominal obesity, dyslipidemia, chronic kidney disease). There is an increased risk for the diseases of the bronchopulmonary system, brain damage, and impaired psychosocial adaptation. There is an adverse effect of fetal growth retardation on the male reproductive system in the future, in particular, infertility.

The review presents the analysis of preventive measures aimed at reducing chronic diseases in patients with a history of growth retardation.

Conclusion: Fetal growth retardation plays a key role in increasing the risk of short- and long-term health effects; therefore, it is necessary to carry out further research and development of preventive and therapeutic measures.

Uterine fibroids are the most common benign tumors in women. Among other gynecological conditions, the prevalence of uterine fibroids is high, ranking second only to inflammatory diseases of the female reproductive system. This disease has a significant impact on the female reproductive health, and it also decreases the quality of life. In addition, uterine fibroids have a negative economic effect on health systems around the world; this impact is estimated at hundreds of billions of dollars annually. According to the literature, risk factors play an important role in the development of this disease.

The analysis of the literature data showed that the risk factors for uterine fibroids are numerous and may include heredity, vitamin D3 deficiency, race (African Americans), obesity, diabetes mellitus, hypertension, early menarche, absence of childbirth in the patient’s history, alcohol, eating habits, stress, low physical activity.

Conclusion: Despite the large amount of evidence on the issue of risk factors for uterine fibroids available in the literature, not all the mechanisms underlying the relationship of certain risk factors with the disease are currently clear and therefore it is necessary to carry out further research on this issue.

Uterine fibroids are common monoclonal tumors of the uterus. Fibroids have components of both smooth muscle and fibroblasts, in addition to a significant amount of fibrous extracellular matrix, and all of them contribute to the pathogenetic process. Fibroids are extremely heterogeneous in their pathophysiology, size, localization and clinical symptoms. They partially refer to a number of diseases, which have aspects of malignant behavior in some cases, but are generally benign. The risk factor for fibroids is associated with race: black women have a higher risk of developing fibroids at an earlier age than white patients, and they also have more severe forms of the disease. In clinical practice, one-third to one-half of all hysterectomies are performed due to fibroids; there is also a significant morbidity and increased health care costs for women of reproductive age. In fact, modern treatment of uterine fibroids includes mainly surgical and interventional methods: about three quarters of all methods of fibroid treatment are hysterectomies. However, there are clinical innovations in the use of progesterone receptor modulators as drug therapy. To date, the information about the genetic subgroup that leads to the formation of fibroids is quite relevant; it can contribute to further understanding of the clinical heterogeneity of this disease and lead to individual treatment. This information is extremely important, as currently there is no high-quality evidence which can be used to base therapeutic decisions.

Conclusion. The prospects for the clinical treatment of uterine fibroids should change dramatically in the next decade, therefore, the current paradigm of treatment requires modernization. The direction for further research is clear: it is necessary to move towards determining predictors of the fibroid prognosis and developing individual therapy, which can be followed by early intervention, as well as strategies for primary and secondary prevention.

Objective: To investigate the mRNA expression levels of pro-inflammatory (IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-23, TNF-α, and IFN-γ) and anti-inflammatory (IL-4, IL-10, TGFβ) cytokines in the membranes of patients with prelabor rupture of membranes at term (PROM).

Materials and methods: During a clinical study at the Samara State Medical University, 40 pregnant women with full-term pregnancies were studied. The inclusion criteria were singleton pregnancy, gestational age 37.0-41.0 weeks without non-obstetric comorbidities, exacerbation of chronic and acute inflammatory diseases, and obstetric complications (placental insufficiency, preeclampsia). All patients delivered via cesarean section. Indications for planned surgery were abnormal fetal position and presentation, and postoperative uterine scar (control group, n=16). An additional indication for emergency cesarean section was premature rupture of the membranes (study group, n=24). The mRNA expression levels of IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-23, TNFα, IFN-γ, IL-4, IL-10, and TGF-β were determined using RT-PCR (RT-PCR DNA technology).

Results: Expression of the mRNA genes IL-1β, IL-8, IL-18, and TNFα was observed in almost all subjects in both groups. The expression of IL-17 mRNA was not determined in any patient; IL-23 – in 7/24 (29.2%) of the study group and 3/16 (18.8%) of the control group; IL-4 expression – in 5/24 (20.8%) and 4/16 (25.0%), respectively, at an extremely low level. Expression of IL-6 and IFN-γ mRNA genes was observed slightly more often in 16/24 (66.7%) and 17/24 (70.8%) patients in the study group and in 6/16 (37.5%) and 7/16 (43.7%) patients in the control group. Significant differences between the groups were observed only for the expression of IL-8 gene mRNA – 105.44 (23.7; 648.93) RU and 33.49 (20.0; 116.6) RU and TGFβ – 216.63 (129.5; 329.9) RU and 112.5 (36.7; 182.4) RU in the study group and control group, respectively.

Conclusion: In patients with PROM, the main changes in the fetal membranes are a 3.1-fold increase in the expression of the IL-8 gene mRNA, which ensures the migration of immunocompetent cells (p=0.022), and a 1.9-fold increase in the expression of the TGFβ gene mRNA, which is responsible for epithelial-mesenchymal transition and thinning of the fetal membranes (p=0.024),

Objective: To investigate the associations between maternal folate cycle gene polymorphisms and newborn birthweight, as well as evaluate their functional effects.

Materials and methods: A molecular genetic study was conducted on five polymorphic gene loci involved in folic acid and methionine metabolism (rs699517 TYMS, rs2790 TYMS, rs1979277 SHMT1, rs1805087 MTR, and rs1801394 MTRR) using the genomic DNA of 317 pregnant women.

Results: The birthweight of newborns with different maternal genotypes for the loci studied showed slight changes, but no significant differences were observed (p>0.05): rs699517 TYMS (3449.63 vs. 3551.44 g), rs2790 TYMS (3441.82 vs. 3511.29 g), rs1979277 SHMT1 (3484.05 vs. 3527.66 g), rs1805087 MTR (3477.50 vs. 3522.08 g), rs1801394 MTRR (3464.74 vs. 3550.98 g). Among the haplotypes, the TA haplotype (rs699517-rs2790 TYMS) occurred at a frequency of 0.13 and showed a significant association with birthweight (β=0.14, p=0.02, pperm=0.03). However, the TG haplotype (frequency 0.17) and the CA haplotype (frequency 0.70) were not significantly associated with birthweight.

Conclusion: The TA haplotype rs699517–rs2790 of TYMS may be associated with higher birthweight.

Objective: To investigate the levels of vasoactive endothelial factors, endothelin-1, and final metabolites of nitric oxide in the blood and follicular fluid, along with the expression levels of endothelial and inducible nitric oxide synthase (eNOS and iNOS) in cumulus cells of women with varying outcomes of hormonal ovarian stimulation during assisted reproductive technology (ART) for infertility treatment.

Materials and methods: In a simple open comparative clinical trial with parallel groups, markers of endothelial dysfunction were analyzed in 71 women from the Volgograd region, aged up to 42 years, undergoing ART for infertility treatment. The control group, with a normal and high response to ovarian stimulation using gonadotropins, included 31 women (≥10 oocytes retrieved). Two groups were formed with suboptimal (5–9 oocytes retrieved) and poor responses (4 or fewer oocytes retrieved), each containing 20 women. All patients had anti-Müllerian hormone levels greater than 1.2 ng/mL. Endothelin-1 levels in the blood and follicular fluid were determined using enzyme-linked immunosorbent assay, while the levels of eNOS and iNOS were assessed in cumulus cell lysates. The concentration of final nitric oxide metabolites (nitrite and nitrate ions) in the blood serum and follicular fluid was determined using the method described by Metelskaya V.A. and Gumanova N.G. (2005).

Results: Women with a poor response had significantly higher levels of endothelin-1 and end metabolites of nitric oxide in the blood serum than those with a high and normal response. The amount of iNOS in cumulus cell lysates from women with suboptimal and poor responses was greater than that in the control group. This, combined with the increased concentration of nitrite and nitrate ions, may indicate the formation of a potent oxidant, peroxynitrite, potentially causing irreversible damage in the cells of patients with a poor response.

Conclusion: Changes in vasoactive endothelial factor levels may contribute to a reduced response to ovarian stimulation with gonadotropins during ART for infertility treatment. Further research into the mechanisms that determine oocyte quality and quantity can enable personalized approaches to infertility treatment, potentially increasing pregnancy rates.

Objective: To evaluate satisfaction in young women (18–35 years old) with a drug containing estradiol valerate/dienogest (E2V/DNG) over a 6-month period in real clinical practice in Russia.

Materials and methods: This was a prospective multicenter study that assessed satisfaction of 504 women (average age is 27.8 years) with the contraceptive containing E2V/DNG. The characteristics of menstrual bleeding, sexual function, and women’s decision to continue using the contraceptive were evaluated in two subgroups: in the presence and absence of abnormal uterine bleeding (AUB). The satisfaction of doctors with this method of contraception was also assessed.

Results: It was found that 98.4% of women and 100% of doctors were “very satisfied” or “satisfied” with this method of contraception, regardless of the presence or absence of AUB. There was a significant decrease in the intensity, duration of menstrual bleeding and pain, and in the frequency of intermenstrual bleeding compared with the baseline indicator. Normalization of the parameters of the FSFI questionnaire was observed in most of the patients (89.7%), although initially these parameters could indicate sexual dysfunction in almost half of the patients (46.0%). The contraceptive E2V/DNG was well tolerated by women, and the overall rate of adverse events was 7.1%. Most women (97.8%) decided to continue taking the medication after completing the study.

Conclusion: The results of the study showed high satisfaction of young Russian women and doctors with the use of E2V/DNG, regardless of the presence or absence of AUB. The medication has a positive effect on the characteristics of bleeding/cycle control and on the quality of sexual function, therefore, the women demonstrated a high adherence to this method of contraception.

Background: Placenta accreta spectrum (PAS) is the cause of maternal mortality due to massive uterine bleeding. These complications can be reduced by improving the algorithm of surgical treatment of PAS.

Objective: To present the experience of managing patients whose pregnancy is complicated by PAS.

Materials and methods: This is a retrospective analysis of the deliveries of 54 patients with PAS which was diagnosed prenatally.

Results: A 10-year experience in managing 54 patients with PAS is divided into two stages. The first stage is the management of the first six cases (2012–2016). Two laparotomies were performed via Pfannenstiel incision with subsequent cesarean section in the lower uterine segment and metroplasty. Supracervical hysterectomy was performed in one case, and total hysterectomy was performed in three cases. The second stage is the management of 48 cases (2017–2023): corporeal cesarean section was performed in 3/48 (6.25%) cases, and transverse uterine fundal incision with metroplasty was performed in 45/48 (93.75%) cases. After childbirth, ligation of internal iliac and ovarian arteries was performed in 100% of cases. Compression sutures were applied in 5/48 (16.6%) cases. Total hysterectomy was performed in 6/48 (12.5%) cases, and one with vesicoplasty was done in 3/48 (6.25%) cases. Postoperative transfusion was performed in 5/48 (16.7%) patients. Intraoperative blood reinfusion was performed in 100% of cases. Complex antianemic therapy included a high dose of non-dextran iron preparation, ferric carboxymaltose.

Conclusion: The following algorithm is proposed: lower midline laparotomy, transverse uterine fundal incision, exclusion of manual placental separation, ligation of ovarian and internal iliac arteries on both sides after childbirth; in cases of secondary uterine hypotonia, application of compression sutures is possible; intraoperative blood reinfusion; antianemic therapy using iron preparations for parenteral administration in the postoperative period.

Ovarian stimulation in the in vitro fertilization (IVF) programs is accompanied by a defect in the luteal phase of the cycle, therefore hormonal support after embryo transfer into the uterine cavity is an integral part of the treatment. Vaginal administration is the most common route for the progesterone delivery.

Objective: To compare efficacy and tolerability of two forms of vaginal micronized progesterone, namely capsules (Utrogestan, Besins Healthcare) and gel (Miragel, Vertex JSC), in the IVF programs.

Materials and methods: The study included 309 patients: the patients of the first group (n=154) received micronized progesterone in the form of a vaginal gel at a dose of 90 mg per day, the patients of the second group (n=155) were administered micronized progesterone in capsules 200 mg 3 times a day vaginally. Efficacy was assessed using the following parameters: clinical pregnancy rate, early pregnancy loss rate, live birth rate. The medication tolerability was compared using the assessment of the patients’ questionnaires.

Results: Clinical pregnancy rate in the first group was 59.1%, and it was 55.2% in the second group; early pregnancy loss rate was 14.2% and 15.1%, respectively; live birth rate in the first group was 49.4%, and it was 45.2% in the second group. There were no statistically significant differences between the groups. The rate of premature births in the first group was 0%, and it was 7.1% in the second group. According to the patients’ survey, micronized progesterone in the form of a gel was better tolerated.

Conclusion: The comparative assessment of the vaginal administration of micronized progesterone in the form of gel and capsules demonstrated high efficacy of the medication. The vaginal gel was better tolerated and more convenient for the patients, according to the survey. Miragel can be administered to support the luteal phase in the IVF programs.

Recurrent mixed vaginal infections (RMVI) have not only become an epidemiological and clinical problem, but they can also lead to serious social and psychological consequences. In order to develop effective strategies for their diagnosis and treatment, it is necessary to understand the mechanisms of both commensalism and pathogenesis. Despite numerous treatment patterns, patients with mixed vaginal infections experience relapses with high frequency, and repeated prescriptions of antibacterial drugs (both systemic and local) only increase microbial resistance. The paper describes the experience of clinical application of complex therapy, including decontamination with a broad-spectrum antiseptic drug (dequalinium chloride), followed by prolonged use of replacement therapy with a probiotic containing lyophilisate of Lactobacillus acidophilus with low doses of estrogens.

Objective: To analyze the clinical and microbiological effectiveness of complex local decontamination (dequalinium chloride) and contamination (Lactobacillus acidophilus in combination with ultra-low-dose estriol) therapy in the treatment of recurrent mixed vaginal infections.

Materials and methods: The study included 124 patients with mixed recurrent vaginal infections (at least two episodes of clinical manifestations per year). Vaginal microbial communities were assessed using microscopic examination (Hay/Ison criteria) and real-time PCR (Femoflor 16). The identification of Lactobacilli species was carried out using the method of mass spectrometry. The vaginal microbiota was assessed in 14 days, 6 and 12 months after the end of the treatment.

Results: Complex local therapy with a prolonged stage of contamination with estriol-containing vaginal probiotics during clinical and microbiological monitoring for 12 months showed a decrease in the number of recurrent mixed vaginal infections by 2.4 times compared with the standard treatment pattern. The patients undergoing prolonged contamination with lactobacillus microflora with donation of microdoses of estriol showed more effective stabilization of the vaginal secretion pH, vaginal microbiocenosis (Hay/Ison criteria) and normalization of the ratio of competitive and weakly competitive lactobacilli, which prevented the development of dysbiotic disorders in the vagina.

Conclusion: The long-term course of contamination therapy with a combination of lactobacilli with ultra-low-dose estriol that promotes the adhesion of lactobacilli to the vaginal epithelium together with local empirical treatment with dequalinium chloride (Fluomizin) is preferable for patients with recurrent vaginal infections.

Gastroesophageal reflux disease is a chronic recurrent disorder caused by an impairment of the motor-evacuation function of the organs of the gastroesophageal zone and characterized by regularly repeated reflux of the stomach contents into the esophagus, and sometimes the duodenum. This disease leads to the appearance of clinical symptoms that worsen the quality of life of patients: damage to the mucous membrane of the distal part of the esophagus, dystrophic changes in non-keratinized stratified squamous epithelium, catarrhal or erosive/ulcerative esophagitis (reflux esophagitis), and columnar cell metaplasia in some patients. The article presents the modern data on epidemiology, etiology, pathogenesis, risk factors, clinical picture, diagnosis, and management of pregnant women with gastroesophageal reflux disease in the outpatient and inpatient environment. Particular attention is paid to the principles, methods and choice of medications for the treatment and prevention of this pathology.

Conclusion: The effectiveness of the treatment of gastroesophageal reflux disease with Gaviscon Forte has been found to reach 80–90%. The prognosis for pregnancy and childbirth with timely treatment is favorable. The algorithm for the management of pregnant women with gastroesophageal reflux disease is presented.

Background: Placenta accreta spectrum (PAS) is an advanced invasive placentation, which is a serious condition associated with high maternal mortality due to massive uterine hemorrhages. These complications can be reduced by early diagnosis of PAS.

Case report: A 35-year-old multiparous patient with a burdened obstetric and gynecological history had indirect signs of abnormally deep invasion of the chorion which were revealed during ultrasound examination at 7+1 weeks gestation. The ultrasound scan showed a heterogeneous structure with the expansion of lacunar spaces and areas of hypervascularization of the myometrium of the anterior uterine wall. The diagnosis of abnormal placental attachment was confirmed by dynamic echography with stereoscopic blood flow imaging (LumiFlow). A planned cesarean section by transverse uterine fundal incision was performed at 37+2 weeks. Metroplasty was performed on both sides after ligation of the internal iliac and ovarian arteries. The diagnosis of PAS was confirmed by a pathology study, and placenta increta (PAS 3a) was verified.

Conclusion: The presented clinical observation clearly demonstrates the real possibility of early ultrasound diagnosis of advanced invasive placentation. The detection of signs of advanced invasive placentation at the earliest possible time of gestation suggests that patients can be referred to a high-risk PAS group for the subsequent search for specific signs of this placental pathology and optimal planning of organ-preserving methods of delivery in these patients.