Obstetrics and Gynecology

The article presents the analysis of circadian regulation disorders contributing to miscarriage and complicating the course of pregnancy. The circadian system of the body provides regulation of the neuroendocrine-immune (NEIM) system, dynamic balance and the process of adaptation of the female body to the developing pregnancy, and fetal growth. The autonomous circadian regulation is formed in the fetus/embryo under the influence of endogenous and exogenous signals that carry information through the placenta during normal pregnancy. The transcription factor genes CLOCK/BMAL1, the light period genes Period 1-3/Cryptochrome 1-2 and their protein products play an important role in the process of circadian regulation. Mutations in genes regulating and controlling the “clock” are accompanied in experiment and clinic by the development of pathologic conditions followed by disruption of estrous cycles, failure of embryo implantation, and increased risk of miscarriage. Dysregulation of non-circadian functions of the clock genes leads to systemic endothelial dysfunction and epigenetic disorders. The disorders of circadian rhythms called desynchronoses appear when the effects of stereotypical internal (deficit and displacement of the sleeping period, typical pathological processes) and/or external (change of work schedule and time zone) environmental factors are altered.

Conclusion: Newly developed or existing disorders in the circadian organization of the maternal body may modulate a number of pathogenetic mechanisms in case of miscarriage: neurogenic, endocrine, immune, and vascular; therefore, a detailed study of the mechanisms of adaptation and integration of rhythms in the emerging multifunctional system “mother-placenta-fetus” is extremely important in obstetric practice.

The options for infertility treatment increase and it is necessary to assess rationally the value of including additional substances in the algorithms for the management of patients. One of the most controversial issues remains the use of antioxidants. Although these substances have a positive effect on molecular levels, the results of their use in clinical practice can be very contradictory. To obtain an up-to-date and comprehensive view of the role of antioxidants in combating oxidative stress observed in various reproductive pathologies, we reviewed the world literature sources in Scopus, Web of Science, MedLine, Cochrane and other databases for the last five years. The data on potential mechanisms of antioxidant action in relation to molecular targets in the female reproductive system were summarized and analyzed. It was observed that the majority of foreign scientists were interested in the potential use of antioxidants in the treatment of infertility associated with endocrine disorders. The review pays special attention to the analysis of experience in the use of the most widely studied antioxidants in the treatment of unexplained infertility.

Conclusion: The analysis of the literature data demonstrated the considerable potential of natural antioxidants, but in most cases their use did not result in statistically significant clinical effects, even for the molecules most studied, such as vitamins C and E, alpha-lipoic acid, L-carnitine, and melatonin. The use of antioxidants in the treatment of unexplained infertility has had disappointing results so far. Nevertheless, there is still hope for achieving this ambitious therapeutic goal which justifies the need to continue further research on this issue.

Poor adherence to breastfeeding is a current problem among women who had cesarean section. The issues of preserving and maintaining lactation in women in the first 4–6 months after planned operative delivery are the most significant. Cesarean section and the postoperative period are influenced by many factors that make it difficult to establish lactation and maintain a positive attitude towards breastfeeding. These factors include postoperative pain, separate care for new mother and infant, difficulty in selecting the proper breastfeeding position, and the influence of public opinion; all of them may lead to a woman’s lack of confidence in her ability to breastfeed effectively.

To maintain a woman’s positive attitude towards exclusive breastfeeding, it is necessary to actively educate pregnant women about lactation at the prenatal stages, after the birth of the child, and after their discharge from the hospital. For successful breastfeeding, it is important to have maternal/newborn skin-to-skin contact immediately after birth and to put the baby to the breast within the first hour of life. In the future it is recommended to continue monitoring the breastfeeding process to correct potential difficulties experienced by women after cesarean section. Various non-medication methods such as taping and massage can be used to reduce pain.

Conclusion: Cesarean section has a significant negative impact on the subsequent breastfeeding of the newborn. Therefore, it is essential to take preventive measures aimed at reducing the incidence of formula feeding among mothers after operative delivery.

Relevance: The incidence of infertile marriages in Russia is steadily increasing, as is the rate of pregnancies after assisted reproductive technologies (ART). However, obstetric and perinatal outcomes of patients undergoing ART have not been fully studied.

Objective: To evaluate the incidence and structure of obstetric and perinatal complications in pregnant women following in vitro fertilization (IVF).

Materials and methods: Obstetric and perinatal outcomes were retrospectively analyzed in 96 patients with singleton pregnancies resulting from IVF (study group) and in 96 patients with spontaneous pregnancy (control group), who were matched by age, parity, and other characteristics.

Results: The incidence of major pregnancy complications in the control group was not significantly different from that in the study group. However, the study group had a significantly higher incidence of anemia (54/96 (56.3%) vs. 24/96 (25.0%); p<0.001) and gestational diabetes mellitus (26/96 (27.1%) vs. 11/96 (11.5%); p=0.01), as well as uteroplacental blood flow abnormalities in the third trimester of pregnancy and before delivery (40/96 (41.7%) vs. 25/96 (26.0%); p=0.03). The majority of patients in the study group underwent cesarean section (71/96 (74.0%) vs. 25/96 (26.0%), respectively; p<0.001). In study group planned surgeries were more common than emergency surgeries (60/71 (84.5%) vs. 9/25 (36.0%), respectively; p<0.001). Opposite dynamics were observed in the control group. Newborns from mothers in the study group were eight times more likely to have septal heart defects (15/96 (15.6%) versus 2/96 (2.1%); p>0.05) and were six times more likely to have transient hypoglycemia (19/96 (19.8%) vs. 3/96 (3.1%); p>0.05). They were also 2 times more likely to require a second stage of nursing (7/96 (7.3%) vs. 3/96 (3.1%); p>0.05).

Conclusion: The identified features of the course of pregnancy and the condition of newborns in patients who became pregnant as a result of IVF indicate that pregnancy in this group of patients should be managed by highly qualified obstetrician-gynecologists. When planning childbirth, it is necessary to assess the risks and choose the optimal method of delivery and a maternity facility where there is a possibility of early neonatal diagnosis of congenital malformations and provision of prolonged postnatal care to newborns.

Relevance: Preterm birth (PB) is a significant issue worldwide as it is the leading cause of perinatal morbidity and mortality. International statistics indicate that 5–18% of pregnancies result in PB.

Objective: This study aimed to investigate changes in blood plasma and cervicovaginal secretion concentrations of matrix metalloproteinase-9 (MMP-9) in pregnant women with threatened PB, as well as the dynamics of MMP-9 concentrations in response to tocolytic therapy with hexoprenaline.

Materials and methods: We examined 45 pregnant women with threatened PB. The control group consisted of 40 women with healthy pregnancies. The inclusion criterion was a singleton spontaneous pregnancy at 24–31 weeks and 6 days of gestation, with signs of threatened PB. Exclusion criteria were multiple pregnancies, acute phase or exacerbation of chronic diseases, history of cervical pathology, cancer and autoimmune diseases, preeclampsia and its complications, chromosomal abnormalities and congenital fetal malformations, pregnancies resulting from assisted reproductive technologies, and premature rupture of membranes.

Results: Blood plasma MMP-9 concentrations in women with threatened PB and those with normal pregnancies were virtually identical, measuring 116 and 120 ng/ml, respectively. In patients with threatened PB, the mean cervical secretion concentration of MMP-9 was 6.48 pc/g. After tocolytic therapy with hexoprenaline, the concentration decreased to 1.5 pc/g, which was comparable to the cervical secretion concentration of MMP-9 in pregnant women in the control group (1.58 pc/g).

Conclusion: Our study demonstrated that blood plasma MMP-9 cannot serve as a marker of PB because we did not observe any changes in its concentration during threatened PB. However, MMP-9 in cervicovaginal fluid may be considered a marker of PB, as its concentration increases in threatened PB and decreases in response to tocolytic therapy with hexoprenaline, reaching levels typical of a normal pregnancy.

Genital prolapse (GP) is a multifactorial disease that is influenced by various factors such as childbirth, obstetric trauma, age, and increased intra-abdominal pressure. However, not all individuals with these factors develop GP, highlighting the importance of gene and protein expression levels for understanding the underlying cause.

Objective: This study aimed to investigate the expression of the α1C subunit of the CaV1.2 calcium channel in the round ligaments of patients with GP.

Materials and methods: This study included 61 patients, with 31 in the GP group (group I, study group) and 30 with other gynecological conditions (group II, control group). The mean age of the patients was 55.6 and 46.5 years, respectively. In group I, 12/31 (38.7%) patients had grade II–III uterine and vaginal wall prolapse, whereas 15/31 (48.38%) and 4/31 (12.9%) patients had incomplete and complete GP, respectively. The control group did not have GP. The level of α1C protein expression in the round ligaments of the uterus was examined using Western blot.

Results: Group I exhibited lower α1C protein expression (3.034 [0.8108; 4.040] RU) than group II (4.098 [2.508; 6.543] RU) (p=0.0045). Reduced α1C protein expression in group I was associated with a sarcopenic phenotype, including muscle wasting and asthenia in 9/31 (29%), myopia in 7/31 (22%), hypotension in 16/31 (51%), constipation in 17/31 (54%), phlebopathy in 11/31 (35%), pelvic floor protrusion and relaxation in 16/31 (51%), apical GP in 24/31 (77%), hypermobility in 24/31 (77%), and flat feet in 15/31 (48%) patients.

Conclusion: Patients with GP had lower α1C protein expression than those in the control group. The low expression of α1C protein is indicative of a clinical symptom complex of connective tissue dysplasia (CTD), which aligns with the concept of a "sarcopenic phenotype." In patients with CTD and a sarcopenic phenotype, the labor process is associated with low α1C protein expression levels, which contributes to the development of GP. The specific form of GP (apical) is influenced by alterations in the calcium channel function, resulting in decreased α1C protein expression.

Relevance: Preventing early reproductive losses in assisted reproductive technologies requires comprehensive examination and preparation of the couple, as well as the use of special methods to select high-quality germ cells for fertilization. A promising method for sperm selection is based on the zeta potential of the membrane. However, the indications for using this selection method have not yet been determined, and its effectiveness in Russian couples with infertility remains unknown.

Materials and methods: We conducted a prospective cohort study involving 120 married couples with a history of infertility and early reproductive loss. The study included 62 couples undergoing ICSI with sperm selected based on membrane zeta potential. The control group consisted of 58 couples who underwent ICSI with standard density-gradient sperm isolation. We compared the groups in terms of fertilization and blastulation rates, embryo quality, clinical pregnancy rates, and pregnancy development up to 12 weeks (early reproductive losses).

Results: We observed a statistically significant trend towards higher-quality embryos in the zeta-potential selection group compared to the control group (p<0.001). The pregnancy rate was 35.4% in the study group and 31.0% in the control group (p=0.69; RR=0.87; 95% CI 0.52–1.45). Reproductive loss rates, based on actual pregnancies, were 4.5% in the study group and 33.3% in the control group (p=0.03; RR 0.13; 95% CI 0.01–1.00).

Conclusion: Based on the results obtained, fertilization using ICSI with sperm selection based on membrane zeta potential is effective in reducing the incidence of early reproductive losses. It can be recommended for married couples with male factor infertility, provided that ejaculatory parameters allow selection.

Objective: To evaluate the course of perinatal and infant periods in children born to mothers who were administered cellular technologies, namely, the injection of exosomes from mesenchymal stromal cells (EMSCs) during cesarean section.

Materials and methods: The course of pregnancy and delivery was evaluated using cellular technologies in 60 pregnant women and women in labor who composed group 1 (main group). Group 2 (comparison group) included 100 patients who did not receive exosome support. The health status of 93 infants was studied, 37 of them were included in group 3 (main group) and were born by spontaneous delivery at term and repeated cesarean section; these infants were born to mothers who were given an injection of 500 μl of EMSCs obtained in the laboratory of cellular technologies at the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology; EMSCs were injected into the incision area during the previous cesarean section after the uterine incision was closed with a single-row vicryl suture. Group 4 (comparison group) included 56 neonates who were born by spontaneous preterm and term delivery and repeated cesarean section; the neonates were born to mothers who had not received exosome support during the previous cesarean section. The results of the course of pregnancy and second delivery of patients with uterine scar who were/were not administered cellular technologies were evaluated as primary outcomes. The condition of newborns and infants up to one year of age was analyzed as secondary outcomes. The presence/absence of pathology in newborns and infants up to one year of age was determined by neonatologists and pediatricians and analyzed on the basis of medical examinations and data from the medical information system (findings from the Novosibirsk City Clinical Perinatal Center, children’s inpatient clinics, and outpatient records).

Results: The prospective analysis did not reveal any infectious or inflammatory manifestations in patients of group 1, however, the postpartum period of patients in group 2 (comparison group) was complicated by endometritis in 6/100 (6%) cases and lochiometra in 2/100 (2%) cases. The study showed that the success rate of vaginal delivery reached 64.9% (24/37) in patients of group 1 (main group) with prior exosome support, and 21.4% (12/56) in women of group 2 (comparison group). The length and weight of body of all newborns in group 3 (main group) corresponded to the parameters of the preterm gestational age; the infants were born without asphyxia with an Apgar score of 8/9 points. Whereas 4/56 (7.1%) neonates of group 4 (comparison group) were delivered at 34⁺⁰–36⁺¹ weeks’ gestation and had an Apgar score of 5/7 points. Congenital pneumonia was diagnosed in 3/56 (5.3%) neonates from group 4 (comparison group), 2/56 (3.57%) infants were diagnosed with patent foramen ovale, which is considered to be normal, and 1/56 (1.78%) newborn had manifestations of hip dysplasia.

Conclusion: The interim prospective analysis found no adverse effect of 500 μl of EMSCs injected during prior cesarean section on subsequent pregnancy, perinatal and infant outcomes.

Genitourinary syndrome of menopause (GSM) refers to a collection of symptoms including dryness, itching, burning, dyspareunia, and frequent recurrent urinary tract infections that occur in postmenopausal women and significantly impair their quality of life, emotional and mental health, and sexual function. Traditionally, local or systemic hormonal therapy aimed at increasing estrogen levels is administered, but not all patients may benefit from it. Laser treatment, including the use of a diode laser, can be an effective and safe alternative.

Objective: To obtain additional data on the safety and effectiveness of the diode laser in treating patients with GSM.

Materials and methods: Twenty-nine patients received laser therapy using the Lasemar 1500 diode device (1470-nm wavelength) once every two weeks for a total of four sessions. The effectiveness was assessed using the Vaginal Health Index (VHI) and the Female Sexual Function Index (FSFI).

Results: The mean VHI score increased from 15.2 to 21.2 after treatment. The VHI score increased by more than 3 points in 27 patients (93%), thus confirming the clinical significance of the changes. There was a considerable increase in the total FSFI score in sexually active patients (n=18), from 16.9 to 28.1. Three patients reported on the resumption of sexual activity after treatment. The procedures were tolerated well by all patients and no serious adverse events were noted.

Conclusion: The results of the observational study of 29 patients showed the effectiveness and safety of using the diode laser for the correction of GSM symptoms in 27 patients. However, the absence of a control group and the limited number of participants make it necessary to continue further research.

Background: According to the current Russian and international clinical guidelines, preeclampsia is a complication of pregnancy, childbirth and postpartum period characterized by an increase in systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg after 20 weeks gestation, regardless of the BP level in the patient’s history, combined with proteinuria or at least another parameter indicating the onset of multi-organ failure. However, preeclampsia is generally known to occur before 20 weeks gestation in patients with molar pregnancy.

Case report: The article presents a clinical observation of a case of severe preeclampsia complicated by HELLP syndrome at 18 weeks gestation in a healthy patient at high risk of developing preeclampsia who did not receive acetylsalicylic acid prophylaxis. The clinical case has a favorable outcome for the mother but it resulted in the fetal loss.

Conclusion: It is recommended to determine biochemical markers (PlGF or PlGF/sFlt-1 ratio) in order to improve the efficiency of prenatal screening and to identify the risk group for the development of preeclampsia before 20 weeks gestation. The effects of acetylsalicylic acid on the prevention of preeclampsia before 20 weeks gestation have not been studied yet due to the rare incidence of atypical course of this complication. It is necessary to conduct international registry studies to establish new criteria for the prognosis of early-onset preeclampsia and to reconsider the current definition.

The medical and social significance of the problems associated with the development of acute appendicitis is due to its high prevalence. Appendectomy is one of the most common surgical procedures performed on women of reproductive age, largely due to overdiagnosis and unnecessary surgeries. Inflammation and surgical intervention in the pelvis lead to adhesive disease which can cause a decrease in female fertility by affecting the patency of the fallopian tubes, the mobility of the fimbria, and the physiological function of the ovary.

The article addresses the issues of pathogenesis and diagnosis of acute appendicitis, as well as the influence of appendectomy on topographic anatomical and physiologic changes in the reproductive system of a woman. The literature on the relationship between the phases of the menstrual cycle and acute appendicitis was reviewed. The anatomical connection of the appendix and the right ovary through the ligamentum appendiculoovaricum (of Clado) explains the generalization of infection and the possibility of hematogenous and lymphogenous spread of the inflammatory process from the appendix to the ovary and vice versa. It is possible that dissection of the ligamentum appendiculoovaricum during appendectomy leads to impaired function of the right ovary due to decreased blood supply, therefore, the risk of infertility may be significantly increased. It has been shown that due to the close location and direct anatomical and physiological connection of the appendix and the internal organs of the female reproductive system, appendicular-genital syndrome often develops during appendicitis and/or appendectomy which dramatically increases the risk of infertility.

Conclusion: Appendectomy leads to reduced female fertility by affecting the patency of the fallopian tubes and mobility of the fimbriae, decreasing mucus secretion into the fallopian tube lumen and causing fibrosis of the ovarian capsule. Given the specific anatomical structure of the female reproductive system, it is necessary for a woman to consult a gynecologist and a surgeon together in case of acute abdominal conditions.

Background: Rudimentary horn pregnancy (RHP) is a rare form of ectopic pregnancy that occurs in women who have abnormalities in the development, growth, and fusion of the Müllerian paramesonephric ducts. RHP can result in lethal outcome if the uterus ruptures and hemoperitoneum develops. Despite the modern level of providing healthcare, there is still a high likelihood of late diagnosing RHP due to the difficulty in making the diagnosis prior to pregnancy.

Case report: A 33-year-old patient M. underwent emergency surgery for a missed miscarriage in the rudimentary uterine horn at 6 weeks’ gestation. Laparoscopy was used to remove the rudimentary horn with pregnancy. After treatment, the patient was discharged from the hospital in satisfactory condition.

Conclusion: MRI, 3D ultrasound, hysterosalpingography and hysteroscopy are recommended to accurately diagnose the unicornuate uterus with rudimentary horn. Given the difficulties of differentiation, especially in ectopic pregnancy in the early stage, there is a need to increase the use of MRI, which will definitely facilitate a better and more timely diagnosis and qualified care.

Background: Tuberous sclerosis complex (TSC) is a rare hereditary disorder characterized by the formation of benign tumors in many systems and organs. This pathology is caused by mutations in the TSC1 and TSC2 genes, which are responsible for encoding hamartin and tuberin proteins that regulate cell growth in various organs and tissues of the body.

Case report: The article presents a description of a clinical case of TSC in a 12-year-old girl. The patient complained of dysmenorrhea since menarche, she also underwent one surgical intervention for uterine cystic mass and extensive pelvic endometriosis. After further thorough examination and diagnostic search involving different specialists from several leading institutions, comparing the clinical picture, results of instrumental and laboratory examinations, as well as the results of genetic testing, which revealed a mutation in the TSC1 gene, the patient was diagnosed with TSC. The clinical observation was characterized by the absence of clear clinical criteria of the disease, such as skin lesions, epileptic seizures, lesions of the central nervous system; however, the symptoms were similar to the clinical manifestations of endometriosis. This caused a delay in making the correct diagnosis and prescribing treatment.

Conclusion: This clinical example may be useful for doctors of different specialties, as the principles of multidisciplinary approach are necessary for timely diagnosis and treatment of such patients.