Obstetrics and Gynecology

Endometriosis is one of the most common gynecological diseases of the female reproductive system, and sex hormones play an important role in its pathogenesis. Sex hormone binding globulin (SHBG), a plasma glycoprotein, specifically binds androgens and estrogens and regulates the levels of biologically active (free) steroid hormones in plasma. The SHBG level in the body is influenced by age, gender, and body mass index. Genetic factors are important in determining the SHBG levels. The SHBG expression is negatively affected by monosaccharides, insulin and androgens, while thyroid and estrogenic hormones as well as phytoestrogens, on the contrary, increase its production. The high levels of estrogen and low levels of testosterone are associated with an increased risk of endometriosis. Since SHBG is important in the regulation of testosterone and estrogen levels, there is obviously an association between the SHBG levels and the likelihood of endometriosis.

Conclusion: The literature review suggests that SHBG plays a significant role in regulating the level of biologically active sex hormones in the body, and this role is frequently underestimated by medical professionals. The SHBG levels and its genetic determinants may be promising biological markers that can predict the risk of endometriosis. Further research in this area is required to provide evidence for the use of SHBG in clinical practice.

The review is based on resources from the following databases: CyberLeninka, PubMed, MedArt, and the Central Scientific Medical Library. Endometriosis is a common non-infectious pathology of the female reproductive system associated with the risk of infertility and obstetric problems. Deep infiltrative endometriosis (DIE) is considered an independent form or a distinct phenotype of endometriosis. Endometriosis in general and DIE in particular are associated with a decrease in both fertility and the effectiveness of assisted reproductive technologies. Pregnant women with DIE are at a higher risk of miscarriage, preterm labor and pre-eclampsia. The labor of patients after surgical treatment of DIE often ends in caesarean section. The present literature review is based on data obtained over the last 16 years and aims to assess the main links in the pathogenesis underlying the negative impact of DIE on women’s fertility.

Conclusion: Extragenital endometriosis, as well as DIE, appears to be a significant reproductive issue. Ovulatory reserve may decrease significantly with recurrent DIE and repeated surgical interventions. Pregnancy in this cohort of women is associated with an increased risk of cervical incompetence, threatened miscarriage and pre-eclampsia. The indications for surgical delivery by caesarean section should not be unreasonably extended due to the presence of colorectal anastomosis and unremoved endometrioid infiltrate.

The human body is greatly influenced by many different pathogenic factors in the external and internal environment throughout the human life. External environmental factors are those that act on the body from the outside, including nature’s polluting chemicals and physical influences. Internal environment factors refer to genetic/epigenetic abnormalities (monogenic mutations, chromosomal aberrations, disorder of methylation of nucleic acid molecules), malignant tumors and many other factors. Their primary effects may be initially asymptomatic, but patients may gradually develop clinical manifestations. Some of these factors can lead to organic and/or functional disorders of the female reproductive system, compromising the ovarian reserve (OR) status. OR is a pool of primordial follicles in the ovaries that determines the functional state of the reproductive system. This is the most important quantitative and qualitative indicator of physiological activity of the female reproductive system. Therefore, pathogenic factors affecting the body increase the chance of reproductive dysfunction (reduced fertility) and early infertility. This review discusses the various factors that directly or indirectly affect the reproductive organs and influence the fertility potential of the female body, as well as ways to treat reduced OR today.

Conclusion: The preservation, restoration and prevention of OR decline have now become significant issues in the field of women’s reproductive health. The control of external and internal factors of gonad damage and timely detection of fertility disorders are priorities. This type of support system for women’s health should increase the likelihood of protection of the reproductive system and improve the targeting of etiopathogenetic therapies for the defects; fertility could be preserved and prolonged until the natural menopausal period.

Background: Fetuses that are large for gestational age pose a risk of macrosomia, particularly when excessive growth occurs at full-term gestational age. However, not all large-for-gestational-age fetuses are born with macrosomia, which can result from either earlier delivery or a decrease in growth rate over time. Existing studies on the outcomes of labor induction for fetal macrosomia typically focus on fetal body weight at the time of induction, with few considering gestational age. Investigating the outcomes of spontaneous labor in large-for-gestational-age fetuses can help to identify the most favorable gestational age for delivery and reduce the incidence of such cases.

Objective: To study obstetric and neonatal outcomes of spontaneous labor with a large fetus depending on gestational age.

Materials and methods: This retrospective cohort study included 571 healthy primiparous women who were divided into two groups based on ultrasound findings. The control group comprised pregnancies with fetal sizes ranging from the 10th to the 80th percentile (n=345), while the study group included pregnancies with large-for-gestational-age fetuses above the 90th percentile (n=226). Each group was further divided into four subgroups: subgroup 1 – gestational age 37 weeks, subgroup 2 – 38 weeks, subgroup 3 – 39 weeks, and subgroup 4 – 40 weeks.

Results: The overall rates of operative deliveries and cesarean sections were significantly higher in the study group – 23% versus 11.6% for operative deliveries (p=0.0004) and 21.2% versus 8.7% for cesarean sections (p<0.0001). Among women with large fetuses at 36–37 weeks of pregnancy, every third observation at 38–39 weeks resulted in the birth of a child with macrosomia, whereas this occurred every in second observation at 40 weeks. The lowest cesarean section rates and occurrence of large fetuses were noted at 38–39 weeks.

Conclusion: Pregnant women with an estimated fetal weight at the 90th percentile or higher, determined by ultrasound at 36–37 weeks, are at an increased risk of higher cesarean section rates and the birth of large fetuses. The optimal delivery window for these cases was between the end of the 37th week and the beginning of the 39^th week, during which the lowest cesarean section rates were observed.

Objective: This study aimed to refine methodologies for implementing assisted reproductive technologies (ART), specifically in vitro fertilization (IVF), to preserve reproductive material in patients diagnosed with breast cancer. A comparative analysis of various ovarian stimulation protocols was conducted along with an evaluation of the impact of incorporating aromatase inhibitors (AIs) or selective estrogen receptor modulators (SERMs) on folliculogenesis and oocyte yield.

Materials and methods: This study included 471 female patients, of whom 346 underwent IVF cycles for oocyte or embryo cryopreservation. Prior to initiating treatment, a comprehensive review of medical records provided by oncologists was conducted, detailing the oncological diagnosis, disease stage, and results of diagnostic imaging (CT, MRI, and PET-CT), as well as morphological and immunohistochemical analyses. Additionally, each patient received a consultation with an oncologist-mammologist on the day of enrollment, which included an evaluation of the patient’s reproductive health, ovarian reserve, and overall gynecological status. The data were integrated to develop a personalized treatment protocol.

Results: The mean age of patients seeking fertility preservation was 29.5 (6.8) years, with the majority (221/346 (63.9%)) being under 35 years of age. All patients exhibited preserved ovarian reserve at the time of enrollment. Of the 346 breast cancer patients, 133 (38.4%) initiated ovarian stimulation during the follicular phase using a conventional protocol, whereas 213 (61.6%) commenced stimulation in the luteal phase using a random-start protocol. This study demonstrated that treatment efficacy, as measured by the number of retrieved oocytes and mature oocytes, depended on the patient’s ovarian reserve and was independent of the menstrual cycle phase at which stimulation was initiated. The administration of letrozole at doses of 2.5 mg and 5 mg yielded comparable outcomes in oocyte retrieval; however, the 5 mg dose was associated with significantly lower preovulatory estradiol levels. In contrast, the inclusion of tamoxifen in gonadotropin-based stimulation protocols resulted in suboptimal outcomes, with a trend toward reduced oocyte yield and quality.

Conclusion: The implementation of IVF protocols in patients with breast cancer should be guided by a multidisciplinary approach that incorporates both oncological and reproductive parameters. The number of oocytes retrieved is primarily determined by the ovarian reserve and is unaffected by the timing of stimulation initiation during the menstrual cycle. Aromatase inhibitors are the preferred pharmacological agents for ovarian stimulation in this patient population, whereas the use of tamoxifen is associated with inferior outcomes, including higher preovulatory estradiol levels and reduced oocyte quantity and quality.

Objective: To evaluate the role of the components of the immune system in the pathogenesis of preterm birth due to severe preeclampsia and placental abruption of normally implanted placenta.

Materials and methods: A total of 80 women with induced preterm birth (the main group) were examined. The sample was divided into two subgroups. Subgroup 1 consisted of patients with abdominal delivery due to progression of severe preeclampsia. Subgroup 2 consisted of patients with preterm birth due to placental abruption of normally implanted placenta. The control group consisted of women with term uncomplicated birth. The levels of interleukin (IL)-8, IL-10, tumor necrosis factor alpha (TNF-α), human chorionic gonadotropin and pregnancy-associated plasma protein A (PAPP-A) were studied as the predictors of preterm birth.

Results: It was found that IL-8, TNF-α and PAPP-A play an important role in the pathogenesis of induced preterm birth due to severe obstetric complications. Elevation of IL-8 level by 1 unit increases the risk of preterm birth by 2.96 times; elevation of TNF-α level by 1 unit increases the risk of preterm birth by 1.56 times, while elevation of PAPP-A level by 1 unit reduces the risk of adverse outcomes by 0.04 times.

Conclusion: The components of the immune system play an important role in the pathogenesis of preterm birth and placental dysfunction. Research in this area expands knowledge of the mechanisms of severe obstetric complications and is important for prediction of adverse obstetric outcomes.

Objective: To evaluate the outcomes of IVF and the follicular fluid metabolomic profile in patients with predicted poor ovarian response who received myo-inositol (MI) 1200 mg, alpha-lactalbumin (α-LA), and folic acid 400 mcg at the preconception stage.

Materials and methods: The study included 80 women with a predicted poor ovarian response, belonging to groups 3 and 4 of the POSEIDON classification, who were planning to undergo IVF as part of their infertility treatment. Patients in group 1 received MI 1200 mg, α-LA, and folic acid 400 mcg (Inofert Forte) daily for three months before ovarian stimulation. The women in group 2 received 400 mcg of folic acid. Amino acid and ceramide levels in the follicular fluid were analyzed.

Results: Group 1 showed a significant increase in the number of mature oocytes, zygotes, total blastocysts, and good-quality blastocysts compared with group 2. The use of MI + α-LA resulted in a statistically insignificant increase in the clinical pregnancy rate (27.0% in group 1 versus 10.8% in group 2, p<0.075, OR=3.05 [95% CI: 0.86–10.84]) and ongoing pregnancy rate (21.6% versus 8.1%, respectively, p<0.102, OR=3.13 [95% CI: 0.76–12.88]). The metabolomic profile of women in group 1 was characterized by increased levels of isoleucine, valine, leucine, alpha-aminobutyric acid, histidine, threonine, and proline, along with decreased levels of ceramides Cer (d18:0/24:1), Cer (d18:0/16:0), Cer (d18:0/22:0), Cer (d18:1/23:0), Cer (d18:1/25:0), Cer (d18:2/23:0), and Cer (d18:0/24:0).

Conclusion: Adjuvant therapy with MI before gonadotropic stimulation in patients with a poor ovarian response influences lipid and ceramide metabolism in the follicular microenvironment. This therapy also results in a greater number of mature oocytes and high-quality blastocysts, which positively affects the clinical outcomes of IVF infertility treatment.

Objective: To analyze maternal mortality in adolescents in the Russian Federation.

Materials and methods: This was a retrospective analysis of 112 maternal deaths of adolescents from 2009–2023 compared to women 20–34 years of age. Medical and social parameters and organization of medical care were analyzed.

Results: The maternal mortality rate in adolescents (9.9 per 100,000 live births) is lower than in women aged 20–34 (12.8 per 100,000 live births) (p<0.05). The main causes of death in adolescents were extragenital diseases (44.6%), preeclampsia and eclampsia (17.0%) and sepsis after delivery and abortions (14.3%). Adolescents had a higher risk of maternal death from preeclampsia and sepsis and a lower risk of death from extragenital diseases. There were more adolescents living in rural areas, unmarried and single. Pregnancies were more likely to be unwanted. Adolescents were more frequently registered in prenatal clinics after 12 weeks gestation and were observed in medical organisations of group I. Adolescents had higher rates of anemia and genitourinary diseases, pregnancy-related vomiting, preeclampsia, eclampsia and fetal hypoxia during pregnancy and delivery, and postpartum infection. Most deaths (50.9%) occurred in specialized and high-tech medical facilities.

Conclusion: To prevent maternal mortality among adolescents, it is necessary to take measures to prevent abortions, improve the quality of medical care and introduce modern organizational and medical technologies.

The article presents a literature review addressing various aspects of hormonal therapy for endometriosis, with a particular focus on the use of dienogest (DNG). The data of studies demonstrating pleiotropic mechanism of DNG action in endometriosis are presented. A comparative analysis of the literature data on the effects of medical therapy in the management of various manifestations of pain symptoms, reduction of endometrioid foci in different forms of endometriosis, and the prevention of postoperative recurrences was carried out. The effects of therapy on bone mineral density and quality of life of reproductive-aged women and adolescents with endometriosis were also analyzed. The review indicates the necessity for long-term hormonal therapy of endometriosis. The duration of this therapy depends directly on a woman’s compliance; therefore, it is reasonable to develop medications that would be bioequivalent to the original medications, have comparable therapeutic efficacy and high safety profile in combination with economic accessibility for patients. Normetrilla, which contains a micronized form of DNG at a dose of 2 mg, is one of these medications. It has been proven to be bioequivalent to the original medication, with a comparable safety and tolerability profile.

Conclusion: Normetrilla can be recommended as medical therapy for various forms of endometriosis in women and adolescent girls over 12 years of age after menarche. Further clinical trials are required in order to evaluate the efficacy and safety of the Russian medication Normetrilla in the treatment of endometriosis.

Objective: To assess the effectiveness of instrumental methods of breast examination in the diagnosis of benign breast diseases (BBD) according to the 2024 clinical guidelines. To evaluate the effectiveness of the Indinol Forto medication in patients with mastalgia according to the visual analogue scale (VAS) for pain.

Materials and methods: This paper presents the results of data analysis of 895 female patients aged 20 to 50 years diagnosed with BBD with mastalgia of varying severity. All the patients were examined at the Russian Scientific Center of Roentgen Radiology, Moscow, from January to December 2024. The evaluation of the patients’ condition was based on a comprehensive approach, including clinical examination, VAS pain assessment and instrumental studies (mammography, ultrasound with colour Doppler mapping (CDM) and elastography, MRI with contrast agents, core (trephine) biopsy of breast masses with subsequent histological examination depending on age and indications). The results of instrumental studies were evaluated according to the Breast Imaging Reporting and Data System (BI-RADS) classification on a scale from 1 to 5, including tissue density assessment by the ACR classification (for mammography). Following the results of the study, treatment with Indinol Forto (indolcarbinol) was recommended to patients with BBD with mastalgia of varying severity according to the VAS scale.

Results: Women with BBD aged 20 to 50 years most commonly have high radiological tissue density (ACR types C and D); the cystic component was predominant on breast ultrasound examination. Therapy with indolcarbinol has a positive effect on reducing the intensity of pain syndrome (mastodynia) within 6 months after treatment. There was a decrease in tissue density on mammograms and a decrease in the cystic component on ultrasound examination after completing the course of therapy.

Conclusion: High radiological tissue density and hormonal instability are risk factors for breast cancer. Indolcarbinol is effective as a first-line therapy for patients with cyclic mastalgia in BBD and it is included in the clinical guidelines of the Ministry of Health of the Russian Federation.

Multiple uterine fibroids (MUFs) are benign hormone-dependent neoplasms with two or more myomatous nodes that affect all stages of the reproductive process. The article presents the analysis of literature data and aims at studying the clinical aspects of complications during the gestational period, delivery and postpartum course in women with MUFs. This pathology has been found to be associated with an increased risk of gestational complications, including spontaneous miscarriage, preterm labor and placental dysfunction. The labor process in patients with MUFs is often complicated by poor uterine contractility and the need for operative delivery. In the postpartum period, uterine hypotonia or atony, massive hemorrhage, infectious and inflammatory complications as well as delayed recovery processes are observed. The article discusses the various factors that determine the prognosis for both mother and child. These factors include the size, localization and number of myomatous nodes. It is evident that personalized approach to the management of patients diagnosed with MUFs is necessary. The paper discusses the association of MUFs with a high incidence of caesarean section due to anatomical changes in the uterus and poor contractility of the myometrium. Infectious and inflammatory complications requiring antibiotic therapy and intensive monitoring are described. It is necessary to conduct further studies in order to identify risk factors and develop clinical guidelines for improving perinatal outcomes in female patients.

Conclusion: The reproductive process in women with MUFs is characterized by an increased risk of complications affecting the gestational, intrapartum and postnatal periods. The patients with this pathology are more likely to have preterm labor, placental dysfunction and other gestational complications, which require careful monitoring during the whole gestational period. Labor in women with MUFs is often accompanied by the need for operative delivery, especially in case of large or low-lying nodes. The postpartum period is characterized by an increased risk of uterine hypotonia, massive hemorrhage and infectious and inflammatory complications that require an individualized approach to monitoring and therapy.

Background: Congenital abnormalities of female reproductive organs result from the abnormal formation, fusion or resorption of Müllerian ducts during the intrauterine period and can lead to adverse reproductive outcomes. A number of studies have identified a higher incidence of ovarian dysfunction in patients with uterine abnormalities; however, other studies do not support this correlation. Uterine defects are frequently associated with syndromic pathologies; yet the etiology of the most prevalent Müllerian anomalies remains unclear or multifactorial.

Case report: This paper presents a clinical observation of a patient with uterus didelphys, longitudinal vaginal septum and diminished ovarian reserve as part of cardiac-urogenital syndrome caused by a likely pathogenic variant p.Ala440ThrfsTer2 in the MYRF gene. The patient was recommended to consider assisted reproductive technologies with preimplantation genetic testing to prevent the birth of an affected child.

Conclusion: This case illustrates the pleiotropic effect of the MYRF transcription factor. Pathogenic variants in the MYRF gene can impair the development of both Müllerian derivatives and ovaries, and lead to diminished ovarian reserve, which is also accompanied by dysfunction of other organs and systems. MYRF should be considered as a candidate gene for a variety of uterine abnormalities, diminished ovarian reserve and premature ovarian insufficiency in female patients in the presence or absence of extragenital manifestations.