Vol 25, No 2 (2023)

Reproductive health care involves helping families in this area with the provision of the necessary information. This is recognized as a key step in improving the health of men, women and children and is a fundamental human right. Everyone has the right to have access to a correct understanding of reproductive health care, choice of contraceptive method and the opportunity to benefit from scientific progress in this area. Over the past 35 years, significant progress has been made in the development of new contraceptives: the content of hormones in combined oral contraceptives has significantly decreased, inert intrauterine contraceptives have been replaced by more progressive, levonorgestrel-containing ones including low-dose generation. Combined hormonal compounds were synthesized in the form of injections, patches and vaginal rings, progestogen implantable and injectable contraceptives. Women who use contraceptives must take into account the state of health (including the presence of endocrine pathology) in order to use them without harm to their health. Based on the World Health Organization Medical Eligibility Criteria for Contraceptive Methods 2015, the Russian Medical Eligibility Criteria for Contraceptive Methods 2023 is designed to become an important tool in daily practice of doctors.

The herpes virus is an urgent problem, particularly in the obstetrician-gynecologist practice. The main objective of this paper was to review and analyze current literature data on the effect of the herpes virus on the mother and child during gestation. A variation of the diagnosis of prenatal herpes infection was reviewed. The treatment and prevention methods of the herpes simplex virus for a pregnant woman are addressed. It was shown that preventive antihomotoxic therapy had a fetoprotective effect, significantly reducing the risk of prenatal infection. Introducing preconception preparation for a wide population cohort, including the suppression of viruses in the mother's body, is relevant. The following methodology was used during work on the article: selection of publications using modern information databases, analysis of the obtained information, systematization of materials, and presentation of conclusions. An electronic search was conducted using publications identified in the following databases: eLIBRARY.RU, Google Scholar, and PubMed.

Aim. To assess the safety and efficacy of non-hormonal agents for mild vasomotor symptoms of menopause.

Materials and methods. The study included 173 females aged 48–55 with mild vasomotor symptoms during the early postmenopausal period. Patients in the study cohort were stratified into two groups by the double-blind method. In group 1 (study), the patients took the homeopathic agent Neoclimsal 1 tablet 4 times a day sublingually until completely dissolved for 4 weeks (n=86). In group 2 (n=87), the patient received a placebo (30 mg of microcrystalline cellulose) in a regimen mimicking the study treatment. Twenty-three patients withdrew from the study due to protocol violation or revoked their consents for reasons not related to medication. At the end of the study, 75 patients remained in both groups. The therapeutic efficacy was assessed based on the Greene and MENQOL scores change. The SF-36 questionnaire was used to evaluate patients' quality of life, and the average rate of falling asleep was calculated to assess the change in sleep disturbance. The change of M-echo and mammography results were reviewed using the BI-RADS scale 12 months after the start of the treatment to assess the agent's safety. Study design: A prospective, double-blind, placebo-controlled study.

Results. The course of Neoclimsal, sublingual tablets, reduced the severity of vasomotor symptoms by 2.3 times, the severity of depression by half (p<0.001), and at the end of treatment after 12 weeks of observation, the therapeutic effect not only persisted but tended to increase (p<0.001). Improvement in the quality of life of patients treated with Neoclimsal was confirmed by an improvement in the MENQOL score by 1.4 times a month after the start of therapy while maintaining the achieved result after 12 weeks of observation (p<0.001). The drug's safety is confirmed by the absence of adverse side effects and allergic reactions, the absence of endometrial thickness change within 3 months after the start of treatment, and mammography results using the BI-RADS scale at 12 months.

Conclusion. The results indicate the effectiveness of non-hormonal therapy in relieving vasomotor symptoms of mild postmenopause with a high safety profile. The drug has a beneficial effect on sleep disorders, reducing the severity of mental distress and improving the general quality of life.

Aim. To study the regulation of apoptosis in the endometrium of women with chronic endometritis (CE) and external genital endometriosis (EGE) based on the study of the expression of its regulators such as transcription factor (NF-Κβ), Bcl-2 and Caspase-8.

Materials and methods. The study evaluated the expression of apoptosis factors such as Caspase-8, NF-κB transcription factor, and Bcl-2, in patients with chronic endometritis (CE, n=23), external genital endometriosis (EGE, n=20), and intact endometrium (control group; n=7). Statistically significant differences were found for all test markers (p<0.05).

Results. The increased expression of apoptosis factors is probably related to high endometrial pro-inflammatory activity in both CE and EGE. For EGE, this effect is more pronounced at the transcription level in the form of an increase in the expression of the transcription factor NF-κB in both glandular and stromal endometrial cells. It is probably due to the systemic nature of the chronic inflammatory process. For CE, despite the antiapoptotic activity of Bcl-2, an increase in Caspase-8 expression in the endometrium may also indicate a predominance of innate immunity activation.

Conclusion. The imbalance of pro- and antiapoptotic factors can be an inducer of both cytotoxic and cytoprotective mechanisms of EGE and CE. However, it requires further research.

Aim. To identify risk factors for uterine leiomyoma (ULM) in women of reproductive age based on the study of clinical and medical history features in various tumor types.

Materials and methods. The study included 82 women of reproductive age with symptomatic ULM (the main group) and 47 somatically healthy women of reproductive age without proliferative gynecological diseases who underwent elective treatment at the Gorodkov Ivanovo Research Institute of Motherhood and Childhood (Director is professor AI Malyshkina, MD, Ph.D.). The study patients underwent general clinical examinations, ultrasound examination of the pelvic organs, histological examination of endometrial biopsy specimens, and myomatous nodes in women of the main group.

Results. The following risk factors and clinical and history features were identified in women with uterine fibroids: late reproductive age (p=0.000), unregistered marriage (p=0.026), employment (p=0.006), history of profuse and painful menstruation (p=0.000 and p=0.000, respectively), inflammatory diseases of the respiratory system (p=0.003), pain syndrome and profuse menstruation (p=0.000 and p=0.000, respectively), endometrial hyperplasia without atypia, and chronic endometritis according to histological examination (p=0.000 and p=0.000, respectively). When comparing the subgroups "Ki67+" and "Ki67-", we obtained the following clinical and history features in women with proliferating uterine fibroids: varicose disease of the lower extremities (p=0.035); and when comparing the subgroups "with secondary changes" and "without secondary changes", we found a higher rate of pain (p=0.038) in women with secondary changes in the myomatous node, as well as a tendency to a higher rate of painful menstruation (p=0.093) and endometrial hyperplasia (p=0.093).

Conclusion. Risk factors for ULM in women of reproductive age can be divided into modifiable ones, which include social disadvantage (unregistered marriage, hard physical work), inflammatory factor (inflammatory diseases of the respiratory system) and unmodifiable (late reproductive age). Clinical and history features of women with Ki67+ ULM compared to women with Ki67- ULM include more frequent use of barrier contraception, high prevalence of varicose vein disease of the lower extremities, and surgical interventions on the pelvic organs. Also, according to histological examination, women with ULM with secondary changes in the myomatous node, compared to women with ULM without secondary changes in the myomatous node, have a higher prevalence of painful menstruation, pain syndrome, and concomitant endometrial hyperplasia.

Aim. To evaluate the effectiveness of the intrauterine levonorgestrel-releasing device (LNG-IUD) in the treatment of atypical hyperplasia and the use of LNG-IUD in combination with a gonadotropin-releasing hormone analog (3.6 mg goserelin depot) in the treatment of stage Ia highly differentiated endometrial adenocarcinoma in women wishing to preserve childbearing function, and to assess reproductive outcomes after treatment in these women.

Materials and methods. A prospective and retrospective series of cases included all patients treated with LNG-IUD or LNG-IUD combined with goserelin 3.2 for atypical hyperplasia or early endometrial cancer (EC) treated in the Department of Innovative Oncology and Gynecology of the Institute of Oncogynecology and Mammology of the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology from January 2018 to March 2022. Response rates and the relationship of the response with clinical and pathological factors were calculated.

Results. Fifty-six patients diagnosed with atypical hyperplasia or stage Ia highly differentiated endometrial adenocarcinoma were treated with LNG-IUD and LNG-IUD combined with 3.2 mg of goserelin. Of the 56 patients who completed a 6-month course of hormonal treatment, 42 (82%) showed a complete response: 22 (91.7%) with atypical endometrial hyperplasia (AEH) and 20 (74.1%) with EC. In 4 (7.8%) patients, a partial response was reported: 2 (8.3%) with AEH and 2 (7.4%) with EC. No response was noted in 5 (9.8%) patients in the EC group only. Childbirth was reported in 13 (23.2%) women: 8 (29.6%) with AEH and 5 (17.2%) with EC. Two (3.6%) women were in the second trimester of pregnancy, and 17 (30.4%) women had an early pregnancy loss; 7 (25.9%) of them had AEH, and 10 (34.5%) had EC. The positive response rate was 90.2% at 6 months: 24 (100%) patients with atypical hyperplasia and 22 (81.5%) with EC. Patients with EC in combination with polycystic ovary syndrome and obesity and patients with the non-obese EC phenotype had a lower therapy efficacy.

Conclusion. LNG-IUD therapy for the conservative treatment of atypical hyperplasia and LNG-IUD therapy combined with goserelin 3.2 for early EC led to a morphological cure in most patients and can be considered for women planning pregnancy.

Background. Issues of the relationship and interaction of menstrual and reproductive function and the mental state of women are not sufficiently studied and need additional research.

Aim. To conduct a comparative assessment of individual indicators of reproductive function in mentally healthy and mentally ill women with infertility.

Materials and methods. Of the 348 women with primary and secondary infertility aged 21 to 40 included in the study, 120 had been treated for a psychiatric disorder in a psychiatric hospital before this study. Patients were clinically evaluated using a specially designed questionnaire card and subsequent statistical processing of the results obtained.

Results. The menstrual-generative function of patients in the study groups significantly differed in several indicators. Mentally ill women with primary infertility were characterized by a later age of menarche, menstruation irregularity or absence during the disease exacerbation, scanty menstruations or heavy menstrual bleeding, inadequate emotional response to menarche, and irregularity and dissatisfaction with sexual life. Spontaneous miscarriages and stillbirths were more common in mentally ill women, especially those with endogenous diseases (schizophrenia, affective disorders), and abortions and gynecological operations were more common in mentally healthy women. Predictors of infertility related to mental health were early onset and chronic course of mental disorder, severity and duration of the disease exacerbations, short and incomplete remissions, and personality changes or a defect (schizophrenic) due to mental illness.

Conclusion. Menstrual and reproductive functions of women depend on their mental state. In women with mental conditions, menstrual function disorders, along with psychopathological symptoms of diseases (a decrease in sexual vigor, communication, anesthesia of feelings), and decreased social and family adaptation, lead to reproductive function disorders. Improving a woman's mental state can contribute to the recovery of her reproductive function.

Background. The study of the recovery and restoration of the mucous membranes of the genital tract with vaginal intimate gels is presented.

Aim. To determine the clinical effectiveness of special cosmetic gels for intimate hygiene, Floragel® and Vagizhenal® for restoration of the mucous membranes of the vulva and vagina.

Materials and methods. Two groups of women were formed, Floragel® and Vagizhenal®, to analyze the clinical efficacy of cosmetic gels for intimate hygiene. Group 1 included 30 women aged 25 to 55 with clinical symptoms of genital tract mucosa atrophic changes and the absence of normal vaginal microflora. For intimate hygiene, this group regularly used the gel for intimate hygiene Floragel® for 1 month. Group 2 included 30 women aged 25 to 55 with clinical symptoms of genital tract mucosa atrophic changes of various etiologies. For intimate hygiene, this group regularly used the gel for intimate hygiene Vagizhenal® for 1 month. The gels were applied regularly, two times a day in the morning and evening, in a thin layer after hygienic procedures. Evaluation of the clinical effectiveness of special cosmetic gels for intimate hygiene Floragel® and Vagizhenal® included assessment of clinical efficacy, indicators of gynecological status, findings of microscopic and microbiological examination of vaginal discharge (Femoflor system), determination of the vaginal health index, and measurement of nonspecific immune protection of the vagina – levels of interferon γ, interleukin (IL)-1β, IL-6, IL-10 in the vaginal discharge using enzyme-linked immunosorbent assay.

Results. As shown by the questionnaires and interviews with patients, the use of special cosmetic gels for intimate hygiene, Floragel® and Vagizhenal® was associated with a significant improvement (p<0.05) in clinical symptoms: an improvement of vaginal discharge, the disappearance of unpleasant odor and itching, and an improvement in the state of the vaginal mucous membranes and vulva. A special gynecological examination showed significant changes in the visual morphological and functional state characteristics of the vaginal mucosa and vulva. An improvement was reported in 90% (27) patients (p<0.05) who used Floragel® and in 80% (24) patients who used Vagizhenal®.

Conclusion. The results demonstrate Floragel® and Vagizhenal® gels' high efficiency in restoring normal microflora and moisturizing mucous membranes by optimizing microbiological indicators, improving the vaginal health index and local immunity factors, indicating that special gels for intimate hygiene Floragel® and Vagizhenal® have not only cosmetic but also therapeutic properties.

Aim. To evaluate the effectiveness of hyaluronic acid anti-adhesion gel in surgical correction of distal tubal occlusion in restoring natural fertility in patients with infertility.

Materials and methods. A prospective cohort study was conducted. The main group (group 1) included 54 women; the comparison group (group 2) included 58 women with tuboperitoneal infertility due to distal occlusion of the fallopian tubes. In group 1 patients, at the final stage of endoscopic reconstructive plastic surgery on the surface of the fallopian tubes, anti-adhesion barrier Anti-adhesion® was applied (5 mL per each operated fallopian tube). Primary outcomes (patency of the fallopian tubes after 3 months) and secondary outcomes (onset of uterine pregnancy during the first year) were assessed. Statistical results were processed using the IBM SPSS Statistics version 25.0 software package.

Results. Within 3 months after surgical treatment, the patency of the fallopian tubes was reported in 32 (59.3%) group 1 patients and 24 (41.4%) group 2 patients (χ²=3.445; p=0.064). The rate of uterine pregnancy in group 1 during the first year after surgical treatment was significantly higher than in group 2: 21 (38.9%) and 12 (20.7%) women, respectively (χ²=4.447; p=0.035).

Conclusion. Endoscopic reconstructive plastic surgeries using hyaluronic acid-based anti-adhesion gel in patients with distal tubal occlusion slightly reduces the frequency of postoperative reocclusions of the fallopian tubes within 3 months after surgical treatment and significantly increase the rate of uterine pregnancy during the year after surgery mainly due to patients with grade III–IV of adhesive process in the pelvis.

Background. Preeclampsia (PE) is a gestation complication that affects not only maternal and perinatal mortality but also the quality of life of women who have undergone PE, as well as their children in later life, which determines the urgency and relevance of the search for early markers of this complication of pregnancy, including genetic determinants.

Aim. To evaluate the associations of GWAS-related hypertension candidate genes with the occurrence of severe PE.

Materials and methods. All patients included in this study (217 females with severe PE and 498 females with physiological pregnancies) underwent a molecular genetic study of five GWAS-significant polymorphic loci of arterial hypertension candidate genes (rs1799945 HFE, rs805303 BAG6, rs4387287 OBFC1, rs633185 ARHGAP42, rs2681472 ATP2B1) and assessed the compliance of the empirical distribution of allelic variants and genotypes theoretically expected under Hardy–Weinberg law (at p_bonf≤0.01). The associative search was performed using logistic regression analysis, and the odds ratio and its 95% confidence interval were calculated in PLINK v. 2.050. For polymorphisms that showed significant associations with severe PE, their regulatory effects were considered when using international projects on functional genomics (GTExportal, HaploReg (v4.1), PolyPhen-2).

Results. The GG genotype of the rs1799945 polymorphic locus of the HFE gene is significantly associated with an increased risk of severe PE within the recessive genetic model (odds ratio 2.41; p_perm=0.01). The polymorphism of rs1799945 of the HFE gene is localized in the histone markers H3K4me1 and H3K4me3 in pathogenetically significant organs and tissues for the development of PE, located in an evolutionarily conserved region located in the area of hypersensitivity to DNase-1. The rs1799945 locus of the HFE gene determines the missense mutation (aspartic acid replaces the amino acid histidine at position 63 in the Hereditary hemochromatosis protein) with the “BENIGN” predictor potential.

Conclusion. The rs1799945 polymorphic locus of the HFE gene is associated with a high risk of severe PE.

Papillomavirus infection is one of the most important infectious diseases of the reproductive system. The genome of human papillomavirus (HPV) transforms the cervical epithelial cells, leading to progressive changes: from cervical epithelial neoplasia to carcinoma in situ and further to invasive cancer. More than 550 000 cases of cervical cancer (CC) are reported yearly. In Russia, the incidence of CC in 2020 decreased for the first time in 20 years, and the average annual rate of increase in incidence was 1.27%. It became possible thanks to the introduction of a new system of diagnosis, treatment, and prevention of cervical cancer, in particular, the introduction of screening and a program of modern methods of diagnosis and treatment. Uniform for all countries, screening cervical diseases aims to diagnose changes in the cervical epithelium that occur due to HPV, which may be silent. Until now, the basis of screening programs was a cytological study (pap-test). Since 2018, most EU countries have switched to primary screening for HPV (HPV test) due to its greater sensitivity compared to the cytological method. No etiopathogenetic methods of HPV therapy have been developed yet. However, numerous studies have described the effective treatment of HPV-associated cervical lesions. It was shown that the most effective is a comprehensive approach involving treatment aimed at abnormal tissues and nonspecific antiviral and immunomodulatory therapy. The basis of the CC prevention strategy, of course, is primary prevention through vaccination. Studies are ongoing on the effectiveness of the new generation of vaccines based on the L2 viral protein and therapeutic vaccines against HPV.

One of the most effective contraception methods is combined hormonal contraceptives. According to the current prescribing information, in addition to their primary effect, they have several concomitant positive effects on the female body – non-contraceptive effects. These include a well-predictable and controlled "menstrual cycle" (menstrual-like reaction), anti-androgenic effect, anti-anemic effect due to reduced menstrual blood loss, reducing the severity of dysmenorrhea and premenstrual syndrome, reducing the risk of pelvic inflammatory diseases, ectopic pregnancy, and some benign and malignant tumors of the reproductive system. Combined oral contraceptives (COCs) also have effects on the central nervous system, hypothalamic-pituitary structures that regulate sex hormones, and the psycho-emotional health of women. For a long time, the main estrogen component of COCs remained ethinylestradiol. Although not well-studied, its mechanisms of action on the nervous system are similar, regardless of the progestogen component. However, the effect was not entirely positive: taking contraceptives containing ethinylestradiol can lead to increased emotional lability, anxiety, and depressive disorders. It drives researchers to search for new estrogen without these adverse properties. Such is the long-known but overlooked esthetrol. Numerous studies indicate a pronounced neuroprotective effect of esthetrol, which can increase patients' satisfaction with hormonal contraceptives and their compliance. It also opens up great opportunities for the use of this drug beyond gynecological practice.

Iron deficiency anemia is widespread among the female population. Pregnant women are a particularly vulnerable group, because the existing iron reserves are inadequate, and during pregnancy the need for iron for the formation of the placenta and fetal growth increases sharply, as a result, there is an imbalance between the intake and consumption of this trace element. Anemia increases the risks of various complications of gestation and multiplies maternal mortality. Note an increase in the frequency of premature childbirth, the threat of termination of pregnancy, placental insufficiency, weakness of labor, fetal development delay, fetal hypoxia, low birth weight of the newborn, the volume of pathological blood loss during childbirth and in the early postpartum period. At the same time, the development of these pathological conditions can be prevented by following modern protocols of pre-pregnancy preparation and pregnancy management. Prevention of anemia includes the use of various iron preparations, as well as new combinations, in particular a combination of 80 mg of elemental iron and 350 mcg of folic acid. In the article, we describe clinical cases demonstrating a rational preventive approach that prevents the development of clinical anemia and promotes safe perinatal outcomes for mother and fetus.

The article describes a clinical case demonstrating the effect of fetal alcohol syndrome on a preschool child's development, demonstrating the challenging diagnosis of this disorder, often leading to irreversible congenital mental and physical defects. The challenging diagnosis is because doctors are unaware of the mother's alcohol consumption during pregnancy. Doctors may suspect that the child has Fetal alcohol syndrome, according to the presence of facial dysmorphism and the state of health of the mother (pronounced signs of alcohol dependence). The clinical manifestations of the adverse effects of alcohol on the development of the child described in the article indicate the need to organize early diagnosis and comprehensive habilitation.