Vol 24, No 4 (2022)

Уважаемые коллеги!

Вот уже пятнадцать лет с нами нет академика Владимира Ивановича Кулакова. Мне выпала большая честь неоднократно посвящать свои выступления Владимиру Ивановичу: и в его звездные, и в его траурные дни. То, как его провожали в последний путь, какой скорбью утраты был наполнен наш Центр, трудно передать словами. Мне кажется, что аура его присутствия до сих пор сохраняется в аудиториях, в благодарных сердцах коллег, учеников, пациентов, а с 2008 г. и в названии Центра.

The review presents data on the management tactics of women with vulvovaginal atrophy in patients of reproductive age and menopause. The influence of vulvovaginal atrophy on the psycho-emotional and sexual spheres, modern methods of diagnosis and therapy of this pathology are considered. Special attention is paid to the role of rehabilitation and an integrated interdisciplinary approach to patients with symptoms of atrophic changes in the urogenital tract: the experience of rehabilitation measures is highlighted on the example of foreign and local studies, the effectiveness of "prerehabilitation" at the stage of the period from diagnosis to treatment is indicated. There is still a need for further studies of complex rehabilitation and its implementation in clinical recommendations.

This review presents information on demographic processes in Russia and the relevance of highly effective contraception for the prevention of artificial abortion. We present data on the etonogestrel implant (68 mg), an innovative single-stranded subcutaneous implant, a long-acting reversible contraceptive option with high efficacy (Pearl index 0.05) with optimal and typical use of the product. We analyzed the results of the studies that showed a favorable safety profile of the etonogestrel implant with no significant effect on the risks of thrombotic events, metabolic processes, depression incidence, bone mineral density, and characteristics of reproductive function after discontinuation of the drug. The article presents data on possible side effects in the form of changes in the characteristics of menstrual bleeding and a slight increase in body weight, which is comparable with the natural gain in an adult with age. The importance of qualified counseling of patients before and during the use of etonogestrel implants is emphasized.

Bacterial vaginosis is associated with severe infectious and inflammatory diseases and reduces the quality of life in women of reproductive age. Its worldwide prevalence is up to 80%. Thus, the development of new effective and safe methods of antimicrobial therapy becomes an urgent problem.

This article provides a review of current antimicrobial therapies for bacterial vaginosis and evaluates the safety and efficacy of short courses of antimicrobial therapy using combined agents for intravaginal use.

Aim. To define the management of realization of reproductive function implementation in patients experienced atypical endometrial hyperplasia and endometrial cancer IA stage.

Materials and methods. 150 patients aged 21–42 years were included. Among them 78 patients with atypical endometrial hyperplasia (group 1) and 72 – with endometrial cancer IA stage (group 2). General clinical, anamnestic and laboratory examination and follow-up with monitoring of gonadotropins and steroid hormones, as well as pelvic ultrasound supplemented with outcomes of reproductive function and in vitro fertilization (IVF) programs.

Results. It was shown a possibility of spontaneous pregnancy in young patients with regular cycles without other infertility factors with pathomorfosis 2–3 stages and the endometrial receptivity. The practicability of IVF-programs with frozen oocytes and embryo transfer in young women with a lower ovarian reserve and high-risk cancer relapse was demonstrated when their reproductive plan was uncertain.

Conclusion. The reproductive function in patients who experienced atypical endometrial hyperplasia and endometrial cancer IA stage might be realized through a personified approach using assisted reproductive technologies and modified IVF-programs with frozen oocytes and embryo transfer.

Aim. To study the association of neoangiogenesis VEGF-A gene polymorphisms C(-460)T (rs833061), C(+936)T (rs3025039) with the risk of genital endometriosis in the population of the Northwestern Federal District; to examine the relationship of polymorphic variants of the VEGF-A neoangiogenesis gene C(-460)T (rs833061), C(+936)T (rs3025039) with the concentration of VEGF-A factor in the blood of females with genital endometriosis.

Materials and methods. Eighty-five female volunteers aged from 19 to 44 (mean age 32.9 (5.8) years) with a histologically confirmed diagnosis of genital endometriosis were included in the stud; also, 79 females without endometriosis according to diagnostic laparoscopy for infertility or ectopic pregnancy, aged 20 to 42 (mean age 32.5 (7.2) years, p=0.71) were included in the study. The obtained data were analyzed using SPSS 20.0 statistical software package; χ² value and p value were estimated.

Results. In our study, we found an association between the C allele and the CC genotype of the C(+936)T (rs3025039) polymorphism of the VEGF-A gene with genital endometriosis: odds ratio (OR) 2.35, 95% confidence interval (CI) 1.03–4.61, p=0.023; OR 1.89, 95% CI 1.03–4.61, p=0.048, respectively. The TT genotype of the C(-460)T (rs833061) polymorphisms and the TT genotype and the C(+936)T (rs3025039) allele of the VEGF-A gene were less common in patients with genital endometriosis: OR 0.43, 95% CI 0.14–1.29, p=0.023; OR 0.06, 95% CI 0.04–3.18, p=0.001; OR 0.43, 95% CI 0.23–1.29, p=0.023 respectively. The blood concentration of VEGF-A cytokine was lower in patients with genital endometriosis at all genotypes of C(-460)T (rs833061) locus of VEGF-A gene than that in females without endometriosis. The analysis of genotype frequency distribution of polymorphic site C(+936)T of the VEGF-A gene showed that the VEGF-A cytokine level was 1.5 times higher in the comparison group with heterozygous ST genotype versus that in homozygous genotypes. Enzyme immunoassay in the examined females showed a 2.5-fold decrease in the level of the VEGF-A angiogenic cytokine in blood serum in patients with endometriosis compared to those without endometriosis.

Conclusion. To better understand the pathogenetic features of the endometriosis course and to make an individual prognosis of the course and therapy efficacy, an additional analysis of the associations between the polymorphisms of the listed genes and the angiogenesis factor level is required.

Introduction. The formation of new blood vessels is called angiogenesis. As the tumor grows, the oxygen and nutrient requirements of the abnormal cells continuously increase, and new blood vessels are formed. These processes are disrupted by angiogenesis inhibitors. Therefore, it is warranted to investigate ways to enhance the capabilities of angiogenesis inhibitors – alkaloids, flavonoids, and glycosides.

Aim. To justify the extension of clinical use of alkaloids, flavonoids and glycosides (Conium maculatum and Hydrastis canadensis, Thuja occidentalis), being a part of the complex medical product Mastopol®, taking into account the obtained data on the angiogenic balance in the nodular form of benign mammary dysplasia (BMD).

Materials and methods. The study included 69 volunteers divided into two groups: Group 1 included 27 patients with medical history of surgery for nodular BMD who received antiproliferative preoperative therapy with Mastopol® for 12 weeks. Group 2 (comparison group), n=42, also included patients with medical history of surgery for nodular BMD but without preoperative therapy with the herbal medicine Mastopol®. We studied angiogenesis markers (VEGF-A [vascular endothelial growth factor] and pVEGF-1) and immunohistochemical marker CD34 (cluster of differentiation – CD).

Results. We found a significantly higher (p<0.001) rate of CD34 detection on medium and small caliber vessels in the comparison group, i.e., in the patients who were not treated preoperatively with alkaloids, flavonoids, and glycosides (Mastopol®), while blood supply to the nodules by the medium and small vessels was 1.4 and 1.8 times lower in the Group 1, respectively. Analysis of VEGF expression shows an increase of angiogenic promoters VEGF-A and pVEGF-1 in serum before treatment with biologically active herbal components of Mastopol® in both groups. There were no statistically significant differences in vascular markers. However, a statistically significant decrease in VEGF-A and pVEGF-1 (p<0.001) was noted in Group 1 after Mastopol® therapy. Note the presence of a moderate direct correlation (r_s=0.49) of CD34 expression with VEGF-A expression in Group 1 and r_s=0.41 in Group 2, which indicated a direct relationship between angiogenesis and proangiogenic factors.

Conclusion. In addition to the proven antiproliferative, anti-inflammatory, cytokine stabilizing, analgesic, and anti-edema properties of Mastopol®, the study also showed the antiangiogenic effect of the herbal drug components. Considering the decreased vascular growth in fibroadenomas during Mastopol® treatment, the indications for its use in patients with fibroadenomas before the surgery can be extended. Specific immunological test to measure VEGF can be proposed as a noninvasive screening method to evaluate the effectiveness of conservative treatment in general clinical practice.

Aim. To reveal the peculiarities of structural reorganization of the endometrium in various variants of pregravid preparation in women with chronic endometritis (CE) and infertility.

Materials and methods. We examined 90 women aged 18–40 who were treated for CE. For all patients, examination with microbiological (cultural) examination of the cervical canal to be separated for aerobic and facultative anaerobic microorganisms with the determination of sensitivity to antibiotics, ultrasound examination (ultrasound) of the pelvic organs and morphological examination of endometrial biopsy samples before and after treatment. All women of the study group were divided into 2 subgroups. Patients of the 1st subgroup (n=30) received standard treatment for CE – antibacterial and non-steroidal anti-inflammatory drugs; in the 2nd (n=60) – an additional course of immunostimulating therapy with a bacterial lipopolysaccharide preparation was prescribed.

Results. According to the cultural method, repeated cultures from the cervical canal after treatment turned out to be sterile more often in women of the 2nd subgroup. Ultrasound diffuse-focal changes in the subendometrial zone of the myometrium occurred in all patients before and after treatment. In the 2nd subgroup, after treatment, significant changes in the endometrium were noted in the form of an increase in its thickness and a 4-fold decrease in the number of hyperechoic inclusions in the basal layer, as well as the disappearance of the irregularity of the endometrial closure line. In the endometrial biopsies of women of the 2nd subgroup, a significant decrease in the specific area of the inflammatory infiltrate, the absence of foci of fibrosis, and an increase in the thickness of the vessel wall were noted.

Conclusion. The addition of a bacterial lipopolysaccharide to the standard CE treatment regimen not only improves the microbiological environment of the female genital tract, but also significantly affects the morphofunctional state of the endometrium.

About 187 million couples worldwide suffer from infertility, with the male factor being diagnosed in 20–70% of cases. The main cause of idiopathic infertility has been recognized as the adverse effects of reactive oxygen species. On the one hand, the cellular antioxidant defense is a highly efficient multilevel system; therefore, the pharmacological targets may vary. On the other hand, antioxidant enzymes (superoxide dismutase, catalase, peroxidase) have high activity and specificity, which limits the pharmacological capabilities of direct antioxidants. Indirect methods, such as the normalization of mitochondrial function, are more promising. Mitochondria play a key role in providing energy for sperm motility (one of the main factors of male fertility). Myo-inositol (MI) derivatives involved in cell signaling regulate intracellular Ca²⁺ ion levels affecting mitochondrial oxidative metabolism and adenosine triphosphate production. Thus, mitochondrial antioxidants are of particular interest for therapeutic strategies. Currently, various routes and regimens of MI use in the treatment of males with oligo-astheno-teratozoospermia (OAT) are being considered in clinical practice. MI-based oral nutraceutical complexes for the treatment of male factor infertility contain both direct and indirect antioxidants. In vitro studies revealed damage to mitochondrial cristae in the sperm intermediate tract in patients with OAT. Experimental studies have demonstrated that mitochondrial structure is restored when sperm are incubated in an MI-containing medium. Clinical studies confirmed that sperm incubation in such an environment leads to increased sperm motility and viability in patients with OAT. Intravaginal administration of MI showed increased total sperm motility and an increased proportion of progressively motile sperm. It is the progressive motility that is considered the best marker for identifying quality and healthy sperm. This type of sperm is usually used for in vitro fertilization techniques. In addition, intravaginal MI administration improved the quality of cervical mucus and reduced its viscosity and crystallization. The effect of intravaginal MI on cervical mucus can be considered as an additional independent factor in increasing fertility.

Most malformations of the female reproductive organs, depending on their features, have a serious impact on reproductive function and the condition of pregnant women. Therefore, all women with uterine and vaginal malformations require counseling in preparation for pregnancy, follow-up during the pregnancy from the early stages, taking into account possible complications, adequate pregnancy management and prevention of complications, as well as fetal monitoring according to gestational age and planning the term and method of delivery.