Nº 6 (2024)

Antihypertensive drugs used in pregnancy can reduce blood pressure (BP) by different mechanisms; however, none of these drugs has an advantage over the other. Due to the comparable efficacy and safety profile as outlined in national and international guidelines, the choice of antihypertensive drug in pregnancy is ultimately dependent on the doctor’s expertise, consideration of potential side effects and contraindications, availability, and cost. The risk for hypertension in pregnancy is determined by a woman’s baseline hemodynamic profile. Thus, as a rule, there is a decrease in cardiac output and increased peripheral vascular resistance in patients with preeclampsia even before pregnancy. Numerous hemodynamic studies with promising results suggest a new, phenotype-based approach to the selection of antihypertensive therapy used in pregnancy. The choice of hypotensive therapy is based on hemodynamic changes in a woman rather than on BP readings. It is recommended to prescribe a beta-blocker if cardiac output is increased (usually it is accompanied by decreased vascular resistance), but if vascular resistance is increased (usually it is accompanied by decreased cardiac output), it is recommended to prescribe a vasodilator. It is possible to correct the prescribed therapy during dynamic monitoring of its effectiveness if hemodynamic parameters normalize. This innovative concept has been shown to lead to better pregnancy outcomes, namely, faster achievement of target BP, lower incidence of severe hypertension, decreased rates of iatrogenic preterm labor and low birth weight babies.

Conclusion: Further large-scale studies are necessary to determine the optimal BP in pregnancy, as currently, there is no general consensus regarding this issue. Additionally, there is a need to investigate the efficacy of hemodynamically-based therapy for hypertension in pregnancy. This will facilitate the development of individualized therapeutic approaches.

Грудное молоко (ГМ) является наиболее сбалансированным продуктом питания для детей раннего возраста. ГМ содержит все необходимые питательные вещества, биологически активные соединения, защитные антитела, которые должен получать ребенок в первые годы жизни. Развитие ребенка напрямую зависит от молока матери, качество которого обусловлено здоровьем матери и качеством ее питания.

Целью данной статьи является популяризация информации о преимуществах ГМ, подтверждение или опровержение корреляционных связей между составом ГМ и рационом питания кормящей женщины.

В статье обсуждаются результаты исследований, проведенных для определения влияния различных компонентов рациона кормящей женщины на содержание жирных кислот, белков, углеводов, витаминов и минералов в ГМ. Кроме того, обсуждаются практические рекомендации по оптимизации питания кормящих женщин, чтобы улучшить качество грудного молока, обогащая его необходимыми питательными веществами и антителами для обеспечения наилучшего старта в жизни для новорожденных. Исследование подчеркивает необходимость информационной поддержки кормящих матерей со стороны медицинских и социальных служб, а также значимость продолжения научных исследований в этой области для дальнейшего развития и улучшения рекомендаций по питанию.

Заключение: Обогащенный и сбалансированный рацион не только способствует улучшению общего состояния здоровья матери, но и значительно влияет на качество ГМ, увеличивая содержание в нем жизненно необходимых витаминов и микронутриентов. Это особенно важно для развития и роста ребенка, обеспечения его потребностей в этих веществах на первых этапах жизни. Употребление разнообразных продуктов, богатых необходимыми витаминами и микроэлементами, должно быть в приоритете для кормящих женщин. Кроме того, при необходимости возможно применение витаминно-минеральных комплексов по рекомендации врача, что позволит обогатить ГМ всеми необходимыми питательными веществами, поддерживая здоровье и гармоничное развитие ребенка.

Objective: This study aimed to evaluate the results of intrauterine correction of open forms of spina bifida performed at V.I. Kulakov NMRC for OG&P of Minzdrav of Russia and compare them with the results of the MOMS trial.

Materials and methods: This study included 30 patients with a confirmed diagnosis of meningomyelocele or fetal rachischisis who underwent intrauterine treatment at the center. The inclusion criteria were completion of a perinatal consultation at the center, maternal age over 18 years, singleton pregnancy, normal fetal karyotype, gestational age between 19 and 25⁺⁶ weeks, presence of Arnold–Chiari malformation type II, cervical length >20 mm, absence of fetal kyphosis >30°, and signed informed consent for surgical intervention. Comparisons were made with 78 women from the MOMS trial whose fetuses underwent intrauterine meningomyelocele repair. Statistical analysis was performed using the StatTech v 3.1.10 (Stattech LLC, Russia) and Prism v. software. 8.0.1 (GraphPad Software, USA).

Results: The most common complication of intrauterine correction for open forms of spina bifida was preterm birth. The mean gestational age at delivery was 33.3 weeks. Premature placental abruption and premature rupture of membranes were observed in 13.3% and 30% of cases, respectively. Delivery was performed via cesarean section in all cases. Correction of Arnold–Chiari II malformation was observed in 100% of the cases, and CSF shunt surgery was performed in one case for intraventricular hemorrhage. Obstetric and neurological outcomes were comparable to those of the MOMS randomized multicenter trial.

Conclusion: Timely diagnosis and careful selection of fetuses for intrauterine correction of open forms of spina bifida lead to regression of Arnold–Chiari II syndrome with subsequent improvements in neurological outcomes in children managed with an integrated multidisciplinary approach.

Objective: To investigate relationship between maternal and fetal complications after novel coronavirus (nCoV) infection (COVID-19 infection) in the presence of polymorphism of gene encoding proteins of the hemostasis system.

Materials and methods: A comparative study of 270 cases of pregnancy and delivery was carried out. Among them, 170 women were infected with novel coronavirus, and 100 women had no COVID-19 with a proven absence of antibodies to SARS-CoV-2 in the blood. Real-time PCR was used for detection of gene polymorphism of F2, F5, F7, F13, FGB, ITGA2, ITGB3, SERPINE1 in the peripheral blood samples. The enzyme-linked immunosorbent assay (ELISA) was used to quantify specific proteins – soluble fms-like tyrosine kinase 1; placental growth factor; tissue plasminogen activator (t-PA); plasminogen activator inhibitor-type 1 (PAI-1).

Results: Gene polymorphism of the hemostasis system influences the course of novel coronavirus infection, the concentration of the major regulatory proteins and determines formation of perinatal complications. Maternal carriage of the plasminogen activator inhibitor-type 1 (675 4G/4G) allele during pregnancy is associated with mild course of COVID-19 infection. At the same time, homozygous carriage of PAI-1(675) 4G/4G determines the development of severe preeclampsia. Carriage of F13(103) T allele is associated with increased risk of infection and clinical significance of the disease with circulation of the most aggressive SARS-CoV-2 Beta variant and increased concentration of t-PA and PlGF in the blood. Moreover, the novel coronavirus infection leads additionally to increased concentration of these proteins at delivery. Homozygous carriage of F13(103) T/T increases the risk of premature placental abruption.

Conclusion: The mechanisms of gestational complications after nCoV infection are mediated by accumulation of supraphysiological concentrations of proangiogenic factors and fibrinolysis activators at delivery, and their action is modulated by the presence of genetic risk factors associated with hereditary thrombophilia.

Aneuploidies in human embryos play a significant role in the development of implantation failures and early reproductive losses in assisted reproductive technology (ART) programs. Preimplantation genetic testing for aneuploidy (PGT-A) is the most commonly used method for assessing embryo ploidy. The introduction of PGT-A into clinical practice has greatly reduced the chances of transferring aneuploid embryos to the uterus and has increased the effectiveness of ART programs.

Different PGT-A methods and sampling techniques have advantages and disadvantages, and there are various reasons for potential false-positive and false-negative PGT-A results. Since only a few cells are used for the study, the uniformity of DNA amplification is crucial for obtaining reliable analysis results. Therefore, the most important stage of PGT-A is whole-genome amplification (WGA).

This article presents an analysis of the current literature regarding the effectiveness and reliability of methods for amplifying small quantities of DNA. The results of our study, which compares different methods of whole-genome amplification of individual trophectoderm cells, are presented in order to obtain reliable data on the molecular karyotype of embryos using NGS. The effectiveness of using domestic WGA kits has been demonstrated.

Conclusion: Comparing PGT-A results using various kits has shown that the "hybrid" protocol we developed, which allows for the use of both foreign and domestic WGA kits, is applicable. This approach has demonstrated the high reliability of WGA kits with SD polymerase for preparing materials for PGT of human embryos, and can also be applied in other areas of biomedicine and forensic research where high reliability and accuracy in amplifying extremely small quantities of DNA is required.

Objective: To analyze the concentrations and balance of serum cytokines that activate (IL-1β, IL-6) and inhibit (IL-4, IL-10) inflammation in healthy individuals and in patients with leiomyoma in general, with and without endometrial lesions.

Materials and methods: The study included 109 women aged 23 to 61 years with uterine fibroids and 92 women of similar age (22–61 years) without uterine fibroids. All women had general clinical, standard instrumental and laboratory examinations. The concentrations of pro-inflammatory and anti-inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA) for ELx800 Plates (BioTek, Taiwan) using Vector-Best (Russia) kits. Descriptive statistical analysis and nonparametric statistical methods were used.

Results: The course of the tumor process in uterine fibroids is accompanied by a fivefold increase in pro-inflammatory cytokines IL-1β and IL-6 in the serum of female patients in comparison with healthy individuals (p<0.001); the concentrations of cytokines with anti-inflammatory activity, namely IL-4, are not so remarkable, but they are also higher (4.09(2.36-6.94) versus 2.42(0.97-5.86) in healthy individuals, p<0.001). Significant increase in IL-6 concentration in all patients with uterine fibroids (8.93(4.95-14.11), p<0.001) was found to be maximal among women with endometrial pathology (9.67(5.22-14.60), p<0.05).

Conclusion: Proliferation of tumor myocytes and development of microcirculatory channel components in patients with uterine fibroids are accompanied by the prevalence of pro-inflammatory activity of the cytokine network and a shift in the balance of its functional state towards dysregulation of control over the processes of myometrial remodeling.

Relevance: Poor response to ovarian stimulation during an IVF program is a pressing issue that limits the effectiveness of assisted reproductive technology (ART). Currently, there are no verified and effective methods in routine clinical practice to improve the success rates of treatment in patients with a poor ovarian response. The use of cell-free therapy as a preparation for IVF/ICSI programs offers a promising alternative to donor oocytes, allowing this group of patients to have genetically related children.

Case report: This article presents three clinical observations that demonstrate the effectiveness of a technique involving the activation of ovarian function through intraovarian administration of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in patients with a history of multiple IVF failures and poor response to ovarian stimulation.

Conclusion: The presented information on the efficacy of MSC-EVs, based on clinical cases of complex and challenging patients with significantly diminished ovarian function, provides hope for the development of a new direction in reproductive medicine based on the use of cellular technologies. Further research is needed to study the intraovarian regulation of folliculogenesis and the mechanisms by which extracellular vesicles influence these processes.

Objective: To evaluate the dynamics of changes in the size of ovarian endometriomas (OMA) in patients receiving the dienogest (DNG) therapy and determine the significant parameters of magnetic resonance imaging (MRI) that affect their reduction.

Materials and methods: This was a prospective study which was conducted at the Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Moscow, in the period from 2021 to 2023. The study included 24 patients with 37 OMA (average age is 33.54 (7.08) years). The patients received DNG (drug "Zafrilla") at daily dosage 2 mg in a continuous mode. Before the start of therapy and after 6 months of its administration, an MRI of the pelvic organs was conducted with a simultaneous calculation of a number of parameters: the size and volume of cysts with the calculation of the reduction coefficient, the measured diffusion coefficient (MDC), the ratio between the maximum and minimum values of MDC, signal intensity on T2-weighted images. The initial and subsequent levels of AMH and CA-125 were determined in the blood serum.

Results: The analysis of the data showed that DNG therapy leads to a decrease in the volume of OMA by 50% or more in 73% of cases, by 75% or more in every 2nd case of the disease. The full effect of the therapy was noted in every 10th case (100%). The reduction coefficient was significantly influenced by the initial MDC values (r=0.559, p=0.068), the degree of uniformity of the cyst contents (r=0.5491, p=0.0081), the time until its detection (r=-0.4432, p=0.0077), as well as its initial dimensions (<2 cm in diameter, p=0.0015). The higher the initial MDC values correlated with more pronounced effect of therapy. It was shown that at an MDC value of ≥0.792, a decrease in OMA volume by 75% or more with a sensitivity of 90.0% and a specificity of 78.57% can be expected (AUC 0.814 (0.093) [95% CI 0.604;0.942], p=0.0007).

Conclusion: DNG suppressive hormone therapy helps to reduce the volume of OMA by an average of 78.91%. MRI of the pelvic organs is not only a method of diagnosing OMA, but it is also a tool for evaluating the effectiveness of therapy with MDC. MDC value of ≥0.792 may indicate a potential decrease in the volume of OMA by 75% or more, which is important for making a decision about the patient’s management tactics.

Objective: To conduct a comparative assessment of the effectiveness of a biologically active complex of phytopreparations and menopausal hormone therapy (MHT) in the treatment of the climacteric syndrome (CS).

Materials and methods: This was a prospective analysis of the effectiveness of using the biologically active complex of phytopreparations NOW Menopause Support 560 mg and MHT in the treatment of CS in women 6 months after receiving therapy. Group 1 included 50 women with CS who received a phytopreparation made on the basis of soy isoflavonoids, cimicifuga rhizome, and red clover isoflavones. Group 2 included 42 patients who received systemic MHT.

Results: According to the Greene Climacteric Scale, the emotional state significantly improved (10.0 (8.0; 14.0) scores) in the group receiving systemic MHT after 6 months from the beginning of therapy, but it was worse than in the other group (p=0.044). The somatic condition effectively improved in the group receiving MHT (3.0 (3.0; 6.0) scores), however it was not different from the condition of women in the group receiving phytopreparations after 6 months of therapy (3.0 (3.0; 6.0) scores), p=0.233. Vasomotor symptom status significantly improved (p<0.001) in both groups after 6 months of treatment. It was assessed as 3.0 (2.0; 5.0) scores in the group of patients after taking MHT and it differed from the group receiving phytopreparations which was 1.0 (1.0; 3.0) scores (p=0.032); it was associated with the presence of milder forms of vasomotor manifestations of CS in the group receiving phytopreparations.

Conclusion: The treatment of CS with phytopreparations and systemic MHT showed high effectiveness. The phytopreparation made on the basis of soy isoflavonoids, cimicifuga rhizome, red clover isoflavone shows positive results in the treatment of the whole spectrum of menopausal disorders, but it can be used with greater benefit for women with moderate severity of symptoms, where the dominant symptoms are somatic and emotional manifestations.

Preeclampsia is one of the most serious pregnancy complications affecting 2-8% of pregnancies. In the last decade, it has become possible to detect preeclampsia early by determining the ratio of angiogenic factors sFlt-1/PlGF; thus, the incidence of maternal and perinatal complications may be reduced.

Objective: To assess the impact of introducing the sFlt-1/PlGF ratio for early diagnosis of preeclampsia into the routine practice of managing pregnancy on clinical outcomes and health care system costs in the Russian Federation.

Materials and methods: The study was based on a mathematical model to determine the ratio of angiogenic factors sFlt-1/PlGF in all pregnant women at high risk of preeclampsia; these factors were determined by first trimester screening. The initial data for building the model were the results of the PROGNOSIS clinical trial, statistical materials and a survey of experts. The early detection of preeclampsia was expected to contribute to the improvement of pregnancy management tactics and reduce the health care costs, including preventive care, emergency and planned hospitalizations, and treatment of pregnancy complications. The developed model was tested in the Moscow region, the Samara region and the Republic of Bashkortostan.

Results: The introduction of testing into the routine practice of managing pregnancy may reduce the incidence of life-threatening complications for the pregnant woman (severe preeclampsia, HELLP syndrome) and fetus/newborn (stillbirth, perinatal mortality, respiratory distress syndrome, periventricular leukomalacia). Due to the decrease in the number of cases of providing medical care for patients who do not develop preeclampsia (misdiagnosed without a test), as well as the decrease in the number of emergency hospitalizations and deliveries for patients who have preeclampsia outside the hospital (in the absence of timely diagnosis), the total costs of the Obligatory Medical Insurance system will not increase if the average number of tests is 1.45 or less per pregnant woman with a high risk of developing preeclampsia.

Conclusion: The introduction of the sFlt-1/PlGF ratio into the routine practice of managing patients at high risk for preeclampsia has the potential to reduce adverse pregnancy outcomes and the cost of managing pregnancy.

A review of existing research suggests that women are more likely to experience sleep disorders than men. Chronic sleep deprivation results in the activation of the hypothalamic-pituitary system and sympathetic nervous system, which increases the risk of menstrual disorders, ovarian dysfunction, spontaneous abortion, decreased ovarian reserve in women over 35 years of age, and low effectiveness of in vitro fertilization in women with infertility. Sleep disorders such as hypersomnia and insomnia associated with premenstrual syndrome and premenstrual dysphoric disorder have been described. Sleep disorders in women with polycystic ovary syndrome are almost twice as common as in healthy women of the same age. Insomnia is a common complaint in menopausal transition period and in postmenopause in more than half of women.

The results of numerous studies emphasize the importance of diagnostics and treatment of sleep disorders for effective correction of the underlying disease that leads to reproductive impairment and reduced quality of life in women.

The first-line drug choice in the treatment of insomnia are herbal sedatives and melatonin. Melatonin is a pleiotropic hormone, produced by the epiphysis, that regulates the circadian and seasonal rhythms of physiological functions of the body. It affects not only sleep-wake cycles, but also neuronal development, metabolic processes, protection and regulation of the immune, endocrine and reproductive systems.

SonNorm Duo is a combined drug containing melatonin, peppermint leaf oil and motherwort herb extract, which has adaptogenic and sedative effect, helps to reduce the nervous system excitability, reduce anxiety and excitement, improve sleep quality; it also normalizes circadian rhythms, including the sleep-wakefulness cycle and adaptation of weather-sensitive people to weather changes. Due to the gradual release of its components, SonNorm Duo has a higher clinical efficacy relative to mono-melatonin-containing drugs, as well as a high safety profile, and can be used with hormone therapy.

Conclusion: The use of the combined drug SonNorm Duo in clinical practice confirms its efficacy and safety in women of reproductive and menopausal age.

Актуальность: Стресс-индуцированная кардиомиопатия (синдром такоцубо) – редкий вид неишемической кардиомиопатии, характеризующийся острым началом и относительно быстрым обратным развитием левожелудочковой систолической дисфункции при отсутствии атеросклеротического поражения коронарных артерий. К ранним осложнениям этой патологии относят остановку сердца, тахи- и брадиаритмии, острую сердечную недостаточность, шок, верхушечное тромбообразование, инсульт, разрыв межжелудочковой перегородки и свободной стенки левого желудочка. Смертность пациентов со стресс-индуцированной кардиомиопатией (синдромом такоцубо) достигает 5,6%.

Описание: Описан редкий случай стресс-индуцированной кардиомиопатии (синдрома такоцубо), осложненной острой сердечно-сосудистой недостаточностью и кардиогенным отеком легких, развившейся в момент оперативного абдоминального родоразрешения в плановом порядке при доношенной беременности, потребовавший участия специалистов мультидисциплинарного профиля для оказания экстренной помощи (акушеров-гинекологов, анестезиологов-реаниматологов, кардиологов, неонатологов, подготовленного среднего медицинского персонала), что способствовало успешному исходу представленного наблюдения.

Заключение: Необходимо помнить о вероятности стрессового повреждения миокарда у пациентов любого профиля, в том числе у беременных женщин, особенно при повышенной тревожности пациентки, предстоящем оперативном вмешательстве.