No 3 (2020)

The review article outlines the legal framework for the regulation of surrogacy as one of the assisted reproductive technology (ART) programs and highlights the shortcomings and difficulties of the legal framework in this matter. It should be noted that the problem of infertility treatment, including ART techniques, is now one of the priority state programs. Surrogacy is one of the ART programs, and, despite the insignificant contribution of this program to the country’s demography, the medical and ethical aspects of using this infertility treatment option cannot be underestimated. Moreover, it is necessary to improve the regulatory framework governing the institution of surrogacy, which will ensure the protection of participants in these legal relations.

Gut microbiota regulates many processes occurring in the intestine, affecting its immune and endocrine functions, the absorption of substances. There is a hypothesis that intestinal dysbiosis plays a role in the pathogenesis of gestational diabetes mellitus (GDM). The paper reviews the data available in the literature of the world’s leading reference bases (MEDLINE, EMBASE, Cochrane) on changes in the microbiota and microbiome in women with GDM. An analysis of the f indings has revealed numerous correlations between specif ic bacterial taxa and changes in the metabolic process in the body during pregnancy. The possible mechanism for the development of GDM is the occurrence of inflammation in the intestinal wall in the presence of gut dysbiosis, which results in barrier dysfunction of enterocytes and in an increase in their permeability and endotoxemia. This leads to overexpression of proinflammatory cytokines and increased insulin resistance. The use of probiotics is a method to correct gut dysbiosis. The administration of probiotics is shown to reduce subclinical inflammatory responses and to restore the balance of absorbed substances. It is probable that this method may also be relevant to the therapy of hyperglycemic states during pregnancy.

The safety of menopausal hormone replacement therapy (MHT) has long been of great interest to a wide range of medical professionals. Currently, there is an abundance of research evidence for the benefits and harms of MHT. Still, it is often the subject of misrepresentation and wrong generalizations regarding risks that continue to form a distorted perception of MHT. Often there is a tendency to overestimate the harms, causing unnecessary and unwarranted concern among doctors and patients. This review provides an analysis of available research evidence for the association between MHT and the risk of developing venous thromboembolism and breast cancer. The issues of managing cardiometabolic risk in postmenopausal women, tailoring treatment for individual patients, and the duration of MHT are also covered. A complete analysis of harm-benefit tradeoffs of MHT tailored for a particular woman should include an assessment of vasomotor symptoms and quality of life, potential beneficial effects of MHT on overall health, including cardiovascular and bone health, prevention of osteoporotic fractures, cognitive impairment, etc.

Objective. To investigate clinical and laboratory criteria for the “reference point” of the progression of severe preeclampsia (PE) into a life-threatening condition with a different outcome (near miss or maternal death). Subjects and methods. The investigators conducted a multicenter study conducted through an examination of 18,130 records of severe PE-complicated labors and deliveries. The study period was January 1, 2013 to December 31, 2018. There were 27 Moscow participating centers. A total of 122 delivery records were selected from women with PE and life-threatening conditions that led to near misses in 100 patients (a near miss group) and to maternal deaths in 22 women (a MD group). Results. Within less than 24 hours, severe PE can develop into a life-threatening condition and result in MD in women aged 18-45 years after natural conception at 24 weeks’ gestation (up to 34 weeks in 50%), with a blood pressure of less than 160/100 mm Hg, the baseline level of creatinine from 33.0 to 349.5pmol/E and its increase by 9.47 times, that of platelets from 10.0 to 362.0109/E and their increase by 0.04-1.0 time, that of bilirubin from 5.0 to 104.0 pmol/E and its increase by 1.56-24.63 times, that of AET from 8.7 to 807.0 U/E and its increase by 1.0-318.8 times, that of AST from 15.0 to 1238.0 U/E and its increase by 1.68-429.53 times, that of EDH from 568,4 to 2315,0 U/E and its increase by 2.79-9.89 times; moreover, 22.73% of cases can have no pathognomonic complaints and have a satisfactory general condition. Conclusion. PE should be considered as a condition with much more variability in outcomes, such as pre-stroke, pre-HEEEP syndrome, pre-hepatic, prerenal, or multiple organ dysfunctions, etc. It is extremely difficult to predict MD. PE can manifest as a life-threatening condition within a few hours, possibly in the absence of elevated blood pressure. Critical liver fa ilure competes by signif icance in the risks of MD with high blood pressure. The reference point from the diagnosis of PE to a life-threatening condition may be accompanied by the values of clinical and laboratory markers, which do not meet not only the criteria for near miss, but also severe PE. Timely delivery tactics is a fundamental measure for the prevention of life-threatening complications and MD.

Aim. To investigate serum levels of DcR3 in women with threatened miscarriage, recurrent miscarriage, and healthy pregnancy. Materials and methods. The study comprised 75 pregnant women, including 46 patients with a threatened miscarriage before12 weeks’ gestation and recurrent miscarriage (study group) and 29 women with a first-trimester pregnancy and no signs of threatened and recurrent miscarriage (control group). The serum level of DcR3 was determined by enzyme immunoassay. Results. Serum levels of DcR3 above 0.87 pg/ml are indicative of the development of placental insufficiency in the second half of pregnancy, both in women of the study and control groups. Conclusion. Elevated serum DcR3 levels in early pregnancy lend support for further studies aimed at predicting placental insufficiency.

Objective. To determine cardiotocographic (CTG) criteria for the risk of hypoxic ischemic encephalopathy (HIE) varying in severity. Subjects and methods. The prospective case-control study included 180 female patients and their newborn infants. After the birth of a baby, the CTG curves were interpreted by a specialist. Results. A pathological CTG curve was predominant in the study patient group (66.7% vs. 16%; p < 0.0001); a suspicious CTG curve was prevalent in the control group (48.6% vs. 16.7%; p < 0.001). A detailed analysis of CTG data showed the higher frequency of late decelerations in the study group (p <0.001); the presence of variable decelerations did not lead to the emergence of HIE. Bradycardia below 100 beats increased the risk of HIE (p < 0.001). Tachysystole was diagnosed significantly more often in the study patient group (44.4% vs. 12.5%, p < 0.001). No relationship was found between the type of a CTG curve and the grade of neonatal HIE. There were 10(4-14.25), 7(1.75-25.25), and 45(38-52) decelerations in grades 1, 2, and 3 HIE, respectively (p = 0.02). The duration of a CTG curve with decelerations was 36.1 (20.4), 40.8 (24.9), and 59.0 (32.5) min, respectively (p = 0.05). The severity of HIE increased with a larger number of late decelerations (p = 0.03). Conclusion. This paper shows the relationship between the CTG curve parameters and the risk of neonatal HIE. The risk factors for the development of HIE are a pathological type of CTG; a decrease in basal heart rate and variability; late decelerations; bradycardia, and tachysystole. The clinical manifestations of neonatal encephalopathy with a normal or suspicious type of CTG in childbirth may suggest that there are causes of HIE, which are unassociated with intranatal fetal hypoxia.

Objective. To study the levels of certain acute-phase proteins (α2-macroglobulin (α2-MG), α- antitrypsin (α-AT)); lactoferrin (LF) and albumin (ALB), cytokines (tumor necrosis factor-α (TNF-a); interleukin-6 and 8 (IL-6 and IL-8), interferon-γ (IFN-γ), as well as total protein (TP) in the infertile patients’ serum and follicular fluid as possible diagnostic markers for grades 1-2 external genital endometriosis (EGE), as well as in the prognosis of in vitro fertilization (IVF). Subjects and methods. Examinations were made in 32 infertile patients with grades 1-2 EGE (a study group) and in 37 healthy women with male factor infertility (a control group) who had undergone IVF treatment for fertility recovery in the Medica-2 Clinic, “Mother and Child” Group of Companies, Novokuznetsk (Russia). The investigators measured the levels of α2-MG and α-АТ by quantitative rocket immunoelectrophoresis; LF and cytokines by enzyme immunoassay; ALB and TP by biochemical assays (based on bromocresol green and biuret reagents, respectively). The results obtained were statistically analyzed in a free software environment for statistical data processing using the R version 3.4. Results. The infertile patients with grades 1-2 EGE versus the women in the control group were noted to have elevated serum levels of acute-phase proteins (a2-MG, a-AT, and ALB), TP, and IFN-γ. The specific feature of the composition of follicular fluid in this patient group was an increase in the concentration of IFN-y and a decrease in LF and IL-8. The serum ALB concentration above 47.5 g/l on the day of follicle puncture in patients with grades 1-2 EGE is an unfavorable background for the occurrence of pregnancy and is associated with the negative outcome of the IVF program. Conclusion. The increased concentrations of acute-phase proteins and cytokines (α2-MG, α-АТ, and IFN-γ), and TP in the blood of infertile women with grades 1-2 EGE can serve as additional diagnostic markers of the disease. The serum albumin level above 47.5 g/l on the day of follicle puncture was associated with the negative outcome of the IVF program in 80% of patients with grades 1-2 EGE, which allows one to recommend that this protein be identified as an additional criterion for predicting the effectiveness of IVF programs in order to expand indications for cryopreservation or delayed embryo transfer in more favorable conditions.

Objective. To analyze the time course of changes in quality-of-life (QoL) indicators in women with deep infiltrating endometriosis (DIE) before and after surgical treatment. Subjects and methods. The investigation enrolled 93 women with DIE who underwent surgical treatment at the Surgical Department, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, in 2017 to 2019 (a study group); 47 of whom completed the study in 2019, and 31 women without endometriosis (a control group). The SF-36 questionnaire was used to assess QoL in the patients at admission to hospital and 6-8 months after surgical treatment. According to the location of a DIE focus, the study group patients were divided into four subgroups, by using the Enzian classification. QoL indicators in the study group patients were comparatively analyzed according to the size of the largest focus, the presence of infertility, and surgical interventions in the history of patients. Results. The study confirmed that DIE significantly affected all components of the women’s QoL. The localization of the lesion and its extent had no considerable impact on QoL. Statistically significantly higher indicators were found on the scales of social functioning, vital activity, pain intensity (PI), and physical functioning (PF) in women with complaints of infertility. Comparative characterization of QoL indicators in women with a history of surgical treatment revealed that the indicators were statistically significantly higher (p < 0.05) on the scales of PI, PF, and a physical health component. Surgical treatment leads to an improvement in all QoL indicators in women with DIE at 6-8 months postsurgery. There were no statistically significant differences on the scales of overall-health self-assessment, PF, and role emotional functioning. Conclusion. DIE leads to a significant decrease in all QoL indicators in women, regardless of the location of a focus and its sizes. QoL in women with DIE, the main complaint of which is infertility, is higher than that in those who have an extensive clinical symptomatology of the disease, but do not suffer from infertility. Surgical removal of foci is an effective method with a long partial effect; however, it should be likely to be supplemented with psychotherapy.

Objective. To develop a computer program for the diagnosis of polycystic ovary syndrome (PCOS) in reproductive-aged women. Subjects and methods. The investigation enrolled 200 women aged 18 to 35 years, who were examined using clinical, anamnestic, laboratory, ultrasound, and statistical studies: Group 1 consisted of100 women with PCOS; Group 2 included 100 women without PCOS. Results. Statistically significant differences were found between the main indicators characterizing the ovarian reserve in reproductive-aged women with PCOS and in healthy ones. Based on the obtained information base, a computer program was developed using the logistic regression method for the diagnosis of factors and the identification of diagnostic markers for PCOS; the program was tested using an independent sample. The sensitivity and specificity of this method to diagnose PCOS were 70.9% and 75.7%, respectively. The computer program “Clinical, anamnestic, laboratory, and ultrasound diagnosis of PCOS” was developed and registered (State Registration Certificate for Computer Program No. 2019662249; the state registration date in the Computer Programs Registry was September 9, 2019 in the Federal Service for Intellectual Property, Moscow). Conclusion. The program “Clinical, anamnestic, laboratory, and ultrasound diagnosis of PCOS”, which is based on the identification of clinical and anamnestic factors, laboratory and ultrasound markers, can be recommended for routine use for the diagnosis of PCOS and a more differentiated approach to implementing therapeutic measures.

Aim. To investigate serum levels of lactoferrin (LF), alpha-2-macroglobulin (a2-MG), alpha-1-antitrypsin (a1-AT), and albumin and their association with neonatal outcomes in pregnant women with preterm prelabor rupture of membranes (PROM). Materials and methods. This study tested serum samples from women with PROM at 24-33 weeks’ gestation, who gave birth to preterm infants without signs of intrauterine infection (IUI) (n = 35), mild IUI (n = 30) and severe IUI (n = 28). A control group comprised 27 healthy women who were tested at 24-33 weeks’ gestation. Serum samples were tested for LFconcentration using ELISA; a2-MG, a1-ATwere determined by a quantitative rocket immunoelectrophoresis assay and albumin by the biochemical method. Results. Women with PROM, regardless of newborns’ health status, had statistically signif icantly higher serum levels of LF and lower levels of albumin than women in the control group. Serum levels of a2-MG and a1-AT in pregnant women with PROM, who gave birth to babies with no signs of IUI, did not differ from those of healthy pregnant women. But they were significantly higher in mothers of neonates with mild forms of IUI and, on the contrary, signif icantly lower in mothers of neonates with severe IUI. The discriminant analysis showed that in a pregnant woman with PROM, the most sensitive prognostic marker for IUI in the fetus and newborn was the serum level of a2-MG. Serum levels of a2-MG ranging from 2.2 to 3.0 g/l were 86% predictive of the birth of a child without IUI; a2-MG level>3.0 was 85% predictive of the birth of a child with a moderate IUI; a2-MG level <2.2 g/l was 86% predictive severe generalized forms of IUI in a newborn. Conclusion. Testing for serum levels of LF, a2-MG, a1-AT, and albumin in pregnant women with PROM can be used to predict their babies’ health status in the early neonatal period.

Objective. To determine the composition and survival of the cellular component of breast milk under various conditions of its single and double pumping and storage. Materials and methods. Eighty-six breast milk samples were collected using a Symphony Medela single (n = 63) or double (n = 23) clinical breast pump. Each sample was divided into two halves and stored for 72 hours when it was cooled to 4°C or room temperature. The fractions of living cells were assessed at 4, 24, and 72 hours after breast milk expression. Flow cytofluorometry was used to determine the expression of specific surface and intracellular markers. Results. The total number of cells in breast milk did not depend on the method of its expression, gestational age, or number of fetuses; the median was about 80,000 cells per ml. The main milk cell populations were epithelial cells and white blood cells; vimentin-positive stromal cells were a minor population. The storage of breast milk, regardless of its expression method, led to a gradual decrease in the number of living cells due to the partial death of short-lived leukocyte subpopulations. After 4 hours, about a third of all cells remained alive; cooling the milk to +4°C could prolong the period of this level of cell survival. Moreover, this effect was more pronounced in the samples obtained using a double clinical breast pump. Conclusion. The total number of cells in breast milk does not depend on its expression method, gestational age, or number of fetuses. To preserve the cellular component of the expressed breast milk, the latter can be stored at room temperature for the first 4 hours when it was cooled to +4°C for 24 hours; in this case double pumping has some advantage over single pumping.

Objective. To assess and analyze the results of 6-68-month treatment with dienogest 2 mg in patients with adenomyosis. Subjects and methods. Sixty-two reproductive-aged patients diagnosed with adenomyosis received therapy with dienogest 2 mg for 6 months, of whom 24.2% continued to take the drug for a longer period. Results. Diffuse adenomyosis was observed in most (87.1%) patients; focal or nodular adenomyosis was seen in 24.2% of patients. During a 6-month dienogest treatment cycle, 53.4% of patients showed a decrease in pain intensity, 31 % had complete pain relief; 70.7% of patients had significant uterine volume reduction. All the patients were noted to have a decrease in the intensity, frequency, and duration of bloody vaginal discharge. Conclusion. The authors’ own studies have established that the use of dienogest eliminates pain and abnormal uterine bleeding and decreases uterine volume in most patients. The therapy is characterized by good tolerance and can be used for a long time.

Objective. To evaluate the effectiveness of a personified approach to treating bacterial vaginosis and its concurrence with vulvovaginal candidiasis, by using the results of clinical and laboratory studies. Subjects and methods. The investigation enrolled 259 female patients aged 18-35 years who were divided into two groups. Group 1 included 174 (67.18+2.92%) patients with verified bacterial vaginosis. Group 2 consisted of 85 (32.82+2.92%) patients with bacterial vaginosis concurrent with vulvovaginal candidiasis. The diagnosis was verified on the basis of clinical (the type of complaints; gynecological examination) and laboratory (bacterioscopy; femoflor-16 real-time polymerase chain reaction, and vaginalpH-metry using a colposcopic test) studies. Results. The authors’findings suggest that the presence of bacterial vaginosis requires a mandatory test for fungal pathogens (C. albicans et non albicans). The concurrence of bacterial vaginosis and vulvovaginal candidiasis requires careful study of the vaginal microbial landscape and subsequent use of combination antibiotic therapy for both nosological entities. Personalized treatment can act upon aerobic and anaerobic bacteria found in higher titers and upon the fungal representatives of the genus Candida. In the authors’ opinion, combined antimicrobial therapy in conjunction with antimycotics eliminates a vaginal inflammatory process and normalizes the ratio of the anaerobic, aerobic, and mycotic spectrum, including the disappearance of A. vaginae, G. vaginalis, and C. albicans. The next stage of therapeutic measures in this study was the correction of vaginal biocenosis. The normalized pH values in the vagina were an indicator for its ecosystem restoration. Conclusion. In addition to routine examinations, the diagnosis of bacterial vaginosis or the latter concurrent with vulvovaginal candidiasis requires that a study of the vaginal microbial spectrum by Femoflor-16 polymerase chain reaction should be included into a package of diagnostic measures. In addition to its diagnostic value, real-time polymerase chain reaction allows for objectively monitoring the results of therapeutic measures that are advisable to be implemented in several steps, including a combined scheme of antimicrobial therapy and vaginal biotope-restoring drugs.

The physiological extinction period of ovarian function is often accompanied by a set of symptoms that substantially worsen the quality of life in women. During and after menopause, the risk of developing a number of somatic diseases increases. Menopausal hormone therapy is an optimal way to correct disorders characteristic of the climacteric syndrome. If it is impossible to perform this type of treatment for objective and subjective reasons, there are alternative therapies. The use of a complex of vitamins, trace elements, and plant substances also effectively prevents the manifestation of the climacteric syndrome.

Background. A near-miss (NM) woman is a pregnant or puerperal woman in the critical condition - near death during pregnancy, childbirth, or within 42 days after delivery and who has survived the specified period. The management of obstetric patients who are on the verge of life and death (near miss) always presents great difficulties and requires a multidisciplinary approach, the use of modern diagnostic and treatment methods, and the mobilization of significant material investments. Analysis of obstetric near misses is the subject of a systematic study, which can assess the quality and level of organization of the work at the health care facilities providing specialized obstetric/gynecological care. Case report. The paper analyzes the management and treatment of a patient from the near-miss category with HELLP syndrome, sepsis, secondary thrombotic microangiopathy, and acute kidney injury, which are manifested after operative delivery. Conclusion. The timely and rapid routing of a patient to a third-level obstetric health care facility, the use of modern high-tech diagnostic and treatment methods contributed to the preservation of life in the patient and her hospital discharge in satisfactory condition.

Background. The issues unveiling the features of the course of familial Mediterranean fever (FMF) concurrent with genital tuberculosis and their effects on fertility and pregnancy have recently become particularly relevant due to the spread of the disease outside the Mediterranean Basin. Description. Foreign and Russian studies on this topic were analyzed. The authors’ clinical example demonstrates the successful experience in recovering fertility in a 36-year-old female patient with infertility lasting 16 years. A relationship was found between long-term pelvic inflammatory diseases and the development of hyperplastic processes and ectopic pregnancy. Conclusion. The phenotypic heterogeneity of FMF, comorbidity, and low compliance are the reasons for delayed diagnosis and restoration of fertility.