No 8 (2018)

The data available in the current literature on the role and place of therapeutic plasma exchange in the treatment of thrombotic microangiopathy (TMA) syndrome characterized by thrombocytopenia, hemolytic anemia, microvascular thrombosis in various organs, and by elevated hepatic enzyme levels and multiple organ dysfunction. Data analysis has shown that therapeutic plasma exchange that has a multicomponent effect is pathogenetically justified and essential in the treatment of patients with pregnancy-associated TMA, which makes it possible to considerably reduce the clinical manifestations of the disease, to rapidly decrease the biochemical markers of hepatic and renal failure, to stabilize the blood coagulation and fibrinolytic potential, to prevent the severe forms of TMA, and to save the life of a female patient. Further multicenter studies of the complex pathophysiology of HELLP syndrome and other TMAs associated with pregnancy are required to prove the efficiency of extracorporeal hemocorrection methods.

The data available in the modern literature on the diagnostic capabilities of current clinical and laboratory markers of ovarian reserve undergo systems analysis. The diagnostic capabilities of current clinical and laboratory markers of ovarian reserve, which reflect the primordial pool of follicles and predictors involved in predicting the onset of spontaneous pregnancy and premature ovarian aging, are discussed. To date, there is no single global consensus for the best test to accurately assess the quantity and quality of eggs. It is necessary to conduct full-scale multicenter, prospective, randomized, controlled studies, the results of which would facilitate the consultation of patients and assist a clinician in drawing an individual treatment plan.

A systems analysis of the data available in the literature on the problem of choosing the optimal folate formulation in order to correct folate status in obstetric and gynecologic practice was carried out. There is plenty of evidence that increasing the folate status reduces the risk of neonatal neural tube defects. Higher folate intake through supplementation with folic acid (FA) or 5-methyltetrahydrofolate (L-methyl-THF) is recommended during pregravid preparation and early pregnancy. L-5-methyl-THF has a number of advantages over FA, since it is a physiological compound and has greater bioavailability. 5-methyl-THF is also available as a crystalline form of calcium salt (metafolin) that has the stability required for use as a supplement. When correcting the folate status in obstetric and gynecological practice, it is recommended that a choice should be made in favor of a formulation that has the best bioavailability, as seen in metafolin.

Aim. To investigate the effectiveness of non-invasive prenatal DNA screening (NIPS) for aneuploidy using high-throughput sequencing for the detection of trisomy 21, 18, 13 and fetal sex chromosomes in maternal plasma of women both with and without a history of recurrent pregnancy loss. Material and methods. NIPS using the high-throughput sequencing was carried out and the results obtained from 600pregnant women with recurrent miscarriage (n=270) and uncomplicated obstetric history (n=330). To confirm chromosomal aneuploidy (CA), karyotyping was used. Results. After 12 weeks of gestation, the frequency of CA in each study group was 3.0% and did not differ between women with recurrent miscarriage and uncomplicated obstetric history. The sensitivity and specificity of NIPS in detecting the most frequent CA was 92% and 99%, respectively. Down syndrome was determined with 100% specificity. Conclusion. The study finding showed that NIPS is accurate in screening for fetal CA from early pregnancy, which is especially important in patients with recurrent miscarriage since it spares them from invasive testing thus preventing iatrogenic complications.

Objective. To identify peptide panel allowing to discern different hypertensive disorders in pregnancy. Material and methods. A case-control study was conducted. 64 enrolled women were classified into 4 groups: preeclampsia (PE), chronic hypertension (CAH), PE superimposed on CAH and control. Urine samples derived from each patient were analyzed with liquid chromatography coupled with mass-spectrometry (HPLC-MS/MS). The data obtained were processed using statistical and bioinformatic approaches. Results. For all four groups common typical 36 peptides were identified, which are mainly fragments of collagen (COL1A1;COL3A1, etc.), and one peptide uromodulin (UMOD). For patients with hypertensive disorders (PE, PE superimposed on CAH, CAH) characteristic 34 peptide fragments of collagen (COL1A1;COL3A1, etc.) and alpha-fibrinogen (FGA) were identified. For the group of patients with preeclampsia (PE, PE superimposed on CAH) characteristic panel of 16 peptides were identified: 13-th of which are fragments of the protein alpha-1-antitrypsin (SERPINA1), one peptide is a fragment of alpha-1 chain collagen 1 (COL1A1), 1 - alpha-2-HS-glycoprotein (AHSG), 1 - apolipoprotein A-I (APOA1). Semiquantitative analysis of the data the four groups (PE, PE superimposed on CAH, CAH, the control group) non-parametric tests Kruskal-Wallis and Mann-Whitney test showed the presence of 12 peptides, differentiating at least one pair of groups. Separately, a study was conducted on the peptide profile of urine from a patient with a GAG from the time of diagnosis GAG (32-33 weeks) until delivery (36-37 weeks) in the dynamics. Correlation was established between increased levels of peptides protein SERPINA1(A1AT) and the emergence and increasing severity of PE. Conclusion. In the comparative analysis the panel of 12 peptides which can reliably differentiate hypertensive disorders in pregnant women was formed. Fragments of alpha-1-antitrypsin confirmed their importance as markers of pre-eclampsia suggested by the authors in earlier papers. Demonstrated the dynamics of changes in the peptide profile in the manifestation of clinical signs of PE from the patient to the background of the GAG shows real possibilities of application peptidome urinalysis in clinical practice with the aim of timely diagnosis and predict 'd PE, including PE superimposed on other hypertensive disorders. Further studies are needed to implement the results in clinical practice.

Objective. To compare the antimicrobial activity of vaginal discharge with the nature of bacterial vaginosis, vaginal pH, and microbiological indicators. Subjects and methods. The investigation enrolled 53 pregnant women, of whom 34 were diagnosed with bacterial vaginosis and 19 were with normal vaginal microbiocenosis. The severity of bacterial vaginosis was estimated from the total scores using a combination of clinical symptoms: itching, burning, the nature and amount of discharge, pain during urination, dyspareunia, perianal dermatitis, swelling, hyperemia, and erosive lesions of the vaginal walls. Vaginal discharge samples were examined to determine the antimicrobial activity of the vaginal epithelium. The antibacterial activity of antimicrobial peptides was determined in the groups of pregnant women depending on the nature of clinical symptoms of bacterial vaginosis. Results. Production of the endogenous antibiotics antimicrobial peptides provides adequate protection against infectious agents. The lowered activity of antimicrobial peptides leads to a quantitative increase in the facultative vaginal microflora and to the depletion of the obligate microflora, which contributes to the more pronounced clinical course of bacterial vaginosis. Conclusion. To expand diagnostic parameters in the set of examinations of pregnant women with inflammatory and dysbiotic disorders in the lower reproductive tract, by including the indicators of systemic and local immunity along with microbiological monitoring and an integrated assessment of the vaginal microbiocenosis, will be able to personify therapeutic approaches for each individual patient.

The problem in the prehospital diagnosis of ectopic pregnancy (EP) in women is due to a significant frequency of errors and, as a consequence, delayed hospitalization for surgical treatment. Reducing diagnostic errors mainly in the prehospital stage can improve the quality of care for patients with EP. Objective. To analyze the errors of prehospital EP diagnosis and to optimize the latter. Subjects and methods. The quality of medical care was retrospectively analyzed in 194 patients with EP. By taking into account the identified defects, the authors elaborated an optimized approach to providing outpatient care for patients with EP and evaluated its efficiency in 332patients with suspected EP. Results. Unavailability of β-human chorionic gonadotropin (β-hCG) test results at the first visit is a main defect in medical care for patients with EP at the prehospital stage. The laboratory diagnosis of pregnancy, which complies with established standards and is based on serum β-hCG determination, does not meet the requirements for emergency outpatient care since it does not ensure the availability of the result at the same visit. The optimized approach increases the diagnosis of EP from 27.1 to 76.1% at the first visit. Conclusion. The correct diagnosis made on the day of a patient visit is a significant reserve to reduce severe and complicated cases.

Objective. To assess obstetric and neonatal outcomes of the second half of pregnancy (after 22 weeks) in women with a habitual miscarriage who received or did not receive periconceptional care and therapy with micronized progesterone (a pharmaceutical product of Utrogestan) in the framework of TRISTAN-2 multicenter study. Materials and methods. A total of 743 women who are 22-24 weeks pregnant and diagnosed with habitual miscarriage (2 or more consecutive interruptions of pregnancy in anamnesis) took part in the study. All patients included in TRISTAN-2 study, previously participated in TRISTAN-1 study (TRISTAN-2 study is a continuation of TRISTAN-1 patients’ observation). Of these, 369patients in Group 1 received periconceptional care with micronized progesterone before conception in the luteal phase of their menstrual cycle and during the first half of pregnancy (intravaginally 200-400 mg / day), 374 patients in Group 2 started taking micronized progesterone only after the clinical confirmation of pregnancy and during the first half of pregnancy (intravaginally 200-400 mg / day). All patients underwent micronized progesterone therapy in the second half of pregnancy (intravaginally 200-400 mg / day) with the appropriate indications described in the instructions for the medical use of Utrogestan). The monitoring of patients in both groups was carried out in late pregnancy (starting from 22 weeks 0 days before discharge from the hospital after delivery). The study collected data on the course of the current pregnancy and its outcomes: gestational age at the time of delivery, neonatal outcomes, use of additional medications, complications and hospitalizations during pregnancy, adverse events on the part of the mother and/or fetus/child during the whole period of observation. All medical procedures performed as part of the study were routine and used in everyday clinical practice. Statistical analysis of the collected data was carried out using IBM SPSS 23 software. Results. The main criterion for the therapy effectiveness was the frequency of preterm delivery before 34 full weeks of pregnancy. In Group 1 (patients who underwent periconceptional therapy with micronized progesterone), the incidence of preterm delivery was 8.9% (2.0% of preterm deliveries in the period of 433+6 weeks), in Group 2 (patients who started taking micronized progesterone only after the clinical confirmation of pregnancy) the incidence was 9.6% (1.7% of preterm deliveries in the period of 433+6 weeks) p> 0,05, which corresponds to the general population level in the world. Very early (before 28 weeks) and early (28-30+6 weeks) premature births in the groups were not observed. On this basis, it can be concluded that the use of micronized progesterone in accordance with approved indications is an effective tool for the prevention of preterm delivery in patients at risk of a habitual miscarriage, regardless of previous periconceptional therapy. The frequency and nature of adverse events were statistically comparable in the groups (p> 0.05). Conclusion. The presented results of the study prove the efficacy and safety of the use of micronized progesterone (the pharmaceutical product of Utrogestan) in accordance with the recorded indications in late pregnancy with a habitual miscarriage.

Background. Endometrial polyps (EP) take an important part in the structure of intrauterine pathology and could be associated with abnormal uterine bleeding (AUB), infertility and the risk of endometrial cancer (EC) development. The data concerning EP’s prevalence and combination with other endometrium pathology’s forms in women of different age varies widely. It causes difficulties for understanding the magnitude of the problem and finding solutions for management. The aim. To evaluate the prevalence of EP and other endometrium conditions at different ages. Materials and methods. Based on the study of 4059 histological samples we analysed the EP’s prevalence and association with other intrauterine pathology in women of different age groups. Results. EP was diagnosed in 27.4% of samples. It’s frequency varied from 21.7 to 27.3% in reproductive age and - 45% in postmenopausal women. 19.8% of EP were concomitant with chronic endometritis (CE), 3.7% with endometrial hyperplasia (EH). Conclusions. EP take 1st place in the structure of intrauterine pathology during all age periods. Their prevalence is 2.7 times higher than CE, and 4.5 times higher than EH.

Objective. To evaluate the informative value of a Russian-made fully automated and computerized antenatal fetal monitor that has no analogues. Material and methods. The health status of 792 normally developing fetuses in the second half of pregnancy and 26 fetuses born with different severity of hypoxia confirmed after birth was analyzed in detail. Results. It was found during the investigation that cardiotocography yielded an erroneous result in 5 of the 792 healthy fetuses. An erroneous result was noted in 1 of the 26 fetuses born with different severity of hypoxia. The fetal functional status could be diagnosed correctly in a total of 812 (99.3%) out of the 818 surveyed fetuses. Conclusion. The main distinctive advantages of this monitor are the following: 1. Full automation of information obtained. 2. The high accuracy for fetal functional status evaluation, which approaches 100% (99.3%). 3. The possibility of monitor curve recording at 22-25 weeks’ gestation. 4. Automatic estimation of the length of a survey. 5. The minimum time of an examination is 2 minutes; that of clinical practice is 10 minutes. 6. The possibility of evaluating the fetal status with complete loss of a cardiosignal on the basis of an analysis of its motor activity.

Objective. To investigate the clinical and laboratory protective effects of heparin in Factor VLeiden (FVL) (1691) GA genotype carriers with a marked activated protein C (APC) resistance. Subjects and methods. A single-center randomized controlled study was conducted in 141 pregnant women [the FVL (1691) GA genotype] with APC resistance by an international normalized ratio (INR) of 0.49 or less. The study group patients (n=70) received heparin prophylaxis cycles at 7-8 weeks’ gestation; the comparison groups of pregnant women (n=71) did not use low-molecular-weight heparin (LMWH). Results. During LMWH treatment, there were thrombin generation decreases determined by the thrombin generation test indicators: peak thrombin by 9-11% (p=0.008), endogenous thrombin potential (ETP) by 4-9% (p=0.013), and APC resistance by 9-14% (p < 0.05). The clinical protective effects of heparin were defined as a reduction in the absolute risk of developing preeclampsia by 29.5% (p=0.0003), fetal growth restriction by 23.8% (p=0.002), and preterm births by 12.6% (p=0.024). Conclusion. Prophylaxis with heparin is pathogenetically justified and causes a significant decline in the number of pregnancy complications in FVL (1691) GA genotype carriers with a marked APCresistance (INR 40.49)

The literature data on the study of the microbiota of female genital organs and assess the clinical and microbiological characteristics of the probiotic strain LCR35, used in the treatment and prevention of vaginal infections were analyzed. Biotherapeutic aspects of treatment and prevention of dysbiotic conditions of vaginal microbiota have been analyzed. A comparative evaluation of the characteristics and requirements of lactobacillicontaining preparations with probiotic activity in obstetric-gynecological practice was carried out. The clinical and microbiological advantages of the original probiotic strain Lactobacillus casei rhamnosus Doderleini (LCR35) in the formulation Lactogynal in the treatment and prevention of vaginal infections were noted. The literary review of data the medical use of the culture of Lactobacillus casei rhamnosus Doderleini (LCR35) testifies to the expediency and validity of its use in the mode of two-stage therapy of the dysbiotic conditions of the vagina. Organization and conduct of additional post-registration clinical studies of medicinal product for medical use Lactogynal will strengthen the position of targeted probiotics in the complex treatment and prevention of bacterial and fungal infections of female genital organs.