В данном учебно-методическом пособии представлена схема практического занятия по акушерству для студентов медицинских вузов, обучающихся по специальности «Лечебное дело». Во втором издании учебного пособия дополнен и обновлен раздел о возможностях применения симуляционных методик обучения дисциплине «Акушерство и гинекология», актуализированы подходы к ведению беременности, родов и послеродового периода. Учебно-методическое пособие издано для подготовки к практическим занятиям по дисциплине «Акушерство и гинекология», рекомендовано преподавателям медицинских вузов, студентам медицинского факультета и клиническим ординаторам.

В данном учебно-методическом пособии представлена схема практического занятия по гинекологии для студентов медицинских вузов, обучающихся по специальности «Лечебное дело». Во втором издании учебного пособия дополнен и обновлен раздел о возможностях применения симуляционных методик обучения дисциплине «Акушерство и гинекология», актуализированы подходы к ведению пациенток с гинекологической патологией. Учебно-методическое пособие издано для подготовки к практическим занятиям по дисциплине «Акушерство и гинекология», рекомендовано преподавателям медицинских вузов, студентам медицинского факультета и клиническим ординаторам.

Objective. To examine the association between the carriage of endothelial dysfunction-related gene polymorphisms and recurrent pregnancy loss (RPL). Patients and methods. This case-control study included 87 patients who were divided into two groups. The study group consisted of 65 patients with a history of two or more consecutive pregnancy losses (2 to 11 losses). Primary RPL was detected in 20 patients, secondary in 26, and tertiary in 19. The control group consisted of 22 women with a history of three or more full-term births without episodes of miscarriage. The frequency of polymorphisms of the VEGFA -634G>C and IL6 -174G>C genes was determined by a ready-to-use real-time polymerase chain reaction (RT-PCR) test kits. Results. Carrying the VEGFA -634G>C GC genotype increases the risk of RPL 4-fold (p = 0.0072) and the IL6 -174G>C GC genotype – 3-fold (p = 0.028). Analysis of the impact of combinations of unfavorable genotypes showed that 65.0% of patients with primary RPL, 61.5% with secondary RPL, 63.2% with tertiary RPL, and 9% of healthy controls had a combination of GC VEGFA -634G>C and CC IL6 -174G>C. One of the key environmental factors determining the realization of susceptibility genes is age: the maximum age at the time of the first intended pregnancy was observed in patients with primary RPL (32.6 years vs. 25.5 years in the control group; p < 0.05), with 9% of healthy controls having a combination of two genotypes associated with pregnancy loss. That is, successful pregnancy at a younger age is possible even when carrying multiple risk alleles. The birth interval length is also important for successful pregnancy: a short inter-pregnancy interval allows to carry out the reproductive function during the most favorable period of the reproductive system before the influence of genotypes predisposing to RPL begins. Other environmental factors leading to the realization of carriage of RPL risk alleles include a history of intrauterine interventions and sexually transmitted infections. Conclusion. Study of the VEGFA -634G>C and IL6 -174G>C gene polymorphisms may serve as an effective method to predict RPL. For patients carrying these unfavorable gene polymorphisms, it is especially important to perform the reproductive function in time, i.e., before the realization of environmental factors. Key words: recurrent pregnancy loss, VEGF, endothelial dysfunction, susceptibility genes

Operative vaginal delivery with obstetric forceps is associated with a high risk of maternal and fetal injury. The lack of reliable and up-to-date knowledge about forceps manipulation and its safety creates a fear of using forceps and leads to a gradual loss of skill in the use of the instrument. This article covers the indications for forceps application according to relevant clinical guidelines, systematizes the results of current national and international studies on the benefits and risks of using obstetric forceps for the mother and fetus. Special attention is paid to the comparison of outcomes of operative vaginal deliveries using different instruments and comparison with operative abdominal deliveries with the same indications for surgery. In the conclusion of the analysis, the evidence for the appropriateness of using obstetric forceps to achieve a better perinatal outcome and avoid unwarranted cesarean section and related complications was formulated. Key words: obstetric forceps, vacuum extraction, cesarean section, maternal morbidity, maternal mortality, operative vaginal delivery, perinatal morbidity, perinatal mortality

Objective. To study the role of fibulin-5 (FBLN5) gene polymorphisms in the genesis of cervical insufficiency (CI). Patients and methods. This observational retrospective study included 49 patients with clinical manifestations of CI and 31 patients without history of CI. Four most studied single-nucleotide polymorphisms (SNPs) in the FBLN5 gene were selected: rs2284337, rs2018736, rs2474028, rs12589592. DNA was extracted from whole venous blood, and genotyping was performed by polymerase chain reaction (PCR). STATISTICA 12.0 and SNPstats software packages were used for statistical data processing. Results. It was found that the rs2474028(T) allele of the FBLN5 gene is associated with a risk of developing CI (p = 0.0019). In addition, a comparison of a high-risk CI subgroup and a control group revealed that carriage of the heterozygous rs2018736(A/C) or the heterozygous rs12589592(A/G) genotypes of the FBLN5 gene is protective and reduces the risk of developing CI (p = 0.019 and p = 0.0021, respectively). Conclusion. The presence of single-nucleotide polymorphisms in the FBLN5 gene is associated with the development of CI. Key words: cervical insufficiency, pathogenesis, fibulin-5, FBLN5, SNP

Objective. To determine the risk of development of placental-related disorders of pregnancy in the presence of single-nucleotide polymorphism rs4065 of the urokinase gene in a mother. Patients and methods. The presence of the genetic variant of the rs4065 urokinase gene was determined in venous blood samples using real-time polymerase chain reaction in patients with placental-related pregnancy disorders and in the control group. Results. Associations between the risk of development of placental-related disorders of pregnancy, such as fetal growth resrtiction and pre-eclampsia, and the maternal rs4065 genotype were found. A correlation between the maternal rs4065 genotype and the degree of fetal growth restriction and the severity of pre-eclampsia was identified. The most unfavorable is the presence of the CC genotype. Conclusion. The presence of single-nucleotide substitutions in the maternal urokinase gene is associated with the development of placental-related disorders of pregnancy. Key words: urokinase-type plasminogen activator, angiogenesis, fetal growth restriction, placental insufficiency, pre-eclampsia, SNP

Плацентарная недостаточность (ПН) и ее осложнения — многофакторные заболевания, ведущие к перинатальной заболеваемости и смертности. Урокиназная система задействована в формировании плаценты и может быть рассмотрена как участник патогенеза ПН. Целью работы было исследовать ассоциацию однонуклеотидных полиморфизмов (SNP) генов белков урокиназной системы с развитием ПН, их влияние на экспрессию соответствующих белков в плаценте и ее строение. Обследованы 114 женщин с физиологическим течением беременности и родов и 48 пациенток с преэклампсией и/или задержкой роста плода (ЗРП), 95 новорожденных детей (беременность с преэклампсией и/или ЗРП — 60, физиологическое течение беременности и родов — 35). Проведено генотипирование при помощи ПЦР в реальном времени, морфометрическое и иммуногистохимическое исследования фрагментов плацент. Выявлены ассоциации между развитием ПН и наличием у матери — аллеля C rs4065 (в группе ПН — СС-СТ 64,1%, TT 35,9%, в контрольной группе — СС-СТ 25,6%, TT 74,49%, ОШ (95% ДИ) — 6,83 (2,63–17,79)), аллеля A rs2302524 (GG-GA 20,5%, AA 79,5% против GG-GA 48,1%, AA 51,9%, ОШ (95% ДИ) — 0,27 (0,1–0,71)), у плода — аллеля C rs4065 (СС-СТ 76,4 %, TT 23,6% против СС-СТ 69,6%, TT 30,4%, ОШ (95% ДИ) — 1,37 (0,45–4,17)), аллеля C rs344781 (TT-TC 69,1%, СС 30,9% против TT-TC 95,7%, СС 4,3%, ОШ (95% ДИ) — 5,02 (1,07–23,6)). Многофакторный анализ подтвердил значимость генотипа плода по rs4065. Экспрессия uPA была ниже при ПН (медиана (95% ДИ) — 116,45 (100,5; 128,74) против 126,09 (113,76; 139,19); р < 0,05). Ассоциации SNP c экспрессией белков выявлено не было. Васкуляризация зависела от генотипа матери по rs4065 (стромально- сосудистое соотношение при генотипе CC — 0,17 (0,15; 0,19), CT — 0,18 (0,15; 0,21), TT — 0,23 (0,2; 0,27); p < 0,05). Таким образом, высокий уровень uPA в плаценте и наличие генотипа rs4065 TT у плода носят протективный характер в отношении развития ПН.

Placental insufficiency (PI) and its complications are multifactorial conditions that cause perinatal morbidity and mortality. Since the urokinase system is involved in placentation, it should have a role in PI pathogenesis. The aim of this work was to study the associations between single nucleotide polymorphisms (SNPs) of genes coding for protein components of the urokinase system and PI, as well as investigate their effect on the expression of these proteins in the placenta and placental structure. We examined 114 women with uncomplicated pregnancy and delivery, 48 female patients with pre-eclampsia and/or intrauterine growth restriction (IUGR), and 95 newborns, (pre-eclampsia and/or IUGR: n = 60; uncomplicated pregnancy and delivery: n = 35). Maternal and fetal DNAs were genotyped using real-time PCR. Placenta fragments were subjected to morphometry and immunohistochemistry. We discovered the associations between PI and the maternal C allele of rs4065 (PI group: СС-СТ 64.1%, TT 35.9%; controls: СС-СТ 25.6%, TT 74.49%; OR (95%CI): 6.83 (2.63–17.79)), the maternal A allele of rs2302524 (GG-GA 20.5%, AA 79.5% vs. GG-GA 48.1%, AA 51.9%, OR (95%CI): 0.27 (0.1–0.71)), the fetal C allele of rs4065 (СС-СТ 76.4 %, TT 23.6% vs. СС-СТ 69.6%, TT 30.4%, OR (95%CI): 1.37 (0.45–4.17)), and the fetal C allele of rs344781 (TT-TC 69.1%, СС 30.9% vs. TT-TC 95.7%, СС 4.3%, OR (95% CI): 5.02 (1.07–23.6)). The multivariate analysis confirmed the significance of the fetal rs4065 genotype. In patients with PI, uPA expression was lower (ME (95%CI): 116.45 (100.5; 128.74) vs. 126.09 (113.76; 139.19); р < 0.05). No associations were established between SNPs and protein expression. The degree of vascularization depended on the maternal rs4065 genotype (the stroma-to-vessel ratio for the CC genotype was 0.17 (0.15; 0.19); for the CT genotype, 0.18 (0.15; 0.21) and for the TT genotype, 0.23 (0.2; 0.27); p < 0.05). We conclude that high placental uPA and the presence of the fetal TT rs4065 genotype are protective against the risk of PI.

Background: Blood of pregnant women contains cell-free fetal DNA (cffDNA), which is widely used in non-invasive prenatal diagnosis. The modern laboratory equipment market provides huge variety of commercial kits for isolation of circulating nucleic acids, but unfortunately none of them are standardized for isolation of cffDNA, which is a crucial step for success of subsequent analysis. Aim: To compare DSPVK and CNAK in terms of cffDNA, cell-free total DNA (cftDNA) yield and resulting cffDNA fraction, as well as to try to explain the possible difference between the efficacy of these kits. Methods: Peripheral blood samples were collected from 18 healthy pregnant women (6th-14th week of pregnancy) and from 12 healthy unpregnant subjects. cftDNA was isolated using QIAamp Circulating Nucleic Acid Kit (CNAK) (Qiagen, Germany) and QIAamp DSP Virus Kit (DSPVK) (Qiagen, Germany) from 1 ml of plasma of each sample. Methylation-sensitive restriction was carried out to isolate cffDNA. Yield of cffDNA and cftDNA was quantified using digital PCR. To explain the difference in resulting efficacy of these two kits PCR inhibitors analysis was performed, as well as the optimal plasma input for DSPVK was investigated. Results: Yield of cffDNA using CNAK was statistically significantly higher than using DSPVK (167.62 (125.34-192.47) vs 52.88 (35.48-125.42) GEq/mL, p < 0.001). The same applies to cftDNA yield, CNAK appears to be statistically significantly superior to DSPVK (743.42 (455.02-898.33) vs 371.07 (294.37-509.89) GEq/mL, p < 0.001). cffDNA fraction using CNAK was also higher than using DSVPK (24.75 (14.5-31.53) vs 14.20 (6.88-25.83) %, p = 0.586), although the difference was not statistically significant due to inconsistency of DSPVK results from sample to sample. PCR inhibitors analysis uncovered increased amount of PCR inhibitors in CNAK cftDNA solution, compared to DSPVK (p = 0.002). Usage of 0.5 mL of plasma for cftDNA extraction with DSPVK over 1 mL demonstrates almost 1.8 times higher cftDNA output (p = 0.028), which suggests that this kit is not so viable for volumes of plasma larger than 0.5 mL. Conclusions: We recommend CNAK over DSPVK for quantitative analysis of cffDNA. Nevertheless, DSPVK is definitely suitable for qualitative analysis as well as for research with limited budget, since it is almost 3 times cheaper than CNAK.