No 4 (2018)

Objective. To present an analysis of the data available in the literature on the role of extracellular fetal DNA (fDNA) in predicting the great obstetric syndromes. Material and methods. Literature sources published in databases, such as Pubmed and Scopus, were sought. Results. There is evidence indicating that increased maternal blood DNA levels can be used as a predictive marker for pregnancy complications, such as preeclampsia, preterm birth, and fetal growth retardation. The most likely mechanism for increasing maternal blood fDNA is the strengthening of apoptotic, necrotic, and inflammatory processes in the placenta. However, not all studies confirm that there is a relationship between the development of the great obstetric syndromes and higher fDNA concentrations. Conceivably, the contradictions are due to the use of a number of procedures to determine fDNA, which limit sampling by sex and rhesus factor. Also, there is no consensus on the time when its concentration starts to increase; the influence of confounding factors has not been investigated. Conclusion. Maternal blood extracellular fDNA is a promising marker for predicting the great obstetric syndromes. There is a need for further investigations, by using the procedures that do not limit sampling and by taking into account the factors that influence the maternal blood concentration of extracellular fDNA.

Objective. To carry out a systems analysis of the data available in the literature on current opportunities for diagnosis and management tactics in patients with chronic cervicitis (CC), by using the results of clinical, colposcopic, morphological, and molecular genetic examinations. Material and methods. The paper reviews 37 Russian and foreign articles from Pubmed and Medscape resources, which have been published since 2012. Results. The literature describes the clinical course of CC, current diagnostic methods aimed at identifying the cause of inflammation, and the differentiated choice of therapy in relation to the etiological factor and the degree of a cervical lesion. Conclusion. The use of current diagnostic and treatment techniques will be able to prevent the chronicity of the process, complications and to avoid overdiagnosis of the degree of a cervical lesion and unfounded invasive procedures.

Objective. To study the significance of detoxication genes’ polymorphisms in preeclampsia development and to create preeclampsia prediction model. Materials and methods. 241 patients who were delivered in Federal State Budget Institution “Research Center for Obstetrics, Gynecology and Perinatology” Ministry of Healthcare of the Russian were involved in the study. All patients were divided into 3 groups: 1А group (43 women) - patients with early-onset preeclampsia (developed before 34 weeks of gestation), 1B group (49 women) - patients with late-onsetpreeclampsia (developed after 34 weeks of gestation), 2 - control group (149 women). We conducted a cross-sectional study in parallel groups: genetic analysis in patients with preeclampsia and patients with normal pregnancy. Genotyping PCR method was performed with melting curve analysis, modified method of «adjacent probes» («kissing probes») by means of commercial test system «Scientific-Production Association (NPO) DNA-Technology ООО» (Limited Liability Company), Russia. Multifactorial analysis was performed for early-onset and late-onsetpreeclampsia individual risk assessment based on genetic, clinical and anamnestic risk factors. Results. We developed an individual risk assessment formula of early-onset and late-onset preeclampsia development based on multifactorial analysis' data, clinical and anamnestic risk factors. Age of patients, BMI, CYP1A1 (rs4646903) polymorphism, a history of preeclampsia and pelvic inflammatory diseases have a great impact on probability of early-onset preeclampsia development. We found that detoxication genes’ polymorphisms could be referred to potential pathogenetic factors of preeclampsia development. Detoxication genes’ polymorphisms (CYP1A1 и GSTP1) are more typical for pregnancy complicated by preeclampsia in comparison to normal pregnancy. This fact proves that detoxication genes’ polymorphisms (CYP1A1 и GSTP1) could be used as preeclampsia development predictors. Conclusion. We investigated 16 single nucleotide detoxication genes' polymorphisms in healthy pregnant women and in patients with early-onset and late-onset preeclampsia. We found significant association of several genes with early-onset and late-onset preeclampsia development. Some of these genes proved to be significant in multifactorial analysis and were used in the creation of a model of individual risk assessment of preeclampsia development.

Different factors caused by both equipment and the course of surgery (conditions under which the operation is performed, the location of incision, the characteristics of suture material, the type of surgical suture, and the amount of blood loss), by the course of the postoperative period, and the peculiarities of repair of damaged tissues influence wound healing of the uterus during cesarean section. Objective. To establish the value of premature amniorrhea and uterine inertia as predictors of impaired myometrial repair after cesarean section, by using clinical and morphological analyses. Subjects and methods. The investigation enrolled 129 patients who had given birth via cesarean section. Of them, 44 patients had delivery before birth activity, 85 during the first stage of labor. 49 and 80 women delivered before and after amniorrhea, respectively. During cesarean section, uterine tissue was taken from the upper edge of the wound after uterine incision. The myometrial biopsy specimens obtained during cesarean section were morphologically and immunohistochemically examined. The patients were divided into 4 groups according to the level of birth activity and the preservation of amniotic fluid at the time of cesarean section. Group 1 included patients with regular labor activity and amniorrhea at the time of caesarean section; Group 2 consisted of those with labor activity in the presence of whole amniotic fluid; Group 3 comprised those without birth activity in the presence of whole amniotic fluid; Group 4 included patients with premature amniorrhea without uterine contractions. 36 cases (9 in each group) were selected by random sampling for morphological and immunohistochemical examinations. The biopsy specimens were fixed in 10% neutral formalin and embedded in paraffin. The serial paraffin-embedded sections underwent histological examination and immunohistochemical tests for the following markers: TGF-p, VEGF, MMP2, TIMP1, types I and III collagen, TNF, and PDGF. Results. The morphological and immunohistochemical analyses revealed the most pronounced signs of myometrial damage during cesarean section in Group 4 patients having premature amniorrhea without uterine contractions. There were decreased VEGF, PDGF, MMP2, and TIMP levels and simultaneously increased TNF-a expression in leiomyocytes, vascular endothelium, and myometrial stromal cells. The findings may indicate the relatively lower reparative potential of the myometrium and the increased readiness for an inflammatory response in the group of women undergoing cesarean section in the presence of premature amniorrhea without uterine contractions. Conclusion. Clinical, morphological, and immunohistochemical analyses have revealed differences in the myometrial status in relation to typical clinical factors, such as amniorrhea and birth activity. Wound healing occurs under the influence of growth factors and the ratio of expression levels for growth factors can vary in different pathological conditions. The reduced expression of VEGF, MMP2, TIMP, and PDGF and the increased expression of TNF in the group having amniorrhea without uterine contractions (P-B+) suggest that there are pronounced inflammatory processes and impaired myometrial repair with the longer latency period in the absence of labor activity, which may refer these women to a group at risk for incompetent scar formation.

Objective. To discover peculiarities of the lipid composition of neoplastically transformed and adjacent cervical epithelium with HPV-associated diseases. Material and methods. The study included 41 patients with neoplastic transformations of the cervical epithelium, caused by human papillomavirus, who applied to outpatient department of Federal State Budget Institution “National Medical Research Center for Obstetrics, Gynecology and Perinatology” Ministry Of Healthcare of the Russian Federation. А biopsy of the cervix uteri (strictly according to the indications for biopsy) with subsequent histological examination of the biopsy specimens and analysis of their lipid composition were performed in all women, included in the study. Qualitative and quantitative assessment of biopsy samples lipid extracts was performed by mass spectrometry with electrospray ionization. Lipids of five classes were identified: phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, di - and triglycerides. The obtained experimental data were analyzed using the multivariate OPLS-DA method. Results. A statistically meaningful change in the levels of lipids, such as phosphatidylcholines (PC 32:0, PC 34:1, PC 36:4, PC 34:0, PC 38:4), phosphatidylethanolamines (PE 0-46:0, LPE 46:0, PE 0-48:0, LPE 48:0, PE O-46:1) and sphingomyelins (SM 34:0, SM 42:2)was identified in cervical tissues with neoplastic transformation, caused by human papillomavirus. Conclusion. This study revealed significant changes in the content of several glycerophospholipids and sphingo-lipids in neoplastically transformed tissues of the cervix uteri compared to adjacent normal tissues. Found lipids can be used as a part of the prognostic panel to predict the course of cervical neoplasias in the direction of regress or malignancy.

Objective. To investigate the effectiveness of assisted reproductive technology (ART)programs in late reproductive-aged (LRA) patients undergoing preimplantation genetic screening (PGS). Subjects and methods. The prospective cohort study enrolled 160 LRA patients (aged >35 years) with infertility of different genesis who were stratified according to PGS: Group 1 included 87 LRA patients who had not undergone PGS; Group 2 consisted of 73 LRA patients who had undergone PGS. The latter was performed by fluorescence in situ hybridization (FISH) or array-based comparative genomic hybridization (aCGH) on day 3 or day 5 of embryo culture, respectively. Results. In LRA patients who had undergone PGS, the chances of getting pregnant were 2.1 times higher and those of live birth were 2 times higher than in LRA patients who had not undergone PGS (OR for pregnancy = 2.1 (95% CI = 1.04; 4.2); OR for live birth = 2.0 (95% CI = 0.98; 4.1)). In vitro fertilization (IVF) with PCS was most effective (by 2.6 times) in a group of patients aged 36 to 39 years. The most effective method of PGS was aCGH on day 5 of embryo culture, which can enhance the efficiency of ART programs by 3.1 times in LRA patients. Conclusion. IVF/PGS in LRA patients aged 36 to 39 years is a technique that can increase the probability of pregnancy and live birth, by selecting euploid embryos.

Objective. To study the prevalence of HPV (human papillomavirus) types in patients with squamous intraepithelial lesions (SIL) of different severity and cervical cancer in comparative perspective. Subjects and methods. This prospective study included 145 women aged 18 to 49 years. The survey consisted of: collecting complaints, anamnesis, gynecological status, conducting extended colposcopy, molecular biological methods (multiplex PCR with detection results in real-time for quantification and typing of HPV 21 types), cytological examination, histological analysis of biopsy material. 5 groups were formed including 145 women: 31 patients (21,3%) - NILM (I group), 30 patients (20,6%) - chronic cervicitis (histologically confirmed) (group II), 37 patients (22,7%) - LSlL (III group), 31 patients (21,3%) - HSIL (IV group ) and 14 patients (9,6%) - cervical cancer (V group). Results. The most significant risk factors for cervical intraepithelial lesions are: early sexual initiation, great number of sexual partners (>4), sexual transmitted infections (STI) history. The most frequent HPV types were 16, 31, 33 and 51 types. We demonstrated that HPV type 16 was significantly more prevalent in the group with HSIL and squamous cervical cancer compared to group II (chronic cervicitis) and group III (LSIL). HPV31 and 33 types are more prevalent in the group with HSIL. According to our results, there is the prevalence of the group A9 HPV in women with LSIL, HSIL and cervical cancer compared to group II (chronic cervicitis). Conclusion. Our results demonstrate the key role of A9 HPV group in the development of premalignant and malignant cervical disease. It should also be noted that in patients with LSIL in addition to A9 HPV group there is a trend to increase the incidence of HPV groups A7, A10, A5.

Objective. To assess the results of abdominal ultrasonography (USG) and f ibrogastroduodenoscopy (FGDS) in pregnant and non-pregnant women with pancreatobiliary diseases. Subjects and methods. The investigation enrolled 260 women who were divided into three clinical groups. Group 1 (a study group) consisted of 95 pregnant women with pancreatobiliary diseases; a comparison group included 71 non-pregnant women of reproductive age who were treated in a surgical hospital for pancreatobiliary diseases; a control group comprised 94 women without pancreatobiliary diseases. Results. Diagnostic USG more frequently detected hepatic ductal changes among the women in the study group (54.6 and 29.4%, respectively; p < 0.001) and diffuse pancreatic enlargement among those in the comparison group (63.2 and 44.1%, respectively; p < 0.01). Conclusion. USG and FGDS are valuable diagnostic techniques for detecting pancreatobiliary diseases in pregnant and non-pregnant women.

Objective. To optimize treatment for endometrial hyperplastic processes (EHP) concurrent with adenomyosis. Subjects and methods. Sixty-five patients with recurrent EHP concurrent with grade 1 adenomyosis were examined and treated using up-to-date diagnostic and therapeutic techniques. Results. The outcome measure is radical removal of pathologically altered tissues, the absence of recurrences, and the presence of hypo- or amenorrhea. At 6 months after surgery, amenorrhea was found in 49 (75.4%) patients; hypomenorrhea was noted in 16 (24.6%). Patients with amenorrhea were diagnosed with grade 1 adenomyosis with endometrial penetration of <1-2 mm. In patients with hypomenstrual syndrome, grade 1 adenomyosis was more pronounced and the depth of endometrial penetration reached 3-4 mm, as evidenced by biopsy. Conclusion. The concurrence of recurrent EHP and grade 1 adenomyosis requires vaporization or resection technology during drug therapy, which will be able to improve the efficiency of the treatment performed. Hysteroscopic endometrial destruction with short-duration surgery and anesthesia, reduced hospital length of stay, a shorter rehabilitation period, and a rapid recovery of working capacity, which is used in combination with gonadotropin-releasing hormone agonists, is an effective treatmentfor concomitant uterine disease.

Objective. To analyze the metadata of modern scientific literature on the most significant changes in algorithms of secondary preventive measures in cervical cancer with link to appraisal of the role of human papilloma virus (HPV) in the nature of cervical cancer. Material and methods. The article includes the data of foreign and local Russian articles published in past years and found in Pubmed. Results. Reported usage of immunomodulating and aniviral medication which helps to increase the efficacy of HPV therapy. Conclusion. Combine therapy with targeted elimination of affected area by electro surgery together with immunomodulating administration helps to increase efficacy of secondary preventive measures in treatment of cervical cancer.

Background. Personalized anticoagulant prevention of venous thromboembolism (VTE) in women with a complicated obstetric history (COH) and thrombophilia can prolong pregnancy and improve its outcome. Therapy can be individually monitored by global tests evaluating the hemostatic system. Case report. The paper gives an example of managing a patient with COH and thrombophilia at high risk for VTE (congenital antithrombin III deficiency) in the assisted reproductive technology (ART) protocol and during pregnancy. The dose of anticoagulants was controlled and adjusted using the routine and global hemostasis tests until the pregnancy was successfully completed: delivery by caesarean section at 38 weeks’ gestation; a full-term baby weighing 3980 g; an Apgar score of 9. Conclusion. Implementation of the ART protocol in women with thrombophilia at high risk for VTE should be accompanied by careful hemostasiological monitoring and individual choice of anticoagulant prevention. When severe underlying pathological hypercoagulation or evident uncontrollable hemostasis is identified by the time of embryo transfer, the latter should be postponed until hemostasis is stabilized.