No 10 (2018)

Antiphospholipid syndrome (APS) is a systemic process that affects all organs and tissues of the body and diagnosed upon fulfilment of clinical and biological criteria. The currently accepted clinical morbidities affect two organs: the vascular tree, leading to thrombotic manifestations, and the utero-placental unit, leading to pregnancy complications. Obstetric APS (oAPS) is an autoimmune disease leading to the synthesis of autoantibodies directly capable of activating key cells of vascular and/or placental pathophysiology. During pregnancy, placenta serves as the most important organ. Violations of the placenta function due to endothelial dysfunction, ischemia, and placenta microthrombosis are responsible for the development of obstetric complications: pre-eclampsia, HELLP-syndrome, placental abruption.This manuscript describes a data of a different clinical experience in the field of APS. APA directly or indirectly affects the implantation process and early embryonic stages. The thorough systematic review on histopathology in the placenta of oAPS women found, on the sincytiotrophoblast (sTB) side, a decreased trophoblast (TB) proliferation, increased TB death rates, a decreased syncytialisation process, an increased sTB death rate with increased cell debris, and areas of sTB denudation and of fibrin deposition. Experimental in vitro data confirmed that ab2GP1 Abs decrease fusion of TB cells, thus inhibiting sTB formation. Reduced eTB invasion was associated with decreased placenta anchorage, reduced transformation of maternal spiral arteries and reduced maternal flow to the placenta, mirroring the conditions in placenta-mediated late pregnancy complications such as preeclampsia. Our studies and over 20 years of clinical experience indicate the presence of etiopathogenetic relation between APS and obstetric complications and the high efficacy of prophylaxis with anticoagulants when it starts early, since the period of preconception.

The paper gives an update on the relationship between genetically determined hemostasiological disorders and the expression level of proangiogenic factors in the formation of the fetoplacental complex and analyzes obstetric and perinatal outcomes following transfer of fresh and vitrified embryos in in vitro fertilization programs based on the data available in the Russian and foreign scientific literature. It shows the role of hemostasiological and proangiogenic factors in the formation of the fetoplacental complex and analyzes obstetric and perinatal outcomes after transfer of fresh and vitrified embryos in in vitro fertilization programs. The authors describe the role of vascular endothelial growth factor and the vascular anticoagulant annexin V in the formation of the placental vascular network that is of particular interest in using the methods of assisted reproductive medicine as the major organ that ensures fetal formation and growth. Further studies will help identify genetic and phenotypic risk factors for placental insufficiency following transfer of fresh and vitrified embryos in in vitro fertilization programs during both hormone replacement therapy and a natural cycle, which will be able to assess perinatal outcomes and to contribute to their improvement.

The prevalence of genital prolapse (GP) among the female population can reach 2.9% and, with regard to different clinical and anamnestic approaches, varies from 6 to 50%. 12.6-18% of patients with GP undergo surgical correction. GP is a multifactorial disease. Childbirth is only a provoking rather than basic factor. There are below 1.8 births per woman in the European countries; but the rate of GP is 4 times higher than that in non-European countries. The proportion of the white population among patients with GP reaches 87.2%. A traumogenic factor during childbirth is traced in no more than 10% of patients; and an inherited factor is seen in 26% of cases. A multifactorial genesis is confirmed by the correlation between GP and polymorphisms of the genes responsible for the synthesis of the collagens COL1A1 (rs1800012) and COL3A1 (rs1800255), the expression of regulatory genes in the pubic-coccygeal muscles MYBP, MYH3, as well as the genes responsible for the synthesis of myosin heavy chains in the smooth muscles ADAMTS1, PPP1R12A. The involvement of the LIN28B and the AGT genes that are interrelated with GP and mitral valve prolapse was found. Surgery is a leading approach in treatment. Physiotherapeutic approaches should be applied as auxiliary methods of treatment while preparing a female patient for surgery so that she can accurately perceive her own body. Sacrocolpopexy is recognized as the gold standard surgical treatment for GP. The paper discusses the results of randomized studies on the choice of this r that surgical technology and its long-term results. In some cases ZFYVE16 gene polymorphism determines the number of recurrences after sacrocolpopexy. The paper discusses approaches to choosing a surgical treatment option in Russia. The main dilemma is what to choose: an individual or standardized approach to choosing surgical technology.

Objective. To investigate the clinical, anamnestic, and biochemical predictors of preeclampsia. Subjects and methods. Clinical, anamnestic, and biochemical examinations were performed in pregnant women, who later formed two groups: pregnant women with late-onset moderate preeclampsia and patients without preeclampsia. Results. The significant clinical markers for late-onset preeclampsia were shown to be increases in body mass index and mean blood pressure at 11-13 weeks’ gestation. The pregnant women with preeclampsia were found to have significantly higher serum levels of retinol-binding protein 4 and disintegrin and metalloproteinase 12. The anamnestic predictors of preeclampsia were ascertained to be hypertension in the history, chronic pyelonephritis, and preeclampsia in previous pregnancies. Conclusion. A prognostic model based on the co-use of the studied predictors has been developed for the early prediction of late-onset moderate preeclampsia.

Objective. To analyze pregnancy outcomes at high risk of trisomy for chromosome 7, as evidenced by noninvasive prenatal DNA screening (NIPS). Subject and methods. The paper describes two clinical cases of female patients aged 35 and 39 years, who have been found to be at high risk of trisomy for chromosome 7, as evidenced by NIPS. The investigators performed the latter for aneuploidies, by applying a genome-wide approach; an examination of four placental fragments, by using the fluorescent in situ hybridization (FISH); standard peripheral blood karyotyping; and a FISH study of chromosome 7 in the blood of a baby. Results. In both cases, pregnancy occurred with the phenomena of threatened miscarriage, oligohydramnios. Full-term low-birth-weight babies were born alive. The application of molecular cytogenetic technique proved the placental mosaicism for trisomy of chromosome 7 in patient M. Conclusion. These observations illustrate that NIPS can detect not only fetal aneuploidies, but also the mosaic forms of placental aneuploidies that can be a marker for complicated pregnancy.

Aim. To investigate the effectiveness of in vitro fertilization (IVF) programs in which the luteal phase support (LPS) was administered in the form of either a combined regimen of gonadotropin-releasing hormone agonist (GnRH-a) and micronizedprogesterone or the standard LPS regimen of micronizedprogesterone. Material and methods. The study comprised 207patients under the age of 38 years with tubo-peritoneal, male, and mixed factor infertility. On the day of transvaginal puncture (TVP), the patients were randomized into two groups with different LPS regimens. In group 1 (n = 92) patients received natural micronized progesterone 600 mg/day given vaginally from day 1 after TVP and a single subcutaneous dose of 0.1 mg trptorelin on day 6 after the TVP. Patients in group 2 (n = 115) were administered vaginal natural micronized progesterone 600 mg/day alone from day 1 after TVP. Results. The patients managed with the combined LPS regimen had higher rates of implantation (30.6 and 16.6%, p <0.05), clinical pregnancy (40.2 and 26.9%, p = 0.04), progressive pregnancy (36.9 and 21.7%, p = 0.01), and live birth rates (31.5 and 19.1%, p = 0.04) compared with patients treated with the standard LPS regimen. Conclusion. Using the combined LPS regimen with GnRH-a has a positive effect on the IVFprogram outcomes in protocols with GnRH antagonists.

Objective. To investigate the associations of the LHCGR polymorphism rs4374421, rs7579411, rs6729809, and rs4953616 with the development of uterine leiomyoma. Subjects and methods. The investigation enrolled 1265 women: 569 patients with uterine leiomyoma and 696 individuals in the control group. Four polymorphic loci (rs4374421, rs7579411, rs6729809, and rs4953616) of the LHCGR gene were genotyped. The associations of LHCGR gene polymorphism with the development of uterine leiomyomas, its regulatory potential, and impact on gene expression were studied. Results. The polymorphic loci rs4374421 and rs7579411 of the LHCGR gene were found to be associated with the development of uterine leiomyoma. The risk factors for the disease were the C/C genotype of rs7579411 (OR = 1.35) and TS haplotype of the polymorphic loci rs4374421-rs7579411 (OR = 1.21). The T allele (dominant model: OR=0.74) and the C/Tgenotype (OR = 0.80) rs7579411, as well as T/Cgenotype of rs4374421 (OR=0.78) are of protective value for the development of uterine leiomyoma. These polymorphic loci have a significant regulatory potential (are located in the region of histones that label promoters and enhancers in the culture cells, precursors of neurons and mesenchymal cells, etc., in the region of regulatory DNA motifs), and the polymorphism rs7579411 is associated with the expression level of the STON1- GTF2A1L gene in the thyroid gland. Conclusion. The LHCGR polymorphisms rs4374421 and rs7579411 are associated with the development of uterine leiomyoma.

Objective. To investigate whether early endometrial cancer can be treated and whether fertility can be preserved in young women, by using a hormonal combination: levonorgestrel intrauterine hormonal system (LNG-IUS; Mirena 52 mg of LH) and gonadotropin-releasing hormone agonists (Zoladex 3.6 mg). Subjects and methods. The investigation covered 79 patients. The case histories of 37 patients with atypical hyperplasia and 42 with stage I A (T1aNxMo) endometrial cancer were analyzed. The patients’ mean age was 33 years. The investigation was conducted at the Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation. Results. Primary treatment was completed in 67 (84.8%) patients and in 12 (15.2%) during hormonal treatment. After completion of special treatment, 8 (11.9%) of the 67 women had 10 pregnancies that resulted in childbirth and spontaneous miscarriage in 8 and 2 cases, respectively. Recurrences and incurable disease were stated in 3 (4.2%) and 9 (12.8%) cases, respectively. Repeated hormone therapy cycles were not performed because the patients had refused organ-sparing treatment. All the 12 (17.1%) patients were successfully operated on. Conclusion. The proposed treatment regimen is a highly effective medical treatment in patients with precancer and early endometrial cancer. Independent hormone therapy is undoubtedly the best alternative to hysterectomy today in this group of patients who want to preserve reproductive function.

Background. Paracetamol is widely used as an antipyretic in not only in outpatient, but also inpatient pediatric practice. Overdose with modified-release paracetamol dosage forms creates problems with antidote dose adjustment, which is associated with difficulties in determining the administered toxic dose. In this connection, to investigate various matrix carriers in order to accurately dose paracetamol and to control the rate and degree of its release is an urgent problem. Objective. To formulate 4 different types of paracetamol matrix tablets obtained using 4 polymers, to investigate their effect on the sustained release of the active ingredient, and to assess potential advantages and disadvantages. Material and methods. The behavior of the drug was evaluated using a dissolution test, by modeling of the gastric contents. Results. Four different types of paracetamol matrix tablets were investigated. Two (carbopol and sodium alginate) of the four formulations showed a higher release level than the reference conventional paracetamol tablet. Unfortunately, it was impossible to achieve a model close to zero-order kinetics, and the resultant release was lower than originally expected; with a sodium alginate delivery system, the release of the drug reached a maximum of 50%. Conclusion. It was found that the paracetamol formulations based on carbopol 974P NF and sodium alginate would be useful to enhance drug dose efficiency, by achieving sustained release (via passage through stomach without degradation and via start of its proper release in the intestine), minimizing the risk of side effects, which may as a result improve drug tolerability and a patient’s general condition.

The article presents an explanation of the relevance of using regimens incorporating highly effective antimycotics in modern society, which is dictated by the lifestyle of large cities and the modern generation. After the symptoms of the disease disappear, many patients discontinue a prescribed drug treatment regimen on their own, interrupting the full cycle, which can lead to recurrences and unresponsiveness to treatment in the future.

The article highlights the clinical and pathogenetic relationships between endometriosis/adenomyosis and chronic endometritis (CE) within reproductive failures. It describes a cause-and-effect relationship between endometriosis/ adenomyosis and CE by the example of its clinical symptomatology and the pathogenic mechanisms involving an autoimmune process, aseptic inflammation, and altered endometrial receptivity. Endometriosis/adenomyosis and CE have a number of common pathogenetic mechanisms of development and clinical manifestations (infertility, recurrent miscarriages, and assisted reproductive program failures). This implies the necessity to qualitatively assess the endometrium in women with endometriosis and adenomyosis during pregravid preparation, as well as the search for new therapeutic ways to correct autoimmune disorders. The use of sodium desoxyribonucleate (derinat) showing the pharmacological properties of an activator of the cellular and humoral immune system and a stimulator of reparative and regenerative processes is a promising approach to drug therapy.

Background. Acute Lipschütz vulvar ulcer (ulcus vulvae acutum) is a rare disease that occurs mainly in girls and is manifested by single or multiple painful ulcers on the inner surface of the labia. This pathology should be differentiated from other genital erosive and ulcerative lesions, including sexually transmitted infections. Case report. The paper describes a clinical case of acute Lipschütz- Chapin vulvar ulcer in a 14-year-old patient who was misdiagnosed as having herpesvirus infection. Conclusion. The characteristic clinical manifestations of the disease make it possible to timely make an accurate diagnosis, to initiate treatment, and to conduct high-quality rehabilitation.