NEWS
ОRIGINAL ARTICLES
Introduction. Inflammatory gynecological disease is among the major causes of recurrent implantation failures (RIF). In hysteroscopy, chronic endometritis (CE) is diagnosed in one of three women with reproductive dysfunction. Search for novel therapeutic strategies aimed at improving the endometrium condition to overcome the RIF, remains an important goal of reproductive medicine.
Aims of the study: 1) identify clinical markers of infertility and RIF; 2) characterize the structural and functional changes in the endometrium of women with infertility and RIF; 3) test the efficacy of the proposed combined therapy in correcting of «uterine factor» of infertility in women with previous in vitro fertilization (IVF) failures.
Materials and methods. This cohort retrospective study included 154 patients: Group 1 – 87 women with the tubal factor of infertility; Group 2 – 67 women with adenomyosis. The inclusion criteria: age < 45, ≥ 2 previous IVF failures, the absence of severe non-gynecological disease. After detailed clinical and laboratory examination, we initiated a series of measures for endometrial rehabilitation by using: non-steroid anti-inflammatory drugs (if indicated); tissue regeneration (physiotherapy); immune modulators; improvement of blood rheology; fibrinolytic medication (conjugated hyaluronidase «Longidase», Petrovax Pharm, Russia).
Results. In women with the tubal factor of infertility, CE was diagnosed significantly more often (р < 0.05) than in patients with adenomyosis; and in women with adenomyosis, the prevalent (compared to CE) diagnoses were endometrial hyperplasia, intrauterine synechiae and decreased uterine perfusion (р < 0.05). In CE, under-expression of estrogen and progesterone receptors of the endometrium was found in 56.5% cases – significantly more often (р < 0.05) than in patients with adenomyosis. Upon the completion of the proposed therapy, the endometrium thickness was significantly greater in patients with adenomyosis (7.6 ± 1.5 mm versus 11.1 ± 1.3 mm; р < 0.05); in 93.1% of the patients, the sex hormone receptors were restored; in 96.8% of these women, normal uterine perfusion was found. Clinical and morphological signs of CE disappeared in 50% of the treated patients. In this group, the pregnancy rate was 57.1%.
Conclusion. Morphologic and functional improvements of the endometrium increase the pregnancy rate in women with the «uterine factor» of infertility. We consider the administration of conjugated hyaluronidase «Longidase» a major factor of the proposed combined therapy. The drug is characterized by fibrinolytic and anti-inflammatory activities. This combined therapeutic approach is expected to contribute to the treatment of RIF.
The aim of the study was to search for a connection between the abnormal location of placenta and the presence of genetic and acquired forms of thrombophilia.
Materials and methods. A total of 132 women with the aggravated obstetrical history were examined: Group 1 – 42 patients with the history of placenta previa; Group 2 – 60 pregnant women diagnosed with placenta previa in the current pregnancy; Group 3 – 30 pregnant women with the history of placenta previa and the same abnormality in the current pregnancy. The control group included 120 women with no abnormalities in their obstetric history and with normal location of placenta during the current pregnancy. All patients were assessed for the antiphospholipid antibodies using an enzyme immunoassay. The presence of genetic forms of thrombophilia was tested (with polymerase chain reaction and three pairs of oligonucleotide primers) for the following mutations: the C677T mutation in the 5,10-methylenetetrafolate reductase gene, the prothrombin mutation in the G20210A gene, mutations in the Leiden factor V gene, polymorphism 675 4G/5G in the gene of the inhibitor of plasminogen activator type 1, polymorphism 455G/A in the fibrinogen gene.
Results. The thrombophilia spectrum in patients with placenta previa during the current pregnancy and those with abnormal placenta location in the past did not significantly differ from each other. However, in patients with both abnormal placental locations in the past and the present pregnancy, there was a greater occurrence of both genetic and acquired forms of thrombophilia. In the control group, much fewer cases of either genetic or acquired thrombophilia were found.
Conclusion. The obtained results suggest a connection between thrombophilia and the abnormal location of placenta. Women with the abnormal placenta location either in the past or during the current pregnancy should be routinely tested for the genetic markers of thrombophilia and for hemostasis abnormalities.
Aim: to study polymorphism of the hemostasis-associated genes in women with physiological pregnancy and those with threatened preterm birth among the population of the Ivanovo region.
Materials and methods. The study included 103 women with threatened preterm delivery and 73 women with physiological pregnancy. The women with threatened preterm delivery were divided into 2 subgroups: subgroup I totaled 53 women who had given birth in a timely manner; subgroup II consisted of 50 women who had had spontaneous birth before 37 weeks of gestation. In all patients, pregnancy was spontaneous and mono-fetal. The inclusion criteria for the main group were abdominal pain and structural changes in the cervix. Total genomic DNA was isolated from 100 µl of whole blood using a kit of «Trial-TOS-Genetics» («DNAtechnology», Russia). Single nucleotide polymorphisms (F2 G20210A, F5 G1691А, F7 G10976A, F13A1 G/T, FGB G -455A, PAI-1 -675 5G/4G, ITGA2 C807T, ITGB3 T1565C) were determined by polymerase chain reaction in real time using an iQS iCycler (Bio-Rad) machine and reagent kits of «Kardiogenetika. Thrombophilia» («DNA-technology», Russia).
Results. In patients with threatened preterm delivery, the presence of polymorphic variants of the hemostasis-associated genes exceeds that in women with normal pregnancy. The observed accumulation of polymorphic genes may play a role in hemostasis dysfunction, which affects the blood fibrinolytic activity. As a result, the incidence of bleeding increases and the utero-placental circulation deteriorates.
Conclusion. The obtained results indicate an adverse genetic background in part of women in this geographical region, which, in turn, might be caused by unfavorable environmental factors.Aim: to study the endothelial system in women with undeveloped pregnancy and their fetuses.
Materials and methods. The study included 180 first trimester pregnant women. The main group was composed of 90 women, whom a 7-10 week miscarriage was diagnosed followed by an instrumental abortion. The control group included 90 somatic healthy pregnant women, who chose to interrupt their pregnancy by an instrumental abortion. To characterize the endothelium system, we determined the number of desquamated endothelial cells together with cytometric evaluation of cell diameter, perimeter, area, shape, and polarization. Following the instrumental abortion, morphology of the fetal chorion was studied in women of both groups. Light microscopy was used to assess the fetal blood vessels and their differentiation. By means of computed cytomorphometry we determined the primary vessel wall thickness, lumen diameter and its area, as well as the Kernogan index.
Results. The cytometric analysis of desquamated endotheliocytes in pregnant women and that of fetal chorion blood vessels showed identical morphological changes in the endothelial systems of all examined women with pathological pregnancy.
Conclusion. The endothelial dysfunction found in the first trimester pregnant women is accompanied with changes in the endothelium of the fetal chorion, which can lead to pregnancy failure.
Aim: to analyze the polymorphic genes of folate metabolism in women with history of non-developing pregnancy and in their embryos/fetuses in order to relate the genetic polymorphism with the risk of early pregnancy loss.
Materials and methods. The main group consisted of 117 women with non-developing 1st trimester pregnancy; the comparison group included 117 women with no history of miscarriage, with physiological 1st trimester pregnancy and a normal fetal karyotype. By polymerase chain reaction in real time using DT-96 machine («DNA-technology», Russia) all women and embryos were analyzed for the following polymorphic variants: MTHFR 677 C>T, MTHFR 1298 A>C, MTRR 66 A>G, MTR 2756 A>G.
Results. The women with non-developing pregnancy and chromosomal abnormalities of the fetus had a significantly higher occurrence of the MTR 2756G allele in comparison with women with non-developing pregnancy and a normal karyotype of the fetus.
Conclusion. The 2756G allele of the polymorphic MTR 2756 A>G gene in women with non-developing pregnancy is associated with a chromosomal imbalance of their fetuses.
REVIEW ARTICLE
Summary Safety of pharmacotherapy during pregnancy is of paramount importance for the woman and the fetus. There is an increasing number of pediatric diseases with unclear or presumably genetic etiology (autism, mental illness, oncology, obesity, diabetes, etc.). In this respect, more attention is being paid to the epigenetic or fetal programming, and the safety of pharmacotherapy during the gestation period and lactation, as well as 3-9 months before conception (periconception period).
Bleeding during pregnancy, labor and delivery is considered the major cause of maternal death or subsequent disability, and various disorders. Currently, obstetricians and gynecologists have a number of effective tools for the prevention and treatment of obstetrical bleedings. Compliance with the Federal clinical protocols (recommendations) and the development of local algorithms for the treatment and prevention of obstetric hemorrhages are consistent with the organ-preserving treatment strategy and will help reduce maternal mortality and morbidity.
Analysis of the published reports indicates the alarming increase in prevalence of infertility that occurs in the current demographic situation and the unfavorable epidemiological trends in tuberculosis. At present, female genital tuberculosis (GT) is considered the cause of 10-27.8% of female infertility cases and seen as a serious medical and social problem in women of reproductive age (24-35 years). Making a diagnosis of GT may become a complex task since: there are no commonly accepted schemes for the diagnostic procedure and patient management; the clinical manifestations of GT are nonspecific; the molecular-genetic, morphological, and microbiological diagnostic methods may not be sufficiently sensitive; the results of using hysterosalpingography are inconsistent (40-60% of discrepancies, high risk of complications); the indications to the Koch test and test-therapy are limited; the use of laparoscopy is still debatable; and the heterogeneity of the endoscopic picture in 13-59.7% of suspected GT cases results in a low rate of confirmed GT – 9-26.3%. Immunological methods, in particular, the serological ones, take a lead in the diagnosis of extra-pulmonary tuberculosis. We propose that testing the local humoral immunity in women with infertility, along with the endoscopy, can improve the diagnosis of GT and avoid irreversible changes in the reproductive system.
Gestational trophoblastic disease (GTD) is a cumulative name of the diseases that occur in pregnant women as a result of abnormal trophoblast proliferation. It includes benign (full or partial hydatidiform mole) and malignant (so-called gestational trophoblastic neoplasias) diseases. Statistically, the incidence of hydatidiform mole varies from region to region. That may be due to either the ethnic factors or related to a specific diet, the quality of diagnosis, representatives of the statistical data and the lack of a uniform protocol of data registration.
CLINICAL CASE
The article describes a clinical case of planning and managing pregnancy and delivery in a woman at high risk of thrombotic and obstetrical complications related to recent severe bilateral recurrent pulmonary embolism and history of pulmonary infarction and thrombosis of the brachial and subclavian veins on the background of receiving hormonal contraceptives. Prior to the first visit to our clinic, the woman was never examined for inherited or acquired forms of thrombophilia, although her medical and family history was indicative of a hereditary element of the disease. Here, homozygous mutation of prothrombin factor II (Thr165Met) and polymorphisms of the folate cycle and platelet receptor genes were detected. Managing of pregnancy, delivery and the postpartum period included carefully selected doses of low-molecular weight heparin under continuous monitoring of hemostasis and heparin dose correction.
FROM HISTORY
The article highlights the main stages of life and work of the outstanding specialist in female diseases – German obstetrician, gynecologist, surgeon, scientist Walter Stoeckel.
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