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Obstetrics, Gynecology and Reproduction

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Vol 11, No 3 (2017)
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74
Abstract

Bacterial vaginosis during pregnancy lead to abnormality of the vaginal flora and is accompanied by a change in the balance of cytokines and antimicrobial peptides. The purpose of this research was to study the bacterial, cytokine and antimicrobial components of nonspecific vaginal immunity in the second and third trimester of pregnancy among patients with recurrent bacterial vaginosis and healthy women. Materials and methods. The study included 40 pregnant women with recurrent bacterial vaginosis, who made the first observation group, and 40 healthy women, who was included in the second group. The average gestational age at the beginning of the study was 14.8 ± 2.0 weeks. We analyzed clinical and laboratory criteria of bacterial vaginosis, a qualitative and quantitative characteristics of the vaginal flora, the vaginal level of β-defensin-2 (HBD-2), interleukin-1β (IL-1β), interleukin-1β (IL-4 ), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-γ (INF-γ). Results. The pregnant women with recurrent bacterial vaginosis in 30 weeks had a moderate vaginal dysbiosis due to anaerobic microorganisms. At the same time, the amount of lactobacillus increased in both groups at the beginning of the third trimester. L. crispatus was prevalent in healthy women and L. iners dominated in patients with recurrent bacterial vaginosis. There were no differences in the concentration of cytokines and antimicrobial peptide among patients with recurrent bacterial vaginosis between the second and third trimester. The levels of HBD-2, IL-1β, IL-6, IL-10, INF-γ were low in this group in comparison with healthy pregnant women, which can increase the risk of the diseases recurrents.

NEWS

ОRIGINAL ARTICLES

5-10 143
Abstract

The aim of the study was to analyze the uterine and fetoplacental hemodynamics in pregnant women with placenta abnormalities.

Materials and methods. Fifty pregnant women with normal placentation (Group 1), 50 women with placenta previa (Group 2) and 28 women with placenta accreta (Group 3) were examined in this study. The ultrasound examination included the traditional fetometry and an assessment of fetus anatomy and localization of the placenta. In addition, the Doppler ultrasound was used to examine the blood flow in the uterine arteries as well as the umbilical artery and the middle cerebral artery of the fetus. The measurements were performed on the 20-22nd, 30-32nd and 35-36th weeks of gestation.

Results. According to the data obtained, the blood flow in the uterine arteries of patients with placenta pervia was much higher as compared with women with normal placental localization. The right uterine artery blood flow indices in the placenta previa cases significantly differed from those in women with placenta accreta. The pulsatility index in the right uterine artery was significantly lower in patients with placenta accreta as compared with the two other groups. The data on fetoplacental hemodynamics indicated differences in the umbilical artery blood flow between women with placenta accreta, placenta previa and normal placental localization on the 20-22nd and 35-36th weeks of gestation. Along with the above findings in the uterine and fetoplacental hemodynamics, the parameters of blood flow in the fetal middle cerebral artery did not differ significantly between the three groups of women at any period of gestation.

Conclusion. The conditions of placenta accreta and placenta previa are associated with a decrease in the peripheral vascular resistance in both uterine arteries during all periods of gestation. This conclusion is supported by the lower values of the pulsatility index in these blood vessels in comparison to the values in patients with normal placental localization.

11-19 363
Abstract

Introduction. Women with infertility and circulating antiphospholipid  antibodies  (APA) may be at risk of reproductive losses. A possible way to improve their in vitro fertilization  (IVF) outcomes is the immunomodulating  therapy using intravenous immunoglobulin (IVIG). Aim: to study the effecacy of IVIG in women with APA who undergo IVF (IVF/ICSI).

Materials and methods. One hundred twenty eight APA-positive women were enrolled: 77 women were  given  IVIG during the IVF procedure at a course dose of 15 g (group 1), 55 women received no IVIG (group  2) and 63 women without APA scheduled for IVF made up the control group (group 3). Women in groups 1 and 2 received prophylactic doses of low weight heparins and reduced doses of acetylsalicylic acid. Women with poor quality embryos were excluded. The implantation rate (positive serum β-HCG), the clinical pregnancy rate (gestational sac and fetal heartbeat) and the live birth rate were used as the endpoints.

Results. There were no differences in the implantation rate between groups 1, 2 and 3 (48.39%, 35.71% and 32%, respectively; p > 0.05). The clinical pregnancy rate was significantly higher in group 1 than in group 2 (45.16% and 21.43%; p < 0.05), in group 3 that was 32%. The difference in the live birth rate was not significant (33.3%, 19.05% and 24%; p > 0.05). Among women who received IVIG within  the IVF (IVF/ICSI)  protocol and during the subsequent pregnancy (prior to 12 weeks), the the live birth rate was 83.3% (15/18), which was 33,3% higher (p > 0.05) than for women who received IVIG only  within  the IVF (IVF/ICSI)  – 50% (6/12).

Conclusion. The use of IVIG in APA-positive women undergoing IVF (IVF/ICSI)  significantly increases the clinical pregnancy rate, but does not increase the implantation rate and the live birth rate. Further studies are needed to evaluate the efficacy of IVIG within  the IVF (IVF/ICSI) protocol  and the continued therapy during pregnancy.

20-32 176
Abstract

Thrombophilia is known for its role in the pathogenesis of spontaneous loss of pregnancy. However, in-depth hemostasis tests are costly, and cannot be routinely used. Therefore, the aim of this study was to develop a method adjustable to screening for thrombophilia in women with recurrent pregnancy loss and also to evaluate its efficacy.

Materials and methods. A comprehensive examination – clinical, laboratory and instrumental – was performed in 103 women with spontaneous pregnancy loss in the past and 33 women (control) with two or more spontaneous deliveries without significant complications. Diagnosis of thrombophilia was made on the basis of full scale hemostasis tests performed for all patients. The tests included measurements and analyses of 30 standard parameters of hemostasis. Statistical processing of the results was carried out using parametric and nonparametric methods.

Results. A thorough assessment of medical history and medical records together with the current results of clinical, instrumental  and laboratory examination allowed us to determine10  major criteria (markers)  for predicting the presence of thrombophilia. These included certain details of medical history, as well as the family and obstetric-gynecological background. The developed markers laid the groundwork for the proposed screening method, where each of the markers gave 1 point to the total score. As part of the screening data analysis, we developed a matrix for the probable risk of having thrombophilia. Selection of patients with a total screening score of 3 or more points allowed increasing 2.6-fold (by 53.4%) the efficacy of laboratory diagnosis of thrombophilia in women with recurrent pregnancy loss.

Conclusion. The novelty of the proposed screening method is that the analysis begins at the stage of pregnancy planning and it precedes the laboratory tests; the approach does not require additional expenses. According to our estimate, the use of this method increased the rate of thrombophilia detection by 160%.

33-42 184
Abstract

The aim of the study was to obtain the cell line secreting the maximum amounts of the human luteinizing hormone (LH) heterodimer without significant amounts of free LH alpha-subunit.

Materials and methods. A pair of original plasmids of the p1.1 family containing long non coding segments of the Chinese hamster translation elongation factor 1 alpha gene and a fragment of the concatemer of the Epstein-Barr virus long terminal repeat were used for the persistent expression of human LH subunit genes in Chinese hamster ovary cells. The open reading frame areas of the LH subunits genes were cloned into vectors with the dihydrofolate reductase (DHFR) or glutamine synthase (GS) genes, transfected into the cells, and amplified by methotrexate; following the final procedure of limiting dilution, clonal producer cells were obtained.

Results. For a pair of plasmids, where the LH alpha subunit gene was associated with GS and the beta subunit gene was associated with DHFR, the rate of LH production by the initial stably transfected cell population was 0.1 pg/cell/day and the doubling time was 37 hours, for the reverse pair of plasmids – 0.3 pg/cell/day and 48 hours, respectively. For the initial cell population and for their clonal lines, we used increasing concentrations of methotrexate to amplify the genetic cassettes in the cell genome. In the polyclonal population an increase in the cell productivity up to 2.2 μg/106 cells was observed at a concentration of methotrexate 8 μM; for the clonal lines – a significant productivity increase up to 0.09 μg/106 cells was achieved in only one of six cell lines. Conclusion. Cell lines secreting significant amounts of heterodimeric LH without a significant admixture of free subunit can be obtained using a pair of plasmid vectors encoding the LH subunit genes and the selection markers DHFR or GS. Co-transfection of the plasmids and their subsequent amplification in the genome of producer cells under the selective pressure of methotrexate results in a significant increase in the biosynthesis rate of both LH subunits. The present study provides a rationale for a potential use of these lines in the industrial production of human luteinizing hormone.

43-49 161
Abstract

Bacterial vaginosis developing in pregnancy is associated with abnormal vaginal flora and with an imbalance of cytokines and antimicrobial peptides.

The aim of this research was to study the bacterial, cytokine and antimicrobial components of the vaginal nonspecific immune system in the second and third trimesters of pregnancy among patients with recurrent bacterial vaginosis. 

Materials and methods. The study included 40 pregnant women with recurrent bacterial vaginosis (Group 1), and 40 healthy pregnant women with no signs of vaginosis (Group 2). At the onset of this study, the average gestational age among the selected women was 14.8 ± 2.0 weeks. We analyzed clinical and laboratory parameters  of bacterial vaginosis,  qualitative and quantitative characteristics of the vaginal flora, the levels of β-defensin-2 (HBD-2), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and interferon-γ (INF-γ) in vaginal washouts.

Results. The pregnant women with recurrent bacterial vaginosis tested at the 30th week of gestation, had moderate vaginal dysbiosis  caused by an increased number of anaerobic microorganisms. Along with that, at the beginning of the third trimester, the number of lactobacillus bacteria increased  in both Group 1 and Group 2. Notably, the predominant species in the healthy women samples was L. crispatus whereas in patients with recurrent bacterial vaginosis that was L. iners. There were no changes in the levels of cytokines and antimicrobial peptide between the second and third trimester in women with recurrent bacterial vaginosis.  In this group (Group 1), however, the levels of HBD-2, IL-1β, IL-6, IL-10, INF-γ were lower in comparison with healthy pregnant women (Group 2), which can be seen as a risk factor of further returns of the disease.

Conclusion. Pregnant women with recurrent bacterial vaginosis as well as women with normal course of gestation have an increased presence of lactobacilli bacteria in their vagina during the third trimester of gestation. No other changes in the bacterial, antimicrobial and cytokine components of the nonspecific immune system in the female reproductive tract were found.

50-58 408
Abstract

The article describes the developing technologies for the production of «designer embryos» also known as genetically improved babies. The authors briefly review these technologies with a special emphasis on their medical, legal and bioethical aspects. We propose and substantiate the point of view why some of these approaches may be illegal.

SCIENTIFIC SURVEYS

59-68 683
Abstract

Aim: to elucidate the role of magnesium deficiency in obstetric complications and to characterize the ways to prevent them by using oral administration of organic magnesium salts.

Materials and methods. We analyzed publications of the Cochrane society, recommendations of obstetrics communities, clinical studies published in official websites and other information available to the public.

Results.According to two multicenter studies conducted in Russia in 2012 and 2013 (MAGIC and MAGIC 2), magnesium deficiency was diagnosed in 81.2% and 80.9% of pregnant women, respectively. Meta-analyzes of the data published by the Cochrane society showed that an oral administration of organic magnesium salts for 3 weeks caused a significant decrease or disappearance of leg cramps in 65.5% of pregnant women (vs 5.7% with placebo). Treatment with magnesium during the period before the 25th week of pregnancy reduced the risk of complications as follows: premature births – by 27%; births of low weight babies – by 33%; mother hospitalization – by 34%; risk of spontaneous abortion – by 62%. In all the studies where pregnant women took oral magnesium medications, there was a low incidence of side effects.

Conclusion.Measures to prevent magnesium deficiency both at the stage of preparation for pregnancy and during gestation, starting from the first weeks, help avoid some complications and improves the outcomes for the fetus and the newborn.

70-81 172
Abstract

The aim of this study was to review and analyze the medical reports on the current aspects of etiology, pathogenesis, diagnosis and treatment of uterine sarcomas. Here, we attempt to summarize the available information concerning the patient management and the many issues related to the diagnosis and treatment of this disease. In this study, the updated classification of uterine sarcomas is presented together with the current concepts on staging of the disease. Although «epidemiologically» rare, this group of diseases represents a serious oncological problem because of its severity and high mortality rate, and the lack of complete understanding of its pathogenesis.

82-87 186
Abstract

Marfan syndrome is dominantly inherited connective tissue diseases, associated with microfibrillar fiber connective tissue deficiency in vascular walls, heart valves, joints, dural membrane,  bones, and other organs. Diagnosis may be confirmed by clinical  criteria and molecular tests. Pregnancy bears a risk of fatal complications,  including aortic dissection, aortic root dilation, mitral valve insufficiency.  Women must be followed and managed in a high risk pregnancy unit by a team from obstetricians, cardiologists, anesthetists, pediatricians, neonatologists  and cardiac surgeons who are skilled in high risk pregnancies. This approach allows to avoid the serious maternal and fetal complications. Caesarean section should be offered for such patients, because it minimizes the hemodynamic changes, associated with vaginal delivery. Some authors recommend to perform post-cesarean hysterectomy, because of the high incidence of massive hemorrhage in postpartum.

CLINICAL CASE

88-93 123
Abstract

This report presents a rare case of thrombophilia – thrombosis of the ovarian vein in combination with thrombosis  of the right common iliac vein. The symptoms were initially interpreted  as acute appendicitis that led to the decision to perform laparoscopy. Thereafter, a different diagnosis – acute endometritis, acute salpingo-oophoritis – was proposed. As the subsequent treatment resulted in no improvement, a CT scan was performed to detect thrombi of a typical localizations and a mass in the uterus area, which turned out to be a poor-differentiated adenocarcinoma. In the patient’s medical history, multiple signs of family thrombophilia were found; further laboratory tests also pointed to the diagnosis of thrombophilia. Considering the previously performed surgery and the confirmed thrombophilia of rare localization, permanent anticoagulant therapy was recommended.

94-97 116
Abstract

The report presents a case of pregnancy management in a woman with a history of obstetric problems and neurosensory hearing loss. After thorough hemostasis tests, the presence of antiphospholipid antibodies in the blood was detected. Given a high risk of thrombophilia in this situation, the patient was treated with antithrombotic therapy – low molecular weight heparin (sodium bemiparin).

REPORTAGES

116-126 367
Abstract

Within the framework of the 27th international conference «Reproductive technologies today and tomorrow», the first Russia-made follitropin alfa biosimilar for controlled ovarian stimulation in assisted reproductive technologies (ART) was presented. The follicle-stimulating hormone (FSH) biosimilar has undergone  all stages  of development in Russia, from the producer cells culture to the release of active FSH. Also the data are presented  on a prospective randomized crossover study of phase I  confirming the similarity of pharmacokinetics between the biosimilar and the original FSH. Another randomized multicenter phase III clinical study is now under way aiming to demonstrate the clinical equivalence between the biosimilar and the original FSH; preliminary  results  of this study are presented and discussed. As planned, the recombinant FSH biosimilar will be produced in disposable injectors (pen-injector) that provide easy-to-use handling, convenient dose setting and wide range dosing.

HISTORIC CASES

127-132 103
Abstract

This article is dedicated to the 195th anniversary of the birth of one of the founders of Russian obstetrics and gynecology, the founder of the first obstetrician and gynecological school in Russia, Professor Anton Yakovlevich Krassovskiy. His contribution to the development of surgical obstetrics and to the improvement of gynecological operations, as well as to the introduction of aseptic methods into practice, is especially appreciated. Particular attention is paid to the period when A.Ya. Krassovskiy headed the Nadezhdinsky maternity hospital (1871-1898). The national school of obstetricians and gynecologists formed under his leadership laid the foundation of scientific and practical obstetrics in Russia.



ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)