Vol 68, No 5 (2019)

Original Researches
Comparative studies of milk removal in lactating women using the Lactopuls breast pump with vacuum and compressive components and the Medela Symphony breast pump
Alekseev N.P., Iliyn V.I., Talalayeva N.E.

Abstract

Hypothesis/aims of study. To date, in the world, including in the Russian Federation, the number of women who use breast pumps (BPs) in the process of breastfeeding has significantly increased. Many mothers of premature and full-term babies are partially or completely breast pump-dependent for weeks or months and need a BP that should be effective and convenient. In this regard, it is of great practical interest to compare the characteristics and, above all, the efficiency of milk pumping using two types of BP — one with vacuum component and another with vacuum and compressive components. The aim of this study was to conduct a comparative assessment of the efficiency of milk removal using the Medela Symphony BP and the Lactopuls BP.

Study design, materials and methods. 14 lactating women of 19–38 years of age who volunteered to be included in this study were examined. Women had been lactating and breastfeeding normally for 5–8 days. The Lactopuls BP with vacuum and compressive components and the Medela Symphony breast pump with a vacuum component were used in the main program mode.

Results and conclusion. It was found that the Lactopuls BP is more effective for milk removal. In particular, the amount of milk expressed using it was on average 14% more than that using the Medela Symphony BP. The Laktopuls BP with vacuum and compression components has shown its higher efficacy compared to the vacuum Medela Symphony BP.

Journal of obstetrics and women's diseases. 2019;68(5):5-10
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Intestinal dysbiosis in women in early pregnancy
Bezmenko A.A., Schmidt A.A., Sadovaya N.D.

Abstract

Hypothesis/aims of study. To date, there have been some publications on the possible role of systemic endotoxinemia resulting from intestinal dysbiosis in the pathogenesis of miscarriage. The aim of this study was to compare the state of intestinal microbiocenosis and the level of endotoxinemia in women with threatened abortion and normal pregnancy.

Study design, materials and methods. The study involved 50 women aged 18 to 35 years (mean age 28.1 ± 0.6 years) in pregnancy from 6 to 18 weeks. The main group consisted of 30 women with threatened abortion. The control group included 20 women with normal pregnancy. Patients of the main and control groups were examined in accordance with the order of the Ministry of Health of the Russian Federation No. 572n. In addition, a qualitative and quantitative microbiological analysis of feces was performed using the real-time PCR method. The level of endotoxinemia was studied to assess the possible systemic effect of intestinal dysbacteriosis on a pregnant woman.

Results. 23.3% of patients of the main group were diagnosed with intestinal dysbiosis of degree I, 60% of degree II, and 16.6% of degree III. In patients of the control group, dysbiotic changes corresponded mainly to degree I (75%) and degree II (25%). Degree III was not detected. Microbiological disorders in the main group were characterized by a decrease in the number of members of intestinal normal flora and a high concentration of opportunistic microorganisms. Microbiological disorders in the control group were characterized by a decrease in the intensity of colonization of the large intestine by lactobacilli and bifidobacteria. The average level of endotoxinemia in patients of the main group was 0.52 ± 0.05 nmol/ml and was classified as “elevated”, significantly exceeding that in patients of the control group — 0.34 ± 0.05 nmol/ml.

Conclusion. In patients with threatened abortion, intestinal microflora was characterized by a decrease in normal flora and a high concentration of opportunistic microorganisms with high a pathogenic potential and their associations. During normal pregnancy, microbiological disorders in the intestinal biocenosis were characterized by a decrease in the intensity of colonization of the large intestine by lactobacilli and bifidobacteria. The level of endotoxemia was directly proportional to the degree of dysbacteriosis of the intestine and was significantly higher in women of the main group.

Journal of obstetrics and women's diseases. 2019;68(5):11-18
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Preeclampsia features in pregnancy with gestational diabetes mellitus
Bettikher O.A., Zazerskaya I.E., Popova P.V., Vasilyeva E.Y., Bart V.A.

Abstract

Hypothesis/aims of study. The high prevalence of gestational diabetes mellitus (GDM) and the social importance of preeclampsia (PE) due to massive perinatal morbidity and mortality, as well as the high rate of PE in GDM pregnancy define the need to study the characteristics of pregnancy course in these women to develop the prevention and management of pregnancy complication. This study aimed at evaluating clinical and laboratory features of PE in GDM pregnancy.

Study design, materials and methods. According to the inclusion criteria, 112 pregnant women were enrolled in this prospective cohort study after 24 weeks of gestation: with GDM and PE (n = 24), with PE (n = 22); with GDM (n = 37), without studied pregnancy complications (n = 37). We assessed serum levels of placental growth factor (PIGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1). Pregnancy course and labour were evaluated using medical history.

Results. Severe PE developed more often (p = 0.0014, Chi-square test) in the PE group (59%, n = 13) compared to the GDM + PE group (13%, n = 3). Elective preterm labour occurred more often in the PE group compared to other study groups (PE: 23%, n = 5; GDM + PE: 9%, n = 2; p < 0.0001, Chi-square test with Yates correction), which is in line with the severity of PE in this group. The rate of preterm labour did not differ between the GDM + PE group and the group without studied pregnancy complications. Moreover, the mean fasting glucose level was higher in the GDM group compared to the GDM + PE group (p = 0.01, Mann–Whitney test). The GDM + PE group was characterized by fasting hyperglycemia episodes and a basal insulin regimen, while the GDM group by postprandial glucose peaks, and a bolus insulin regimen. Women with GDM + PE were notable for the high pre-pregnancy body mass index (29.0 ± 6.58 kg/m2), and a family history of DM was more typical for women with GDM without PE (59%, n = 19). The sFlt-1/PIGF ratio did not differ between the GDM + PE, GDM and control groups and was lower compared to the PE group (p < 0.0001, Fisher’s LSD test). PIGF level was not different in the GDM + PE and GDM groups, but was lower compared to the control group.

Conclusion. Our study showed that PE in women with GDM is more benign than in patients without GDM, taking into account both clinical and laboratory signs. At the same time, obesity appears to be one of the most important risk factors for the both pregnancy complications. The data of this study, in addition to those described in the literature, suggest that initial carbohydrate disorders play a disease-limiting, protective role in a vicious cycle of PE due to angiogenesis stimulation. The use of angiogenesis factors as markers of PE in GDM patients is limited, which requires further research.

Journal of obstetrics and women's diseases. 2019;68(5):19-36
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Importance of cytokines in the pathogenesis of preeclampsia in pregnant women with iron deficiency anemia
Dzhabbarova Y.K., Ismoilova S.T., Musakhodzhayeva D.A.

Abstract

Hypothesis/aims of study. The frequency of hypertension in iron deficiency anemia (IDA) reaches 32–45%. The pathogenesis of pregnancy complicated with anemia and preeclampsia, including immunological aspects, has been little studied. The aim of this study was to clarify the role of general and local cytokine status violations in pregnant women with anemia in the genesis of preeclampsia and to justify the need for inclusion of immunosuppressive agents for the prevention and treatment of preeclampsia.

Study design, materials and methods. The cytokine status (IL-1β, IL-6, IL-8, TNFα) and the level of lactoferrin in peripheral blood serum and in extracts of the placental decidual tissue were examined by ELISA in 96 pregnant women with IDA and preeclampsia in the third trimester of gestation. Pregnant women were divided into four groups: 24 with mild anemia, 18 with moderate anemia, 26 with preeclampsia and mild anemia, and 28 with preeclampsia and moderate anemia.

Results. It has been shown that preeclampsia, along with IDA, is accompanied by a significant increase in the level of pro-inflammatory cytokines and the acute phase protein lactoferrin at the systemic and, to a greater extent, local level, that is in the decidual membrane of the placenta, in the development of preeclampsia against the background of moderate anemia. The data obtained confirm the involvement of the immune system in the pathogenesis of preeclampsia, one of the triggers of which is the immune imbalance in IDA. A pathogenetic rationale for the use of immunosuppressive therapy for combined pathology is given.

Conclusion. The use of placental hormone progesterone as an immunosuppressive drug in terms of substantiating new immunotherapy strategies for the prevention and treatment of preeclampsia is a topical trend in obstetric practice.

Journal of obstetrics and women's diseases. 2019;68(5):37-44
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Vitamin D and mineral metabolism after childbirth with the use of preventive doses of cholecalciferol
Novikova T.V., Zazerskaya I.E., Kuznetsova L.V., Shelepova E.S., Khazova E.L.

Abstract

Hypothesis/aims of study. According to the literature, the prevalence of vitamin D deficiency and its deficiency in pregnant women reaches 60–80%, which is a significant factor in reducing bone mineral density (BMD), osteopenia, and the risk of fractures after childbirth. Hormone-mediated changes in calcium-phosphorus metabolism during lactation are an independent factor in the reduction of BMD. Therefore, the study of the relationship between vitamin D deficiency and insufficiency after childbirth and the possibility of correction is relevant. The aim of this study was to evaluate the effect of prophylactic doses of cholecalciferol and calcium carbonate over time on calcium-phosphorus metabolism indicators after childbirth.

Study design, materials and methods. A randomized controlled trial was conducted based on V.A. Almazov National Medical Research Center, Saint Petersburg. 64 puerperas, who lived in St. Petersburg from 2013 to 2014, were surveyed on the 3–5th day after childbirth. The age of women ranged from 20 to 35 years. Blood serum levels of calcium, phosphorus, magnesium, 25-hydroxycalciferol (25(OH)D), and parathyroid hormone (PTH) were determined for all the puerpera. Using the blind envelope method, the postpartum women were randomized into groups: group I received cholecalciferol 400 IU and calcium carbonate 1000 mg after delivery for 6 months; group II received cholecalciferol 900 IU and calcium carbonate 1000 mg after delivery for 6 months. Blood sampling was performed over time to assess the levels of 25(OH)D, PTH, calcium, phosphorus, and magnesium.

Results. In group I after childbirth, the initial level of 25(OH)D in the blood serum was 22.46 ± 4.35 ng/ml, which corresponds to vitamin D insufficiency. An increase in 25(OH)D level by 3.56 ng/ml was observed after 3 months from the start of taking cholecalciferol 400 IU. After 6 months, the level of 25(OH)D reached normal values in 20% of women (p = 0.0001). In group II after childbirth, the initial level of 25(OH)D in the blood serum was 20.64 ± 5.37 ng/ml, which corresponds to vitamin D insufficiency. An increase in 25(OH)D level by 7.60 ng/ml was observed after 3 months from the start of taking cholecalciferol 900 IU. After 6 months, the level of 25(OH)D reached normal values in 56% of women, while the average level of 25(OH)D in these women corresponded to its normally low values. The levels of PTH, calcium, phosphorus, and magnesium remained within the reference values in both groups; however, there was an increase in PTH concentration 6 months after delivery, which may indicate that the cholecalciferol dose is insufficient to stabilize PTH.

Conclusion. Vitamin D deficiency and insufficiency occurred in 80-97 % of those examined after delivery. The use of prophylactic doses of cholecalciferol has a positive effect on calcium-phosphorus metabolism; however, they are not sufficient to stabilize PTH level. The cholecalciferol dose of 400 IU is insufficient to normalize the level of 25(OH)D within 6 months of administration. The cholecalciferol dose of 900 IU leads to normally low values of 25(OH)D in 56 % of women after 6 months of administration, but this does not stabilize PTH level either.

Journal of obstetrics and women's diseases. 2019;68(5):45-53
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An alternative method of surgical treatment of ovarian endometriomas from the standpoint of preservation of the ovarian reserve
Popov E.N., Rusina E.I., Sudakov D.S., Dymarskaya Y.R., Koleboshina M.A.

Abstract

Hypothesis/aims of study. Ovarian endometriomas are a great danger to the female reproductive function. In addition to the negative impact of the disease itself on ovarian reserve, the reproductive capabilities of women are influenced by surgery on the ovaries and subsequent hormonal therapy. Ovarian reserve after cystectomy of the endometriomas suffers more than after removal of other benign ovarian tumors. The solution of the problem can be obtained using sclerotherapy during laparoscopy. The aim of this study was to assess the impact of sclerosing endometriomas during laparoscopy on the ovarian reserve.

Study design, materials and methods. The study involved 36 patients aged 25–35 years. Inclusion criteria were genital endometriosis, endometrioma of one of the ovaries with a volume of 15–100 cm3, and pregnancy planning. Exclusion criteria were uterine fibroids, endometrial hyperplasia, polycystic ovary syndrome, and the previous operations on the ovaries and uterine tubes. The main group consisted of 18 patients who underwent sclerotherapy of an endometrioma during laparoscopy with a 70% ethanol solution. The comparison group comprised 18 patients who underwent cystovariectomy with bipolar coagulation of the tumor lining. Within 4 months after surgery, gonadotropin-releasing hormone agonists were administered. An ultrasound examination of the pelvic organs and determination of anti-Müllerian hormone (AMH) level were performed before surgery, after surgery, and after hormonal treatment.

Results. In both study groups, AMH level decreased immediately after surgery: in the main group, it reduced by 1.4 times, in the comparison group by 2.4 times. After termination of therapy with gonadotropin-releasing hormone agonists and recovery of the menstrual cycle, AMH level increased slightly (it was 2.9 ± 0.40 ng/ml in the main group, and 1.8 ± 0.24 ng/ml in the comparison group). Within 12 months after surgery, pregnancy occurred in 44.4% of patients in the main group and in 33.3% of patients in the comparison group. Over 16 months of follow-up, not a single case of recurrence of the disease was subsequently detected.

Conclusion. Sclerotherapy of endometriomas during laparoscopy is supposed to be an effective and promising technique aimed at preserving the ovarian reserve in this category of patients.

Journal of obstetrics and women's diseases. 2019;68(5):55-62
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The efficiency of treatment of vaginal infections in women with a history of miscarriage
Siniakova A.A., Shipitsyna E.V., Budilovskaya O.V., Bolotskikh V.M., Savicheva A.M.

Abstract

Hypothesis/aims of study. The problem of vaginal infections during pregnancy is of high importance in obstetric practice. To predict the risks and reduce the frequency of pregnancy and childbirth complications, it is necessary to dynamically assess the vaginal microflora and treat its disorders. The aim of the study was to investigate the vaginal microflora and evaluate the effectiveness of treating vaginal infections in pregnant women with a history of miscarriage.

Study design, materials and methods. The study included 153 pregnant women in the first trimester. The main group (group I) consisted of 99 women with a history of miscarriage, 35 of whom had signs of threatened abortion (subgroup IA) and 64 did not (subgroup IB). The control group (group II) comprised 54 women without a history of miscarriage and signs of threatened abortion. The vaginal microflora was examined using microscopic, bacteriological and quantitative real-time PCR methods. All patients with an established vaginal infection (bacterial vaginosis, aerobic vaginitis, and vulvovaginal candidiasis) received etiotropic therapy, depending on the microorganisms identified and their sensitivity to antimicrobial drugs. After treatment, in order to assess the effectiveness of the therapy, the vaginal microflora was examined in the second trimester and the outcomes and complications of present pregnancy were evaluated.

Results. In women of subgroup IA, vulvovaginitis and bacterial vaginosis were detected 3.5 times more often compared to the control group, and 1.6 times more often compared to subgroup IB (66% and 19%, respectively, p < 0.001; 66% and 42%, respectively, p < 0.05). Aerobic vaginitis was the most frequent vaginal infection in the first trimester of pregnancy in women of the main group (p < 0.05). After treatment, the frequency of the vaginal infections in the second trimester in women of the main group significantly decreased: by 1.9 times in subgroup IA and by 1.5 times in subgroup IB (p < 0.05). There were no significant differences in the frequency of adverse pregnancy outcomes in women with bacterial vaginosis or vulvovaginitis as compared to women with normal vaginal microflora. Nevertheless, pregnancy and childbirth complications were diagnosed 4 times more frequently in the main group (23% and 6%, respectively, p < 0.05), with the complications occurring significantly more often in the cases of vulvovaginitis or bacterial vaginosis and signs of threatened abortion in the first trimester (p < 0.05).

Conclusion. Etiotropic therapy of vaginal infections diagnosed in the first trimester of pregnancy in women with a history of miscarriage was highly effective. In 40% of women, vaginal microbiocenosis normalized, and the clinical symptoms of vaginosis/vaginitis disappeared. Differences in the frequency of adverse pregnancy outcomes in women with vulvovaginitis or bacterial vaginosis in the first trimester and in women with normal vaginal microbiocenosis were not significant. However, the treatment of vaginal infections in the group of pregnant women with a history of miscarriage did not significantly affect the frequency of pregnancy and childbirth complications.

Journal of obstetrics and women's diseases. 2019;68(5):63-74
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Early pregnancy loss as an indication for preimplantation genetic testing
Smirnova A.A., Zyryaeva N.A., Zhordanidze D.O., Anshina M.B., Kira E.F.

Abstract

Hypothesis/aims of study. Approximately 10–15% of clinical pregnancies end in spontaneous abortions. The main cause of early miscarriages is chromosomal aberrations of the embryos. Chromosomal abnormalities are detected in 70% of sporadic miscarriages and in 30–50 % of recurrent miscarriage. Modern assisted reproductive technologies allow not only to treat infertility, but also to provide access to embryos, which makes it possible to test them for hereditary diseases and chromosomal abnormalities before implantation. This study aimed to assess the efficacy of preimplantation genetic testing (PGT) in patients with infertility and early pregnancy loss.

Study design, materials and methods. IVF outcomes were studied retrospectively in 84 patients under the age of 39 years. The first group consisted of 22 women with a normal karyotype, who underwent 34 IVF cycles with PGT for aneuploidies and 22 transfers of euploid embryos. The second group comprised 48 women with a normal karyotype, who underwent IVF treatment without PGT. In this group, we preformed 45 frozen and 18 fresh embryo transfers. The third group included 14 couples with chromosomal structural rearrangements, who underwent 22 IVF cycles with PGT for chromosomal structural rearrangements.

Results. The cumulative pregnancy rate and the birth rate did not significantly differ between the study groups. The early miscarriage rate and the multiple pregnancy rate were significantly lower in groups with PGT compared to the group without PGT. The aneuploidy rate was significantly higher in women with two or more pregnancy losses in history compared to patients with only one pregnancy loss.

Conclusion. The data obtained allow recommending IVF with PGT to women with recurrent pregnancy loss in order to avoid subsequent miscarriage.

Journal of obstetrics and women's diseases. 2019;68(5):75-82
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In vitro antimycotic sensitivity of the genus candida yeast and lactobacillus rhamnosus probiotic strain
Spasibova E.V., Savicheva A.M.

Abstract

Hypothesis/aims of study. Vulvovaginal candidiasis (VVC) is one of the most common inflammatory diseases of the vagina. Herewith, a synergistic effect of lactobacilli and antifungal drugs in VVC treatment is suggested. In this regard, it seems relevant to study the effect of antimycotics used to treat VVC on the enhanced L. casei rhamnosus 35 (LCR35) probiotic strain. This study was aimed to determine the sensitivity to antimycotic drugs of the probiotic LCR35 strain included in the Lactoginal® vaginal capsules, as well as the sensibility of the genus Candida yeast under separate and joint cultivation with lactobacilli.

Study design, materials and methods. LCR35 was cultured on a MRS agar. Identification of bacteria grown on the medium, as well as clinical isolates of C. albicans and C. parapsilosis, isolated from the vagina, was performed by MALDI-TOF mass spectrometry. The sensitivity of yeast was determined on a modified Müller-Hinton agar with 40% glucose and methylene blue. Discs with fluconazole, voriconazole, itraconazole, ketoconazole, clotrimazole, and nystatin were used. Interpretation of growth inhibition zones was carried out according to EUCAST-2018 or according to the recommendations of the disc manufacturer.

Results. The probiotic LCR35 strain is resistant to antimycotics that are effective against C. albicans and C. parapsilosis. When determining the sensibility of C. albicans and C. parapsilosis to antimycotics in separate and joint cultivation with LCR35, no differences were found in the degree of yeast-like fungi growth suppression.

Conclusion. The probiotic LCR35 strain, which is part of the Lactoginal® vaginal capsules, is resistant to antimycotic drugs and does not affect the sensitivity of the tested yeast-like fungi to antimycotics.

Journal of obstetrics and women's diseases. 2019;68(5):83-89
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Reviews
Inhibin as a reproductive biomarker part 2. Clinical significance of inhibins in reproductive medicine
Abdulkadyrova Z.K., Yarmolinskaya M.I., Gzgzyan A.M., Dzhemlikhanova L.K., Abashova E.I.

Abstract

In the early 2000s, the determination of inhibin levels was used actively for the diagnosis of ovarian tumors, as a diagnostic marker for prenatal screening of Down syndrome, as well as a prognostic marker for ovarian reserve when conducting assisted reproductive technologies. However, to date, inhibin is rarely used as a marker for reproductive function. At the same time, numerous studies of recent years indicate the crucial role of inhibin in folliculogenesis and spermatogenesis, as well as in implantation and placentation. This allows to significantly expand the diagnostic spectrum of inhibin levels in various disorders of the reproductive system of both women and men.

Journal of obstetrics and women's diseases. 2019;68(5):91-106
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Аnti-inflammatory effects of vitamin K on women's health
Zagaynova V.A., Bespalova O.N.

Abstract

This article presents the latest research data on the role of vitamin K in the implementation of its multiple “non-classical” extra-coagulation effects associated with the regulation of a number of physiological and pathological processes in the human body. In recent years, numerous studies have been performed on vitamin K function to better understand the effects of this micronutrient and its significance in various biological reactions. Vitamin K is well known to be a cofactor of the γ-carboxylation of a number of proteins, which is necessary for their activation and is part of the so-called vitamin K cycle. The cycle enzymes, metabolites and vitamin K-dependent proteins are identified and expressed in many cells and tissues of the human body: skin, lungs, liver, kidneys, vascular endothelium, nervous and bone tissues, reproductive (endometrium, ovaries, placenta) and immune systems. There were analyzed the main mechanisms of vitamin K action through vitamin K-dependent proteins. The results of epidemiological and experimental studies prove the association of reduced vitamin K levels with the increased risk of cardiovascular diseases, overall mortality, insulin resistance, metabolic syndrome, type 2 diabetes mellitus, progression of rheumatoid arthritis and osteoporosis. On the contrary, vitamin K increased intake has a positive effect on the immune and nervous systems, as well as on a number of other somatic pathologies, including breakdowns in the reproductive sphere. These data confirm the multifunctional role of vitamin K in various organs and systems of organism, presenting as high potential further studies in the field of determining vitamin K levels.

Journal of obstetrics and women's diseases. 2019;68(5):107-114
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Optimization of methods for the diagnosis and treatment of urinary tract infections in pregnant women
Khudovekova A.M., Mozgovaya E.V.

Abstract

A urinary tract infection (UTI) during pregnancy remains one of the most important problems of obstetrics, urology, and nephrology. Pregnancy as physiological process contributes to UTI. This is caused by urinary clinical signs changing during pregnancy, approaches to diagnosis and treatment, as well as to the risk of developing urological, obstetric and neonatal complications. This article analyzes contemporary literature over the past 10 years.

Journal of obstetrics and women's diseases. 2019;68(5):115-122
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