Vol 23, No 4 (2021)

EDITORIAL

Dedicated to Ekaterina Mikhailovna Vikhlyaeva (08/05/1925– 02/22/2021)

Prilepskaya V.N.

Abstract

XXVII All-Russian Congress with international participation "Outpatient and polyclinic care at the epicenter of women's health from menarche to menopause", held in Moscow on April 21-23, 2021, chaired by Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor G.T. Sukhikh and Doctor of Medical Sciences, Professor V.N. Prilepskaya, was dedicated to the memory of Corresponding Member of the Russian Academy of Sciences, Professor E.M. Vikhlyaeva - an amazing person, an excellent doctor, a great scientist. The presented material is a tribute to a woman whose life is an example of selfless service to people, medical science, her teachers and students.

Gynecology. 2021;23(4):284-285
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REVIEW

Bacterial vaginosis: modern concepts, approaches to diagnosis and treatment

Uruimagova A.T., Prilepskaya V.N., Mezhevitinova E.A., Donnikov A.E., Ivanova A.A.

Abstract

Microbiota – a set of human microorganisms that exist with him in normal and pathological conditions, are involved in physiological and pathophysiological reactions, metabolism. The classic manifestation of a violation of the vaginal microbiota is a clinical non-inflammatory syndrome – bacterial vaginosis (BV), characterized by certain changes in the composition of the vaginal microbiota and excessive reproduction of microorganisms, which are normally present in small quantities. To date, literature data emphasize that the issues of the etiology, pathogenesis of BV, the reasons for the recurrence of the process are not fully understood, the reasons for the lack of long-term effectiveness of BV therapy are unknown. Further research in this area should be aimed at studying predictors and prognostic signs of recurrence and persistence of the process, differences in vaginal microbiota in patients with recurrent and persistent BV.

Gynecology. 2021;23(4):286-293
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State of the problem of early diagnosis and treatment of benign ovarian tumors in postmenopausal patients (literature review)

Podzolkova N.M., Kuznetsov R.E., Glazkova O.L., Sozaeva L.G., Tumgoeva L.B.

Abstract

As life expectancy increases, older people require strict individualization of management and treatment, taking into account all age and pathophysiological characteristics of a particular patient, a more attentive approach to the features of clinical manifestations of diseases, the presence of comorbid pathology. Timely diagnosis and comprehensive treatment of postmenopausal patients with benign ovarian tumors is a debatable issue, since none of the existing diagnostic methods of research in practice provides sensitivity and specificity equal to or at least approaching 100% of the indicator. The progressive aging of the population raises the question of whether it is necessary to operate on menopausal patients with benign ovarian tumors of small size (up to 5 cm), given the low percentage of malignancy of these formations and the high risk of deterioration in the patients’ quality of life after surgical interventions.

Gynecology. 2021;23(4):294-299
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Current views on the pharmacological correction of iron deficiency conditions in gynecological practice

Dukhanin A.S.

Abstract

The review considers features of iron and folic acid (FA) pharmacokinetics, which affect the effective micronutrient support: molecular mechanisms of absorption and distribution, homeostatic processes of maintaining plasma vitamin and mineral levels by the feedback mechanism, including by regulating the deposition. An important characteristic of ferrokinetics is the presence of unique iron exporter ferroportin which is controlled by a family of iron regulatory proteins. Systemic ferrotherapy and oral rout of iron delivery are distinguished. In general, parenteral iron preparation complexes consist of Fe(III) oxide/hydroxide core stabilized by a carbohydrate polymer shell. Once entering the bloodstream, iron complexes are absorbed by resident macrophages of the reticuloendothelial system of the liver, spleen and bone marrow. Systemic Fe(III) preparations are prodrugs, the active part of which, i.e. iron is released in the lysosomal matrix of phagocytes. Oral iron preparations are divided into those containing bivalent (ferrous) and trivalent (ferric) iron. The article discusses factors determining the differences in the absorption of oral ferrous and ferric iron preparation, the spectrum of side effects, as well as key pharmaceutical approaches to increase the tolerance and adherence of ferrotherapy. These include using preparations containing Fe(II) organic compounds that have a lower dissociation rate than inorganic iron salts as well as slowing down the release of the active Fe(II) pharmaceutical substance from the drug. The review pays special attention to folates as iron synergists and examines the features of FA pharmacokinetics, the molecular basis of synergism, and substantiates the use of combined iron and FA preparations.

Gynecology. 2021;23(4):300-306
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Key management issues of heavy menstrual bleeding in adolescents and young women

Uvarova E.V.

Abstract

Despite high prevalence of heavy menstrual bleeding (HMB) in adolescents and young women, most recommendations are not specific for this population, which makes the diagnosis and management challenging. Gynecologists should be able to establish underlying causes of HMB, which most common are nonstructural in adolescents, and the severity of bleeding, to provide early diagnosis, using appropriate therapy for improving quality of life  and iron deficiency prevention. First line management consists of hormonal therapy approved for HMB treatment, capable to normalize menstrual blood loss and iron metabolism parameters.

Gynecology. 2021;23(4):370-376
pages 370-376 views

ORIGINAL ARTICLE

Clinical and diagnostic aspects of deep infiltrative endometriosis (diagnosis, treatment, recurrence)

Muftaidinova S.K., Faizullin L.Z., Chuprynin V.D., Ruseikin N.S., Smolnova T.I., Buralkina N.A.

Abstract

Aim. To analyze the recurrence of endometriosis after surgical treatment of patients with deep endometriosis.

Materials and methods. The case histories of 90 patients aged 19 to 45 years were retrospectively analyzed. The study group consisted of 70 endometriosis patients: 20 with peritoneal endometriosis and 50 with deep infiltrative endometriosis (DIЕ). The comparison group included 20 women without endometriosis. There was an in-depth study of anamnestic data in the cohort of patients under study. The results of preoperative laboratory tests, including serum levels of the CA-125 and CA 19-9 oncomarkers, were processed.

Results. Analysis of the obtained data showed that about half of the DIE patients (54%) in the main group had a history of surgical interventions for endometriosis. The number of operations was significantly higher in patients compared to the peritoneal endometriosis group (68% vs 20%, respectively; р=0.0012). Two subgroups were formed from the group of women with DIE: patients who had no history of previous surgical treatment for endometriosis and those hospitalized for repeated surgical treatment of endometriosis (patients with recurrent endometriosis). Patients with recurrent endometriosis had a significantly higher incidence of heavy menstruation, pregnancy terminations (abortions), and a high proportion of gastrointestinal diseases. Analysis of the hormonal therapy received in patients with DIE showed that every second patient with relapses (18/53%) after surgical treatment and every third patient without a prior history of surgery (5/31%) received hormonal therapy. Examination of the preoperative serum levels of CA-125 and CA 19-9 serum markers in patients with DIE showed an increase in their serum levels and a correlation with the frequency of endometriosis recurrence and the size of DIE foci.

Conclusion. Despite the conservative and surgical treatment of DIE patients, the recurrence rate is still high. At present, there is no satisfactory therapy for all endometriosis patients. Therefore, the development of therapy for the conservative treatment of the disease remains an urgent task.

Gynecology. 2021;23(4):307-313
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The effectiveness of therapy for endometriosis-associated pelvic pain resistant to surgical treatment

Orazov M.R., Radzinsky V.E., Orekhov R.E.

Abstract

Aim. To assess the efficacy and safety of 24-week therapy with dienogest in patients with endometriosis-associated pelvic pain resistant to surgical treatment.

Materials and methods. The study included 126 patients aged 33–40 years with external genital endometriosis (EGE) confirmed by laparoscopy and morphological examination (International classification of diseases, 10th revision [ICD-10] – N80.1, 80.2, 80.3, 80.4) and with pelvic pain that occurred in 3–6 months after surgical treatment of EGE (ICD-10 – N94.8 "Pain and other conditions associated with female genital organs and menstrual cycle"). The participants were stratified into 3 groups by pain syndrome severity according to the Verbal Analog Scale (VAS). The group-1 included patients with 10–40 mm, the group-2 – with 41–70 mm, and the group-3 – with more than 71 mm pain score according to VAS. Patients of all 3 groups were prescribed the denogest (Zafrilla®, Gedeon Richter, 2 mg/day) for 24 weeks (according to the current pack insert). Follow-up and assessment of treatment outcomes were carried out over 6 months. Study design: prospective, observational, comparative study.

Results. In 3 and 6 months after the start of therapy, there was a stable statistically significant decrease in pain syndrome severity by all scales (Biberoglu & Behrman Scale, Numeral Rating Scale, VAS) in each of the groups (p<0.01). In all 3 groups, treatment led to an improvement in sexual function, assessed with the Female Sexual Function Index scale, in 3 and 6 months after the start of therapy (p<0.01). According to the quality of life in endometriosis (Endometriosis Health Profile) questionnaire, the analyzed indicators significantly improved in all study participants (p<0.01).

Conclusion. Dienogest is an effective and safe method for the treatment of endometriosis-associated pelvic pain resistant to surgical treatment. Treatment with dienogest for 24 weeks effectively relieves pain, improves symptoms, and improves quality of life and sexual functioning.

Gynecology. 2021;23(4):314-323
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Septostomy during laser surgery for twin-to-twin transfusion syndrome

Bugerenko A.E., Shcherbakova L.N., Panina O.B.

Abstract

Aim. To assess the perinatal outcomes of monochorionic diamniotic (MCDA) pregnancy after fetoscopic laser coagulation of anastomoses (FLCA) performed for twin-to-twin transfusion syndrome (TTTS), accompanied by induced or unintentional septostomy, and to identify the factors leading to septostomy.

Materials and methods. The retrospective study included 231 cases of FLCA performed in pregnant women with TTTS: in 19 cases septostomy was performed, and in 212 cases intertwin membrane remained intact.

Results. The incidence of septostomy during FLCA for TTTS was 8.2%. In 47.3% the rupture of the intertwin membrane occurred during trocar insertion (unintentional septostomy); in 42.1% septostomy was needed to perform laser coagulation of anastomoses located on the placental surface in the donor's amnion (forced septostomy). The placenta was located on the anterior uterine wall in 78.9% in the septostomy group and in 47.6% with an intact intertwin membrane (p=0.01). Anastomoses were located on the “donor” half of the placenta significantly more often when septostomy was needed to perform selective coagulation of anastomoses located far from the intertwin membrane and obstructed by the body of the donor fetus (42.1%). In 15.8% of patients with septostomy and 2.4% with intact intertwin membrane, umbilical cords of the donor and the recipient fetus were attached closer than 2 cm to each other (p=0.003). In the septostomy group premature rupture of membranes was more frequent (42.1% vs 18.4%, p=0.03) and a delivery time was shorter [26.3 (18.0, 37.0) vs 34.4 (20.3, 40.0) weeks, respectively, p=0.01] than in patients with an intact intertwin membrane. The survival rate after FLCA was lower after septostomy compared to intact intertwin membrane: at least one of the twins survived in 47.4% vs 80.7%, respectively (p=0.002), both fetuses survived in 36.8% vs 75.0%, respectively (p=0.001). Logistic regression analysis showed increased risk of septostomy in patients with the anastomoses located on the “donor” half of the placenta and when the donor and the recipient umbilical cords are attached close to each other, regardless of the localization of the placenta, gestational age and the stage of TTTS.

Conclusion. Lower incidence of unintentional septostomy during FLCA achieved by using modern equipment and surgical techniques will lead to better perinatal outcomes in patients with MCDA twins with TTTS.

Gynecology. 2021;23(4):324-329
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The rs5918 polymorphism in the ITGB3 gene increases the risk for preeclampsia in pregnant women with fetal growth retardation

Golovchenko O.V., Ponomarenko I.V., Churnosov M.I.

Abstract

Aim. To assess the relationship of rs5918 ITGB3, rs1126643 ITGA2 and rs5985 F13A1 polymorphic loci with the risk for preeclampsia (PE) in pregnant women with fetal growth retardation (FGR).

Materials and methods. The study included 272 pregnant women, of which 76 had a combination of PE and FGR and 196 had FGR. In the studied groups, genetic testing was carried out for three polymorphic loci of candidate genes for hereditary thrombophilia (rs5918 ITGB3, rs1126643 ITGA2, and rs5985 F13A1).

Results. The rs5918 genetic variant in the ITGB3 gene is associated with the development of PE in pregnant women with FGR: C allele of rs5918 ITGB3 increases the risk for this complication of pregnancy by 1,8 times (OR 1.76–1.77, p≤0.036, pperm≤0.038). The rs5918 polymorphism determines an increase in the affinity of DNA motifs for seven transcription factors (BDP1, ELF1, IRF, NRSF, Pax-5, Sp1, and Zfx), is a missense mutation and causes the Leu59Pro amino acid substitution in the β3 subunit of integrin, is multidirectionally associated with the expression of five genes (EFCAB13, TBKBP1, NPEPPS, MRPL45P2, THCAT158) and alternative splicing of two genes (EFCAB13, MRPL45P2), is located in the region of functionally important DNA regions (promoters and enhancers) in cell cultures and organs which are pathogenetically important for the formation of PE and FGR.

Conclusion. The rs5918 polymorphism in the ITGB3 gene increases the risk for PE in pregnant women with FGR.

Gynecology. 2021;23(4):330-334
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Diagnosis of Ia–Ic stages of serous high-grade ovarian cancerby the lipid profile of blood serum

Iurova M.V., Frankevich V.E., Pavlovich S.V., Chagovets V.V., Starodubtseva N.L., Khabas G.N., Ashrafyan L.A., Sukhikh G.T.

Abstract

Background. Ovarian cancer is the first fatal malignancy of the female reproductive system. Early detection is associated with better outcomes, but is significantly difficult because of asymptomatic or low-symptomatic course.

Aim. To study the possibility of detecting of OC in early stages (Ia–Ic) by the lipid profile of blood serum obtained using high-performance liquid chromatography with mass spectrometric (MS) detection.

Materials and methods. An observational "case-control" study was conducted in period November 2019 – July 2020 in the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology. 41 patients were included: group 1 (main) – 28 patients with histologically verified high grade serous ovarian cancer of I–IV FIGO stage, group 2 (control) – 13 conditionally healthy women. Venous blood samples were collected immediately before the operation. Extracts of serum lipids were obtained in accordance with the modified Folch method. The composition of the samples was analyzed by electrospray ionization MS. Using the method of discriminant analysis and orthogonal projections to latent structures (OPLS-DA) were building OPLS-models based on profile of significant lipids. The comparison based on the non-parametric Mann–Whitney test.

Results. The presence of 128 lipids in blood serum samples makes a major contribution to the OPLS-models, that are different for patients with I–IV OC stage and controls. The OPLS-model parameters are: R2=0.87 and Q2=0.80, the area under the ROC curve reached 1, sensitivity and specificity of the model – 100%. The second OPLS-model was developed to assign patients to 13 blood serum samples of the control group or to 5 blood samples of patients with I-II stages of OC: 108 lipids made the main contribution to this model (R2=0.97, Q2=0.86). The third OPLS-model was constructed to distinguish patients with earlier (Ia–Ia stages; n=5) and advanced (IIa–IVa; n=23) stages: R2=0.96 and Q2=1.00, AUC=0.99. Diglycerides, triglycerides, phosphatidylcholines, ethanolamines, sphingomyelins, ceramides, phosphatidylserines, phosphoinositols and prostaglandins significantly differ in the blood serum samples of patients with Ia–Ic stages of OC and patients with II–IV stages and controls, that indicates the diagnostic value.

Conclusion. It is possible to distinguish a healthy person from patient with Ia–Ic or II–IV stages of OC. Serum oncolipids profile obtained by high-performance liquid chromatography with MS detection can be used as markers of early stages of OC, that are associated with better prognosis.

Gynecology. 2021;23(4):335-340
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Comparative evaluation of the results of an immunocytochemical study of P16/Ki-67 coexpression in patients with cervical intraepithelial neoplasia associated with human papillomavirus

Klinyshkova T.V., Samosudova I.B., Buyan M.S.

Abstract

Aim. To evaluate the results of an immunocytochemical study of p16/Ki-67 double staining in the cervical epithelium of patients with cervical intraepithelial neoplasia (CIN) associated with high-risk human papillomavirus (HPVhr) in comparison with patients without cervical pathology.

Materials and methods. The comparative study included the results of examination of 75 patients divided into 4 groups. Patients with CIN1 comprised the 1st main group (n=21), women with CIN2–CIN3 – the 2nd main group (n=26), the comparison group consisted of patients with latent HPV infection (n=15) and the control group (n=13). The average age of women with cervical HPV infection was 26.4±6.13 years. Methods of investigation: liquid cytology, colposcopic, histological examination; methods for determining HPVhr DNA; immunocytochemical examination for determining double staining of p16/Ki-67 markers, statistical analysis.

Results. A positive p16/Ki-67 double staining test prevailed among patients with CIN (31.9%) compared to patients without cervical pathology (3.6%) (p=0.003) and correlated with the severity of colposcopic signs (rs=+0.397, p=0.0004). In the 1st main group of patients with verified CIN1 and in the comparison group of patients with latent infection, isolated cases of a positive test of double staining of p16/Ki-67 markers in the epithelium were recorded without significant differences between the groups (9.5 и 6.6%, p>0.05). In the 2nd main group of patients with verified CIN2, CIN3, a positive test of double staining of p16 and Ki-67 was observed in every second case, dominating relative to the 1st group, the comparison group and the control group (p=0.003, p=0.005, р=0.001 respectively). In the control group, a negative double staining test was established in all cases.

Conclusion. Every second patient with CIN2+ associated with HPVhr has a positive test of double staining of the cervical epithelium, with CIN1 it is observed in 9.5% of cases (p=0.003). Among patients with CIN1, there were no differences in the expression of p16/Ki-67 in epithelial cells compared to women without cervical pathology. The data of the immunocytochemical study of p16/Ki-67 in the cervical epithelium of HPVhr – positive patients with CIN should be taken into account when choosing a differentiated management strategy.

Gynecology. 2021;23(4):341-345
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Stress-protective effects of micronized progesterone in treatment of anxiety disorders in pregnant women after in vitro fertilisation

Tapilskaya N.I., Nekrasov M.S., Krikheli I.O., Ob'edkova K.V., Gzgzyan A.M., Kogan I.Y., Glushakov R.I.

Abstract

Aim. To study a stress-protective efficacy of micronized progesterone (MP) in pregnant women with anxiety disorders after in vitro fertilisation (IVF).

Materials and methods. We conducted a prospective, comparative open-label randomized trial in two IVF-clinics. A total of 98 pregnant women after IVF with anxiety disorders were recruited at the 9th week of pregnancy. Progesterone supplementation after IVF for luteal phase support was administered out until 9 weeks gestation. Then, after randomization, group 1 (n=35) received 400 mg per day of MP vaginally, group 2 (n=33) received 400 mg of MP orally, group 3 (n=30) was comparative for the other groups. The duration of progesterone treatment was 12 weeks. The Spielberger State Trait Anxiety Inventory (STAI), the Montgomery–Åsberg depression rating scale (MADRS), Hospital Anxiety and Depression Scale (HADS), and the Epworth Sleepiness Questionnaires (ESQ) were used to compare maternal mood at 9 weeks (day of randomization) after delivery and at 28±3, 56±5, 84±7 days after randomization.

Results. The mean STAI sumscore in MP-groups was significantly lower than in group 3 starting from day 56±5 and continued until the end of the study. There were no significant differences between vaginal and oral administration of progesterone. There were no significant differences between the mean sumscores when questioning on the HADS, MADRS and ESQ.

Conclusion. Prolonged use of MP in pregnant women with anxiety disorders led to the prevention of manifestations of an increase in anxiety and depression. The stress-protective and neuromodulating properties of MP can determine additional indications for its prolonged administration in women with anxiety disorders and/or premorbid history.

Gynecology. 2021;23(4):346-353
pages 346-353 views

Mastalgia in infertility: search for additional possibilities of therapy

Krasnopolskaya K.V., Balan V.E., Ershova I.Y., Skorik E.O., Malygin S.E., Orazov M.R., Toktar L.R., Lagutina E.V.

Abstract

Aim. To assess the efficacy and safety of using the homeopathic drug Mastopol for the relief of mastalgia in women with infertility, including those associated with endometriosis, as well as to study the drug tolerability and adherence to the treatment, as well as to determine its antiproliferative and analgesic effects in patients of the study cohort. Study design: open-label, randomized, non-comparative, observational study.

Material and methods. 79 infertile women with mastalgia (67 with cyclic mastalgia and 12 with acyclic mastalgia) were examined and treated with Mastopol. Mastopol was prescribed 1 tablet 3 times a day sublingually. The course of treatment was 8 weeks. The efficacy of mastalgia relief was assessed using a Visual Analogue Scale (VAS). Treatment outcomes were considered good if pain severity by the VAS decreased by 4 or more points from the baseline levels at the end of Mastopol treatment course.

Results. One Mastopol treatment course provided good treatment outcomes in 76,2% of patients with cyclic mastalgia and in 33,3% of patients with acyclic mastalgia. There were no adverse reactions or complications in patients treated with Mastopol.

Conclusions. Mastopol has established itself as a quite effective and safe drug in patients of the study cohort; if there is an insufficient effect, Mastopol can supplement traditional pharmacological agents recorded in the current clinical guidelines.

Gynecology. 2021;23(4):354-363
pages 354-363 views

Effectiveness of therapy for endometriosis-associated pelvic pain resistant to surgical treatment

Orazov M.R.

Abstract

Summary: to evaluate the efficacy and safety of dienogest therapy for 24 weeks in patients with endometriosis-associated pelvic pain resistant to surgical treatment.Material and methods. The study included 126 patients aged 33-40 years with external genital endometriosis confirmed by laparoscopy and morphological examination (NGE; ICD-10-N80. 1, 80.2, 80.3, 80.4) and with pelvic pain that occurred 3-6 months after surgical treatment of NGE (ICD-10 — N94.8 "Pain and other conditions associated with female genital organs and menstrual cycle"). The participants were stratified into three groups depending on the severity of the pain syndrome according to the verbal rating scale (VAS; Verbal Analog Scale). Group 1 included patients with a VAS pain score of 10-40 mm, group 2-41-70 mm, and group 3 — more than 71 mm. Patients of all three groups were prescribed the drug Zafrilla (dienogest 2 mg/day) for a course of 24 weeks (according to the current instructions

Gynecology. 2021;23(4):
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BEST PRACTICE

Important questions to ask when choosing hormonal contraception. Myths about contraception

Prilepskaya V.N., Bostandzhian L.L.

Abstract

Due to the introduction of modern methods of contraception in Europe and, in particular, in Russia, the abortion rate has decreased significantly. This is largely due to the use of such a progressive method as hormonal contraception. However, the level of use of modern methods of contraception in Russia remains low, which is often due to fear of side effects and existing myths, especially in relation to hormonal contraception. Combined oral contraceptives are well studied, have a favorable profile of efficacy and safety, the risks of taking them are minimal and are reflected in the instructions for use. When properly prescribed, hormonal contraception is a reliable method of protection against unwanted pregnancy, which also has additional benefits, including therapeutic effects.

Gynecology. 2021;23(4):364–369
pages 364–369 views

Key issues in the management of adolescents and young women with heavy menstrual bleeding

Uvarova E.V., Salnikova I.А., Khashchenko E.P., Sokolova A.P.

Abstract

Despite high prevalence of heavy menstrual bleeding (HMB) in adolescents and young women, most recommendations are not specific for this population, which makes the diagnosis and management challenging. Gynecologists should be able to establish underlying causes of HMB, which most common are nonstructural in adolescents, and the severity of bleeding, to provide early diagnosis, using appropriate therapy for improving quality of life and iron deficiency prevention. First line management consists of hormonal therapy approved for HMB treatment, capable to normalize menstrual blood loss and iron metabolism parameters. 

Gynecology. 2021;23(4):370-376
pages 370-376 views


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