News. Findings and events
Actual problem
The review examines a role of HPV in the development of pre-cancer and cancer of the anogenital region. It presents the current data on the incidence of cervical (CIN) and anal intraepithelial neoplasia (AIN), the HPV infection of the anal region in women at risk (CIN, VIN, VaIN). Methods for the diagnosis of HPV-associated diseases of the anogenital region are considered. The article reviews the literature on the importance of AIN screening development in patients with CIN, VIN, VaIN. It also provides the results of own studies of HPV infection of the anal region in patients with cervical neoplasias, data on the HPV trophicity to the epithelium of the cervical canal and the anal region. Type 16 HPV is the dominant type of HPV in patients with CIN in the cervical canal and in the anus. HPV-associated cervical diseases, in particular CIN, create a risk of infection and development of HPV-associated diseases of the anal region, including AIN. A quadrivalent HPV vaccine is now available in Russia. Although initially created and used to protect against injuries to the cervix caused by HPV, it should also be considered for the prevention of other types of HPV-associated anogenital pre-cancer and cancer.
Vitamin D deficiency is the pandemica for real in the modern world [1]. The role of vitamin D in the reproductive function regulation has been proven in light of the achievements over the past few years. Being a steroid hormone, this vitamin is essential for a wide range of normal physiologic functions. Vitamin D insufficiency as defined by serum 25(OH)D ≤ 30 ng/ml is widespread globally, with the frequency of registration of this condition among the population of Russia over 90% [2]. The elderly and pregnant women (especially in the presence of fat metabolism disorders, gestational diabetes and infectious pathology), who did not undergo a vitamin correction medication, is the main risk group for vitamin D deficiency. Objective of the study: Evaluate the efficacy of colcalciferol in vitamin D-deficient therapy in women of reproductive age. Material and methods of the study: clinical and laboratory examination and treatment of 31 patients with various reproductive system pathologies, aged 21 to 45 years who were hospitalized to the Department of Gynaecology. In addition to the general clinical examination, all patients had their vitamin D, total and ionized calcium levels in blood plasma assessed. In order to correct the vitamin D deficiency and insufficiency, the vitamin D supplementation by colcalciferol (vitamin D3) intake was prescribed to all examined patients in addition to the treatment of the underlying disease. Results of the study: all examined patients showed the decreased vitamin D concentration in the blood plasma below the reference indices. The vitamin D deficiency was discovered in 64.5% cases. At the same time, a significant increase in the concentration of 25(OH)D3 in blood plasma was noted against the background of therapy.
CLINICAL OBSERVATION
The article presents the pathogenesis aspects of dysmenorrhea based on the role of prostaglandin hyperproduction in the development of the disease. The presence of severe painful cramps in dysmenorrhea resulting in a temporary decline in labour productivity contributes to not only on a significant decrease in the patients’ quality of life, but also to economic costs. In this regard, seeking a solution to the dysmenorrhea therapy problem acquires not only medical, but also social significance. The use of nonsteroidal anti-inflammatory drugs (nimesulide) as a pathogenetically validated therapy for dysmenorrhea proves their efficiency and is a feasible option for therapy.
Contraception
Recently, the use of drospirenone-containing microdosed hormonal contraceptives containing folates has come at an opportune time. The common use of these contraceptives is associated with not only high efficacy and acceptability, but also with a positive effect on the symptoms of premenstrual syndrome, which is mediated by impact on the central nervous system. Drospirenonecontaining COCs are also known as products leading to a reduction in sebum excretion rates, which makes it possible to use them in acne therapy. Metafolin as part of microdosed hormonal contraceptive Yaz® plus compensates for the folate concentration required to prevent neural tube defects in the fetus in 27–30 days of pregnancy to some extent. Consequently, the use of drospirenone-containing hormonal contraceptives with folates provides not only a contraceptive, but also a therapeutic effect when fluid is retained in the body tissues. Thus, Yaz® plus product is indicated for use not only for contraceptive, but also for therapeutic purposes, as indicated in the patient information leaflet.
ЭНДОМЕТРИОЗ
Objectives of the study: improve early non-invasive diagnosis of external genital endometriosis (EGE) using the mass spectrometry method, and determine the risk factors for recurrence of EGE after surgical treatment. Material and methods: a prospective cohort study included 100 patients with EGE who underwent surgical treatment during the 2014 to 2016 period. The EGE diagnosis was made on the basis of diagnostic and therapeutic laparoscopic findings and finally confirmed at histological exam. All patients underwent blood sampling before and after surgical treatment to detect recurrence of endometriosis using direct mass spectrometry method. Results: recurrences of EGE were diagnosed in 22% of patients at 18–36 months postoperatively. High incidence of recurrent EGE was reported in the group of patients who did not receive post-surgical hormonal therapy. The hormone therapy with dienogest 2 mg for 6-9 months, as well as with goserelin 3.6 mg for 3-6 months showed the greatest efficacy for the prevention of recurrent EGE. Significant predictive factors of recurrence after surgical treatment for EGE include intensive acyclic pelvic pain; presence of surgical interventions for the history of EGE; infertility; stimulation of ovulation with hormonal drugs as part of the Assisted Reproductive Technologies Program; degree 3-4 disease spread; pronounced adhesions of the small pelvis; infiltrative forms of endometriosis; endometrioid cysts of large size; bilateral ovarian lesions. The plasma lipid profile including determination of phosphatidylcholines, phosphoethanolamines, diglyceride and sphingomyelin in the patients with endometriosis provides an approach for noninvasive early diagnosis of recurrence of this disease by mass spectrometry (sensitivity 93%, specificity 95%). Conclusion: This study developed an individual comprehensive approach to the prevention of recurrent EGE, including surgical treatment, hormonal therapy and diagnosis of the disease at an early stage of development. Timely administration of a-GnRH or dienogest 2 mg at the post-surgery stage is associated with a minimal or total absence of recurrent EGE. The administration of COCs showed no efficacy in preventing the recurrence of EGE, and therefore COCs cannot be recommended as a prophylactic drug, but exclusively for contraceptive use.
Inflammatory pelvic diseases (IPD) are associated with increased incidence of sexually transmitted infections. The modern features of the PID course raise the question of including drugs improving therapy outcomes in the combination PID therapy. The development of chronic inflammatory processes is accompanied by changes in the body’s immune system, which serves as a basis for developing and finding new therapeutic agents and methods that have an effective therapeutic effect aimed at restoring the function of the impaired human immune status as a whole. The synthetic low molecular weight immunomodulating drug with anti-inflammatory activity aminodihydrophthalazinedione sodium possesses the above described therapeutic potential.
Objective of the study: analysis of the data presented in the modern literature on the relationships between chronic endometritis (CE) and miscarriage. Material and methods: the review includes data from foreign and domestic studies published in the electronic databases Medline, Pubmed over the past 15 years. Results: this review analysed the data on the diagnosis of CE, and pathophysiological processes leading to habitual miscarriage. It also showed the role of the microbial factor, the level of cytokines, leptins, expression of metalloproteinases, immune factor, dysbiotic disturbances of vaginal microflora.
Pregnancy and childbirth
Magnesium is a unique microelement in the human body which is necessary for all organs and systems to be sustained. During pregnancy, the need for magnesium is significantly increased due to functioning of the mother-placenta-fetus system, the intrauterine growth and development of the fetus. Maternal hypomagnesemia during pregnancy is associated with an increased risk of placental insufficiency, delayed fetal growth, threatened abortion, premature birth, gestational diabetes, and preeclampsia. Given the high prevalence of magnesium deficiency among pregnant women (up to 81.2%), it is necessary to conduct a timely assessment of the magnesium status of all pregnant women and, if necessary, to conduct timely therapy aimed at replenishing the magnesium deficiency. In the treatment of magnesium deficiency we would recommend organic magnesium salts, such as magnesium citrate, as it has the highest solubility and bioavailability.
Venous thromboembolism is a rare complication of the postpartum period. However, it holds a stable position in the maternal mortality pattern throughout the world, classified as the so-called group of beyond control causes. We have conducted a retrospective analysis of labour in puerperas, who were admitted to the Vascular Surgery Department of Inozemtsev State Clinical Hospital with venous thromboembolic complications in the period from 2015 to 2017. The analysis identified the most significant risk factors for postpartum venous thrombotic complications. These risk factors should be carefully examined to choose a thromboprophylaxis method in the postpartum period.
Objective. To evaiuate the course of pregnancy against the background of use of the micronized progesterone (Prajisun) at women with missed abortion in the anamnesis. Subjects and methods. In a research 230 women with missed abortion in the anamnesis. From them 128 patients received preconception treatment by the micronized progesterone of 300 mg per a day intravaginally in a luteal phase of menstrual cycle for 3 months and 200 mg twice a day after positive pregnancy test up to 12 weeks (the I group); 102 pregnant women have begun intake of medicine of the micronized progesterone of 200 mg twice a day intravaginally from the moment after diagnostics of pregnancy up to 12 weeks of a gestation (the II group). To all patients the full range of all-clinical trials according to the Order MOH Russian Federation № 572n «About the statement of the Order of delivery of health care on the «obstetrics and gynecology (except for use of auxiliary reproductive technologies)» profile was carried out. In the course of the research the courses of the real pregnancy given relatively were fixed: existence of complications from mother and a newborn. The statistical analysis of data is made with use of Statistica 10.0 Rus. Results. The main criterion for the therapy effectiveness was prolongation of the pregnancy up to 22 weeks of a gesattion. In the I group (the patient who have pregravid preparation by micronized progesterone), the frequency of termination of pregnancy was 0,8% whereas in the II group (intake of the micronized progesterone has been begun after the pregnancy diagnostics) – 7,8% (р<0,05). As a result of the analysis of the obtained data decrease in risk of termination of pregnancy at patients with a cancelled abortion has been shown in the anamnesis at use of medicine of the micronized progesterone from a pregravidarny stage in comparison with primeneiy the micronized progesterone only with pregnancy approach (р<0,05). Conclusion. Results of a research demonstrate effectiveness and safety of micronized progesterone (Prajisun) in a complex of pregravid preparation of women with missed abortion in the anamnesis. Use of the micronized progesterone after the diagnostics of pregnancy is less effective.
Objective: Evaluate the efficacy of combination therapy for the prevention of obstetric and perinatal complications in women with amniotic fluid (AF) ‘sludge’. Study Design: 29 women (of which 8 with the length of the cervix (LC) > 25 mm, 21 with the LC ≤ 25 mm) with AF ‘sludge’ detected by transvaginal ultrasound (TV-US) at 15-24 weeks of gestation received antibacterial therapy, additionally prescribed Indometacin and/or vaginal progesterone (VP). The women underwent the dynamic monitoring of the LC, the amount of AF ‘sludge’, the course of pregnancy, the postnatal and early neonatal period. A histological study of the secundines was conducted in women with preterm labor (PL). Results: the presence of AF ‘sludge’ is associated with the longterm infectious-inflammatory diseases during pregnancy. The outcomes of pregnancy and the probability of the development of infectious complications in the postpartum and early neonatal period were directly determined by the presence of additional risk factors and the antibiotic therapy regimen as part of the combination treatment. Thus, the antibacterial therapy in women with the LC> 25 mm was associated with congenital pregnancy and the absence of infectious complications in the postnatal and early neonatal period in 62.5% of women, whereas in women with the LC ≤ 25 mm in 52.3% of women. The most unfavorable prognosis was identified in women with threatening PL and AF ‘sludge’. The intravenous antibacterial therapy is much more efficient than oral /vaginal one as part of the combination therapy to prevent adverse pregnancy outcomes and the manifestation of intrauterine infection (IUI) in the newborns.
Genital herpes (GH) is top-ranked in the sexually transmitted infection (STIs) rating, which is associated with a lifelong persistence of the virus in the infected patients, polymorphism of clinical manifestations of herpes infection, high percentage of relapsing forms of disease progression. Combination therapy with local use of activated glycyrrhizic acid-containing drug contributes to reducing the duration of GH relapse, more rapid healing of skin and mucosal lesions, increasing duration of the remission period. A patient can plan pregnancy in the absence of GH recurrence during pregravid preparation, in normotsenoze vagina and the absence of type 1 herpes simplex virus (HSV) DNA and type 2 HSV in the genital tract according to PCR test results, sufficient type-specific antiherpetic antibodies titer and absence of GH relapse in sexual partner.
Iron deficiency anemia occurs frequently in pregnancy and in the postnatal period. It is associated with the increased maternal, fetal and infant morbidity. The article considers the main points of iron deficiency diagnosis and the existing options of its correction depending on the duration of pregnancy, the severity of anemia, the necessary rate of recovery of iron deficiency, contraindications and adherence to the therapy. It emphasizes the high efficacy and safety of treatment of iron deficiency anemia with intravenous administration of iron carboxymethyltosate during the 1st, 2nd and 3rd trimesters of pregnancy, and in the postnatal period.
Sensitization occurs when an Rh-negative mother is exposed to Rh-positive fetal red blood cells during pregnancy in 1% of cases and after delivery in 10% of cases, when fetal antigens enter mother’s circulation [1, 2]. A major cause of HDN is an incompatibility of the Rh blood group between the mother and fetus. The article substantiates the necessity of prophylaxis of rhesus sensitization after surgical correction of istmicocervical insufficiency.
Objective of the study: estimate the prevalence of magnesium deficiency (MD) in women using hormonal contraception (HC), who are enrolled in the MAGYN2 study, determine the clinical features of MD and the efficacy of Magne B6 Forte in replenishing magnesium deficiency and improving the patients’ quality of life.Material and methods: 1,904 women using HC were examined. At stage I,the prevalence of DMwas assessed on the basis of the MDQ questionnaire and/or serum magnesium levels were determined. Then the patients were divided into two groups: I – without magnesium deficiency (n = 996) and II – with identified MD (n = 908) during the study. The following parameters were determined: clinical symptomatology caused by MD, and the women’s quality of life using the WHOQOL-BREF questionnaire. At stage II, patients with MD received Magne B6 Forte for 4 weeks with an assessment of its efficacy. Results: The prevalence of MD in the population of patients taking HA is 47.7%. The most severe manifestations of MD included irritation, increased fatigue, chronic stress state. The clinical efficacy of Magne B6 Forte was confirmed by increased serum magnesium levels (from 0.67 ± 0.09 to 0.79 ± 0.26 mmol/L, p< 0.001), normalization of the MDQ score (from 42.5 ± 11, 4 to 22.7 ± 14.9 points, p< 0.001), double reduction of severity of more than half the symptoms of MD, improved quality of life in the range of 20 to 32% in 5 domains of the WHOQOL-BREF questionnaire. Conclusion: The use of Magne B6 Forte in women using HC helps to reduce symptoms of MD and improve the quality of life.
This article provides the evaluation results of the efficacy of low-dose dipyridamole (CurantylÒ) [1, 2] taken to prevent placental insufficiency in women in the group with a high risk of perinatal pathology and feto-maternal disease in past medical history. The early use of low-dose dipyridamole in high-risk groups contributes to a significant reduction in the frequency of intrauterine growth retardation, premature labour and birth of low birth-weight babies.
INFECTIONS
Vaginitis is a gynecologic inflammatory disease that is characterized by multiple lesions occupying the mucous membrane of the vulva and the walls of the vagina. Rational etiotropic therapy for vaginal infection to be performed during pregnancy is a special problem, because nonspecific vaginitis increases the likelihood of premature rupture of membranes, chorionamionitis in childbirth, and development of purulent-inflammatory complications in the postpartum period. A prerequisite for antibiotic therapy during pregnancy is the drug safety for the mother and fetus, eradication of the pathogen and restoration of the impaired microcenosis of the vagina. The article describes the results of the use of Egis (Hungary) – Betadine in 57 pregnant women at the gestational age of 34–36 weeks, aged 19 to 38 years with the clinical signs of vaginitis. Our study showed a high efficacy of Betadine for the treatment of nonspecific vaginitis in pregnant women in as little as a month after therapy. The treatment results remained in the postpartum period, which ensured the absence of purulent-inflammatory complications in all patients included in the study. Betadine can be used as a drug of choice for the treatment of nonspecific vaginitis during pregnancy in the clinical obstetrician-gynaecologist practice.
The most frequent infectious disease of the female reproductive system is bacterial vaginosis (BV). The increased interest in this nosology is explained by the clinical manifestation severity of the disease, rather than numerous data indicating the inextricable connection between BV and inflammatory diseases of female genitourinary system and the complications of pregnancy and delivery. The bacterial biofilm formation, which is found in 90% of cases, have been shown to provide bacteria with protection against antimicrobial agents, representing the specificity of the BV pathogenesis, which militates against the effectiveness of the treatment. The official guidelines recommend to use metronidazole and clindamycin as the first-line therapy for BV in Russia and abroad. However, the present-day concept of BV therapy provides for a comprehensive two-stage treatment with a wide range of combination drugs to eradicate BV-associated microorganisms. Due to the lack of a systemic effect, the preference should be given to combination drugs designed for local therapy. Tergynan is one of the most popular drugs used for topical BV therapy, which demonstrated clinical efficacy and ease of use. Analogue of Tergynan, ornidazole + neomycin + prednisolone + econazole is a topical drug with antibacterial, antifungal and anti-inflammatory components, but has more modern antibacterial (ornidazole) and antifungal (econazole) components. The Russian studies showed convincing efficacy, safety and ease of use of a drug containing ornidazole + neomycin + prednisolone + econazole in BV therapy, which makes it possible to recommend it for practical use.
The article presents the current data on bacterial vaginosis, issues of epidemiology, clinical manifestations and treatment using oral probiotic.
Reproductive health and ART
The effectiveness of the basic in vitro fertilization (IVF) and embryo transfer (PE) programs that were state funded using the funds of the Mandatory Health Insurance Fund (MHIF) was compared with the comprehensive programs that were co-financed (along with the funds of the MHIF, the parallel payment of donor oocytes (DO), donor embryos (DE) (or a donor program from own funds)) in patients of older reproductive age with low ovarian reserve and the forecast of “poor” and reduced ovarian response to controlled ovarian hyperstimulation (COH) on the basis of the Assisted Reproductive Technology (ART) Department of the Moscow Regional Perinatal Center (MRPC). We analysed the outcomes of the programs that have been implemented using the funds of the MHIF on the basis of the ART Department for 2015 and 2016 in patients, who were divided into 2 groups. Group 1 consisted of 69 patients who underwent a basic IVF and PE program in 2015, Group 2 included 60 patients who underwent the basic and comprehensive IVF and PE programs in 2016. In addition, Subgroup 2 has been singled out from Group 2 and included 26 patients out of 60 who underwent the comprehensive IVF and PE programs. The groups were comparable by the main indicators of the ovarian reserve, the average age and the anamnestic data. The embryos were cultivated up to 5 days, their quality was assessed according to the Gardner scale. The number of oocytes obtained (of which mature ones per 1 patient) was (p< 0.05): in Group 1 - 3.7 ± 1.1/2.7 ± 1.8, in Group 2 - 4.7 ± 2.2 / 4.1 ± 1.2, in Group 2a - 7.7 ± 3.4 / 5.7 ± 2.4. The number of embryos received per patient (of which, the highest quality embryos) (p< 0.05): in Group 1 - 2.1 ± 1.1/1.1 ± 0,4, in Group 2 - 2.9 ± 1.4/1.8 ± 0,8; in Group 2a, 4.4 ± 1.8/2.7 ± 1.2. In all patients, the embryos were transferred on Day 5 of the cultivation. In the course of the comprehensive programs, two embryos were transferred: one embryo was obtained by fertilizing the patient’s oocytes with the husband’s semen (of medium or low quality), the other embryo was obtained from a donor by fertilizing with the husband’s sperm (of high quality). In the absence of their own embryos, two high quality DE or embryos obtained by fertilization with the husband’s semen were transferred. The effectiveness of the IVF program (frequency of pregnancy) was as follows: Group 1 - 11.6% per IVF cycle; Group 2 - 21.6% per cycle (13), Group 2a - 38.4% per cycle.
PRE- AND POSTMENOPAUSE
Vasomotor symptoms, including hot flashes (HF), are the most common symptoms of the menopause, which require the hormone replacement therapy with estrogens and/or progestogens. Recent international clinical guidelines recognize the need to use the lowest effective doses of hormone therapy. Drospirenone (DRSP) in combination with 17β-Estradiol (E) is used as hormone therapy (HT) to relieve the postmenopausal symptoms and prevent osteoporosis. The objective of this review is to perform a meta-analysis of the studies evaluating the efficacy and safety of low-dose E2 and DRSP for the treatment of vasomotor symptoms of menopausal syndrome, as well as assessing the state of the endometrium in postmenopausal women. The review presents data from the largest randomized controlled trials that evaluated the lowest effective dose of the E2/DRSP combination, the safety of this dose for endometrium, idetified features of its pharmacokinetics and pharmacodynamics, depending on various factors. The first randomized trial showed that 0.25 mg/E2 DRSP 0.5 mg combination is the lowest effective dose for the relief of HF in postmenopausal women. The efficacy of low doses of DRSP/E2 correlated with E2 and DRSP exposure in serum, while smoking adversely affected the effectiveness of treatment. Evaluation of the risk of endometrial hyperplasia and bleeding peculiarities on the background of DRSP reception 0.25 mg/E2 0.5 mg for 12 months did not reveal hyperplasia or atypia of the endometrium, which confirmed the safety profile of the DRSP 0.25 mg/E2 0.5 mg combination. Thus, 0.25 mg/E2 0.5 mg DRPP is the lowest effective dose for relieving HF, which does not significantly affect the endometrial state. DRSP 0.25 mg/E2 0.5 mg reverses vasomotor manifestations of menopausal syndrome, reduces the frequency and severity of genitourinary syndrome symptoms, which, in turn, improves the patients’ quality of life.
Menopausal disorders with varying degrees of severity occur in women due to the development of the estrogen-deficient condition in the peri- and postmenopausal period. Despite a wide range of medications for menopausal hormone therapy (MHT), a certain number of women with contraindications to MHT and/or hormone-phobia need the use of non-hormonal drugs that relieve the symptoms of menopausal syndrome. Balanced diet and replenishing vitamin and mineral deficiencies plays a key role in correcting menopausal disorders. Vitamins increase the adaptive capacity and participate in the synthesis and metabolism of hormones. The use of vitamin and mineral complexes that do not have side effects and contraindications to MHT is a valid and effective method of the long-term non-hormonal therapy for the treatment of menopausal disorders.
Practice
During pregnancy, venous thromboembolic events (VTE) (absolute VTE rates) are relatively low and occur with a frequency of approximately 0.06% or 0.5–2.2 per 1000 deliveries [1–3]. Nevertheless, VTE is one of the key causes of maternal mortality (on top of that, conditionally avoidable). It is believed that during pregnancy the risk of VTE is increased dramatically - about three to tenfold [4] compared to non-pregnant women, provided that most of the women do not have VTE before pregnancy. According to some authors [5–6], in the postpartum period the risk of VTE is increased 15– to 35-fold compared to age-matched non-pregnant women and remains elevated for 3–6 months after delivery.
The article is devoted to the issues of surgical treatment and prevention of recurrence of intrauterine sinechia (IUS) and its severe condition Asherman syndrome. The topicality of the IUS is characterized by a high incidence of infertility, common miscarriage, amenorrhea and hypomenstrual syndrome. The article describes the principles for management of patients with IUS, the features of surgical treatment and the prevention of recurrence of the disease. The authors present their own clinical data summarizing the experience in treating 64 women with IUS. All patients underwent a hysteroscopic adhesiolysis. In the postoperative period, 48 women (group 1) received an adhesion barrier based on hyaluronic acid and carboxymethylcellulose – Antiadhesin injected into the cavity of the uterus. 16 women (control group 2) did not receive Antiadgesin. The study showed that significantly fewer relapses and a significant increase in commenced pregnancy were detected among patients in group 1. As can be seen from the above, not only the careful and complete dissection of the adhesions, but also the active postoperative rehabilitation period, which includes the prevention of relapsing adhesiogenesis using intrauterine injections of adhesion barriers, is crucial for the comprehensive treatment of patients with IUS.
ISSN 2658-5790 (Online)