[Resolution of the national interdisciplinary council of experts "High-dose vitamin D (Devilam) in the practice of an obstetrician-gynecologist"].

On March 28, 2024, the Council of Experts "High-dose vitamin D (Devilam) in the practice of obstetrician-gynecologist, gynecologist and endocrinologist" was held in Moscow with the participation of leading experts gynecologists, endocrinologists and obstetricians-gynecologists, during which new possibilities for the use of high-dose vitamin D in patients of various ages who need correction of existing vitamin D deficiency or insufficiency.

Vitamin D insufficiency as a risk factor for reproductive losses in miscarriage.

OBJECTIVE: To study the relationship between vitamin D deficiency, VDR gene polymorphism rs10735810 (A > G), and a missed abortion in the first trimester of gestation; to determine the predictors of its risk. RESEARCH METHODS: 178 women aged between 18 and 41 were surveyed. The main group consisted of patients with miscarriage (n = 101), verified at the hospital stage (O02.0; O02.1), which were stratified by I group (n = 58, patients with the first miscarriage) and II groups (n = 43, patients with repeated miscarriage). The control group (n = 77) consisted of women with a successful pregnancy (Z34.0), which subsequently ended in delivery at term with a live fetus. Patients were surveyed and data was extracted from primary medical records. The level of 25(OH)D in the blood serum was investigated by mass spectrometry (n = 99). Genotyping for the vitamin D receptor gene polymorphism rs10735810 (VDR A > G) was performed for 177 patients. Statistical data analysis was performed via Statistica 10 and SAS JMP 11 application packages, using single-factor prediction for quantitative and binary factors, ROC analysis, and CHAID decision tree construction. RESULTS OF THE STUDY: WE found that patients with miscarriage in the first trimester of gestation (n = 60) more frequently than those in the control group (n = 39) had vitamin D insufficiency (93.3% versus 76.9%, p = .0183) including its deficiency, occurring at 25(OH)D of blood <20 ng/ml (71.7% versus 51.3%, p = .0392). This pattern was found in patients with the first miscarriage, where significant differences in the frequency of vitamin D deficiency were also detected in comparison with the control group (80.0% versus 51.3%, p = .0026). No direct correlation was found between the frequency of miscarriages in the first trimester and the variant of the polymorphism of the vitamin D receptor gene (VDR A > G [rs10735810]); the GG genotype in patients with repeated miscarriages was even less frequent compared to the control group (14.0% versus 23.7%, p = .3344). However, the decision tree has identified four risk classes and has determined that the highest risk of missed abortion in the cohort studied is formed by three predicates: smoking, serum level 25(OH)D < 6.5 ng/ml and VDR AA and GG genotypes. CONCLUSION: The data obtained show that vitamin D insufficiency plays a pathogenetically significant role in early reproductive losses associated with miscarriages, both first and recurrent.

[Histamine metabolism disorder in pathogenesis of chronic pelvic pain in patients with external genital endometriosis].

Objective. To study features of histamine metabolism in patients with chronic pelvic pain associated with external genital endometriosis. Methods. For quantitative assessment of histamine level in peripheral blood was taken from 100 patients which than was centrifuged. In blood serum histamine concentration was determined by enzyme-linked immunosorbent assay method with reagents «Histamine ЕLISA¼ on the machine BAE-1000 Histamine (Labor Diagnostika Nord - LDN, Hermany). A pain syndrome was assessed by Visual Analog Scale (VAS), quality of life assessment - by Endometriosis Health Profile Questionnaire (EHR-30), level of anxiety was determined by Spielberger-Khanin questionnaire. The results. Showed statistically higher histamine level in patients with severe pain according to VAS. After assessment of results obtained from Spielberger-Khanin questionnaire 100% experimental group's women with external genital endometriosis (n = 60) were noted to be have high level of state and trait anxiety, then 40% women of control group (n = 16) have moderate level of anxiety. The incidence of depression in women with chronic pelvic pain was 58.3% (n = 35) and the main part (n = 20) were women with severe stage of pelvic pain according to VAS. Conclusions. Psycho emotional condition of women with external genital endometriosis associated pelvic pain characterized by higher depression and anxiety levels, with significant decrease quality of life. Direct relationship also was found between pain syndrome intensity and histamine level in peripheral blood in patients with external genital endometriosis.

Immune-inflammatory predictors of the pelvic pain syndrome associated with adenomyosis.

The aim of the study was the analysis of immune inflammatory processes in the development of the pelvic pain syndrome associated with adenomyosis. For morphological examination were used 54 fragments of the myometrium obtained from patients after hysterectomy with pelvic pain on a background of diffuse adenomyosis of II-III degree, and 20 patients with painless form of adenomyosis. The identification of the macrophages distribution was held by means of an immune-hysto-chemical analysis of MAT (monoclonal antibody) for CD68. (Clone PG-M1, 'Diagnostic BioSystems', USA). The results of the study showed a significantly higher expression of CD68 (49.3 ± 2.3 vs. 21.2 ± 1.7 units. p < .01) in patients with painful adenomyosis form in areas of the ectopic endometrium, in the perivascular regions of the myometrium, as compared to those areas in women with painless group. We assume that these factors increase neurogenic inflammation and sensitivity of nociceptors in myometrium, activation of peripheral nerve fibers and, can act as triggers of the pelvic pain syndrome associated with adenomyosis.

Combination therapeutic options in the treatment of the luteal phase deficiency.

Luteal phase deficiency (LPD) is described as a condition of insufficient progesterone exposure to maintain a regular secretory endometrium and allow for normal embryo implantation and growth. There is evidence that both follicular and luteal phase abnormalities can result in LPD cycles. The aim of this randomized prospective noncomparative study is to evaluate the effectiveness of combination therapy in patients with LPD. This prospective study included 35 women of the reproductive age. They were diagnosed with the LPD with sonographically and laboratory-verified methods. The age of patients was 36 ± 0.46 years. The results of the study sonographically demonstrated an increase in the diameter of the corpus luteum from 1.36 ± 0.32 (initially) to 2.16 ± 0.21 mm after combination therapy. In addition, there was a statistically significant increase in the level of estrogens and progesterone in the corresponding phases of the menstrual cycle. Thus, the combination therapy for patients with LPD contributes to the recovery of cyclic events in the hypothalamic-pituitary-gonadal system, which determines the restoration of the endocrine function of the ovaries and promotes adequate secretory rearrangement of the endometrium in women of reproductive age.

Treatment strategies for pelvic pain associated with adenomyosis.

OBJECTIVE: To observe the effects of levonorgestrel-releasing intrauterine system (LNG-IUS) in treatment of chronic pelvic pain associated with adenomyosis (AM) and in prevention of its recurrence. METHODS: A prospective continuing study including 180 patients with chronic pelvic pain associated with AM who received insertion of LNG-IUS who were divided into three groups depending on the pain severity. The visual analog scale (VAS) was used for pain assessment before and during the treatment and transvaginal ultrasonic measurement of the uterine size, while various side effects, were observed and recorded. RESULTS: After placement of LNG-IUS, scores of pain and ratio of severe pelvic pain decreased significantly compared with baselines (p < 0.01), the scores of VAS were 9.0 ± 0.8, 6.5 ± 2.8, 4.3 ± 1.8, 3.3 ± 2.2, 2.2 ± 2.1, 2.2 ± 1.8, 1.4 ± 1.6 and 1.3 ± 1.3 at 0, 3, 6 and 12 months, respectively. During 12 months after placement of LNG-IUS, scores of pain had improved significantly compared with preceding period (p < 0.01). We found no universal dependent factors predicting improvement of pain, which was neither relevant with simultaneous changes of menstruation patterns nor with adverse effects (p > 0.005). CONCLUSION: The obtained results allowed to confirm the possibility of using LNG-IUS in the treatment of pelvic pain syndrome associated with AM, particularly with mild and moderately severe pelvic pain syndrome. This is a cost effective, reversible and long-term treatment for women with pelvic pain associated with AM, which reduces the need for surgical interventions.

Proangiogenic features in chronic pelvic pain caused by adenomyosis.

AIM: The study of peculiarities of expression of vascular endothelial growth factor (VEGF) in the tissues of the endometrium and myometrium in patients with adenomyosis, associated with chronic pelvic pain syndrome. MATERIALS AND METHODS: Uterus macro-preparations obtained after hysterectomy in 60 patients with pelvic pain on a background of diffuse adenomyosis II-III degree were used for morphological examination, and macro-preparations received from 30 women with adenomyosis without pain syndrome. The diagnosis of adenomyosis was confirmed by sonography and magnetic resonance imaging. The expression of VEGF in tissues of the endometrium and myometrium was determined using the immune-histochemical method. The significance of differences of the compared parameters was determined using the criterion of Wilcoxon and Mann-Whitney. The differences were considered statistically significant when p < 0.05. RESULTS: It was found that a higher expression of VEGF is characteristic for patients with pelvic pain associated with adenomyosis, compared to women with adenomyosis and abnormal uterine bleeding, both in epithelial cells of ectopic endometrium (14.7 ± 1.6% against 10.7 ± 1.6%, p < 0.01), and in smooth myocytes of the myometrium (12.6 ± 1.4% against 9.6 ± 1.2%, p < 0.01) and in the stromal cells of the myometrium (10.1 ± 1.9% versus 7.4 ± 1.8%, p < 0.01). CONCLUSIONS: An increased expression of VEGF in the tissues of the uterus is one of the most important pathogenetic mechanisms of algogenesis with adenomyosis, associated syndrome of chronic pelvic pain, compared to the silent form of the disease.

Occult form of premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a life-changing diagnosis, with profound physical and psychological consequences. Despite the description of different genetic, immune and iatrogenic factors of POI, the etiology of most cases of this disease are unexplained, and optimal management strategies are still unclear. Recent data showed that POI may have a long period of oligomenorrhea before the fully developed form (complete ovarian failure stage), with the occurrence of amenorrhea and climacteric symptoms. The main problem in the recognition of early stages of POI is the lack of proper diagnostic criteria. Patients with an undiagnosed occult form of POI may present with menstrual irregularities, unexplained infertility or repeated IVF failures. We evaluated 23 patients with unexplained oligomenorrhea and/or infertility. After a proper evaluation of these patients, a low ovarian reserve was identified, and an occult form of POI was diagnosed.

Reproductive health of adolescents in Russia: statistics, problems and prospects of improvement.

At the beginning of the 21st century we still face the problem of reproductive health of women, children and adolescents in Russia. Final overcoming of the "Russian Cross" primarily relates to preventing further decline of women in reproductive age and children aged 0-17 years.The following medico-social determinants of women's reproductive health are considered: family prosperity, somatic growth and sexual maturation, chronic extragenital diseases, sexual and reproductive behavior, environmental wellbeing of territory and gynecological care organization. Analysis of gynecological morbidity of Russian girls and adolescents at the beginning of this century spots an upward trend. The results of our anonymous questionnaire survey of socially adapted students among 3327 girls of 13-19 years testify that 59.9% of respondents in this age cohort do not practice daily genitalia toilet. According to our population-based studies, 24.0% of women have first pregnancy at the juvenile age followed by labor in 18.4% of young women, abortion in 81.6%. Menstrual disorders represent the most common symptoms and strong indications of reproductive health problems related, inter alia, to progesterone deficiency which can lead to serious consequences (infertility, miscarriage, breast disease). The choice of medication for the menstrual disorders treatment should consider instruction indications, the lack of limitations and contraindications, need for contraception, concomitant diseases and states, proved efficacy of the medication. Prospects of solving reproductive and demographic problems in the twenty-first century are largely beyond the control of clinicians being aggravated by unresolved environmental and social problems.