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.

Diagnostic significance of chronic endometritis macrotypes differentiation among women with reproductive losses.

To evaluate the prognostic value of a comprehensive endometrial study after early reproductive losses (RL). A group of 306 women with early RL (missed abortion (n = 120), spontaneous miscarriage (n = 120), and ineffective in vitro fertilization attempts (n =66) were prospectively examined up to 6 months after the discharge of the uterus at the hospital bases of the Department of Obstetrics and Gynecology with the Сourse of perinatology at the PFUR Medical Faculty. Hysteroscopic macrotypes differentiation - hyperplastic (n = 89), hypoplastic (n = 94) and mixed (n = 87) - was carried out on the basis of features grouping characterizing the thickness, color and structure of the mucosa, the intensity of a vascular pattern in the presence of a chronic endometritis (CE). Evaluation of sonographic accuracy after hysteroscopic CE macrotypes differentiation showed the presence of false-negative conclusions: about unchanged mucosa (6.9%); endometrium polyps (3.5%); intrauterine synechiae (4.2%). Immunohistochemical staining with CD138 isolation showed higher diagnostic accuracy in CE detecting in comparison with the morphological method: in a hyperplastic macrotype (90.5% and 84.1%, respectively), hypo- (93.7% and 89.8%) and mixed (81.6% and 79.4%). Great diagnostic value is shown in identifying histopathic CE features in the context of hysteroscopic macrotypes differentiation in groups of women with RL.

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.

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.

[STATE-OF-THE-ART OF REALIZATION OF THE FERTILITY POTENTIAL IN THE WOMEN OF LATE REPRODUCTIVE AGE].

Biological potential of childbearing in the women of late reproductive age is limited by natural impairment and loss offertility. Despite a considerable progress in clinical application of new diagnostic and reproductive technologies, the problem of infertility remains a most serious challenge. Women's age is one of the main factors responsible for the outcome of in vitro fertilization. The low effectiveness of in vitro fertilization programs is attributed to discoordination in the hypothalamic-pituitary system, depletion of ovarian resources, and deterioration of quality of reproductive material. Bearing in mind the role of melatonin in synchronizing circadian and seasonal biorhythms and regulating physiological and pathological processes, it is natural to suggest its role in the enhancement of efficiency of in vitro fertilization programs for women of late reproductive age.