Objective: Genital endometriosis (GE) is a widespread gynecological disease which requires its further pathogenesis investigation and search for new effective treatments. The known data of oxytocin receptor presence in endometrioid heterotopy smooth muscle cells give some grounds to assume oxytocin participation in the pathogenesis of endometriosis. The present study objective was to evaluate oxytocin level in peripheral blood (PB) in patients with endometriosis associated pain syndrome and to estimate the efficacy of oxytocin receptor inhibitors (IOXTR) administration based on animal endometriosis model. Materials and methods: The basic group comprised 61 patients with endometriosis associated pain syndrome, while 21 patients formed the control group. VAS, MPQ, and BBS objective tests were applied for pain syndrome evaluation. Oxytocin level in PB was measured by immunoenzyme method. After confirmation of endometriosis experimental model formation in rats and further randomization, a daily IOXTR intra-abdominal injection was performed in a dose of 0.35 mg/kg/24 h in the basic group (n ¼ 12) or saline solution administration in the control (n ¼ 12). On the final stage, endometrioid heterotopy size measuring was performed along with histological examination. Results: Oxytocin level in PB was authentically higher in patients with GE compared to the control: 51.45 (35.54-62.76) pg/mL and 27.64 (23.23-34.12) pg/mL, respectively (p<.001). Positive correlation between oxytocin PB level and pain syndrome expression was established in patients with GE: VAS (r ¼ 0.76; p<.001), MPQ (r ¼ 0.52; p<.001), and BBS (r ¼ 0.57; p<.001). Based on the experimental disease model authentical decrease of endometrioid heterotopy average area was observed after IOXTR therapy compared to the control (7.3 ± 1.8 mm 2 and 22.2 ± 1.2 mm 2 , respectively, p<.05). Conclusions:The obtained results confirm the oxytocin role in the pathogenesis of endometrioid associated pain syndrome. The high efficacy of IOXTR administration based on animal model of surgically induced endometriosis allows viewing this method as a perspective therapy.

Hypothesis/aims of study. Endometriosis is a chronic recurrent disease that leads to a significant decrease in the quality of life. Despite the existing therapeutic methods, the prevalence of the disease is steadily increasing. The pathogenesis of endometriosis has not been studied enough, resulting in failure to achieve high efficiency in its treatment. Due to chronic pelvic pain, infertility, and dissatisfaction with the quality of life, women suffering from endometriosis present with various mental disorders of different degrees of severity. This study aims to summarize the literature discussing the possible role of oxytocin in the pathogenesis of both endometriosis and affective disorders. Study design, materials, and methods. Literature data for the period from 1986 to 2019. Conclusion. The role of oxytocin in the pathogenesis of endometriosis needs further study. Oxytocin receptor antagonists can be considered promising in the treatment of this medical condition, as well as in prevention and management of affective disorders in patients with endometriosis.

Introduction. Habitual pregnancy failure (HPF) has long been a pressing problem of modern medicine and is characterized by multiple pathogenetic mechanisms of early pregnancy termination. The aim of the study was to examine the expression of estrogen, progesterone, progesterone-induced blocking factor and stromal cell factor-1 receptors in endometrial biopsy specimens from patients with HPF. Materials and methods. Histological and immunohistochemical studies were performed on 75 endometrial biopsies: 50 endometrial biopsies were taken from patients with HPF and chronic endometritis with no more than three pregnancies, and 25 endometrial biopsies were taken from conditionally healthy patients. Endometrial biopsy was performed on days 19 to 22 of the menstrual cycle. Histological examination of endometrial biopsy specimens was performed according to the standard technique with hematoxylin and eosin staining. The expression of estrogen receptor (ER), progesterone receptor (PR), progesterone-induced blocking factor (anti-PIBF), and stromal cell factor-1 (anti- SDF-1) was assessed by immunohistochemistry. Results. In patients with HPF, the endometrium corresponded to the middle stage of the secretion phase in 32 % of cases. Immunohistochemical study in patients with HPF verified multifocal decrease of estrogen and progesterone receptor expression in the stromal component in 82 % of cases. Assessment of PIBF and SDF-1 expression in the glands and stroma of the endometrial mid-stage secretion phase in patients with HPF revealed a statistically significant decrease compared to the control group. Discussion. The presence of chronic endometritis in patients with HPF leads to impaired endometrial secretory transformation, decreased expression of estrogen and progesterone receptors in the endometrial stroma, and decreased expression of PIBF and SDF-1 in the glands and endometrial stroma. The results of the study suggest the need for pathogenetic therapy of chronic endometritis and pregravidarial preparation in patients with HPF. Conclusion. Regardless of the completeness of endometrial transformation, desynchronosis of the receptor profile, altered expression of immunological markers (PIBF and SDF-1) against the background of chronic endometritis, and structural and molecular disturbances serve as factors of early pregnancy loss.

The problems of pathological diagnosis of recurrent miscarriage are relevant in modern reproductive medicine. One of the important molecular markers of endometrium is the progesterone-induced blocking factor, which is induced by progesterone under the influence of activated lymphocytes and has an immunomodulatory effect on the implantation characteristics of the endometrium. In the process of trophoblast invasion, a special role is also played stromal cell factor molecules synthesized by endometrial and trophoblast cells, as a mechanism that potentiates the susceptibility of the endometrium to the onset and development of pregnancy, trophoblast invasion and embryogenesis in general. The purpose of the study was the histological and immunohistochemical features of the transformation of the endometrium in recurrent miscarriage. It were studied 100 samples of endometrium in case of non-developing pregnancy at a development period of 5-8 weeks, 85 samples in habitual miscarriage and 15 samples in pregnancy interrupted surgically at the request of the woman. The presence of 2 non-developing pregnancies was verified in 57 cases (67,1%), the presence of 3 non-developing pregnancies in 28 cases (32,9%). A histological examination of the abortion material stained with hematoxylin and eosin was performed to verify the morphological transformation of the endometrium. Immunohistochemical study included detection of estrogen and progesterone receptors, stromal cell factor (SDF1), progesterone-induced blocking factor (PIBF). The results of histological and immunohistochemical studies showed that with a complete morphological transformation of the endometrium in the group of patients with habitual miscarriage, there is a violation of the receptor profile. The decrease in PIBF expression in the glands and the stromal component and the expression of SDF1 in the glands of the compact layer of the endometrium is a reflection of the immunological imbalance in the endometrium in recurrent miscarriage. The development of a unified morphological algorithm, taking into account the basic indicators of the processes of transformation of the endometrium with an assessment of its receptor profile and diagnostically significant immunological factors, makes it possible to verify the pathology of the endometrium at the molecular level and justify the need for using pathogenetically substantiated therapy at recurrent miscarriage.

Background. Endometriosis is a chronic progressive recurrent disease associated with pelvis pain, menses disorders and infertility. The prevalence of endometriosis (EGE) tends to increase steadily and reaches 15% among women of reproductive age. Endometriosis-associated pain can persist despite surgical and drug treatment of this disease, resulting in a significant decrease in the quality of life of patients. The main causes of EGE-associated pain are local inflammatory, adhesive, neuro- and angiogenic processes. Currently, the search for alternative methods of pathogenesis-based therapy of the disease is one of the priority tasks. Given its anti-inflammatory, enzymatic, antioxidant effects and anti-adhesion mechanism of action, bovhyaluronidase azoximer, an enzyme agent with hyaluronidase activity, is a promising drug in the complex therapy of EGE. Aim. To compare bovhyaluronidase azoxymer efficacy in complex therapy of patients with EGE using dienogest (2 mg) versus monotherapy with this progestogen in real clinical practice. Materials and methods. 149 female patients of reproductive age were enrolled in the study after surgical treatment for EGE. The patients were divided into two groups: the first group (n=94) was treated with complex therapy by dienogest (2 mg) daily within 6 months in combination with suppositories containing bovhyaluronidase azoxymer (3000 IU): 1 suppositorium once within 3 days,10 administrations; and then 1 suppositorium once in 7 days, 17 administrations, within 120 days; the second group (n=55) received monotherapy with dienogest (2 mg) daily up to 6 months. EGE-associated pelvic pain intensity, uterine bleeding severity and life quality were assessed during the study, after 30, 90, 150 and 180 days with regard to the basic values. Results. There was a statistically significant reduction of pain intensity observed in both groups compared to the basic level, using visual analogue scale of pain (VAS), the Biberoglu and Berman scale, but there was a distinct trend towards a more significant decrease in pelvic pain score basing on VAS in patients received complex therapy versus monotherapy with dienogest 2 mg after 30 days of treatment (p=0.051). Life quality assessment of patients in both groups revealed statistically significant increase in scores for all values of the SF-36 life quality scale just after the second follow-up visit. More significant life quality improvement in patients was observed with complex therapy with regard to such descriptors of the SF-36 Questionnaire as Physical functioning, Role-physical functioning, Pain intensity (p0.05). Conclusion. Bovhyaluronidase azoxymer in combination with dienogest (2 mg) improves the overall therapy effectiveness for EGE and is associated with more significant reduction in pelvic pain intensity, inflammatory and adhesive processes in the pelvis, and significant life quality improvement compared to monotherapy with 2 mg dienogest.