Применение дидрогестерона в комплексном лечении пациенток с эндометриомами яичников

Cyclooxygenase-2 overexpression in ovarian endometriomas is associated with higher risk of recurrence

Introduction: Ovarian endometrioma has a significantly high recurrence rate after surgery. Postoperative hormonal therapy may be useful in preventing recurrence. This study assesses recurrence rates, timing, and risk factors for patients with ovarian endometrioma who had conservative surgery and received hormonal therapy for ≤6 months and >6 months. Methods: A retrospective study involved 111 endometriosis patients who underwent conservative surgery, divided into two groups based on postoperative hormonal therapy duration (≤6 months and >6 months). Recurrence rates, time to recurrence, and influencing factors were documented. Results: The cumulative recurrence rate was 35.1% (39 patients) postoperatively in the first 24 months. Patients receiving hormonal therapy for ≤6 months had a 41.6% recurrence rate with a median recurrence at 14 months, while those with therapy for >6 months had a 9.1% recurrence rate with a median recurrence at 24 months. Significant recurrence factors included age at surgery (p = 0.006, OR 0.89, 95% CI 0.83 - 0.97), prior surgery history (p = 0.010, OR 4.94, 95% CI 1.46 - 16.78), therapy duration (p = 0.005, OR 11.04, 95% CI 2.04 - 59.65), and surgical technique (p = 0.001, OR 6.042, 95% CI 2.17 - 16.79). BMI, bilaterality, and cyst size were not statistically significant. Conclusion: Younger age at surgery and prior surgical history correlate with a higher recurrence rate, and long-term postoperative hormonal therapy (> 6 months) and laparoscopy decrease the recurrence rate.

ObjectiveTo evaluate the effect of second-line conservative surgery on in vitro fertilization (IVF) outcome in comparison with IVF without second-line surgery in infertile women with ovarian endometrioma recurrence after primary conservative surgery.MethodsIn this retrospective cohort study, 121 consecutive IVF/intracytoplasmic sperm injection cycles that were performed after second-line surgery (n=53) or without second-line surgery (control group, n=68) between January 2006 and December 2011 in 121 infertile women with ovarian endometrioma(s) recurrence after primary conservative surgery for moderate to severe endometriosis were included. The two groups were compared in terms of controlled ovarian stimulation and IVF outcomes.ResultsThere were no differences in patients' characteristics between the two groups. Total dose and days of gonadotropins administered were significantly higher in the second-line surgery group than in the control group (P<0.001, P=0.008). The numbers of oocytes retrieved, mature oocytes and grade 1 or 2 embryos were significantly lower in the second-line surgery group (P=0.007, P=0.001, P<0.001, respectively). Clinical pregnancy rate per cycle and embryo implantation rate were also significantly lower in the second-line surgery group of 24.5% and 11.8% compared with 48.5% and 25.3% in the control group (P=0.008, P=0.005, respectively).ConclusionOvarian response to controlled ovarian stimulation and IVF outcome after second-line surgery is worse than thosein IVF cycles without second-line surgery in infertile women with ovarian endometrioma recurrence after primarysurgery for moderate or severe endometriosis.

The objective: to study the effect of hormone therapy on menstrual function of women with adenomyosis in combination with endometrial hyperplasia. Patients and methods. We evaluated the effects of hormone therapy in 160 women of reproductive age with adenomyosis in combination with endometrial hyperplasia: I group – 60 women used the progestogen (6 months); II – 60 women, took an agonist of gonadotropin-releasing-hormone – а-GnRH) (6 months), III – 40 women who received the complex therapy including а-GnRH during the first 6 months and immunomodulator intramuscularly every other day No. 20, with subsequent use of tablets of 0.15 g of 1 times a week (course - 6 months), then for the next 6 months was used progestogen in the second phase of the menstrual cycle from 16 to 25 day. Evaluation of indicators of health status were performed after 3, 6 and 12 months of therapy. Assessment of volume of menstrual blood loss was performed using maps of menstrual blood loss and were assessed on a special scale. The total rating for the month, which exceeded 100 points, consistent with menstrual blood loss greater than 80 ml. Results. The influence of hormonal monotherapy progestogen and а-GnRH on menstrual function of women with adenomyosis in combination with endometrial hyperplasia during the follow-up throughout the year. The assessment of indicators of volume of blood loss with the help of monitoring charts. Developed a comprehensive hormone therapy for women of reproductive age with combined benign uterus pathology and the evaluation of its impact on indicators of volume of blood loss and menstrual function of women. Conclusions. Monoterapia by the progestogen and а-GnRH for 6 months of treatment normalizes the indicators of volume of blood loss and menstrual function of women, and the 12-month follow-up in women of these groups also increased the volume of blood loss and each 3 women is marked polimenorea. Developed a comprehensive phased hormone therapy for women with adenomyosis in combination with endometrial hyperplasia normalizes on the 3rd month of treatment indicators of blood loss and has a tendency to decrease during the 12 months of observation (the volume of menstrual blood loss has decreased in 4 times from initial). Key words: complex therapy, adenomyosis, endometrial hyperplasia, gestagene, а-GnRH, menstrual function, volume of blood loss.

Impact of GnRH agonist treatment on recurrence of ovarian endometriomas after conservative laparoscopic surgery

To assess the effect of dienogest on recurrence of ovarian endometriomas and severity of pain after laparoscopic surgery, a retrospective study of 81 patients was performed at three institutions in Osaka, Japan. Patients had a six-month minimum follow-up after laparoscopic surgery for ovarian endometriomas performed between June 2012 and August 2014. Patients who chose to receive 2 mg dienogest daily and those who were managed expectantly postoperatively were included. Recurrence was defined as the presence of endometriomas of more than 2 cm. A visual analog scale (VAS) was used to score the intensity of pelvic pain. The cumulative recurrence rate and absolute VAS score changes between the baseline and at 6, 12, 18 and 24 months after the start of administration were evaluated in both groups. The recurrence rate was 16.5% and 24.0% in the expectant management group at 12 and 24 months, respectively. No recurrences occurred in the dienogest treatment group. The rate of VAS score reduction was significantly higher in the dienogest than in the expectant management group. Dienogest is effective on the recurrence of ovarian endometrioma and relieving pelvic pain after laparoscopic surgery.

Background: Ovarian endometriomas are a common gynecological disease in women of childbearing age. Laparoscopic surgery is the gold standard surgical procedure for treating patients with ovarian endometriomas. However, laparoscopic postoperative bleeding, recurrence, and pregnancy failure are still unavoidable problems for many patients. Methods: A retrospective analysis was performed of 212 patients with ovarian endometriomas treated by laparoscopic surgery in our hospital from January 2016 to December 2020, with postoperative follow-up for 2 years. The researchers completed the follow-up by telephone, email, and outpatient review. Chi-square test was used to analyze the relationship between their clinical characteristics and postoperative bleeding, recurrence, and pregnancy along with logistic regression analysis of the risk factors for postoperative bleeding and recovery. Also, the use of logistic regression analysis may influence the factors influencing pregnancy outcome after laparoscopy. Results: The postoperative pregnancy success rate in 212 patients with ovarian endometriomas was 63.7%. The incidence of bleeding after surgery was 31.6% and the recurrence rate was 21.2%. The results of the logistic-regression analysis demonstrated that, age (odds ratio (OR) = 1.208, p = 0.001), combined with deep infiltrating endometriosis (DIE) (OR = 5.18, p = 0.023), cystic diameter ≥5 cm (OR = 0.076, p = 0.005), bleeding during the operation ≥50 mL (OR = 25.769, p = 0.000) and intraoperative bleeding (OR = 1.295, p = 0.000) were independent risk factors for postoperative bleeding. Severe dysmenorrhea (OR = 6.189, p = 0.004), cystic diameter ≥5 cm (OR = 8.502, p = 0.001), bilaterality (OR = 85.214, p = 0.001) and intraoperative bleeding (OR = 0.911, p = 0.003) were independent risk factors for the recurrence of ovarian endometriomas. By logistic regression analysis, age, bilaterality, the revised American Fertility Society (r-AFS) stage ≥Ⅲ were all related factors for postoperative pregnancy (p &lt; 0.05). Conclusions: Age, combined with deep infiltrating endometriosis, cystic diameter, bleeding during the operation and intraoperative bleeding were all independent risk factors for postoperative bleeding. Severe dysmenorrhea, bilaterality, cystic diameter and intraoperative bleeding were independent risk factors for the recurrence of ovarian endometriomas. Age, bilaterality, r-AFS stage ≥Ⅲ were related factors for postoperative pregnancy.

RECURRENCE, RE-OPERATION, AND PREGNANCY RATES AFTER SURGICALLY TREATED OVARIAN ENDOMETRIOMA IN A SINGLE INSTITUTION: LONG-TERM FOLLOW UP OF 756 WOMEN

To investigate the expression of proliferation and apoptotic factors (Ki-67, Bcl-2), inflammatory factors (NF-kβ p65, COX-2), adhesion factors (β-catenin), estrogen (ER-α) and progesterone receptors (PR-α) in ovarian endometrioma (OE) in patients with recurrent OE by an immunohistochemical assay. This investigation enrolled 48 reproductive-aged patients with OE. According to the course of the disease during a follow-up period of 1.5 years after surgical treatment, the biomaterial obtained from the examined patients was divided into two groups: 1) an OE capsule from 19 patients with recurrent OE (a study group); 2) an OE capsule from 28 patients without recurrent OE (a comparison group). This investigation used histological and immunohistochemical examinations. The histological analysis of the OE capsule was performed following a standard procedure. Their immunohistochemical analysis was carried out using the Tissue-Tek Quick-Ray kit that allows the preparation of paraffin blocks with a large number of tissue samples (tissue microarrays). Antibodies to Ki-67 (clone 30-9, VENTANA), Bcl-2 (clone 124, VENTANA), NF-kβ p65 (clone p65, 'Spring Bioscience Corp.'), COX-2 (clone CX-294, Agilent), β-catenin (clone 14, VENTANA), ER-α (clone SP1, VENTANA), and PR-α (clone 1E2, VENTANA) were also employed in the investigation. The specimens were prepared according to a standard protocol using a Ventana Ultra immunohistostainer. Positive and negative controls were used to correctly carry out immunohistochemical tests. Statistical analysis was performed using the applied statistical analysis programs Statistica 10.0 and Microsoft Excel. The patients with recurrent OE had a significantly decreased expression of Ki-67 (2.86% vs. 9.69%; р=0.044) in the epithelial component of the OE capsule; a significantly lower expression of NF-kβ p65 (2.54 vs. 3.5; р=0.0082) and СОХ-2 (0.231 vs. 1.381; р=0.0025) in the stromal component of the OE capsule, a significantly increased expression of β-catenin (2.5 vs. 1.59; р=0.017) in the stromal component of the OE capsule; a significantly increased expression of PR-α (188.46 vs. 71.15; р=0.028) in the epithelial component of an OE capsule. The expression of ER-α (stromal component, 266 vs. 256.84; p=0.48; epithelial component, 251.54 vs. 233.85, p=0.82) and Bcl-2 (stromal component, 0.33 vs. 0.25; p=0.85; epithelial component, 0.944 vs. 0.625; p=0.31) in the OE capsule is not statistically significantly different between the study patient groups. The immunohistochemical difference in the expression of a number of the markers under study can serve as the basis for a further investigation of these markers as predictors of recurrent OE after surgical treatment. Further investigations of these factors will also be able to examine the molecular mechanisms underlying the pathogenesis of recurrent OE, which will make it possible to affect these mechanisms in order to eliminate the fundamental causes of a recurrence of this disease.

The efficacy of long-term maintenance therapy with a levonorgestrel-releasing intrauterine system for prevention of ovarian endometrioma recurrence

Aim. To identify risk factors for recurrence of ovarian endometriomas after surgical treatment. Materials and methods. The retrospective cohort study included 82 patients operated on for the first time for ovarian endometriomas, the follow-up period was 30 months. The recurrence developed in 19 patients (group 1), in 63 the recurrence was not diagnosed (group 2). Data prior to surgery (clinical characteristics, level CA-125), during surgery (cytokine concentration in peritoneal fluid, immunohistochemical analysis in capsule of ovarian endometriomas), postoperative therapy were evaluated as risk factors for recurrence. The Mann-Whitney U-test, the Fisher exact test was used to compare the groups. Specificity, sensitivity, accuracy, AUC ROC and threshold values were calculated. Results. The recurrence rate of ovarian endometriomas was 23%. There were no differences between groups according to age, proportion of smokers, body mass index, gynecological anamnesis, obstetric status and postoperative hormone therapy. Preoperative concentrations of CA-125 in group 1 were higher than in group 2: 62.5 U/ml [40.7; 112.3] vs 40.3 U/ml [20.3; 68.8], р &lt; 0.05. The concentration of IL-6, IL-8, TNFα, IL-1β, IL-17, VEGF, MCP 1 in peritoneal fluid taken during surgery was statistically significantly higher in group 1. The highest AUC ROC was received for VEGF 0.875 (0.778–0.973) and IL-8 0.953 (0.896–1.009). For VEGF the threshold value was 125.6 pg/ml, sensitivity 100%, specificity 71%, accuracy 79.8%. For IL-8 the threshold value was 128.78 pg/ml, sensitivity 93%, specificity 87.1%, accuracy 88.9%. In group 1, higher expression values of VEGF and CD34 angiogenesis markers in ovarian endometriomas were recorded. The highest AUC ROC was noted for CD34 — 0.844 (0.683–1.000), threshold value was 2.5%, sensitivity 90%, specificity 75%, accuracy 80.8%. Conclusion. Risk factors for recurrence of ovarian endometriomas after operative treatment include VEGF and IL-8 levels in peritoneal fluid and expression of CD34 in the capsule.

BACKGROUND: In some cases, women with uterine fibroids have heavy menstrual bleeding and dysmenorrhea. Combined hormonal contraceptives are used both for contraception and to alleviate the clinical manifestations of uterine fibroids that do not require surgical treatment. Publications on the effect of combined hormonal contraceptives on the clinical course of uterine fibroids are rare. AIM: The aim of this study was to evaluate the characteristics of menstrual function, as well as clinical and biochemical blood test parameters, blood lipid spectrum and hemostatic screening test parameters in dynamics in women with uterine fibroids using low-dose multiphasic and monophasic combined hormonal contraceptives with ethinyl estradiol. MATERIALS AND METHODS: This study included 148 women, out of whom there were 118 patients with uterine fibroids without indications for surgical treatment [54 patients used multiphasic (ethinyl estradiol ans desogestrel) and monophasic (ethinyl estradiol and various gestagens) combined hormonal contraceptives, 64 patients did not] and 30 healthy participants using combined hormonal contraceptives with ethinyl estradiol. At baseline, after six and 12 months, the study participants were assessed for the duration, volume, and painfulness or painlessness (visual analogue scale, McGill pain questionnaire) of menstrual blood loss, as well as laboratory examination parameters. RESULTS: In women with uterine fibroids using various combined hormonal contraceptives (n = 54), a decrease in the duration (5.6 ± 1.2, 4.1 ± 1.0, and 4.1 ± 1.2 of a day respectively; p 0.05) and volume of menstrual bleeding was noted after 6 and 12 months. 6 of 16 patients with uterine fibroids and heavy menstrual bleeding used combined hormonal contraceptives (2 patients used multiphasic contraceptives, and 4 others monophasic ones). In these 6 women, normal hemoglobin (124–132 g/l) and ferritin (35.4–42.4 μg/l) levels were recorded after 12 months. In patients with uterine fibroids, a reduction in dysmenorrhea or a decrease in its intensity was observed with the use of multiphasic (n = 7; 5.1 ± 1.5, 2.0 ± 0.7, and 1.6 ± 0.5 of a point, respectively) and monophasic (n = 2; 4.6 ± 1.2, 3.7 ± 1.1, and 3.0 ± 0.4 of a point, respectively) combined hormonal contraceptives (p 0.05). No changes were recorded in the initially normal parameters of biochemical blood analysis, lipidogram and coagulogram in the study participants. CONCLUSIONS: The use of multi- and monophasic combined hormonal contraceptives with ethinyl estradiol in patients with uterine fibroids leads to a decrease in the duration and volume of menstrual blood loss. It helps maintain normal levels of hemoglobin and ferritin and reduce the frequency and intensity of dysmenorrhea associated with uterine fibroids. Apart from that, it does not lead to changes in the parameters of biochemical blood analysis, blood lipid spectrum and hemostatic screening in the absence of contraindications to the use these drugs.

Relugolix Combination Therapy Improves Uterine Fibroid Symptoms Independent of Fibroid Location over 24 Weeks

INTRODUCTION: In the Phase 3, replicate, institutional review board-approved LIBERTY 1 and 2 studies, relugolix combination therapy (Relugolix CT; once daily relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) improved uterine fibroid (UF)-associated heavy menstrual bleeding (HMB), pain, and quality of life (QoL). We report the impact of location (submucosal, intramural, or subserosal) of the largest fibroid on treatment outcomes through 24 weeks. METHODS: Premenopausal women were randomized to relugolix combination therapy or placebo for 24 weeks. Location of the largest fibroid was investigator-defined using ultrasound; FIGO type 0/1 fibroids were excluded. Menstrual blood loss (MBL) volume was measured by alkaline hematin method (responders: MBL volume &lt; 80mL and ≥50% reduction from baseline over last 35 days of treatment). Pain and other UF-associated symptoms were evaluated using the Numerical Rating Scale and UF-QoL Questionnaire (Symptom Severity) in this post-hoc analysis. RESULTS: In the relugolix combination therapy (N=253) and placebo (N=256) groups, the largest fibroid was categorized by location as subserous (N=50 and N=58), intramural (N=115 and N=130), submucosal (N=46 and N=43) or “other/unknown” (N=119 and N=106). Baseline characteristics, including MBL volume, pain and QoL scores, were similar between subgroups. In all fibroid subgroups, women randomized to relugolix combination therapy had comparable responder rates of 76.0%, 79.1%, 80.4%, and 65.6% at week 24 that were higher than with placebo: 24.1%, 16.2%, 14.0%, and 16.0% (all nominal P&lt;.0001). Across all subgroups, women randomized to relugolix combination therapy experienced significant reductions in MBL volume, UF-associated pain and symptom severity versus placebo. CONCLUSION: Relugolix combination therapy improves HMB and other UF-associated symptoms independent of the location of the largest fibroid.

To investigate the efficacy and safety of estradiol valerate (EV)/dienogest (DNG) for the management of heavy menstrual bleeding (HMB) in Asian and non-Asian women desiring contraception. In this multicenter, double-blind, phase III study, women were randomized 2:1 to receive EV/DNG or placebo tablets daily for seven 28-day cycles. The primary endpoint was the absolute change in menstrual blood loss (MBL) volume between the run-in and efficacy phases (90 days each). Secondary endpoints included the proportion of women with successful treatment (i.e., no episodes of MBL ≥80 mL and a decrease of <50% in MBL), percent change in MBL from the run-in phase, and change in hemoglobin and serum ferritin levels. Adverse events (AEs) were monitored throughout the study. Of the 341 women (mean age 34.7 ± 7.7 years; 309 Asians, 32 non-Asians) randomized, 270 completed the study. Mean reduction in MBL volume from run-in phase was significantly greater with EV/DNG than placebo (366.75 mL vs. 149.14 mL; p < 0.0001), with ∼52% and 12% of women, respectively, experiencing successful treatment. Percent decrease in MBL volume from the run-in phase was significantly greater with EV/DNG than placebo (63.5% vs. 24.8%; p < 0.0001). Hemoglobin and serum ferritin levels were increased with EV/DNG compared with placebo. Study drug-related AEs were reported in 16.3% and 8.2% of women with EV/DNG and placebo, respectively, none of which were of severe intensity. EV/DNG may be a safe and effective option in the treatment of HMB in Asian and non-Asian women who desire contraception.