Abstract Background Uterine fibroids (UFs) may be treated with progesterone receptor modulators (PRMs), which have been shown to reduce heavy menstrual bleeding and the size of UFs. To date, one PRM ...(ulipristal acetate) has received regulatory approval for the treatment of UFs; therapy comprises intermittent treatment courses of up to 3 months each, followed by a break to allow two menstruations to occur. We report the design of ASTEROID (Assess Safety and efficacy of vilaprisan in patients with uTERine fibrOIDs) 2, a phase 2 study examining the efficacy and safety of a novel PRM, vilaprisan, in women with UFs. Methods/design In this randomized multi-arm study, vilaprisan (2 mg daily) will be administered in different regimens: continuous treatment for 12 or 24 weeks, or two 12-week treatment periods separated by a break to allow one menstruation to occur. Efficacy and safety will be compared with that of ulipristal acetate (5 mg daily) and placebo. Patients randomized to receive placebo for 12 weeks will also be given active treatment for 12 weeks. The primary measure of efficacy will be amenorrhoea rate; secondary measures include time to normalized menstrual bleeding and percentage change in UF volume. Endometrial changes will be monitored throughout the study. Discussion The placebo- and active comparator-controlled trial ASTEROID 2 is the first study to evaluate systematically the efficacy and safety of different treatment regimens of PRMs in women with UFs. The findings of this study will direct the planning of future clinical trials of vilaprisan.
This study compares the effect of Hyalobarrier Gel and 4DryField® PH on the formation of postoperative adhesions after myomectomy in an experimental study on rabbit does. Thirty experimental animals ...were divided into three groups: group A – control, group B – use of 4DryField® PH, and group C – use of the Hyalobarrier Gel. A simulated myomectomy was performed in each group. The animals were euthanised 14 days after the procedure and the antiadhesive effect of the above-mentioned preparations was evaluated according to the criteria. Statistical evaluation clearly showed differences in the antiadhesive effect in the scoring systems for groups B and C compared to control group A at a high level of significance. We demonstrated an obvious, statistically confirmed antiadhesive effect of the Hyalobarrier Gel and 4DryField® PH in an experimental model of the rabbit uterus. Comparing both preparations, the Hyalobarrier Gel shows a higher level of effectiveness. Based on the results of the experiment, both preparations can be unambiguously recommended for routine practice.
An ectopic pregnancy within a Cesarean scar represents a rare type of extrauterine pregnancy in which the fertilized egg nidates in the myometrium of the uterine wall within a scar left from a ...previous Cesarean delivery. An unrecognized growing Cesarian scar pregnancy may result in uterine rupture, uncontrollable metrorrhagia, and bleeding into the abdominal cavity; therefore, early diagnosis and therapy are necessary to prevent the development of severe complications.
A 34-year-old woman after a previous Cesarean delivery presented with amenorrhoa of 7 weeks' duration. Transvaginal ultrasonography revealed an ectopic pregnancy in the Cesarean scar, and a laparoscopic removal of the gestational sac was performed with no complications.
Three months later, another laparoscopy with chromopertubation showed no signs of penetration in the suture, both the Fallopian tubes being bilaterally passable. The patient was advised that she could try to achieve pregnancy through spontaneous conception, after which monitoring of the gestational development and a careful assessment of the nidation site would be needed.
Laparoscopic surgical management of a viable ectopic pregnancy is technically simple, and is followed by a good recovery. (J GYNECOL SURG 30:309).
Endometriosis is a common gynecological disease characterized by the presence of endometrial tissue outside the uterus causing chronic inflammation, severe pain, and infertility. However, the innate ...immunity of gamma-delta (γδ) T lymphocytes in endometriosis has not been characterized. Women with endometriosis present numerous endocrine and immune dysfunctions and elevated risk for endometrial, ovarian, and breast cancers. The tyrosine kinase EphA2 is often overexpressed in cancer including endometrial carcinoma.
We analyzed Vδ1 and Vδ2 γδ T cells in peripheral blood and paired peritoneal fluid samples in endometriosis patients (
= 19) and compared the counts with that of age- and sex-matched healthy donors (
= 33) using flow cytometry. Vδ1 and Vδ2 T cells isolated from healthy donors were used against KLE, RL-95, and Ishikawa endometrial tumor cells in 4 h flow cytometric cytotoxicity assays. The EphA2 blocking studies were performed using antibody, small-molecule inhibitor ALW-II-41-27, and the CRISPR/Cas9.
We determined Vδ1 T cells substantially reduced in patients' peripheral blood (
< 0.01) and peritoneal fluid (
< 0.001). No differences were found for circulating Vδ2 T cells compared with peritoneal fluid samples. We observed inherent cytotoxic reactivity of Vδ1 and Vδ2 γδ T lymphocytes against endometrial tumor cells. Importantly, we found reduced specific lysis of EphA2-positive cell lines KLE and RL-95 by Vδ1 T cells in the EphA2 antibody blocking studies and by the EphA2 inhibitor. Furthermore, Vδ1 T-cell-mediated killing was significantly decreased in RL-95 cell EPHA2 knockout. Finally, potent cytolytic activity exerted by Vδ1 T cells was significantly reduced in EPHA2 knockouts in renal A-498 and colon HT-29 carcinoma cell lines.
We determined variable levels of Vδ1 and Vδ2 γδ T cells in endometriosis patients. We observed inherent cytotoxic reactivity of γδ T-cell subsets against endometrial cell lines. Specifically, we found that blocking of EphA2 expression resulted in significant inhibition of endometrial tumor killing mediated by Vδ1 γδ T cells. These results suggest that EphA2 is involved in tumor cell lysis and contributes to susceptibility to Vδ1 γδ T cells cytotoxic reactivity.
Objective To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. Design Double-blind, ...randomized administration of two 12-week courses of ulipristal acetate. Setting Gynecology centers. Patient(s) A total of 451 patients with symptomatic uterine fibroid(s) and heavy bleeding. Intervention(s) Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate. Main Outcome Measure(s) Amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), pain. Result(s) In the 5- and 10-mg treatment groups (62% and 73% of patients, respectively) achieved amenorrhea during both treatment courses. Proportions of patients achieving controlled bleeding during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10 mg of ulipristal acetate, respectively. Pain and QoL improved in both groups. Ulipristal acetate was well tolerated with less than 5% of patients discontinuing treatment due to adverse events. Conclusion(s) Repeated 12-week courses of daily oral ulipristal acetate (5 and 10 mg) effectively control bleeding and pain, reduce fibroid volume, and restore QoL in patients with symptomatic fibroids. Clinical Trial Registration Number NCT01629563 (PEARL IV).
Objective To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. Design Double-blind, ...randomized administration of four 12-week courses of ulipristal acetate. Setting Gynecology centers. Patient(s) Four hundred fifty-one subjects with symptomatic uterine fibroid(s) and heavy menstrual bleeding. Intervention(s) Four repeated 12-week treatment courses of daily 5 or 10 mg ulipristal acetate. Main Outcome Measure(s) Endometrial safety and general safety, laboratory parameters, amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), and pain. Result(s) Efficacy results, such as bleeding control and fibroid volume reduction, were in line with previously published data. Pain and QoL showed marked improvements from screening, even during the off-treatment intervals. The safety profile of ulipristal acetate was confirmed, and repeated treatment courses did not increase the occurrence of adverse reactions. There were no significant changes in laboratory parameters during the study. The percentage of subjects with endometrial thickness ≥16 mm was 7.4% (all subjects) after the first treatment course and returned to below screening levels (4.9%) in subsequent treatment courses. As in previous studies, ulipristal acetate did not increase the occurrence of endometrial features of concern. The frequency of nonphysiological changes did not increase with repeated treatment. They were observed in 17.8% and 13.3% of biopsies after treatment courses 2 and 4, respectively, and were reversible after treatment cessation. Conclusion(s) The results of this study demonstrate the efficacy and further support the safety profile of repeated intermittent treatment of symptomatic fibroids with ulipristal acetate. Clinical Trial Registration Number NCT01629563.
A review of diagnostic options and standardized methods for specifying clinical symptoms associated with uterine myomatosis.
A literature search of databases aimed at finding validated metrics for ...assessing myomas symptomatology.
Summary of obligatory and optional examination methods in the diagnosis of uterine fibroids and methods of examination of reproductive parameters of the couple in relation to myomatosis. Defining the metrics of bleeding manifestations of myomatosis with emphasis on the "Pictorial Bleeding Assessment Chart". Reviewing metrics of algic manifestations of myomatosis and quality of life with emphasis on the "Quality of Life Questionnaire - Myomatosis - Severity Symptom Scale".
The purpose of the applicable metrics, which summarize objective findings and subjective complaints of patients, is to describe and evaluate possible correlations and dynamics of changes in the health status, depending on the chosen therapy.
The aim of this study is to compare the extent of ovarian endometriosis diagnosed at preoperative staging with subsequent perioperative findings. Definition of discrepancies observed according to the ...#Enzian 2021 classification.
The cohort includes 62 patients of reproductive age with preoperative findings of ovarian endometrioma. Patients were divided according to the #Enzian 2021 classification into subgroups (O1, O2 + O3) with unilateral and bilateral findings. The percentage concordance of preoperative and perioperative findings was evaluated.
In the evaluation of ovarian involvement, the preoperative ultrasound diagnosis shows almost 100% agreement with the findings on the ovaries during surgery. Periadnexal adhesions were predicted preoperatively in only half of the cases. The difference in laterality was confirmed with T3 involvement in the O2 + O3 subgroup. In the bilateral involvement, the finding of the presence of grade 3 adhesions was doubled. An association of ovarian form of endometriosis (O2-O3) with deep infiltrating endometriosis of the small pelvis was observed in 50% of the cohort.
The ovarian form of endometriosis is associated with the occurrence of other endometriosis lesions in the small pelvis. In this study, it was confirmed that preoperative staging underestimates the extent of endometriosis in the small pelvis. In the surgical management of ovarian endometriosis, extensive adhesive process should be expected.
: Objective: Endometriosis is a chronic disease with a relatively high prevalence in the female population. Both the disease itself and its surgical treatment can adversely affect the fertility of ...patients. For this reason, endometriosis is offered as a possible indication for fertility preservation by cryopreservation methods. The aim of this paper is to present the current knowledge on the options of fertility preservation in this subpopulation.
Search of relevant literature in PubMed/Medline, Web of Science and Scopus databases.
Fertility preservation by cryopreservation methods has so far been used mainly in the care of women with cancer. With increasing experience, the effectiveness and availability of these methods have increased significantly and the indication spectrum has been extended to selected benign diseases such as endometriosis. Three techniques are currently established in practice: embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. Oocyte cryopreservation is the most commonly used technique, since it is the most advantageous for the patient and, according to the available data, is an effective way to increase the chances of future pregnancy for patients with endometriosis The purpose is to realize the protection of reproduction before the planned operation.
The diagnosis of endometriosis negatively affects the fertility of women. For some patients, the solution is fertility preservation by cryopreservation methods. Further clinical studies are needed to define exact, practically applicable indication criteria, potential risks of procedures and their benefits and cost-effectiveness.
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