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Clathrin-mediated endocytosis is an essential cellular internalization pathway involving the dynamic assembly of clathrin and accessory proteins to form membrane-bound vesicles. The evolutionarily ancient TSET-TPLATE complex (TPC) plays an essential, but ill-defined role in endocytosis in plants. Here we show that two highly disordered TPC subunits, AtEH1 and AtEH2, function as scaffolds to drive biomolecular condensation of the complex. These condensates specifically nucleate on the plasma membrane through interactions with anionic phospholipids, and facilitate the dynamic recruitment and assembly of clathrin, as well as early- and late-stage endocytic accessory proteins. Importantly, condensation promotes ordered clathrin assemblies. TPC-driven biomolecular condensation thereby facilitates dynamic protein assemblies throughout clathrin-mediated endocytosis. Furthermore, we show that a disordered region of AtEH1 controls the material properties of endocytic condensates in vivo. Alteration of these material properties disturbs the recruitment of accessory proteins, influences endocytosis dynamics and impairs plant responsiveness. Our findings reveal how collective interactions shape endocytosis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: A review of diagnostic options and standardized methods for specifying clinical symptoms associated with uterine myomatosis., Methods: A literature search of databases aimed at finding validated metrics for assessing myomas symptomatology., Results: 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"., Conclusion: 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.

Aim: 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., Material and Methods: 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., Results: 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., Conclusion: 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., Methods: Search of relevant literature in PubMed/Medline, Web of Science and Scopus databases., Results: 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., Conclusion: 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.

Objective: An illustrative review of the indications for relugolix combination therapy (RCT) in the management of symptoms associated with uterine myomatosis., Methods: A set of annotated case reports from outpatient and clinical practice., Results: The file includes a non-invasive methodology for defining excessive menstrual bleeding using the pictorial bleeding assessment chart (PBAC). It also presents the use of RCT as a fertility-sparing procedure prior to elective myomectomy and the management of isthmic fibroids as an uterine factor of infertility. Cases of RCT of adenomyosis in primary sterility and in extragenital forms of endometriosis are commented. Emergent events associated with complications of myomatosis in pregnancy are represented by a case report of necrotizing diff use myomatosis in puerperium. The differential-diagnostic confusion of adnexal pathology and myomatosis, RCT as a final solution to failed pharmacotherapy, and the alternative of hysterectomy in premenopause illustrate the diverse spectrum of indications for pharmacological treatment, including the possibility of dual therapy with RCT and aGnRH., Conclusion: Relugolix combination therapy as an effective and safe causal treatment expands the therapeutic spectrum and options for reproductive medicine specialists and registering gynaecologists. The availability of conservative treatment in combination with surgical treatment leads to optimalization and greater effectiveness of therapeutic procedures and increased quality of life for women with myomatosis.

Aim of the Study: Comparison of two types of uterine manipulators used in total laparoscopic hysterectomy (TLH) and clinical evaluation of the method in patients in a two-year group supplemented by subjective evaluation., Design: Prospective observational study., Setting: Department of Gynecology and Obstetrics, Masaryk University, Faculty of Medicine and University Hospital Brno., Material and Methods: A group of patients operated in the years 2018-2019 by the TLH method using one of two types of uterine manipulators - Karl Storz HOHL (group No. 1) vs. plastic ring of Koh's manipulator (group No. 2). We compared surgical time (min), blood loss (ml), perioperative complications, length of hospital stay (days), early and late complications. We were interested in the possible influence of BMI, uterine on these parameters. Subjective evaluation of the method by patients took place before the procedure and 12 weeks after the operation with a standardized questionnaire., Results: A total of 134 patients were enrolled in the study (75 in group 1 vs. 59 in group 2). The monitored parameters: age, BMI, operative time, blood loss and length of hospitalization did not differ statistically significantly. When comparing the individual groups with different manipulators, the total number of complications (mild difficulties, serious complications) was without statistical significance (p = 0.58), but the spectrum of symptoms was different in both groups. More than a third of the patients in the group were obese. There were more serious complications than non-obese ones, the performance was longer, however, for a small number it was statistically insignificant (p = 0.11). In patients with uterine surgery, we recorded more adhesiolysis. We did not show that previous surgery on the uterus was associated with a higher incidence of complications (p = 0.6). We did not notice any statistically significant difference in the subjective evaluation (p = 0.3)., Conclusion: TLH is the dominant method of uterine removal in our workplace. In a group of 134 women, we did not show a statistically significant difference in the monitored parameters. The HOHL manipulator has proved to be more user-friendly due to its technical parameters and better clarity of the operating field. Subjective evaluation of the method was positive in patients.

Objective: The aim of this prospective, unicentric, cohort study was to evaluate the effect of dienogest use in the therapy of symptomatic endometriosis of rectovaginal septum in patients of fertile age., Study Design: Prospective, unicentric, cohort study., Setting: Department of Obstetrics and Gynaecology, Brno University Hospital and Masaryk University Medical School, Brno., Material and Methods: Prospective analysis of the group of 32 patients in reproductive age who have previously been diagnosed with endometriosis of rectovaginal septum. These patients were treated conservatively with dienogest 2 mg per day during a 24-week period. Through questionnaires and clinical assessment, we have studied the presence of symptoms like dyspareunia, diffuse pelvic pain, Biberoglu-Behrman(B-B) score assessment and subjective pain perception using Visual Analogue Scale (VAS) of pain. Data were collected at the beginning of therapy, after 4, 12 and 24 weeks of dienogest use., Results: Continual use of dienogest during the 24-week period diminishes symptoms of dyspareunia by 62% (p.

Objective: Evaluation of radiofrequency endometrial ablation (RFEA) clinical efficacy in patients with heavy menstrual bleeding (HMB)., Design: Original article., Setting: Department of Gynecology and Obstetrics, University Hospital and Masaryk University Medical School, Brno., Methods: Study included 20 patients with HMB who had failed hormonal therapy and met the study inclusion criteria. All RFEA procedures were performed in the operating theater in general anesthesia by two experienced surgeons according to a standardized protocol. All RFEA were performed using specific disposable electrodes and radio frequency generator M-3004 (RF Medical Co., South Korea). Study outcomes were evaluated three months post-surgery included percentage of women with amenorrhoea or menstrual bleeding persistence measured by the modified Pictorial Blood Assessment Chart (PBAC) score. Furthermore, chronic pelvic pain intensity assessed by visual analogue scale (VAS), patient satisfaction (Patient Global Impression of Improvement, PGI-I score), and the incidence of complications were evaluated., Results: All RFEAs were performed without operational or technical complications, the average age being operated was 43.0 ± 2.9 years and the operating time did not exceed ten minutes. In the early postoperative follow-up, patients did not require any analgesics and were all released to outpatient care the following day. Percentage of amenorrhea at three months post-treatment was 35.0%, mean PBAC score for women with menstrual bleeding was 1.8 ± 0.6. Patients satisfaction with the treatment was evaluated by 1.6 ± 0.6 on the PGI-I scale and long-term pelvic pain was on average 2.1 ± 0.8 by VAS, which counts an improvement of 31.0%., Conclusion: The HMB treatment with RFEA achieves good clinical results in three-month evaluation with objective and also subjective parameters. The technique is suitable for outpatient treatment and is an alternative to hysteroscopy endometrial ablation. Its wider clinical usage is limited by the high cost of the radiofrequency generator and disposable probes. Keywords heavy menstrual bleeding, hysteroscopy, radiofrequency endometrial ablation, amenorrhoea, complication.

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 3months 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 (2mg daily) will be administered in different regimens: continuous treatment for 12 or 24weeks, 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 (5mg daily) and placebo. Patients randomized to receive placebo for 12weeks will also be given active treatment for 12weeks. 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., (Copyright © 2017 Bayer AG. Published by Elsevier Inc. All rights reserved.)

Objective: Analysis of radical fertility preserving surgery, oncogynaecological treatment including their pregnancy effort., Design: Prospective study., Setting: Department of Obstetrics and Gynaecology, Masaryk University and Faculty Hospital Brno., Methods: The group of 13 patients in age fifteen to thirty-six, who underwent radical fertility preserving surgery of oncogynecological tumors (cervix, ovarium), 9 patients with ovarian cancer and 4 patients with carcinoma of cervix., Results: Histology showed seven times ovarial epithelial carcinoma, twice nonepithelial ovarial carcinoma, twice spinocelular cervical carcinoma, one adenosquamous and one lymfoepithelioma like carcinoma. We reported lymphocele as the most often postoperative complication by five patients with ovarial carcinoma, lymphoedema of lower limbs in one case and one of them complicated by bilateral hydronephrosis. After surgery procedures of cervical carcinoma, there was a stenosis of cervical canal with postoperative correction. In one case there was provided vaginal revision of cervix followed by embolisation of uterine arteries because of heavy bleeding in early postoperative period. After two years follow up, there are 12 patients in remission. There were four patients with fertlity plan, two with ovarial carcinoma, two with cervical carcinoma. The first group describes two pregnancies - one misscariage and one spontaneus labour in the date of delivery. There were 4 pregnancies in two patients wit cervical carcinoma. One patient has an intrapartal cesarean section because of scarring of the cervix after the operation. Next patients has two labours in due date, three labours in 34-37th week of pregnancy and one misscariage in 23 week of pregnancy. One patient has ovarial cancer during pregnancy, so the radical fertility preserving surgery was done after delivery., Conclusion: Methods and procedures of surgery with fertility preserving goals in our oncogynecological centre are in concordance with actual knowledge of medicine and respect oncological safety of patients with malignancies, who currently wish for fertility preserving treatment. Presented group of patients is relatively small, but results of oncological treatment and fertility plan demonstrate right-fulness of this treatment.

Objective: The purpose of this study is to evaluate the surgical treatment of stress urinary incontinence by the single incision sling Ophira (Promedon)., Design: Prospective observational study., Setting: Department of Obstetrics and Gynaecology, Masaryk University and University Hospital Brno, Brno., Methods: Patients with confirmed urodynamic stress urinary incontinence (SUI) were included in the study. Patients with urgent urinary incontinence or mixed incontinence with predominance of urgent folder, patients with insufficiency of internal sphincter of the urethra and pelvic organ prolapse, as well as after previous surgical treatment, patients with pelvic organ prolapse or with other serious pathology of organs of small pelvis were excluded. All patients included in the study received single incision sling (SIS) Ophira (Promedon). The length of the surgery and blood loss and complication was observed. Postoperative observation one year after the treatment was set and evaluated objective and subjective parameters of SUI., Results: In the study were 138 patients examined, total of 45 (34.8%) were included. Postoperative observation completed 44 (97.7%) patients. Mean age was 62.3 years. The mean follow-up was 12.9 months, when 40 patients (90.9%) had a negative cough standardized test (CST). Total of 41 patients (93.1%) evaluated the operation as a major improvement by using a questionnaire Patient Global Impression of Improvement (PGI-I). Quality of life scores were evaluated by International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF). Before the surgery ranged from 14.8 ± 2.5 points, after the surgery 3.3 ± 2.0 which is an improvement of 11.5 ± 3.1 points. There weren't serious perioperative and postoperative complications., Conclusion: Our results are comparable with literary data and are correlated with other studies evaluating the effectiveness of other types of SIS. The method seems to be safe and efficient enough. Observing the group of patients will be continued in order to assess the short- and long-term results.

Objective: To review the incidence of histologic variants of uterine fibroids of patients in reproductive age and postmenopause. Analysis of potential relations between histological fibroids variants and hormonal activity of the patient., Design: Retrospective analysis., Setting: Department of Obstetrics and Gynecology, Masaryk University and University Hospital Brno., Material and Methods: Retrospective analysis of 2,397 women who underwent myomectomy or hysterectomy at the Department of Obstetrics and Gynecology, Masaryk University and University Hospital Brno in years 2008-2014. According to input criteria - age of patients between 18-65 years, ultrasound confirmed uterine fibroid. Exclusion criteria was irregular menstrual cycle, hormonal therapy in history or hysterectomy performed for tumors of the small pelvis or for cancer of the uterus or cervix.Group A consisted of 235 patients with regular menstrual cycles, between ages 18-40. Myomectomy was chosen for these patients.Group B consisted of 433 postmenopausal patients between ages 50-65. Laparoscopic and abdominal hysterectomy was performed to these patients., Results: A statistically significant difference was observed in the occurrence of epithelioid type of leiomyoma between women age groups 18-40 and 50-65. In the group of postmenopausal women four malignant forms of leiomyoma were recorded, which were not statistically relevant., Conclusion: After evaluating statistical analysis it was found, that there is a statistically significant difference in epithelioid type of uterine leiomyoma. Four patients were detected malignant variant of leiomyoma - leiomyosarcoma in the group of postmenopausal women.

Background: 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. Case: 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. Results: 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. Conclusions: Laparoscopic surgical management of a viable ectopic pregnancy is technically simple, and is followed by a good recovery. (J GYNECOL SURG 30:309).

Objective: To review current methods in the diagnosis of dysplasia and cervical cancer., Design: Review article., Setting: Reprofit International Ltd., Brno; Department of Gynecology and Obstetrics, University Hospital and Faculty of Medicine, Masaryk University, Brno; Biopticka laborator Ltd., Pilsen., Methods and Results: Nowadays, there are non-invasive methods for more accurate and timely detection of uterine cervix lesions. Digital images of the uterine cervix can be analysed by a computer for characteristic features and colour patterns, which may enhance the objectivity of the colposcopic examination. Digital image processing technology and biomarkers detection (p16/Ki-67) are useful in liquid based cytology (LBC). At the molecular genetic level different tests are used to detect deoxy- or ribonucleic acid (DNA, RNA) of high-risk types of human papillomavirus (HR HPV). The introduction of HPV testing in screening procedures in the Czech Republic will further in-crease the sensitivity of screening. However, the most specific identification of cervical high-grade lesions appears to be an mRNA detection of oncogenes E6 and E7. The advanced method for the assessment of cervical lesion progress in HR HPV positive women is to determine the methylation of tumor supressor genes that normally prevents the cancer growth., Conclusion: Screening programs, inviting women to direct preventive gynecological examinations by health insurance, but also efficient utilization of available methods could lead to early detections of cervical dysplasias., Keywords: cervical dysplasia and cancer, SIL, colposcopy, LBC, HPV, methylation, mRNA.