Metrics of uterine myomatosis symptomatology in clinical practice.

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.

Discrepancies in staging and perioperative classification of pelvic endometriosis according to #Enzian 2021.

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.

Methods and techniques of fertility preservation in patients with endometriosis.

: 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.

Relugolix combination therapy and symptoms of uterine myomatosis - selected case reports of indication spectrum and treatment outcomes.

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.

Complete androgen insensitivity syndrome - rare case of malignancy of dysgenetic gonads.

OBJECTIVE: A case report of a young patient with primary amenorrhea who was diagnosed with agenesis of the uterus and was genetically confirmed for complete androgen insensitivity syndrome with already developed malignancy of dysgenetic gonads. CASE REPORT: The 17-year-old patient visited a gynecological clinic for primary amenorrhea. Both ultrasound and vaginal examination revealed suspicion of uterine agenesis, which was subsequently verified during diagnostic laparoscopy. Genetic testing showed karyotype 46,XY, and a rare diagnosis - complete androgen insensitivity syndrome. A secondary finding from a left gonadal biopsy was a Sertoli-Leydig cell tumor. The patient underwent bilateral gonadectomy and was given estrogen replacement therapy. She is now regularly examined by a pediatric oncologist. CONCLUSION: Complete androgen insensitivity syndrome is a rare genetic disease characterized by varying degrees of feminization in individuals with a male karyotype. It should not be neglected, especially in the differential diagnostic work-up of primary amenorrhea. Genetic testing of the karyotype should be performed whenever uterine agenesis is suspected.

Selected pathological conditions affecting endometrial receptivity.

OBJECTIVE: A summary of new knowledge on embryo implantation in dependence on quality of the endometrium. METHODS: Literature review from August 2022 of the relevant publications in Web of Science, Scopus and PubMed/Medline databases, focused on "endometrial receptivity", "polycystic ovary syndrome", "endometriosis", "SARS-CoV-2". RESULTS: The receptive state of the endometrium is a result of physiological remodeling and immune system activity modulated by the microbio-me. This balance can be disturbed by myomas, polyps, sactosalpings, adenomyosis, endometriosis, polycystic ovary syndrome, infections. The effect of SARS-CoV-2 infection is being discussed. For a successful implantation, timing of transfer is crucial. The ultrasound examination is used conventionally. In specific cases, hysteroscopy and endometrium bio-psy are recommended. Histological and immunohistochemical evaluation is performed together with examination of microbio-me or transcriptome. To support the implantation, gestagenes are used, or metformin in the patients with polycystic ovary syndrome. In cases of a repeated implantation failure, the intrauterine infusion of mononuclear cells or platelet rich plasma is used, subcutaneous application of granulocyte colony stimulating growth factor, intravenous application of atosiban or intrauterine application of human chorionic gonadotropin. CONCLUSION: Recent research in the field of transcriptomics, proteomics and reproductive immunology uncovers the process of implantation more deeply and opens a new stage of the assisted reproduction.

Cryopreservation of sperm before gonadotoxic treatment at the University Hospital Brno in the years 1995-2020

OBJECTIVE: Sperm cryopreservation before gonadotoxic treatment is the basic and mos teffective method of preserving reproduction, which can be used during adolescence. The communication summarizes 26 years of experience in the operation of an oncological sperm bank, analyzes spermiograms of oncological patients, assesses the relationship between sperm pathology and diagnosis, and determines the number of deaths and the use of frozen sperm. METHODS: During the existence of CAR 01 (assisted reproduction center), more than 50,000 spermiograms were performed. From January 1995 to December 2020, a total of 24,729 men were examined within the sperm bank, of which 1,448 (5.9%) had an oncological diagnosis. The spermiograms were evaluated according to current WHO (World Health Organization) manuals. Cryopreservation of sperm has undergone a major development. The rules for the storage of frozen cells have been laid down by Act No. 296/2008 Coll. since 2008. In 2019, the methodology "Cryopreservation of reproductive cells and tissues in patients before cancer treatment" was updated. In all cases, the standard thawing technique was used. The sperms were processed by the swim-up method. As part of the treatment with assisted reproduction methods, oocytes were fertilized by the ICSI (intracytoplasmatic sperm injection) micromanipulation technique. RESULTS: Out of 1,448 examined spermiograms in men with oncological diagnoses, testicular cancer was present in 43.7% of patients and malignant diseases of lymphatic and hematopoietic tissue were found in 24.1%, of which 70,1% included Hodgkin's lymphomas and 29,9% were non-Hodgkin's lymphomas. Leukemia was found in 7.9%, bone and cartilage cancers in 6.8%. The age of the clients of the whole group ranged from 13 to 64 years (27.2 ± 6.8 years). A total of 38.3% of men had normozoospermia, 54.2% of spermiograms showed pathological findings in 1 to 3 evaluated parameters and 7.5% of patients had azoospermia. Severe asthenozoospermia (mobility ≤ 10%) was detected in 57.2% of men and severe oligozoospermia (concentration ≤ 1 × 106 mm3) in 22.3% of patients. The lowest values of the spermiogram were found in men with testicular cancer; the best values were seen in CNS (central nervous system) cancers. The cryopreservation of sperm was performed in 1,340 cases (92.5%). So far, a total of 160 men (11.9%) have used frozen sperm, of which 6.2% in our center. In these 83 cases, the ICSI technique was always used, 38 clinical pregnancies (45.8%) and 32 births were achieved. We have registered 424 completed storages of semen (31.6%), of which 148 (11.0% of all oncology patients) were made due to death and the others at patients' request. Using the sperm of the dead is a specific issue. CONCLUSION: In cancer patients, sperm pathologies occur in high percentage. The lowest spermiogram values were found in men with testicular cancer. It is necessary to take into account long-term storage and fertilization by micromanipulation methods. The number of men who die is significantly higher than the number of those who use sperm to treat infertility. Cryopreservation of sperm should be offered to each patient prior to the therapy leading to the destruction of spermatogenesis.

Prospective randomized comparison of the transobturator mid-urethral sling with the single-incision sling among women with stress urinary incontinence: 1-year follow-up study.

INTRODUCTION AND HYPOTHESIS: The objective was to compare the efficacy and safety of an innovative single-incision sling (SIS) with the inside-out transobturator sling (TOT) in the treatment of female stress urinary incontinence (SUI). METHODS: A prospective randomized trial was performed in a tertiary referral urogynecology center from January 2012 to December 2013. The study included women with pure urodynamic SUI. Patients were randomized to either the SIS or the TOT anti-incontinence procedure. Surgery duration, blood loss, and groin pain scores were recorded for each patient. The 1-year follow-up visit included objective and subjective cure parameters, postoperative de novo urgency, complications, and the impact on the patient's life quality. RESULTS: Of 285 patients assessed for eligibility, a total of 93 patients (32.6 %) were randomized into TOT (n = 48) and SIS groups (n = 45). There were no significant differences in either operating time or blood loss. A statistically significant difference between the two groups was found in pain scores three (5.6 ± 1.8 vs 3.1 ± 2.1, p < 0.001) and 12 h postoperatively (3.8 ± 1.7 vs 2.1 ± 1.7, p < 0.001). After 1 year, there were no significant differences between the TOT and SIS groups in objective cure rates (87.0 % vs 90.9 %; p = 0.399) or patient-reported success rates (91.3 % vs 93.2 %; p = 0.999). Incidence of postoperative de novo urgency did not differ between TOT and SIS patients. Both groups registered a significant improvement in quality of life. CONCLUSIONS: The Ophira SIS procedure has 1-year success rates comparable to standard TOT with significantly less groin pain in the early postoperative period. Both methods were safe and effective in terms of postoperative urgency and life quality improvement.

Uterine Fibroid Morphology and Histology with Respect to Reproductive Age.

OBJECTIVE: To evaluate histological uterine fibroid incidence among reproductive age women and to deter- mine correlations between fibroid histological type, patient age, and number and size offibroids. STUDY DESIGN: The study cohort consisted of 103 women desiring preg- nancy who underwent myo- mectomy for symptomatic uterine fibroids. The primary endpoints were histological type of fibroid, myomectomy incidence among 2 age groups (18-34 vs. 35-40), solitary or multiple fibroids, and <5 cm vs. >5 cm fibroid diameter. Secondary anal- ysis endpoints evaluated correlations between uterine fibroid histological type, 2 age groups of women,.and uterine fibroid number and size. RESULTS: Following myomectomy, 84.5% exhibited benign histology, and myomatosis malignancy was not detected. Of the 103 women, 50.5% were aged <34 and 49.5% were aged 35-40; 71.8% had a solitary fibroid and 28.2% had α 2 fibroids; 58.3% had a fibroid of <5 cm. and 41.7% had a fibroid >5 cm in diameter. Cellular fibroid incidence was higher (10.3%) in cases of multiple myomatosis in comparison to the solitary fibroid group (n=0) (p=0.021). Among women with multiple myomatosis (n=29), almost all (n=28, 96.6%) had only 1 histological type. CONCLUSION: Among women of. child-bearing age having myomectomy, most have benign histology with no significant differences in histological type with regard to patient age and fibroid size. A higher incidence of cellular fibroids was observed only in multiple myomatosis cases.

Efficacy and Safety of Perioperative Use of Epinephrine for Laparoscopic Myomectomy in Infertile Women with Symptomatic Solitary Intramural Uterine Fibroids A Randomized Clinical Trial.

OBJECTIVE: To determine the efficacy and safety of intramyometrial application of epinephrine during a laparoscopic myomectomy in women of reproductive age desiring pregnancy and with clinically symptomatic uter- ine fibroids, in comparison with a placebo-based patient control group. STUDY DESIGN: The study group (n=96, 53.3%) underwent an application of 12 µg epinephrine hydro- chloride diluted in 20 mL of NaCl solution, while the control group (n=84, 46.7%) received 20 mL of NaCl only. Perioperative blood loss, duration of surgery, length of hospital stay, and incidence of perioperative and postoperative complications were evaluated. RESULTS: A significantly lower blood loss (mean ±SD: 57± 23 mL) was observed in the group with local appli- cation of epinephrine as compared to the control group (143±106 mL) (p<0.001), along with a significantly shortened duration of surgery (53 ±16 min) vs. control group (72±26 min) (p=0.006), and a significantly shortened hospital stay (3.0± 1.2 days) vs. the control group (4.3 ±1.4 days) (p= 0.003). No serious perioper- ative complications were observed in either group, and no statistically significant difference in the incidence of postoperative complica- tions was recorded with our study group when compared to the control group (2.1% vs. 7.1%) (p=0.143). CONCLUSION: Epineph- rine use during a laparo- scopic myomectomy is both effective and safe.

Laparoscopic Treatment of Cesarean Scar Ectopic Pregnancy.

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).

Safety and Efficacy of Single Incision Sling Versus Midurethral Sling in the Treatment of Stress Urinary Incontinence: A Randomized Controlled Trial.

IMPORTANCE: This study compares the long-term efficacy and safety of an innovative single-incision sling (SIS) with the inside-out transobturator tape (TOT) sling in the treatment of female stress urinary incontinence. OBJECTIVES: Women with urodynamic stress urinary incontinence were randomized to either SIS or TOT groups and followed up for 4 years. The primary outcome was objective cure defined with a negative cough stress test result. Secondary outcomes involved subjective cure reported via patient's satisfaction scale, surgery complications, postoperative de novo urgency, and patient's life quality. STUDY DESIGN: This is a randomized noninferiority controlled trial. RESULTS: A total of 168 women were randomized (84 in both groups). After 4-year follow-up, 130 patients were analyzed (66 in the SIS group and 64 in the TOT group). The objective (86.4% vs 84.4%; risk difference [95% confidence interval], 0.020 [-0.101 to 0.141]; P = 0.807) and subjective cure rates (83.3% vs 81.3%; risk difference [95% confidence interval], 0.020 [-0.111 to 0.151]; P = 0.821) were similar with the SIS and TOT groups. Both procedures were associated with low complication rates. Repeated surgery rates were 7.6% in the SIS group and 6.3% in the TOT groups. The mesh exposure rate was 1.5% for the SIS group and 3.1% for the TOT group. Incidence of de novo urgency did not vary between TOT and SIS patients. Both groups registered significant life quality improvement. CONCLUSION: After long-term follow-up, anti-incontinence SIS surgery proved noninferior to the inside-out TOT procedure in terms of objective and subjective cure rates.

Blocking of EphA2 on Endometrial Tumor Cells Reduces Susceptibility to Vδ1 Gamma-Delta T-Cell-Mediated Killing.

Background: 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. Methods: We analyzed Vδ1 and Vδ2 γδ T cells in peripheral blood and paired peritoneal fluid samples in endometriosis patients (n = 19) and compared the counts with that of age- and sex-matched healthy donors (n = 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. Results: We determined Vδ1 T cells substantially reduced in patients' peripheral blood (p < 0.01) and peritoneal fluid (p < 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. Conclusions: 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.

Efficacy and safety of vilaprisan in women with uterine fibroids: Data from the phase 2b randomized controlled trial ASTEROID 2.

OBJECTIVE: To assess the efficacy of vilaprisan compared with placebo in the management of the symptoms of uterine fibroids (UF), with a secondary objective to provide a descriptive comparison with ulipristal acetate. STUDY DESIGN: The randomized, parallel-group, double-blind, placebo- and active-controlled, multicenter ASTEROID 2 trial assessed the efficacy and safety of vilaprisan versus placebo and ulipristal acetate for two 12-week treatment periods in women with ≥1 UF experiencing heavy menstrual bleeding (HMB). The primary endpoint compared the efficacy of vilaprisan with placebo at 12 weeks, assessed as the absence of bleeding/spotting by bleeding diary. Secondary endpoints compared the efficacy of vilaprisan with ulipristal acetate. Results of the first 12-week treatment period are reported here. RESULTS: Women (mean age 42.5 years) were enrolled from 1 June 2015. At baseline, mean menstrual blood loss per 28 days was 214.1 mL and the volume of the three largest UF was 106.2 mL. In total, 155 women completed the initial 12-week treatment period. Complete absence of bleeding/spotting until the end of the 12-week treatment period was achieved by 62.9 % of women receiving vilaprisan versus 0.0 % with placebo (p < .001); 55.4 % of women treated with ulipristal acetate reported absence of bleeding/spotting. The predefined HMB response (<80 mL and >50 % reduction from baseline during the last 28 days of treatment) was observed in 95.7 % of subjects treated with vilaprisan and 86.5 % of subjects treated with ulipristal acetate. Vilaprisan and ulipristal acetate treatment reduced the sum of the volume of the three largest UF by 29.9 % and 23.8 %, respectively, whereas an increase of 6.3 % was observed in the placebo group. No safety concerns, including multiple laboratory parameters, were identified. CONCLUSION: Daily administration of vilaprisan 2 mg induced amenorrhea, controlled bleeding, decreased UF size, and was well tolerated in women with HMB associated with UF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02465814 https://clinicaltrials.gov/ct2/show/NCT02465814.

Pelvic floor dysfunction after vaginal and cesarean delivery among singleton primiparas.

OBJECTIVE: To compare the prevalence of pelvic floor dysfunction symptoms, including pelvic organ prolapse (POP), urinary incontinence (UI), and fecal incontinence (FI) among primiparous women after vaginal and cesarean delivery. METHODS: In a prospective cohort study at a University hospital in the Czech Republic, singleton primiparas with cephalic presentation who delivered at term were enrolled between 2002 and 2007. In 2013, 5-10 years after delivery, women who had not delivered again completed an internet-based survey about current symptoms of POP, UI, and FI, which were evaluated using validated questionnaires. The relative risk (RR) of POP, UI, and FI symptoms was calculated. RESULTS: Complete questionnaire data were obtained from 641 women who delivered vaginally and 224 who delivered by cesarean. The mean UI score (ICIQ-SF) was 2.3 ± 3.6 in the vaginal group and 1.0 ± 2.7 in the cesarean group (P=0.005). The mean POP scores (POPDI-6) were 2.2 ± 2.3 and 2.1 ± 2.0, respectively (P=0.944). The mean Wexner scores to evaluate FI were 1.3 ± 1.7 and 1.0 ± 1.5, respectively (P=0.220). The RR of pelvic floor dysfunction after vaginal delivery was highest for women with UI symptoms (RR 1.15, 95% confidence interval 0.92-1.42). CONCLUSION: Significant differences in the occurrence of symptoms of UI were observed after vaginal delivery as compared with cesarean delivery. ClinicalTrials.gov: NCT02661867.

Rationale and design of ASTEROID 2, a randomized, placebo- and active comparator-controlled study to assess the efficacy and safety of vilaprisan in patients with uterine fibroids.

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.

Long-term medical management of uterine fibroids with ulipristal acetate.

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.

Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids.

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).

Effect of a selective progesterone receptor modulator on induction of apoptosis in uterine fibroids in vivo.

Aim. To determine if hormonal treatment induces apoptosis in uterine fibroids. Methods. Immunohistochemical examination of fibroid tissue, using avidin-biotin complex and cleaved caspase-3 antibody for detecting apoptosis, was performed in premenopausal women who underwent 12-week treatment with oral SPRM (6 patients with 5 mg and 5 patients with 10 mg of ulipristal acetate per day) or gonadoliberin agonist (GnRHa, 17 patients) and subsequent myomectomy or hysterectomy for symptomatic uterine fibroids. Ten patients with no presurgical hormonal treatment were used as controls. Results. Apoptosis was present in a significantly higher proportion of patients treated with ulipristal acetate compared to GnRHa (P = 0.01) and to patients with no hormonal treatment (P = 0.01). In contrast to an AI of 158.9 in SPRM patients, the mean AI was 27.5 and 2.0 in GnRHa and control groups, respectively. No statistical difference in the AI was observed between the two groups of patients treated with ulipristal acetate (5 mg or 10 mg). Conclusion. Treatment with ulipristal acetate induces apoptosis in uterine fibroid cells. This effect of SPRM may contribute to their positive clinical effect on uterine fibroids.

Survival and infertility treatment in male cancer patients after sperm banking.

OBJECTIVE: To evaluate the relationship between sperm pathology and cancer diagnosis, determine the mortality rate, and evaluate the outcomes of the use of frozen sperm from the sperm bank. DESIGN: Prospective study. SETTING: University fertility center. PATIENT(S): A total of 619 male patients were referred for sperm freezing before gonadotoxic therapy from 1995 to 2006. INTERVENTION(S): Semen analysis, data verification in the National Oncologic Register, assisted reproduction technologies, and statistical evaluation. MAIN OUTCOME MEASURE(S): Cancer diagnosis and sperm pathology analysis, survival of patients, and infertility treatment success. RESULT(S): Malignant testicular cancer was diagnosed in 43.6% of patients, and malignant neoplasms of the lymphatic and hematopoietic tissues were found in 31.7% of patients. Azoospermia or severe oligospermia (