The use of LNG-IUS-19.5 mg in daily gynecological routine practice in Germany: data from the Kyleena™ Satisfaction Study (KYSS).

PURPOSE: The Kyleena™ Satisfaction Study (KYSS) provided the first data on 19.5 mg levonorgestrel-releasing intrauterine system (LNG-IUS-19.5 mg) use in routine clinical practice. Here we report results from the German participants in KYSS. METHODS: This prospective, observational, single-arm cohort study recruited women who independently chose to use LNG-IUS-19.5 mg during routine counseling in Germany. Overall satisfaction and bleeding profile satisfaction, continuation rates, and safety profile were evaluated at 12 months or premature end of observation (EoO). RESULTS: In the German study population, LNG-IUS-19.5 mg placement was attempted in 508 women and successful in 506 women. Mean age was 32.3 years, and 60.0% (n = 305/508) were parous. Placement was considered easy and associated with no more than mild pain, even in younger and nulliparous participants. Of those with satisfaction data available, 87.6% (n = 388/443) were satisfied with LNG-IUS-19.5 mg at 12 months/EoO. Satisfaction was similar for parous (86.9%, n = 238/274) and nulliparous (88.8%, n = 150/169) women, and was independent of age, prior contraceptive method, or reason for choosing LNG-IUS-19.5 mg. Most participants (73.6%, n = 299/406) were also satisfied with their bleeding profile at 12 months/EoO, independent of parity, age, prior contraceptive method, presence of amenorrhea or dysmenorrhea severity. The 12-month continuation rate was 84.1% (n = 427/508). Most discontinuations were due to loss to follow-up (8.5%, n = 43/508) or treatment-emergent adverse events (TEAEs) (4.7%, n = 24/508). TEAEs were reported in 12.6% (n = 64) of participants, with 9.3% (n = 47) considered to have an LNG-IUS-19.5 mg-related TEAE. CONCLUSION: Our real-world findings on LNG-IUS-19.5 mg use in German KYSS participants reflected its suitability for a broad population, including young and nulliparous women. CLINICAL TRIAL REGISTRATION: NCT03182140 (date of registration: June 2017).

Transcervical radiofrequency ablation of focal adenomyosis: pilot results.

Objective: Adenomyosis is a common gynecological disease, which occurs in women in reproductive age and is characterized by the presence of endometrial glands and stroma within the myometrium. Abnormal uterine bleeding, pelvic pain as well as infertility can be associated with adenomyosis. There are two main types of adenomyosis: diffuse and focal. Previously, adenomyosis was diagnosed only upon histopathological examination after hysterectomy and/or adenomyomectomy. However, the development of imagining techniques such as transvaginal ultrasound and magnetic resonance imaging enables the diagnosis of adenomyosis (diffuse and focal) without any surgical intervention. When medical therapy is contraindicated or ineffective, or if patients have a fertility desire, a surgical treatment may be necessary.Methods: In this study, a total of 13 patients with 16 areas of focal adenomyosis were treated. All patients provided their informed consent to undergo transcervical adenomyosis ablation treatment with the Sonata System, aware that the safety and effectiveness of transcervical radiofrequency (RF) ablation for the treatment of adenomyosis has not been established. Follow-up was performed six months after Sonata treatment.Results: The positive results relating to the improvement of symptoms and reduction of adenomyosis lesion size were observed in our study.Conclusion: Transcervical RF ablation with the Sonata System may be a promising therapeutic alternative method to conventional procedures such as hysterectomy for the treatment of focal adenomyosis, disease which has limited therapeutic approach, and may enable a minimally invasive, uterine preserving option.

The significance of transcervical ultrasound-guided radiofrequency ablation in the treatment of symptomatic fibroids: results of an expert consensus from German-speaking countries.

Uterine fibroids are one of the most common diseases in female patients, lead mainly to bleeding disorders and lower abdominal pain, and reduce the chance of having children. In recent years we have seen a trend towards more and more pharmacotherapies and minimally invasive organ-preserving treatments. One novel and innovative procedure for an organ-preserving treatment of symptomatic uterine fibroids is the transcervical ultrasound-guided radiofrequency ablation (TRFA). TRFA has been used in Germany since 2013 and later found use in other German-speaking countries as well. There have now been more than 1200 TRFA treatments performed in Germany, Austria, and Switzerland. Experts from these three countries came together for a consensus meeting to analyze the significance of the procedure in the overall concept of the treatment of symptomatic uterine fibroids.

A novel estetrol-containing combined oral contraceptive: European expert panel review.

PURPOSE: Despite considerable advances in recently developed combined oral contraceptives (COCs), resulting in lower rates of adverse events while maintaining contraceptive efficacy, there is interest in further innovation. MATERIALS AND METHODS: Estetrol (E4), a native oestrogen, and progestin drospirenone (DRSP) were combined in a new COC. A European expert panel reviewed the pharmacology, efficacy, and safety and tolerability of this combination. Their findings are presented as a narrative review. RESULTS: E4 15 mg/DRSP 3 mg in a 24/4 regimen provided effective contraception with good cycle control, characterised by a predictable regular bleeding pattern and minimal unscheduled bleeding, together with a good safety profile. The combination was associated with high user satisfaction, well-being, and minimal changes in body weight. The effects on endocrine and metabolic parameters were limited, and the combination was found to have a limited impact on liver function and lipid and carbohydrate metabolism. Moreover, its effect on several haemostatic parameters was lower than that of comparators containing ethinyl oestradiol (EE) 20 µg/DRSP 3 mg and EE 30 µg/levonorgestrel 150 µg. CONCLUSION: E4 15 mg/DRSP 3 mg provides safe and effective contraception, with high user satisfaction and predictable bleeding. Further research will evaluate the long-term safety of the COC.

A novel estetrol-containing combined oral contraceptive: European expert panel review.

PURPOSE: Despite considerable advances in recently developed combined oral contraceptives (COCs), resulting in lower rates of adverse events while maintaining contraceptive efficacy, there is interest in further innovation. MATERIALS AND METHODS: Estetrol (E4), a native oestrogen, and progestin drospirenone (DRSP) were combined in a new COC. A European expert panel reviewed the pharmacology, efficacy, and safety and tolerability of this combination. Their findings are presented as a narrative review. RESULTS: E4 15mg/DRSP 3 mg in a 24/4 regimen provided effective contraception with good cycle control, characterised by a predictable regular bleeding pattern and minimal unscheduled bleeding, together with a good safety profile. The combination was associated with high user satisfaction, wellbeing, and minimal changes in body weight. The effects on endocrine and metabolic parameters were limited, and the combination was found to have a limited impact on liver function and lipid and carbohydrate metabolism. Moreover, its effect on several haemostatic parameters was lower than that of comparators containing ethinyl oestradiol (EE) 20mg/DRSP 3 mg and EE 30mg/levonorgestrel 150mg. CONCLUSION: E4 15 mg/DRSP 3 mg provides safe and effective contraception, with high user satisfaction and predictable bleeding. Further research will evaluate the long-term safety of the COC.

Pregnancy Outcomes After Transcervical Radiofrequency Ablation of Uterine Fibroids with the Sonata System.

Objective: To describe pregnancy outcomes in women who conceived after undergoing transcervical fibroid ablation (TFA) as treatment for symptomatic uterine fibroids. Materials and Methods: TFA was used to treat symptomatic uterine fibroids with radiofrequency energy, both under clinical trial protocol and commercial usage in hospitals in Europe, the United Kingdom, Mexico, and the United States. All women who reported pregnancies to their physicians after undergoing TFA with the Sonata® System and provided consent for use of their data were included. Results: There have been 36 pregnancies representing 20 deliveries among 28 women who were treated with TFA. Five women conceived more than once postablation, and four conceived as a result of assisted reproductive technology (ART). Outcomes include 8 vaginal deliveries, 12 Cesarean sections, 3 therapeutic abortions, and 8 first trimester spontaneous abortions (four occurring in a patient with a history of recurrent pregnancy loss and an immunologic disorder). Five women are currently pregnant, two of whom previously delivered after TFA. There were no 5-minute Apgar scores <7, and all neonates weighed >2500 g. All deliveries occurred at ≥37 weeks except for one delivery at 35 6/7 weeks. There were no uterine ruptures or abnormal placentation and no reports of postpartum hemorrhage or stillbirths. Ablated fibroids included transmural, submucous, and intramural myomata up to 7 cm in diameter. Conclusions: Normal pregnancy outcomes at term have occurred after TFA with the Sonata System, including in women with recurrent abortion and in those undergoing ART. There were no instances of low Apgar scores, low birthweight, stillbirth, postpartum hemorrhage, or uterine rupture (FAST-EU, NCT01226290; SONATA, NCT02228174; SAGE, NCT03 118037). (J GYNECOL SURG 38:207).

Satisfaction and continuation with LNG-IUS 12: findings from the real-world kyleena® satisfaction study.

PURPOSE: The Kyleena® Satisfaction Study (KYSS) aimed to assess satisfaction and continuation with levonorgestrel-releasing intrauterine system (LNG-IUS) 12 (Kyleena®) in routine clinical practice and to evaluate factors that influence satisfaction. MATERIALS AND METHODS: This prospective, observational, multicentre, single-arm cohort study, with 1-year follow-up, was conducted in Belgium, Canada, Germany, Mexico, Norway, Sweden, Spain and the United States from 2017 to 2018. During routine counselling, women who independently selected to use LNG-IUS 12 were invited to participate in the study. KYSS assessed LNG-IUS 12 satisfaction, continuation and safety. RESULTS: Overall, there were 1126 successful LNG-IUS 12 placements, with insertion attempted in 1129 women. Most participants (833/968, 86.1%, 95% CI 83.7-88.2%, with satisfaction outcome data available) reported satisfaction with LNG-IUS 12 at 12 months (or at the final visit if the device was discontinued prematurely). Satisfaction was not associated with age, parity or motivation for choosing LNG-IUS 12. The majority of women (919/1129, 81.4%) chose to continue after 12 months. Discontinuation was not correlated with age or parity. Overall, 191 women (16.9%) reported a treatment-emergent adverse event. CONCLUSIONS: Results from KYSS provide the first real-world evidence assessing LNG-IUS 12, and demonstrate high satisfaction and continuation rates irrespective of age or parity. Clinical trial registration: NCT03182140.

Coincidence of uterine malformations and endometriosis: a clinically relevant problem?

INTRODUCTION: It is suspected that uterine malformations and endometriosis have a high coincidence. Furthermore, it is expected that obstructive uterine malformations are significantly higher affected than non-obstructive malformations. The correlation between endometriosis and uterine malformations may be due to increased retrograde menstruation, which would explain a higher coincidence of obstructive malformations and endometriosis [14]. METHODS: This retrospective study investigates whether patients with uterine malformations have a higher prevalence of endometriosis. The study includes patients with uterine malformations who were admitted to our hospital in the period from 01.12.2014 to 30.11.2019. RESULTS: 279 cases were analysed. 263 (94.2%) patients had a non-obstructive uterine malformation, 12 (4.3%) patients had an obstructive uterine malformation and 4 (1.4%) patients had uterine agenesia/hypoplasia. 209 (74.9%) patients had histologically confirmed endometriosis (peritoneal, ovarian or deep infiltrating) and 70 (25.1%) had no endometriosis. In 27 cases, deep infiltrating endometriosis (ENZIAN ABC) was detected additionally to peritoneal and ovarian endometriosis. CONCLUSION: The study shows a high prevalence of endometriosis in women with uterine malformations. For this reason, endometriosis should always be specifically sought in uterine malformations.

Correction to: Long-term treatment of endometriosis with dienogest: retrospective analysis of efficacy and safety in clinical practice.

In the original publication of the article, the word laparotomy has been presented in the proofs instead of laparoscopy in the below places.

Long-term treatment of endometriosis with dienogest: retrospective analysis of efficacy and safety in clinical practice.

PURPOSE: Endometriosis is a debilitating disease with high recurrence rates requiring long-term management. Progestins such as dienogest are used empirically when first symptoms occur and post-surgery to reduce recurrence. This retrospective, practice-based study assessed the efficacy and safety of dienogest in women with endometriosis treated for at least 60 months. METHODS: 37 women (age 39 ± 8 years) with laparoscopically diagnosed endometriosis received dienogest 2 mg orally once daily. Endometriosis-associated pelvic pain (EAPP) was measured on a 0-100 mm visual analog scale at baseline and every 12 months. Laboratory measures of lipid and liver metabolism, hemostatic and hormonal parameters were investigated in a subgroup of 15 women. Adverse events including bleeding disturbances and depressive symptoms were recorded. RESULTS: In 22 women, dienogest was begun after laparoscopy; median EAPP score was 70 mm pre-surgery and 10, 10, 20, 20, and 20 mm, respectively, after 12, 24, 36, 48, and 60 months of dienogest treatment. Another 15 women began dienogest without prior surgery; median EAPP score was 80 mm pretreatment and 20, 20, 30, 30, and 30 mm, respectively, after 12, 24, 36, 48, and 60 months. All laboratory parameters remained within the normal range. Mean serum estradiol was 28 ± 12 pg/ml after 60 months. Seven women experienced spotting episodes and four women presented with phases of depressed mood, which could all be clinically managed. CONCLUSIONS: Long-term (60-month) treatment with dienogest 2 mg once-daily in women with endometriosis effectively reduced EAPP and avoided pain recurrence post-surgery. Dienogest was well tolerated and adverse effects were clinically managed.

Symptoms of uterine myomas: data of an epidemiological study in Germany.

PURPOSE: Currently, no reliable data are available concerning the type and frequency of symptoms in premenopausal women with uterine myomas. METHODS: 2296 women were examined by means of vaginal ultrasound for the presence of myomas in seven gynaecological outpatient departments in Germany. From this population, 1314 premenopausal women between the ages of 30 and 55 years were evaluated to determine the type and frequency of myoma-related symptoms and their relationship to anamnestic factors, and the number, size, and location of the myomas. Standardised questionnaires were used to record the symptoms. RESULTS: Prevalence: In almost every second premenopausal woman (n = 639; 48.6%), uterine myomas were diagnosed. The frequency of myomas increased continuously with age and was highest in women between 46 and 50 years (65.2%). Age itself was found to be the main risk factor for the presence of myomas (p < 0.001). SYMPTOMS: 54.3% (n = 347) of the women suffered from myoma-related symptoms. The four main symptoms were identified as: Heavy menstrual bleeding (40.7%), dysmenorrhoea (28.2%), lower abdominal pain (14.9%), and intermenstrual bleeding (14.1%). In the majority of cases, the symptoms occurred simultaneously. Determinants for symptoms: Symptoms did not follow a clear age-related trend, whilst the number and size of the myomas did determine the presence of symptoms. The main influencing factor for the presence of intermenstrual bleeding was the location of the myomas. CONCLUSIONS: The high prevalence of uterine myomas highlights the importance of the diagnosis uterine myomas in standard gynaecological practice: The presence of only one myoma caused symptoms in 46.5% and small myomas of up to 2 cm in diameter resulted in symptoms in 39.5%.

Diaphragm endometriosis: Random localization or extended form of pelvis endometriosis. A large comparative analysis of 202 cases.

OBJECTIVE: The aim of this study was to investigate and present the clinical characteristics of diaphragm endometriosis, to approach the pathogenetic mechanisms, and to answer the question of whether this disease can be considered an extended form of pelvic endometriosis. STUDY DESIGN: It was a retrospective comparative one-to-one analysis of 202 cases. Two groups of patients were compared: Group 1 patients with diaphragm endometriosis vs Group 2 (control group) with pelvis endometriosis, each with 101 patients. RESULTS: Patients with diaphragm endometriosis had extreme significantly higher prevalence of severe pelvis endometriosis included deep infiltrated endometriosis and severe adhesions in term of complete Douglas obliteration (p value = 0.0001). There was neither age nor BMI difference in two groups. Besides of cyclic shoulder or upper abdomen pain there was no difference of symptoms. CONCLUSION: Diaphragm endometriosis is a rare condition with an approximate prevalence of 1.1% of all endometriosis cases. Since the symptoms are very specific and patients do not associate the pain with diaphragmatic endometriosis, the symptoms should be asked about explicitly. If patients with diaphragmatic endometriosis have no symptoms, the lesions do not necessarily need to be removed. The pathogenesis is still unclear. The authors of this study consider this disease to be an extended form of severe pelvic and deep infiltrated endometriosis. However, the right-side dominance still cannot be explained. Further research is needed to fully understand the origin of diaphragmatic endometriosis.

TMEM16A(a)/anoctamin-1 shares a homodimeric architecture with CLC chloride channels.

TMEM16A/anoctamin-1 has been identified as a protein with the classic properties of a Ca(2+)-activated chloride channel. Here, we used blue native polyacrylamide gel electrophoresis (BN-PAGE) and chemical cross-linking to assess the quaternary structure of the mouse TMEM16A(a) and TMEM16A(ac) splice variants as well as a genetically concatenated TMEM16A(a) homodimer. The constructs carried hexahistidyl (His) tags to allow for their purification using a nondenaturing metal affinity resin. Neither His-tagging nor head-to-tail concatenation of two copies of TMEM16A(a) noticeably affected Ca(2+)-induced measured macroscopic Cl(-) currents compared with the wild-type TMEM16A(a) channel. The digitonin-solubilized, nondenatured TMEM16A(a) protein migrated in the BN-PAGE gel as a homodimer, as judged by comparison with the concatenated TMEM16A(a) homodimer and channel proteins of known oligomeric structures (e.g. the voltage-gated Cl(-) channel CLC-1). Cross-linking with glutaraldehyde corroborated the homodimeric structure of TMEM16A(a). The TMEM16A(a) homodimer detected in Xenopus laevis oocytes and HEK 293 cells dissociated into monomers following denaturation with SDS, and reducing versus nonreducing SDS-PAGE provided no evidence for the presence of intersubunit disulfide bonds. Together, our data demonstrate that the Ca(2+)-activated chloride channel member TMEM16A shares an obligate homodimeric architecture with the hCLC-1 channel.

[Hypermenorrhoea]. / Hypermenorrhö.

Many treatment options of hypermenorrhoea are available. After exclusion of organic causes, which need often on operative treatment, many medical treatments can be performed. Tranexamic acid and oral contraceptives, preferable in extended cycle, can be used, but it should be also used Qlaira and Mirena, which have a label for the indication hypermenorrhoea. If the medical treatment has no success or is contraindicated, an operative treatment should be performed. Endometrial ablation is often a successful alternative treatment to hysterectomy in patients suffering from hypermenorrhoea.

Delayed expulsion of a large fibroid after transcervical radiofrequency ablation: A case report.

Fibroids are the most common type of benign uterine tumor, which occur up to 68.6% of women. Hypermenorrhea is the most common symptom with a general prevalence of 40%-54%, followed by dysmenorrhea and low abdominal pain. Transcervical fibroids ablation was developed as a minimally invasive, incisionless treatment of fibroids in a short time. This method is safe and effective with an excellent record of safety. We present the case of a 40-year-old woman, who attended in our fibroid excellence center. She reported severe hypermenorrhea and dysmenorrhea. Family planning was definitely completed. Using vaginal ultrasonography a FIGO 2-5 fibroid of 5 cm in diameter was detected. Different treatment options were discussed: medical treatment, laparoscopic fibroidectomy, hysterectomy, and transcervical radiofrequency ablation with Sonata System. Because of advantages of transcervical radiofrequency ablation (minimal invasive treatment without incision, effectivity of method, short surgical time) the patient decided on this method. Three months later, the patient came to the first follow up. She reported a significant improvement of hypermenorrhea. A vaginal ultrasonography was carried out. The fibroid changed its position from FIGO 2-5 to FIGO 2. The patient was very satisfied with the result. After 2 months, she attended in our department again because of severe clear vaginal discharge. She had no bleeding, no pain as well as no fever. We examined her immediately. A fibroid expulsion was detected. The fibroid was removed vaginally. There was no severe bleeding during the operation and the fibroid could be removed completely. The surgery time was 25 minutes.

Laparoscopic Approach in Bladder Endometriosis, Intraoperative and Postoperative Outcomes.

BACKGROUND/AIM: Endometriosis is a benign condition affecting 10-20% of women at reproductive age. The urinary tract is affected in 0.3-12.0% of women with endometriosis and in 19.0-53.0% of women with deep infiltrating endometriosis. The bladder is the most commonly affected organ in the urinary tract with a prevalence of up to 80%. Bladder endometriosis is defined as the occurrence of endometrial glands and stroma in the detrusor muscle. The aim of the study was to present the detailed technique and intraoperative and postoperative outcomes of laparoscopic resection of bladder endometriosis. PATIENTS AND METHODS: This was a retrospective study analyzing all surgical procedures, carried out at the Academic Hospital Cologne Weyertal between January 2014 and December 2022. In total 23,862 surgical reports were analyzed, and only patients (n=33 patients) with bladder endometriosis were included in the study. RESULTS: Follow-up was performed in 25 patients by phone contact. Twenty-three patients (92%) reported an improvement of symptoms, especially of dysuria, and an increase of quality of life. Only two patients (8%) reported no change in symptoms (dysmenorrhea and dyspareunia). Two patients (8%) reported bladder dysfunction. Mild postoperative pollakiuria was reported by two patients (8%). Four patients (with mild bladder dysfunction and pollakiuria) were satisfied with postoperative results owing significant improvement of symptoms and increasing the quality of life. CONCLUSION: Surgical treatment of bladder endometriosis can be performed by a gynecologist. In cases where a ureteroneocystostomy is required or the localization of endometriosis nodule is unfavorable, an intervention by a multidisciplinary team is recommended. Laparoscopic partial cystectomy and shaving seem to be an appropriate method for improving urinary symptoms. This surgical approach requires excellent laparoscopic skills.