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).

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.

Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022). Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer, Geriatric Assessment and Supply Structures.

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented.

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.

Clinical and Surgical Characteristics of Abdominal Wall Endometriosis: A Multicenter Case Series of 80 Women.

BACKGROUND/AIM: Endometriosis of the abdominal wall (AWE) is poorly understood because of its rarity and heterogeneous nature. The aim of this study was to investigate and present the clinical and surgical characteristics of AWE and to propose its classification. PATIENTS AND METHODS: This was a multicentric retrospective study. For this analysis, the data from three endometriosis centers were collected. In total 80 patients were included in this study. The Academic Hospital Cologne Weyertal is a certified, level III endometriosis center in Germany with 750-1,000 endometriosis surgeries being performed annually; Barzilai University Medical Center is a certified endometriosis center in Ashkelon, Israel; and Baku Health Center is an endometriosis Center in Baku, Azerbaijan. RESULTS: The size of nodule (histological specimen) was significant larger in women with than those without adenomyosis (3.34±1.4 vs. 2.55±1.33 cm, p=0.016). The incidence of subfascial involvement was also found to be significantly higher in these women (42% vs. 19%, p=0.03). No significant difference was found in patients with and without obesity. In 78% of cases, the proliferation level (Ki67 marker) was less than 30%. CONCLUSION: AWE has a high prevalence of symptoms such as abdominal wall pain and swelling, as well as bleeding. The strengths of the current study are the investigation of the proliferation marker Ki67 in AWE, the impact of adenomyosis, as well as the suggested classification.

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.

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.

Clinical Diagnosis and Early Medical Management for Endometriosis: Consensus from Asian Expert Group.

This work provides consensus guidance regarding clinical diagnosis and early medical management of endometriosis within Asia. Clinicians with expertise in endometriosis critically evaluated available evidence on clinical diagnosis and early medical management and their applicability to current clinical practices. Clinical diagnosis should focus on symptom recognition, which can be presumed to be endometriosis without laparoscopic confirmation. Transvaginal sonography can be appropriate for diagnosing pelvic endometriosis in select patients. For early empiric treatment, management of women with clinical presentation suggestive of endometriosis should be individualized and consider presentation and therapeutic need. Medical treatment is recommended to reduce endometriosis-associated pelvic pain for patients with no immediate pregnancy desires. Hormonal treatment can be considered for pelvic pain with a clinical endometriosis diagnosis; progestins are a first-line management option for early medical treatment, with oral progestin-based therapies generally a better option compared with combined oral contraceptives because of their safety profile. Dienogest can be used long-term if needed and a larger evidence base supports dienogest use compared with gonadotropin-releasing hormone agonists (GnRHa) as first-line medical therapy. GnRHa may be considered for first-line therapy in some specific situations or as short-term therapy before dienogest and non-steroidal anti-inflammatory drugs as add-on therapy for endometriosis-associated pelvic pain.

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.

Are double-J stents in surgery for deep infiltrating endometriosis always necessary? A retrospective analysis.

Introduction: The therapy of deep infiltrating endometriosis places the highest demands. Double-J (DJ) stent insertion is recommended preoperatively. However, we could not find any publication in PubMed that showed the relevant advantages of double-J stent insertion in surgery of deep infiltrating endometriosis (DIE). Aim: To report the advantages and disadvantages of inserting double-J stents in surgery for deep infiltrating endometriosis. Material and methods: All patients who underwent surgery for deep infiltrating endometriosis at Academic Hospital Cologne Weyertal (a level III endometriosis center with up to approximately 900 endometriosis laparoscopic procedures annually) between January 2017 and September 2021 were included in this retrospective analysis. A total of 197 cases were included. The urinary tract complications were analyzed and they were divided into infections, pyelonephritis, urosepsis, intraoperative and postoperative ureteral lesions. Patients were divided into three groups: 1) with DJ stents in whom DJ stents were left in place postoperatively for at least 2 weeks, 2) with DJ stents in whom DJ stents were removed directly at the end of the surgery, 3) without DJ stents. Results: There was a significant difference between all three groups in urinary tract complications: group 1 - 32%, group 2 - 11.6% and group 3 - 7%. The p-value of 0.01 shows statistical significance between group with DJ stents and the group without DJ stents. Urinary tract infection occurred in 25.5% in the first group, 11.6% in the second group and 3.6% in the third group. Here, too, the p-value shows statistical significance between the group with DJ stents and the group without DJ stents. Ureteral injury, on the other hand, occurred rarely and no statistically significant difference was found between group 3 and the total population, 3.6% versus 2.5%. In group 1, the injury rate was minimally higher, 6.4%. After comparing groups 1 and 2 with group 3, there was also no significant difference in ureter injury (6.4% vs. 3.6%, p = 0.42). Conclusions: The authors of this study recommend that DJ stent insertion should not be part of the general preoperative preparation.

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).

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.

Transcervical intrauterine radiofrequency ablation of fibroids in high-risk patients with bleeding disorder.

OBJECTIVES: To show the advantages of transcervical radiofrequency ablation (TRFA) in high-risk patients with bleeding disorder. MATERIAL AND METHODS: It is a retrospective analysis. The study included only patients with known pre-existing conditions (obesity, cardiac and neurological disease, coagulation disorder, anaemia) or post-surgical conditions who were treated with the Sonata® System for fibroid-related bleeding complaints at Academic Hospital Cologne Weyertal between January 2015 and March 2021. These patients were classified as high-risk patients. The fibroids were mostly determined due transvaginal sonography. Thirty patients were included, and 43 fibroids were determined. RESULTS: Therapy with the Sonata® system could be performed without complications in all cases. In our analysis, improvement of fibroid-related symptoms was observed in 89% of cases. CONCLUSIONS: The Sonata® System is on the one hand minimally invasive, uncomplicated and fast and on the other hand a successful method of fibroid therapy, which is particularly suitable for high-risk patients with various pre-existing conditions, for whom a minimally invasive, bloodless and short surgical procedure has great advantages.

Combined procedure of the transcervical radiofrequency ablation (TRFA) system and surgical hysteroscopy. Increased risk or safe procedure?

Introduction: The advantage of transcervical radiofrequency ablation (TRFA) is that it is minimally invasive, incision-free, and treats a wide spectrum of fibroids, including those that are not accessible by surgical hysteroscopy (FIGO 3, 4, 5, 6, and 2-5). However, there are no publications describing a combined procedure of operative hysteroscopy and TRFA yet, so it was still unknown whether a combined procedure is associated with additional risks. Aim: To report the combined technique of transcervical intrauterine radiofrequency ablation of fibroids and surgical hysteroscopy. Material and methods: Our study was designed to show the results of our case series with 21 patients. The retrospective study included only patients who were treated with the combined procedure of surgical hysteroscopy with fibroid and/or endometrial resection and fibroid ablation using the Sonata System. Results: The combined procedure was performed without any complications in all cases. Two days after surgery, no increased morbidity was observed compared to only conventional surgical hysteroscopy and/or therapy with the TRFA. All patients were satisfied with the procedure. No late complications were observed within the first 6 months postoperatively. Seventeen patients with bleeding symptoms were asked about their subjective assessment of improvement. Fifteen patients reported significant improvement in symptoms and 1 patient reported only minimal improvement. Only 1 patient, who underwent TRFA and endometrial resection, did not report any improvement. No increase in symptoms was observed. Conclusions: Although TRFA is an approved method, it is not yet widely used worldwide. The combined procedure has been rarely used. The aim of our work is to show through our case series that transcervical radiofrequency ablation can be combined with surgical hysteroscopy for fibroid and/or endometrial resection without any additional risk.

Significance of Ki67 expression in endometriosis for infertility.

OBJECTIVE: The aim of the study was to show the significance of Ki67 expression in endometriosis for infertility. STUDY DESIGN: It was a retrospective analysis. 670 cases were analyzed. In 484 cases, immunohistochemical proliferation analysis was performed to determine the expression of Ki67. The indicated percentages of Ki67 expression were divided into three groups. An expression below 10% is considered low, 10-30% intermediate, and over 30% is considered high. RESULTS: There was a significant correlation between Ki67 expression and postoperative pregnancy onset: 66,7% of patients with high proliferation activity became pregnant within one year postoperatively, whereas the 38,7% of patients with moderate and only 17,3% of patients with low Ki67 expression became pregnant. CONCLUSION: In this work, high Ki67 expression was more frequent than low Ki67 expression in women with infertility than in patients without infertility. These results contribute to the importance of endometrial resection in the context of infertility treatment.

Laparoscopic Isthmocele (Niche) Correction as prevention in patients with fertility desire.

OBJECTIVES: To report the technique of Laparoscopic Isthmocele (Niche) Correction and surgical outcomes. MATERIAL AND METHODS: The retrospective study included only patients with current or potential fertility desire who had laparoscopic surgery for an isthmocele at the Academic Hospital Cologne Weyertal between the beginning of 2014 and the end of 2020. A total of 28 patients were included. Sonographic follow-up of myometrial thickness was performed in 67% cases. RESULTS: In 18% cases myometrial thickness was 5-7 mm, in 11% cases > 7-10 mm and in 39% cases > 10 mm. In the group with postoperative myometrium of 5-7 mm, two patients had preoperative residual myometrium of 2 mm, one patient of 2.5 mm and in one patient residual myometrium was not measurable (< 1 mm). In 11 patients, the postoperative myometrium was either greater than 10 mm and/or no isthmoceles were detectable. There was an increase in mean preoperative myometrial thickness from 2 mm to a mean myometrial thickness of 8.7 mm (myometrial thickness increase to 335%). CONCLUSIONS: In this study, laparoscopic correction of the isthmocele resulted in an increase in myometrial thickness from 2 mm to 8.7 mm (average values). This represents an increase in myometrial thickness of 335%. According to the literature review performed and based on our own results, we recommend prophylactic isthmoceles correction in patients with fertility desire by means of laparoscopic procedure. Laparotomy should be performed only in special cases. Surgical hysteroscopy is not suitable for this purpose, but sufficient studies are still lacking.