Fetoscopic laser coagulation for twin-to-twin transfusion syndrome: a comparison of flexible 1.0/1.2 mm fetoscopes with curved sheaths of 2.7/3.3 mm2 vs. 2 mm fetoscopic lens technique with sheaths of 6.6/11.3 mm2.

OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

Cross-sectional study for derivation of a cut-off value for identification of an early versus delayed diagnosis of endometriosis based on analytical and descriptive research methods.

BACKGROUND: Endometriosis is a benign, hormone-dependent, chronic inflammatory gynecological disease accompanied by cyclic and acyclic pelvic pain and other complaints. The long lists of research recommendations in the AWMF guideline (Burghaus et al., Geburtshilfe Frauenheilkd 81:422-46, 2021) and ESHRE Endometriosis Guideline (ESHRE Endometriosis Guideline Development Group, Endometriosis: Guideline of European Society of Human Reproduction and Embryology, 2022) show that there is still a great need for research in all aspects of the disease. Diagnostic delay, defined as the mean time between symptom onset and confirmed diagnosis, is a particular problem associated with endometriosis. Some quantitative and qualitative studies have investigated possible reasons for this. A range of physician-related (Dixon et al., Br J Gen Pract 71:e668-e676, 2021; van der Zanden and Nap, Reprod Biomed Online 32:527-31, 2016) and patient-related factors (Sayer-Jones and Sherman, Health Psychol Behav Med 9:456-79, 2021) as well as stigmatization of the topic of menstruation by society have been identified (Kruckenberg, Frauenarzt 59:2-5, 2018; Seear, Soc Sci Med 69:1220-7, 2009). The consequences of the disease being diagnosed late (or too late) on the course of disease, the quality of life and the costs of the disease have already been documented in studies (Sims Int J Environ Res Public Health 18(15):8210, 2021; Surrey Adv Ther 37:1087-99, 2020). However, a systematically derived cut-off value that clearly distinguishes between short and long delay is still lacking. Therefore, the aim of our study was to derive a threshold value for the definition of a target corridor for endometriosis diagnosis based on descriptive and analytical methods. METHODS: Since our review of the rather sparse publications on diagnostic delay did not yield satisfactory results, we used descriptive statistics and location parameters to calculate a cut-off value for German population data from the EndoCost study. Statistical methods were used for correlation analysis of shortDD versus longDD (correlation analysis and logistic regression) and group membership (discriminant analysis). RESULTS: Five years was identified as the cut-off value that significantly differentiated between shortDD and longDD based on various disease-related variables. This suggests that endometriosis should be definitively diagnosed within less than five years to minimize the risk of an unfavorable course of the disease. CONCLUSION: Our findings confirmed that an early onset of endometriosis-related symptoms is the most important risk factor for a long diagnostic delay. Consequently, adolescent females should receive increased attention as an especially vulnerable group. Evidently, there is an urgent need to develop adequate concepts to improve the endometriosis education and care among this target group.

Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance.

PURPOSE: Post-treatment follow-up in women with cervical pre-cancers (CIN3) is mandatory due to relapse in up to 10% of patients. Standard follow-up based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our prospective, multicenter, observational study was to test the hypothesis that an individualized viral-cellular-junction test (vcj-PCR) combined with cytology has a lower false positive rate for the prediction of recurrence compared to standard co-testing. METHODS: Pre-surgical cervical swabs served for the identification of HPV16/18 DNA integration sites by next-generation-sequencing (NGS). Samples taken at 6, 12 and 24 months post-surgery were evaluated by cytology, hrHPV-DNA and the patients' individual HPV-integration sites (vcj-PCR on the basis of NGS). RESULTS: Integration sites were detected in 48 of 445 patients (10.8%), 39 of them had valid follow-up data. The false positive rate was 18.2% (95% CI 8.6-34.4%) for standard hrHPV/cytology at six months compared to 12.1% (95% CI 4.8-27.3%) for vcj-PCR/cytology, respectively (McNemar p = 0.50). Six patients developed recurrences (1 CIN2, 5 CIN3) during follow-up. Standard co-testing detected all, whereas vcj-PCR/cytology detected only five patients with recurrences. Data of 269 patients without evidence of HPV16/18 integration were subject to post-hoc analyses. Standard co-testing revealed a false positive rate of 15.7% (95% CI 11.7-20.7%) and predicted ten of fourteen recurrences at six months. CONCLUSIONS: Although highly specific on its own vcj-PCR could not detect all recurrent CIN2/3. Possible reasons for this unexpected result may be multifocal lesions, intratumoral heterogeneity with respect to HPV integration and/or incident CIN.

Diagnosis and Treatment of Endometriosis. Guideline of the DGGG, SGGG and OEGGG (S2k Level, AWMF Registry Number 015/045, August 2020).

Aims The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society for Gynaecology and Obstetrics (OEGGG) and the Swiss Society for Gynaecology and Obstetrics (SGGG) was to provide consensus-based recommendations for the diagnosis and treatment of endometriosis based on an evaluation of the relevant literature. Methods This S2k guideline represents the structured consensus of a representative panel of experts with different professional backgrounds commissioned by the Guideline Committee of the DGGG, OEGGG and SGGG. Recommendations Recommendations on the epidemiology, aetiology, classification, symptomatology, diagnosis and treatment of endometriosis are given and special situations are discussed.

Rare Ectopic Pregnancies - A Literature Review for the Period 2007 - 2019 on Locations Outside the Uterus and Fallopian Tubes.

The majority of ectopic pregnancies (EP) are tubal pregnancies, but other implantation sites outside the uterus and tubes are also found. These rare EP locations present a particular diagnostic and therapeutic challenge. We present an overview of potential very rare locations of ectopic pregnancies, their symptoms, diagnosis and treatment, based on a systematic analysis of case reports. A literature review of the databases PubMed, Livivo and Google Scholar for the period 2007 to 2019 was carried out. A total of 113 publications were included in our review. These studies describe EP implantations in the posterior cul-de-sac, on the uterine serosa and uterine ligaments, in the vicinity of almost all intraperitoneal organs, on the abdominal wall as well as in retroperitoneal sites. The most common presenting symptom was abdominal pain occurring in different locations. The diagnostic procedures included various imaging procedures and/or explorative surgery at different advanced stages of pregnancy. The most common and preferred option was laparotomy for surgical treatment. The placenta was successfully resected in the majority of cases. A rare EP location should be considered when making a differential diagnosis in patients of child-bearing age with abdominal pain.

Selective Progesterone Receptor Modulators for the Medical Treatment of Uterine Fibroids with a Focus on Ulipristal Acetate.

Uterine fibroids are the most frequent benign tumours in women of child-bearing age. Their symptoms are diverse and the quality of life of the women affected can be significantly impaired. While treatment to date has been primarily by means of surgical intervention, selective progesterone receptor modulators (SPRMs) open up new medication-based treatment options. EMA's Pharmacovigilance Risk Assessment Committee (PRAC) has recently completed its review of ESMYA® (ulipristal acetate, 5 mg), following reports of serious liver injury, including liver failure leading to transplantation in postmarketing settings. We will provide some information on the PRAC's recommendations to minimize this risk. Nevertheless, the effectiveness and safety of the SPRM ulipristal acetate (UPA), both with regard to preoperative administration and with regard to an intermittent administration as long-term treatment for patients with symptomatic uterine fibroids, have been shown in several clinical studies (PEARL I-IV).

Daily Vaginal Application of Dienogest (Visanne©) for 3 Months in Symptomatic Deeply Infiltrating Rectovaginal Endometriosis: A Possible New Treatment Approach?

A 27-year-old patient suffering from deeply infiltrating rectovaginal endometriosis was treated with 2 mg/day dienogest vaginally for 3 months. The therapy was tolerated very well. The patient reported less side effects compared to the oral use of dienogest. After 3 months of dienogest treatment, the rectovaginal gynecological examination identified the visible vaginal part of endometriosis in remission. The firm endometriosis node approximately 3 cm in size and approximately 10 cm ab ano was still palpable, but it was much less painful. The laboratory values for luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were unremarkable, with an LH/FSH quotient of 0.7 during dienogest treatment, while 17-ß estradiol and progesterone were suppressed. At palpation and vaginal ultrasonography, there was no change in the findings before and after 3 months of dienogest treatment, but the patient was now de facto asymptomatic. To the best of our knowledge, this is the first report of a vaginal dienogest treatment in symptomatic deeply infiltrating rectovaginal endometriosis. Vaginal administration of dienogest should receive further investigation in pharmacokinetic and clinical studies.

Corrigendum to "Selective Progesterone Receptor Modulators for the Medical Treatment of Uterine Fibroids with a Focus on Ulipristal Acetate".

[This corrects the article DOI: 10.1155/2018/1374821.].

Dienogest 2 mg Daily in the Treatment of Adolescents with Clinically Suspected Endometriosis: The VISanne Study to Assess Safety in ADOlescents.

STUDY OBJECTIVE: To study the safety and efficacy of dienogest 2 mg in adolescents with suspected endometriosis. DESIGN: A 52-week, open-label, single-arm study. SETTING: In 21 study centers, in 6 European countries. PARTICIPANTS: Adolescents aged 12 to younger than 18 years with clinically suspected or laparoscopically confirmed endometriosis. INTERVENTIONS: Dienogest 2 mg once daily. MAIN OUTCOME MEASURES: The primary end point was relative change in lumbar spine (L2-L4) bone mineral density (BMD) measured using dual-energy x-ray absorptiometry. A key secondary end point was change in endometriosis-associated pain assessed using a visual analogue scale. RESULTS: Of 120 patients screened, 111 comprised the full-analysis set (ie, patients who took ≥1 dose of study drug and had ≥1 post-treatment observation) and 97 (87.4%) completed the study. Mean lumbar BMD at baseline was 1.1046 (SD, 0.1550) g/cm2. At the end of dienogest treatment (EOT; defined as at 52 weeks or premature study discontinuation), mean relative change in BMD from baseline was -1.2% (SD, 2.3%; n = 103). Follow-up measurement 6 months after EOT in the subgroup with decreased BMD at EOT (n = 60) showed partial recovery in lumbar BMD (mean change from baseline: -2.3% at EOT, -0.6% 6 months after EOT). Mean endometriosis-associated pain score was 64.3 (SD, 19.1) mm at baseline and decreased to 9.0 (SD, 13.9) mm by week 48. CONCLUSION: In adolescents with suspected endometriosis, dienogest 2 mg for 52 weeks was associated with a decrease in lumbar BMD, followed by partial recovery after treatment discontinuation. Endometriosis-associated pain was substantially reduced during treatment. Because bone accretion is critical during adolescence, results of the VISanne study to assess safety in ADOlescents (VISADO) study highlights the need for tailored treatment in this population, taking into account the expected efficacy on endometriosis-associated pain and an individual's risk factors for osteoporosis.

Evaluation of SprayShield™ Adhesion Barrier in a single center: randomized controlled study in 15 women undergoing reconstructive surgery after laparoscopic myomectomy.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of SprayShield™ Adhesion Barrier in preventing and/or reducing postoperative adhesion during gynecological surgery. DESIGN: This was a prospective, controlled, blinded, and randomized study. Patient blinding was performed intraoperatively. Subjects were randomly assigned to the SprayShield™ or the control group in a 2:1 ratio. SETTING: The study was conducted at the Clinic of Gynaecology and Obstetrics, at the University Hospital for Gynecology in Germany. PATIENTS: Fifteen patients participated in this study; nine patients were assigned to the SprayShield™ and six patients to the control group. INTERVENTIONS: During first operation (FLL) in the SprayShield™ group, the agent was applied to all myomectomy suture lines. Patients in the control group did not receive any anti-adhesion treatment, only good surgical practice. A second-look laparoscopy (SLL) was performed 8-12 weeks after myomectomy to evaluate adhesion formation. MAIN OUTCOME MEASURES: Main outcome measures were incidence, severity, and extent of uterine adhesions. RESULTS: No significant differences were found between the two study groups. CONCLUSIONS: SprayShield™ is easy to use. No serious adverse event related to SprayShield™ was observed. Efficacy data are inconclusive regarding the performance of SprayShield™. Further studies are needed to better understand this performance.

Bladder endometriosis: characterization by magnetic resonance imaging and the value of documenting ureteral involvement.

OBJECTIVES: To characterize bladder endometriosis by MRI and assess aspects of ureteral involvement. STUDY DESIGN: From 2007 to 2013, bladder endometriosis was diagnosed, surgically treated and histopathologically verified in 18 patients (mean age 31.7±4.6 years) retrospectively enrolled under a published MRI protocol at our hospital's Endometriosis Center. Preoperatively, to diagnose disease spread, cystoscopy was performed and MRI in the following sequences: T2-TSE and T1-SE with and without fat saturation in the sagittal and transversal planes after rectovaginal opacification. Nine patients additionally underwent a diffusion-weighted sequence, including calculation of the apparent diffusion coefficient (ADC). By consensus, two experienced radiologists, without prior knowledge of the surgical or cystoscopic findings, retrospectively characterized bladder endometriosis on the MRI scans, also determining anatomic position, size, sequence-dependent features and incidence of hemorrhages, and calculating ADC. The scans were also investigated to determine if MRI could detect ureteral involvement intercurrent with bladder endometriosis. RESULTS: Endometriosis localizations were bladder roof, n=1 (5.6%) and back wall, n=17 (94.4%). Mean lesion size was 3.65±1.5ml. Lesions exhibited a lower signal intensity in T2- than in T1-weighted images. High-signal-intensity spots showed an occurrence of 72.2% in fat-suppressed T1-weighted and 61.1% in T2-weighted sequences. Mean ADC was 1251.6±220.9mm(2)/s. By MRI, it was not possible to differentiate wall layers and hence infiltration depth. The bladder endometriosis of two women showed direct involvement with the right ureter. Furthermore, one woman had endometriosis of the left distal ureter in addition to bladder endometriosis. All cases of ureteral involvement were detected by MRI. CONCLUSIONS: Characteristic MRI features of bladder endometriosis were found to be low signal intensity in T2-weighted and high-signal-intensity spots in T1- and T2-weighted sequences. Standard-sequence MRI was capable of detecting ureteral involvement, but not bladder wall infiltration depth.

Splenosis: an uncommon differential diagnosis in gynecology.

Splenosis consists of ectopic functioning splenic tissue that can be located anywhere within the abdomen or pelvis. It is a benign condition usually found incidentally and is usually asymptomatic. The need for therapy is controversial, and treatment is suggested only in symptomatic cases, primarily those related to pelvic or abdominal implants.