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Background: Caesarean section (CS) rates are rising globally. Long-term adverse outcomes after CS might be reduced when the optimal uterine closure technique becomes evident.Objective: To determine the effect of uterine closure techniques after CS on maternal and ultrasound outcomes.Search Strategy: Literature search in electronic databases.Selection Criteria: Randomised controlled trials (RCTs) or prospective cohort studies that evaluated uterine closure techniques and reported on ultrasound findings, perioperative or long-term outcomes.Data Collection and Analysis: Twenty studies (15 053 women) were included in our meta-analyses for various outcomes. We calculated pooled risk ratios (RR) and weighted mean differences (WMD) with 95% CI through random-effect analysis.Main Results: Residual myometrium thickness (RMT), reported in eight studies (508 women), decreased by 1.26 mm after single- compared with double-layer closure (95% CI -1.93 to -0.58), particularly when locked sutures were used. Healing ratio [RMT/adjacent myometrium thickness (AMT)] decreased after single-layer closure (WMD -7.74%, 95% CI -13.31 to -2.17), particularly in the case of locked sutures. Niche prevalence increased (RR 1.71, 95% CI 1.11-2.62) when the decidua was excluded. Dysmenorrhea occurred more often in the single-layer group (RR 1.23, 95% CI 1.01-1.48), whereas incidence of uterine rupture was similar (RR 1.91, 95% CI 0.63-5.74).Conclusion: Double-layer unlocked sutures are preferable to single-layer locked sutures regarding RMT, healing ratio and dysmenorrhoea. Excluding the decidua seems to result in higher niche prevalence. As thin residual myometrium or niches may serve as intermediates for gynaecological and reproductive outcomes, future studies should focus on these outcomes. TWEETABLE ABSTRACT: #Uterineclosuretechniques after #caesarean affect #longtermoutcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to compare the 2 years' efficiency of uterine artery embolization (UAE) with hysterectomy in the treatment of menorrhagia caused by uterine fibroids in a randomized controlled trial. STUDY DESIGN: Twenty-eight Dutch hospitals recruited patients with uterine fibroids and menorrhagia, who were eligible for hysterectomy. Patients were randomized to UAE or hysterectomy. The primary endpoint was if UAE could avoid a subsequent hysterectomy in at least 75% of cases. Secondary endpoints were changes in pain, bulk-related complaints, and uterine and dominant fibroid volume reduction. RESULTS: One hundred seventy-seven patients were randomized to UAE (n = 88) or hysterectomy (n = 89). Two years after treatment 23.5% of UAE patients had undergone a hysterectomy. There were no significant differences in improvement compared to baseline in pain and bulk-related complaints. Uterine and dominant fibroid volume reduction in UAE patients was 48.2% and 60.5%, respectively. CONCLUSION: UAE is a valuable alternative treatment for symptomatic uterine fibroids. Nevertheless, when patients seek for certainty on the cessation of bleeding problems, a hysterectomy remains the treatment of choice. [ABSTRACT FROM AUTHOR]

Introduction: Imaging fibroid vascularity may predict fibroid growth and aid to determine most appropriate therapy. Microvascular (MV) flow imaging is relatively new and is able to detect slow flow in small vessels. Data on feasibility, reproducibility, and reliability of MV-flow imaging in fibroids is lacking. The purpose of our study was to determine the reproducibility of MV-flow imaging and to explore this technique for clinical practice for assessing blood flow in fibroids., Material and Methods: Thirty patients with one or multiple fibroids (diameter 1.5-12.0 cm) were prospectively included. Transvaginal ultrasound scanning was performed in B-mode, 2D MV-Flow™, 2D and 3D power Doppler mode (HERA W10, Samsung) by two experienced gynecologists at a tertiary care clinic from February to December 2021. The primary outcome was intra- and interobserver agreement of the vascular index (VI) and color score (CS). The following parameters: '2D MV-flow VI', '3DPD VI', '2D MV-flow CS' and '2DPD CS' were measured offline in the center, pseudocapsule, and entire fibroid. Secondary offline outcomes for exploring 2D MV-flow for clinical practice, included (1) ability to discern vascular structures, (2) assessing the degree of vascularity via CS and calculating a VI, and (3) determining penetration depth of the ultrasound signal in both power Doppler and MV-flow imaging., Results: All scans of the 30 included patients were of sufficient quality to analyze. Inter- and intra-observer correlations of all studied parameters were good to excellent, both for 2D MV-flow and 2D power Doppler (intercorrelation coefficient 0.992-0.996). Using 2D MV-flow different vascular structures were visible in detail, in contrary to using 2D and 3D power Doppler. In significantly more fibroids central flow could be visualized using 2D MV-flow (63%) than with 2D power Doppler (13%, p = 0.001). Finally, penetration of the ultrasound signal was deeper using 2D MV-flow (3.92 cm) than with 2D power Doppler (2.95 cm, p = 0.001)., Conclusions: Using 2D MV-flow imaging for determining vascularity is highly reproducible. It has potential added value for clinical practice as it depicts detailed vascular structures and the degree of vascularity, especially in the center of the fibroid., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To investigate patient perspectives on climate change and climate change mitigation strategies in healthcare., Methods: A cross-sectional survey among gynaecological patients from two Dutch outpatient clinics. Main outcomes included patients' climate-related knowledge and worry, climate friendly healthcare perspectives and willingness to opt for climate friendly treatment alternatives. Multivariable linear regression analyses were performed to explore patient characteristics associated with climate friendly healthcare perspectives., Results: 274 surveys were included. Most patients (79 %) were worried about climate change. Although almost all (91 %) found it important to contribute to climate protection, patients showed hesitance regarding healthcare measures that would impinge on individual choices. 62 % was willing to opt for climate friendly treatments, but this proportion varied by medical condition. Climate-related knowledge and worry were both positively associated with climate friendly healthcare perspectives., Conclusion: Gynaecological patients are concerned about climate change and possess substantial self-reported climate-related knowledge. Patients vary in their support of climate action that involves individual patient care, but the majority is open to choose climate friendly treatment alternatives for certain medical conditions., Practice Implications: This exploratory study holds implications for the feasibility of integrating climate impact into clinical decision-making and provides a foundation for normative evidence for decarbonizing healthcare., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Many women experience bleeding disorders that may have an anatomical or unexplained origin. Although hysterectomy is the most definitive and common treatment, it is highly invasive and resource-intensive. Less invasive therapies are therefore advised before hysterectomy for women with fibroids or bleeding disorders. This study has two aims related to treating bleeding disorders and uterine fibroids in the Netherlands: (1) to evaluate the regional variations in prevalence and surgical approaches; and (2) to assess the associations between regional rates of hysterectomies and less invasive surgical techniques to analyze whether hysterectomy can be replaced in routine practice., Material and Methods: We completed a register-based study of claims data for bleeding disorders and fibroids in women between 2016 and 2020 using data from Statistics Netherlands for case-mix adjustment. Crude and case-mix adjusted regional hysterectomy rates were examined overall and by surgical approach. Coefficients of variation were used to measure regional variation and regression analyses were used to evaluate the association between hysterectomy and less invasive procedure rates across regions., Results: Overall, 14 186 and 8821 hysterectomies were performed for bleeding disorders and fibroids, respectively. Laparoscopic approaches predominated (bleeding disorders 65%, fibroids 49%), followed by vaginal (bleeding disorders 24%, fibroids 5%) and abdominal (bleeding disorders 11%, fibroids 46%) approaches. Substantial regional differences were noted in both hysterectomy rates and the surgical approaches. For bleeding disorders, regional hysterectomy rates were positively associated with endometrial ablation rates (β = 0.11; P = 0.21) and therapeutic hysteroscopy rates (β = 0.14; P = 0.31). For fibroids, regional hysterectomy rates were positively associated with therapeutic hysteroscopy rates (β = 0.10; P = 0.34) and negatively associated with both embolization rates (β = -0.08; P = 0.08) and myomectomy rates (β = -0.03; P = 0.82)., Conclusions: Regional variation exists in the rates of hysterectomy and minimally invasive techniques. The absence of a significant substitution effect provides no clear evidence that minimally invasive techniques have replaced hysterectomy in clinical practice. However, although the result was not significant, embolization could be an exception based on its stronger negative association., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Many risk factors in uterine fibroid development have been identified, but women and their physicians are less aware of the influence of lifestyle on uterine fibroid development. The objective of this systematic review is to investigate and summarize modifiable prognostic factors associated with uterine fibroid development., Methods: Pubmed and Embase were searched for relevant articles according to PRISMA guidelines. References from included articles were screened and when relevant also included. Human in vivo studies on modifiable factors in fibroid development were included. Studies on non-modifiable factors and treatment, in vitro studies and animal studies were excluded. 607 articles were screened and 33 articles were included. Two independent investigators collected data from the report., Results: The strongest risk factor for fibroid development was a high BMI, while the strongest protective factors were a high fruit and vegetable intake and high vitamin D intake., Conclusion: More high-quality studies are necessary to better understand the impact of the abovementioned factors as well as the role they play in the growth of already existing fibroids.

Introduction: Pain experience, physical reaction, image quality and adverse events during Gel Instillation Sonohysterography (GIS) can differ using gels with different compositions. As a result, patient satisfaction can also be affected. The effect of two instillation gels, Endosgel versus ExEmgel, using both the Visual Analogue Scale (VAS) and a Continuous Pain Score Meter (CPSM) was therefore compared., Methods: This single centre double blind randomised controlled trial included 80 women planned for outpatient GIS, diagnosed with abnormal intrauterine bleeding or fertility disorders and suspicion on an intrauterine abnormality. Patients were randomly allocated to the instillation of Endosgel containing chlorhexidine or ExEmgel without chlorhexidine. Primary outcome was reported pain during the procedure using VAS. Secondary outcomes included pain score measured using CPSM, satisfaction to the procedure and preference at 3 weeks and 3 months after the procedure and image quality. A cost benefit analysis was also performed., Results: The reported median VAS concerning pain during gel instillation was comparable in the Endosgel and ExEmgel group, 2.50 (IQR 0.00-5.00) and 2.00 (IQR 0.00-5.75) respectively (p = 0.69). The median VAS of the entire procedure was also similar: both 2.00 (IQR 0.00-5.00) (p = 0.86). CPSM-scores were not significantly different either. Both groups were similar in image quality (p = 0.83) and patient's satisfaction (p = 0.36)., Conclusion: Concerning the pain experienced during a GIS procedure and patients' satisfaction, the ExEmgel was not proven to be superior to the Endosgel. Our advice is to use the gel that is available at the lowest costs, as the image quality is the same for both Endosgel and ExEmgel., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Resnik and Pugh recently explored the ethical implications of routinely integrating environmental concerns into clinical decision-making. While we share their concern for the holistic well-being of patients, our response offers a different clinical and bioethical stance on green informed consent and patient autonomy. Contrary to the authors' lack of data to support their concerns about provider and patient willingness to engage in climate-related conversations, we provide evidence supporting their sustainability engagement and stress the importance of a proactive, anticipatory approach in healthcare to align with evolving societal values. If climate change is perceived as a politicised issue, though it is not inherently so, healthcare providers are professionally trained to address sensitive subjects and have a duty to inform patients about potential health risks. Recognising the environmental crisis as a health crisis underscores the direct connection between environmental hazards and patients' well-being. Our perspective advocates for integrating individual considerations, societal responsibilities and systemic changes to promote environmentally sustainable healthcare., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The healthcare sector is responsible for 4%-10% of global greenhouse gas emissions. Considering the broad range of care that obstetricians and gynaecologists provide, mitigation strategies within this specialty could result in significant reductions of the environmental footprint across the whole healthcare industry., Objectives: The aim of this review was to identify for what services, procedures and products within obstetric and gynaecological care the environmental impact has been studied, to assess the magnitude of such impact and to identify mitigation strategies to diminish it., Search Strategy: The search strategy combined terms related to environmental impact, sustainability, climate change or carbon footprint, with the field of obstetrics and gynaecology., Selection Criteria: Articles reporting on the environmental impact of any service, procedure or product within the field of obstetrics and gynaecology were included. Included outcomes covered midpoint impact categories, CO 2 emissions, waste generation and energy consumption., Data Collection and Analysis: A systematic literature search was conducted in the databases of MEDLINE (Ovid), Embase (Ovid) and Scopus, and a grey literature search was performed on Google Scholar and two websites of gynaecological associations., Main Results: The scope of the investigated studies encompassed vaginal births, obstetric and gynaecological surgical procedures, menstrual products, vaginal specula and transportation to gynaecological oncologic consultations. Among the highest yielding mitigation strategies were displacing disposable with reusable materials and minimising content of surgical custom packs. The lowest yielding mitigation strategy was waste optimisation, including recycling., Conclusions: This systematic review highlights opportunities for obstetricians and gynaecologists to decrease their environmental footprint in many ways. More high-quality studies are needed to investigate the environmental impact of other aspects of women's and reproductive health care., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objectives: To assess the environmental impact of the non-invasive Magnetic Resonance image-guided High-Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids, we aimed to perform a full Life Cycle Assessment (LCA). However, as a full LCA was not feasible at this time, we evaluated the CO 2 (carbon dioxide) emission from the MRI scanner, MR-HIFU device, and the medication used, and analyzed solid waste produced during treatment., Methods: Our functional unit was one uterine fibroid MR-HIFU treatment. The moment the patient entered the day care-unit until she left, defined our boundaries of investigation. We retrospectively collected data from 25 treatments to assess the CO 2 emission based on the energy used by the MRI scanner and MR-HIFU device and the amount and type of medication administered. Solid waste was prospectively collected from five treatments., Results: During an MR-HIFU treatment, the MRI scanner and MR-HIFU device produced 33.2 ± 8.7 kg of CO 2 emission and medication administered 0.13 ± 0.04 kg. A uterine fibroid MR-HIFU treatment produced 1.2 kg (range 1.1-1.4) of solid waste., Conclusions: Environmental impact should ideally be analyzed for all (new) medical treatments. By assessing part of the CO 2 emission and solid waste produced, we have taken the first steps towards analyzing the total environmental impact of the MR-HIFU treatment of uterine fibroids. These data can contribute to future studies comparing the results of MR-HIFU LCAs with LCAs of other uterine fibroid therapies., Critical Relevance Statement: In addition to (cost-) effectiveness, the environmental impact of new treatments should be assessed. We took the first steps towards analyzing the total environmental impact of uterine fibroid MR-HIFU., Key Points: • Life Cycle Assessments (LCAs) should be performed for all (new) medical treatments. • We took the first steps towards analyzing the environmental impact of uterine fibroid MR-HIFU. • Energy used by the MRI scanner and MR-HIFU device corresponded to 33.2 ± 8.7 kg of CO 2 emission., (© 2024. The Author(s).)

Novel gonadotrophin releasing hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid-related heavy menstrual blood loss in comparison to placebo. Marketing authorization has been granted by several agencies including those in Europe, the United Kingdom and the United States. While the registration trials report a robust effect on the reduction of heavy menstrual blood loss and improvement in quality of life scores, reticence is advised before widespread prescription. In this review, we demonstrate limitations in the trial data, namely a lack of generalizability due to the restricted study population, the lack of transparency in the distribution of disease-level characteristics limiting the predictability of treatment success in the real-world diverse population, and the absence of any comparison to current alternative treatment methods. Importantly, no clinically meaningful volume reductions were found with GnRH antagonist combination preparations, and long-term safety data, particularly concerning modest but stable bone mineral density decline, need further addressing. Symptoms related to uterine fibroids adversely affect many women's quality of life and effective medical treatments are lacking. However, despite the urgent need for conservative treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness and cost-effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Cervical incompetence is an important cause of extremely preterm delivery. Without specialized treatment, cervical incompetence has a 30% chance of recurrence in a subsequent pregnancy. Recently, the first randomized controlled trial showed significant superiority of abdominal cerclage compared with both high and low vaginal cerclage in preventing preterm delivery at <32 weeks of gestation and fetal loss in patients with a previous failed vaginal cerclage., Objective: This study aimed to assess surgical and obstetrical outcomes in patients with pre- and postconceptional laparoscopic abdominal cerclage placement. Furthermore, it also aimed to perform subgroup analysis based on the indication for cerclage placement in order to identify patients who benefit the most from an abdominal cerclage., Study Design: A retrospective multicenter cohort study with consecutive inclusion of all eligible patients from 1997 onward in the Dutch cohort (104 patients) and from 2007 onward in the Boston cohort (169 patients) was conducted. Eligible patients had at least 1 second- or third-trimester fetal loss due to cervical incompetence and/or a short or absent cervix after cervical surgery. This includes loop electrosurgical excision procedure, conization, or trachelectomy. Patients were divided into the following subgroups based on the indication for cerclage placement: (1) previous failed vaginal cerclage, (2) previous cervical surgery, and (3) other indications. The third group consisted of patients with a history of multiple second- or early third-trimester fetal losses due to cervical incompetence (without a failed vaginal cerclage) and/or multiple dilation and curettage procedures. The primary outcome measure was delivery at ≥34 weeks of gestation with neonatal survival at hospital discharge. Secondary outcome measures included surgical and obstetrical outcomes, such as pregnancy rates after preconceptional surgery, obstetrical complications, and fetal survival rates., Results: A total of 273 patients were included (250 in the preconceptional and 23 in the postconceptional cohort). Surgical outcomes of 273 patients were favorable, with 6 minor complications (2.2%). In the postconceptional cohort, 1 patient (0.4%) had hemorrhage of 650 mL, resulting in conversion to laparotomy. After preconceptional laparoscopic abdominal cerclage (n=250), the pregnancy rate was 74.1% (n=137) with a minimal follow-up of 12 months. Delivery at ³34 weeks of gestation occurred in 90.5% of all ongoing pregnancies. Four patients (3.3%) had a second-trimester fetal loss. The indication for cerclage in all 4 patients was a previous failed vaginal cerclage. The other subgroups showed fetal survival rates of 100% in ongoing pregnancies, with a total fetal survival rate of 96%. After postconceptional placement, 94.1% of all patients with an ongoing pregnancy delivered at ³34 weeks of gestation, with a total fetal survival rate of 100%. Thus, second-trimester fetal losses did not occur in this group., Conclusion: Pre- and postconceptional laparoscopic abdominal cerclage is a safe procedure with favorable obstetrical outcomes in patients with increased risk of cervical incompetence. All subgroups showed high fetal survival rates. Second-trimester fetal loss only occurred in the group of patients with a cerclage placed for the indication of previous failed vaginal cerclage, but was nevertheless rare even in this group., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia. However, studies evaluating safety and effectiveness of hysteroscopic myomectomy under procedural sedation are lacking. This study aims to investigate whether hysteroscopic myomectomy under procedural sedation and analgesia with propofol is noninferior to hysteroscopic myomectomy under general anesthesia., Methods and Findings: This was a multicenter, randomized controlled noninferiority trial conducted in 14 university and teaching hospitals in the Netherlands between 2016 and 2021. Inclusion criteria were age ≥18 years, maximum number of 3 type 0 or 1 fibroids, maximum fibroid diameter 3.5 cm, American Society of Anesthesiologists class 1 or 2, and having sufficient knowledge of the Dutch or English language. Women with clotting disorders or with severe anemia (Hb < 5.0 mmol/L) were excluded. Women were randomized using block randomization with variable block sizes of 2, 4, and 6, between hysteroscopic myomectomy under procedural sedation and analgesia (PSA) with propofol or under general anesthesia (GA). Primary outcome was the percentage of complete resections, assessed on transvaginal ultrasonography 6 weeks postoperatively by a sonographer blinded for the treatment arm and surgical outcome. Secondary outcomes were the surgeon's judgment of completeness of procedure, menstrual blood loss, uterine fibroid related and general quality of life, pain, recovery, hospitalization, complications, and surgical reinterventions. Follow-up period was 1 year. The risk difference between both treatment arms was estimated, and a Farrington-Manning test was used to determine the p-value for noninferiority (noninferiority margin 7.5% of incomplete resections). Data were analyzed according to the intention-to-treat principle, including a per-protocol analysis for the primary outcome. A total of 209 women participated in the study and underwent hysteroscopic myomectomy with PSA (n = 106) or GA (n = 103). Mean age was 45.1 [SD 6.4] years in the PSA group versus 45.0 [7.7] years in the GA group. For 98/106 women in the PSA group and 89/103 women in the GA group, data were available for analysis of the primary outcome. Hysteroscopic resection was complete in 86/98 women (87.8%) in the PSA group and 79/89 women (88.8%) in the GA group (risk difference -1.01%; 95% confidence interval (CI) -10.36 to 8.34; noninferiority, P = 0.09). No serious anesthesiologic complications occurred, and conversion from PSA to GA was not required. During the follow-up period, 15 serious adverse events occurred (overnight admissions). All were unrelated to the intervention studied. Main limitations were the choice of primary outcome and the fact that our study proved to be underpowered., Conclusions: Noninferiority of PSA for completeness of resection was not shown, though there were no significant differences in clinical outcomes and quality of life. In this study, hysteroscopic myomectomy for type 0 and 1 fibroids with PSA compared to GA was safe and led to shorter hospitalization. These results can be used for counseling patients by gynecologists and anesthesiologists. Based on these findings, we suggest that hysteroscopic myomectomies can be performed under PSA in an outpatient setting., Trial Registration: The study was registered prospectively in the Dutch Trial Register (NTR 5357; registration date: 11 August 2015; Date of initial participant enrollment: 18 February 2016)., Competing Interests: No support from any organization for the submitted work was received, apart from the grant that was received from The Dutch organisation for Health Research and Development (ZonMW), as described in our funding statement; HvV received fees from Medtronic on an hourly basis for consultancy and lecturing on hysteroscopic morcellation. All the fees were donated to a foundation which promotes research in obstetrics and gynecology. NS received fees from Applied Medical for vNOTES courses and proctorship. These industries were not involved in the design, performance, analysis of this study nor the content or approval of this manuscript. All other authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; SC is a board member of the Dutch gynaecologic endoscopy working party ‘Werkgroep gynaecologische endoscopie’. All other authors report no other relationships or activities that could appear to have influenced the submitted work., (Copyright: © 2023 van der Meulen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: After incomplete healing of the uterine cesarean section scar, a niche can be observed; 24% of the women develop large niches with a residual myometrial thickness <3 mm. In these cases a laparoscopic resection is possible. The effect of this new treatment on fertility outcome is not known yet. This paper describes reproductive outcomes 2 years after a laparoscopic niche resection and compares women with or without secondary infertility at baseline., Material and Methods: A prospective cohort study was performed, with consecutive inclusion of women between 2011 and 2019. Women with a niche in the uterine cesarean scar, with a residual myometrial thickness of <3 mm and with a desire to become pregnant, were scheduled to undergo a laparoscopic niche resection because of one or more of the following problems (1) postmenstrual spotting; (2) midcycle intrauterine fluid accumulation diagnosed during the fertility workup or (3) difficulties with a previous embryo transfer and preferring a surgical therapy. The study is registered in the ISRCTN register (ref. no. ISRCTN02271575) on April 23, 2013., Results: There were 133 (62%) women included with a desire to become pregnant, 88 with secondary infertility. In all, 83 had an ongoing pregnancy at the 2-year follow-up. The ongoing pregnancy rate in patients with previous fertility problems was 60.2% compared with 66.7% in patients without infertility (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.32-1.7). The OR for live births was 0.57 (95% CI 0.02-1.2). Overall, 8.3% of the pregnancies resulted in miscarriages by the 2-year follow-up., Conclusions: The reproductive outcomes in women with and without previous fertility problems undergoing resection of a large niche are very promising and quite comparable in both groups. These results suggest, but do not prove, a beneficial effect of this therapy for these indications. The results support the design of future randomized controlled trials to evaluate the effect of niche resection vs expectant management to assess its additional value in women with or without fertility problems who desire pregnancy., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Study Objective: Although it is assumed that myomectomy improves uterine myoma-related symptoms such as pelvic pain and heavy menstrual bleeding (HMB), validated measures are rarely reported. This study aimed to verify the effect of myomectomy on myoma-related symptoms., Design: A retrospective cohort study., Setting: A university-affiliated hospital., Patients: Our study included 241 patients with a myoma diagnosis and received a myomectomy between 2004 and 2018. Data were collected from the patient medical file and patients responded in 1 questionnaire., Interventions: Transcervical resection of myoma (TCRM) and laparoscopic or abdominal myomectomy (LAM)., Measurements and Main Results: One year after TCRM, a significant number of women experienced symptom improvement for pelvic pain (79% [19/24, p = .01]) and HMB (89% [46/52, p <.001]). For other myoma-related symptoms, abdominal pressure (43%, 10/23), sexual complaints (67%, 2/3), infertility (56%, 10/18), and other complaints (83%, 5/6), improvements were not statistically significant. One year after LAM, a significant number of women experienced symptom improvement for pelvic pain (80%, 74/93), HMB (83%, 94/113), abdominal pressure (85%, 79/93), sexual complaints (77%, 36/47), and other complaints (91%, 40/44). One year after myomectomy, 47% (30/64) (TCRM) and 44% of women (78/177) (LAM) described no myoma-related symptoms. Most women (82% [172/217]) were satisfied with the postoperative result after 1 year and 53% (114/217) would have liked to receive the myomectomy earlier in life. Average quality of life (measured on a 10-point Likert scale) increased from 6.3 at baseline to 8.0 at 1 year after TCRM and from 6.2 to 8.0 1 year after LAM, resulting in a difference of 1.7 points (p <.001; 95% confidence interval, 1.1-2.3) and 1.9 points (p <.001; 95% confidence interval, 1.4-2.3), respectively., Conclusion: One year after myomectomy, most women have benefited from myomectomy, concluded by a significant number of women who experienced myoma-related symptom improvement, positive patient satisfaction, and a significant improvement in reported quality of life. Validation of results after conventional treatment such as myomectomy is essential in counseling patients for surgical treatment in today's evidence based practice. In addition, it is necessary to make an adequate comparison with new treatment options for myomas. To provide this, further research should preferably be conducted prospectively or by randomization., (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

Of all neonates, 21% are delivered by cesarean section (CS). A long-term maternal complication of an SC is a uterine niche. The aim of this review is to provide an overview of the current literature on imaging techniques and niche-related symptomatology. We performed systematic searches on imaging and niche symptoms. For both searches, 87 new studies were included. Niche evaluation by transvaginal sonography (TVS) or contrast sonohysterography (SHG) proved superior over hysteroscopy or magnetic resonance imaging. Studies that used SHG in a random population identified a niche prevalence of 42%-84%. Niche prevalence differed based on niche definition, symptomatology, and imaging technique. Most studies reported an association with gynecological symptoms, poor reproductive outcomes, obstetrical complications, and reduced quality of life. In conclusion, non-invasive TVS and SHG are the superior imaging modalities to diagnose a niche. Niches are prevalent and strongly associated with gynecological symptoms and poor reproductive outcomes., Competing Interests: Declaration of competing interest The authors have no conflicts of interests., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: A uterine niche is a defect at the site of the uterine caesarean scar that is associated with gynaecological symptoms and infertility. Promising results are reported in cohort studies after a laparoscopic niche resection concerning reduction of gynaecological symptoms in relation to baseline and concerning pregnancy outcomes. However, randomised controlled trials to study the effect of a laparoscopic niche resection on reproductive outcomes in infertile women are lacking. This study will answer the question if laparoscopic niche resection in comparison to expectant management improves reproductive outcomes in infertile women with a large uterine niche., Methods and Analysis: The LAPRES study is a randomised, non-blinded, controlled trial, including 200 infertile women with a total follow-up of 2 years. Women with the presence of a large niche in the uterine caesarean scar and unexplained infertility of at least 1 year or failed IVF will be randomly allocated to a laparoscopic niche resection within 6 weeks or to expectant management for at least 9 months. A large niche is defined as a niche with a depth of >50% of the myometrial thickness and a residual myometrium of ≤3 mm on transvaginal ultrasound. Those receiving expectant management will be allowed to receive fertility therapies, including assisted reproductive techniques, if indicated. The primary outcome is time to ongoing pregnancy, defined as a viable intrauterine pregnancy at 12 weeks' gestation. Secondary outcome measures are time to conception leading to a live birth, other pregnancy outcomes, received fertility therapies after randomisation, menstruation characteristics, patient satisfaction, quality of life, additional interventions, and surgical and ultrasound outcomes (intervention group). Questionnaires will be filled out at baseline, 6, 12 and 24 months after randomisation. Ultrasound evaluation will be performed at baseline and at 3 months after surgery., Ethics and Dissemination: The study protocol was approved by the medical ethics committee of the Amsterdam University Medical Centre. (Ref. No. 2017.030). Participants will sign a written informed consent before participation. The results of this study will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBER DUTCH TRIAL REGISTER REF NO NL6350 : http://www.trialregister.nl., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Abnormal uterine bleeding (AUB) has a significant socioeconomic impact since it considerably impacts quality of life. Therapeutic options are frequently based on trial and error and do not target disease aetiology. Pathophysiological insight in this disease is required for the development of novel treatment options. If no underlying cause is found for the AUB (e.g. fibroids, adenomyosis, polyps), endometrial-AUB (AUB-E) is usually caused by a primary endometrium disorder. When AUB is induced by prescribed (exogenous) hormones, it is classified as iatrogenic-AUB (AUB-I). Considering vascular modulation and function, AUB-E and AUB-I both could potentially result from abnormal vascularization in the endometrium due to alterations in the process of angiogenesis and vascular maturation., Objective and Rationale: We aim to investigate the fundamental role of angiogenesis and vascular maturation in patients with AUB and hypothesize that aberrant endometrial angiogenesis has an important role in the aetiology of both AUB-E and AUB-I, possibly through different mechanisms., Search Methods: A systematic literature search was performed until September 2021 in the Cochrane Library Databases, Embase, PubMed, and Web of Science, with search terms such as angiogenesis and abnormal uterine bleeding. Included studies reported on angiogenesis in the endometrium of premenopausal women with AUB-E or AUB-I. Case reports, letters, reviews, editorial articles, and studies on AUB with causes classified by the International Federation of Gynecology and Obstetrics as myometrial, oncological, or infectious, were excluded. Study quality was assessed by risk of bias, using the Cochrane tool and the Newcastle-Ottawa Scale., Outcomes: Thirty-five out of 2158 articles were included. In patients with AUB-E, vascular endothelial growth factor A and its receptors (1 and 2), as well as the angiopoietin-1:angiopoietin-2 ratio and Tie-1, were significantly increased. Several studies reported on the differential expression of other pro- and antiangiogenic factors in patients with AUB-E, suggesting aberrant vascular maturation and impaired vessel integrity. Overall, endometrial microvessel density (MVD) was comparable in patients with AUB-E and controls. Interestingly, patients with AUB-I showed a higher MVD and higher expression of proangiogenic factors when compared to controls, in particular after short-term hormone exposure. This effect was gradually lost after longer-term exposure, while alterations in vessel maturation were observed after both short- and long-term exposures., Wider Implications: AUB-E and AUB-I are most likely associated with aberrant endometrial angiogenesis and impaired vessel maturation. This review supports existing evidence that increased proangiogenic and decreased antiangiogenic factors cause impaired vessel maturation, resulting in more fragile and permeable vessels. This matches our hypothesis and these mechanisms appear to play an important role in the pathophysiology of AUB-E and AUB-I. Exploring the alterations in angiogenesis in these patients could provide treatment targets for AUB., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between fibroids and infertility has been established, especially if the fibroid protrudes in the uterine cavity. Hormonal therapy is associated with side-effects and as well as hysterectomy, which is incompatible with a desire to conceive. To improve treatment, it is essential to unravel the etiology of fibroid-related symptoms. We aim to evaluate endometrial angiogenesis in women with fibroids, with and without AUB, and the influence of pharmaceutical therapies in these patients. Furthermore, we explore the possible role of altered angiogenesis in patients with fibroids and infertility. We performed a systematic review according to PRISMA-guidelines (PROSPERO: CRD42020169061), and included 15 eligible studies. Endometrial expression of vascular endothelial growth factor (VEGF) and adrenomedullin was increased in patients with fibroids. This suggests aberrant angiogenesis, potentially involving disturbed vessel maturation, resulting in immature and fragile vessels. Treatment with gonadotropin-releasing hormone agonist, ulipristal acetate, and continuous oral contraception pills reduced several angiogenic parameters, including VEGF. If infertile and fertile patients with fibroids were compared, a significant decreased expression of the bone morphogenetic protein/Smad-protein pathway was found, possibly caused by the increased expression of transforming growth factor-beta. For future therapeutic development, these different angiogenic pathways could be of interest as possible targets to treat fibroid-related symptoms.

Background: There is a dramatic rise in cesarean deliveries worldwide, leading to higher complication rates in subsequent pregnancies. One of these complications is a cesarean scar pregnancy. During the last decades, treatment options for cesarean scar pregnancies have changed, and less invasive interventions have been employed to preserve fertility and reduce morbidity. However, the optimal treatment approach and the influence of various treatments on reproductive outcomes have to be determined., Objective: This study aimed to evaluate the short- and long-term outcomes after cesarean scar pregnancy management., Study Design: We conducted a retrospective cohort study of women determined to have a cesarean scar pregnancy from 2010 to 2021 at a tertiary referral center, the Amsterdam University Medical Center, in the Netherlands. Outcomes of the following management strategies were compared: expectant management, methotrexate, curettage with temporary cervical cerclage, or a laparoscopic niche resection. We performed a curettage if the cesarean scar pregnancy did not cross the serosal line of the uterus, and a laparoscopic niche resection was performed if the cesarean scar pregnancy crossed the serosal line. The main outcomes were treatment efficacy and time to subsequent ongoing pregnancy or pregnancy leading to a live birth., Results: Of the 60 included women, 5 (8.3%) were managed expectantly, 8 (13.3%) were treated with methotrexate, 31 (51.8%) were treated with a curettage, and 16 (26.7%) with a laparoscopic niche resection. The groups were not comparable. The gestational age and human chorionic gonadotropin levels were generally higher in women who received methotrexate or a laparoscopic niche resection. Additional treatment in the conservative group was needed for 4 (80%) women after expectant management and for 7 (87.5%) women after methotrexate treatment. In the surgical group, all 31 women treated with a curettage and all 16 treated with a laparoscopic niche resection did not require additional treatment. The subsequent ongoing pregnancy rate after cesarean scar pregnancy management was 81.1% (30/37) among women who wished to conceive, with a live birth rate of 78.4% (29/37); 1 woman was in her third trimester of pregnancy at the time of analyses. The time between cesarean scar pregnancy management and subsequent ongoing pregnancy was 4 months (interquartile range, 3-6; P =.02) after expectant management, 18 months (interquartile range, 13-22) after initial methotrexate treatment, 5 months (interquartile range, 3-14; P =.01) after a curettage, and 6 months (interquartile range, 4-15; P =.03) after a laparoscopic niche resection., Conclusion: Surgical treatment of a cesarean scar pregnancy led to a high success rate without additional interventions, high pregnancy rates with a short time interval between treatment, and subsequent pregnancy leading to an ongoing pregnancy or live birth. Conservative management, both with expectant management and methotrexate treatment, led to high (re)intervention rates. Different management approaches are indicated for different types of cesarean scar pregnancies., (© 2022 The Authors.)

Background: Reduced residual myometrial thickness before and during pregnancy is associated with uterine rupture or dehiscence after vaginal birth after cesarean delivery. Laparoscopic niche resection performed in case of gynecologic symptoms has shown to increase residual myometrial thickness 6 months after surgery., Objective: This study aimed to evaluate the change in residual myometrial thickness from baseline value before pregnancy to the third trimester of pregnancy in women with and without laparoscopic niche resection and evaluate niche presence, niche size during pregnancy vs before pregnancy, and obstetrical outcomes, including uterine rupture and dehiscence in both study groups., Study Design: This was a prospective cohort study conducted in an academic medical center. Of note, 2 groups of pregnant women with a previously diagnosed niche were included: (1) women with a large symptomatic niche (residual myometrial thickness of <3 mm) followed by laparoscopic niche resection (LNR group) and (2) women with a niche without niche resection because of minimal symptoms or a residual myometrial thickness of ≥3 mm diagnosed before current pregnancy (expectant group). Participants underwent a transvaginal ultrasound at 12, 20, and 30 weeks of gestation. Changes in residual myometrial thickness and changes in niche measurements over time were analyzed with linear mixed models., Results: A total of 100 women were included, 61 in the LNR group and 39 in the expectant group. The change in residual myometrial thickness from baseline value before niche resection to the third trimester of pregnancy was +2.0 mm in the LNR group vs -1.6 mm in the expectant group (P<.001). Residual myometrial thickness decreased from the first trimester of pregnancy onward in both groups. Although residual myometrial thickness was thinner at baseline in the LNR group, it was thicker in the LNR group than in the expectant group during all trimesters: 3.2 mm (P<.001) in the first trimester of pregnancy, 2.5 mm (P<.001) in the second trimester of pregnancy, and 1.8 mm (P=.001) in the third trimester of pregnancy. Uterine dehiscence was reported in 1 of 50 women (2%) in the LNR group and 7 of 36 women (19%) in the expectant group (P=.007) and was related to the depth of niche-to-residual myometrial thickness ratio before pregnancy (after niche resection) and residual myometrial thickness in the second trimester of pregnancy. No uterine rupture was reported. Most patients received a scheduled cesarean delivery in both groups. There was more blood loss during subsequent cesarean delivery in the LNR group than in the expectant group., Conclusion: Here, laparoscopic niche resection resulted in an increased residual myometrial thickness during a subsequent pregnancy. Moreover, a lower number of dehiscence was found in the LNR group than in the expectant group without niche surgery. Per-section blood loss was higher in the LNR group than in the expectant group. In general, laparoscopic niche resection is performed to improve gynecologic symptoms. Currently, there is no evidence to support a laparoscopic niche resection to improve obstetrical outcomes, but the trend toward more uterine dehiscence encourages further research., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Transcervical resection of myoma (TCRM) is a widely implemented treatment for submucous fibroids. The aim of this study is to evaluate the effect of TCRM on menstrual bleeding, fibroid related symptoms and quality of life and hemoglobin (Hb) levels., Study Design: A prospective cohort study was conducted in three teaching hospitals and two academic hospitals in the Netherlands. Patients with HMB (PBAC score > 150) and submucous fibroids (type 0, 1, 2, 3, 4 and hybrid type 2-5) scheduled for TCRM were eligible. At baseline and 3 months after TCRM a Trans Vaginal Ultrasound (TVU) was performed and a Hb sample was taken. Patients filled out the Pictorial Blood Assessment Chart (PBAC) and the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire at baseline and up to 6 months after surgery. Primary outcome was improvement in PBAC score 6 months after surgery. Secondary outcomes were improvement in PBAC score and Hb level 3 months after surgery and UFS-QOL scores 3 and 6 months after surgery., Results: 126 patients were included and 104 were operated. PBAC were obtained from 98 patients. Six months after surgery, 56.6% of patients went from HMB to normal menstrual bleeding (PBAC < 150). A significant reduction in median PBAC scores of 427 (IQR 198 - 1392) (p <.0001) was found (86% improvement). UFS-QOL scores were obtained from 91 patients. Symptom severity improved from a median of 54 on a scale of 100 (IQR 44-66) at baseline to 22 (IQR 9-41) after 6 months (p <.0001) (59% improvement). Health related quality of life (HRQOL) improved from a median score of 44 on a scale of 100 (IQR 33-62) to 89 (IQR 67-97) 6 months after surgery (p <.0001) (102% improvement)., Conclusion: TCRM significantly reduces the amount of menstrual bleeding, severity of fibroid related symptoms and improves HRQOL in patients with submucous fibroids., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate whether the Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis need to be better defined and, if deemed necessary, to reach consensus on the updated definitions., Methods: A modified Delphi procedure was performed among European gynecologists with expertise in ultrasound diagnosis of adenomyosis. To identify MUSA features that might need revision, 15 two-dimensional (2D) video recordings (four recordings also included three-dimensional (3D) still images) of transvaginal ultrasound (TVS) examinations of the uterus were presented in the first Delphi round (online questionnaire). Experts were asked to confirm or refute the presence of each of the nine MUSA features of adenomyosis (described in the original MUSA consensus statement) in each of the 15 videoclips and to provide comments. In the second Delphi round (online questionnaire), the results of the first round and suggestions for revision of MUSA features were shared with the experts before they were asked to assess a new set of 2D and 3D still images of TVS examinations and to provide feedback on the proposed revisions. A third Delphi round (virtual group meeting) was conducted to discuss and reach final consensus on revised definitions of MUSA features. Consensus was predefined as at least 66.7% agreement between experts., Results: Of 18 invited experts, 16 agreed to participate in the Delphi procedure. Eleven experts completed and four experts partly finished the first round. The experts identified a need for more detailed definitions of some MUSA features. They recommended use of 3D ultrasound to optimize visualization of the junctional zone. Fifteen experts participated in the second round and reached consensus on the presence or absence of ultrasound features of adenomyosis in most of the still images. Consensus was reached for all revised definitions except those for subendometrial lines and buds and interrupted junctional zone. Thirteen experts joined the online meeting, in which they discussed and agreed on final revisions of the MUSA definitions. There was consensus on the need to distinguish between direct features of adenomyosis, i.e. features indicating presence of ectopic endometrial tissue in the myometrium, and indirect features, i.e. features reflecting changes in the myometrium secondary to presence of endometrial tissue in the myometrium. Myometrial cysts, hyperechogenic islands and echogenic subendometrial lines and buds were classified unanimously as direct features of adenomyosis. Globular uterus, asymmetrical myometrial thickening, fan-shaped shadowing, translesional vascularity, irregular junctional zone and interrupted junctional zone were classified as indirect features of adenomyosis., Conclusion: Consensus between gynecologists with expertise in ultrasound diagnosis of adenomyosis was achieved regarding revised definitions of the MUSA features of adenomyosis and on the classification of MUSA features as direct or indirect signs of adenomyosis. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Ulipristal acetate (UPA) is a medical treatment for uterine fibroids and was authorized for surgical pre-treatment in 2012 after the conduct of the PEARL I and II randomized controlled trials and for intermittent treatment after the observational PEARL III and IV trials. However, UPA came into disrepute due to its temporary suspension in 2017 and 2020 because of an apparent association with liver injury. This clinical opinion paper aims to review the process of marketing authorization and implementation of UPA, in order to provide all involved stakeholders with recommendations for the introduction of future drugs. Before marketing authorization, the European Medicines Agency (EMA) states that Phase III registration trials should evaluate relevant outcomes in a representative population, while comparing to gold-standard treatment. This review shows that the representativeness of the study populations in all PEARL trials was limited, surgical outcomes were not evaluated and intermittent treatment was assessed without comparative groups. Implementation into clinical practice was extensive, with 900 000 prescribed treatment cycles in 5 years in Europe and Canada combined. Extremely high costs are involved in developing and evaluating pre-marketing studies in new drugs, influencing trial design and relevance of chosen outcomes, thereby impeding clinical applicability. It is vitally important that the marketing implementation after authorization is regulated in such way that necessary evidence is generated before widespread prescription of a new drug. All stakeholders, from pharmaceutical companies to authorizing bodies, governmental funding bodies and medical professionals should be aware of their role and take responsibility for their part in this process., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: To develop a standardized sonographic evaluation and reporting system for Cesarean scar pregnancy (CSP) in the first trimester, for use by both general gynecology and expert clinics., Methods: A modified Delphi procedure was carried out, in which 28 international experts in obstetric and gynecological ultrasonography were invited to participate. Extensive experience in the use of ultrasound to evaluate Cesarean section (CS) scars in early pregnancy and/or publications concerning CSP or niche evaluation was required to participate. Relevant items for the detection and evaluation of CSP were determined based on the results of a literature search. Consensus was predefined as a level of agreement of at least 70% for each item, and a minimum of three Delphi rounds were planned (two online questionnaires and one group meeting)., Results: Sixteen experts participated in the Delphi study and four Delphi rounds were performed. In total, 58 items were determined to be relevant. We differentiated between basic measurements to be performed in general practice and advanced measurements for expert centers or for research purposes. The panel also formulated advice on indications for referral to an expert clinic. Consensus was reached for all 58 items on the definition, terminology, relevant items for evaluation and reporting of CSP. It was recommended that the first CS scar evaluation to determine the location of the pregnancy should be performed at 6-7 weeks' gestation using transvaginal ultrasound. The use of magnetic resonance imaging was not considered to add value in the diagnosis of CSP. A CSP was defined as a pregnancy with implantation in, or in close contact with, the niche. The experts agreed that a CSP can occur only when a niche is present and not in relation to a healed CS scar. Relevant sonographic items to record included gestational sac (GS) size, vascularity, location in relation to the uterine vessels, thickness of the residual myometrium and location of the pregnancy in relation to the uterine cavity and serosa. According to its location, a CSP can be classified as: (1) CSP in which the largest part of the GS protrudes towards the uterine cavity; (2) CSP in which the largest part of the GS is embedded in the myometrium but does not cross the serosal contour; and (3) CSP in which the GS is partially located beyond the outer contour of the cervix or uterus. The type of CSP may change with advancing gestation. Future studies are needed to validate this reporting system and the value of the different CSP types., Conclusion: Consensus was achieved among experts regarding the sonographic evaluation and reporting of CSP in the first trimester. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Uterine fibroids present differently, from well vascularised up to calcified, with some causing heavy menstrual bleeding (HMB)., Objectives: To investigate the association between fibroid vascularisation and HMB, other fibroid related symptoms and quality of life (QOL)., Materials and Methods: A single centre pilot study was carried out in the Netherlands. Women with a maximum of two fibroids who chose expectant management were included. 3D sonography including power doppler was performed at baseline and at 3, 6 and 12 months follow up. Women were asked to complete the Pictorial Blood Assessment Chart (PBAC) and Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaires at every visit., Main Outcome Measure: Main outcome measure: The association between fibroid vascularisation and HMB., Results: 53 women were included in the study. Baseline fibroid vascularisation, measured as vascular index (VI) is associated with PBAC score; a 1% higher VI at baseline leads to an 11 point increase in PBAC score over time (RC 10.99, p=0.05, 95% CI -0.15 - 22.12). After correction for the baseline variables ethnicity and fibroid type the association becomes stronger (P<0.05). Fibroid volume at baseline and HMB are also associated: a 1 cm3 larger fibroid leads to 0.6 points increase in PBAC score over time (RC 0.56, p=0.03, 95% CI 0.05 - 1.07)., Conclusions: Conclusions: This study highlights that both fibroid vascularisation and fibroid volume may be associated with an increase in menstrual blood loss, other fibroid related symptoms and QOL over time., What Is New?: What is new? We used 3D power doppler to predict symptomatic fibroids.

Background: Magnetic resonance image-guided high-intensity-focused ultrasound (MR-HIFU) is a rather new, noninvasive option for the treatment of uterine fibroids. It is safe, effective, and has a very short recovery time. However, a lack of prospectively collected data on long-term (cost-)effectiveness of the MR-HIFU treatment compared with standard uterine fibroid care prevents the MR-HIFU treatment from being reimbursed for this indication. Therefore, at this point, when conservative treatment for uterine fibroid symptoms has failed or is not accepted by patients, standard care includes the more invasive treatments hysterectomy, myomectomy, and uterine artery embolization (UAE). Primary outcomes of currently available data on MR-HIFU treatment often consist of technical outcomes, instead of patient-centered outcomes such as quality of life (QoL), and do not include the use of the latest equipment or most up-to-date treatment strategies. Moreover, data on cost-effectiveness are rare and seldom include data on a societal level such as productivity loss or use of painkillers. Because of the lack of reimbursement, broad clinical implementation has not taken place, nor is the proper role of MR-HIFU in uterine fibroid care sufficiently clear., Objective: The objective of our study is to determine the long-term (cost-)effectiveness of MR-HIFU compared with standard (minimally) invasive fibroid treatments., Methods: The MYCHOICE study is a national, multicenter, open randomized controlled trial with randomization in a 2:1 ratio to MR-HIFU or standard care including hysterectomy, myomectomy, and UAE. The sample size is 240 patients in total. Women are included when they are 18 years or older, in premenopausal stage, diagnosed with symptomatic uterine fibroids, conservative treatment has failed or is not accepted, and eligible for MR-HIFU. Primary outcomes of the study are QoL 24 months after treatment and costs of treatment including direct health care costs, loss of productivity, and patient costs., Results: Inclusion for the MYCHOICE study started in November 2020 and enrollment will continue until 2024. Data collection is expected to be completed in 2026., Conclusions: By collecting data on the long-term (cost-)effectiveness of the MR-HIFU treatment in comparison to current standard fibroid care, we provide currently unavailable evidence about the proper place of MR-HIFU in the fibroid treatment spectrum. This will also facilitate reimbursement and inclusion of MR-HIFU in (inter)national uterine fibroid care guidelines., Trial Registration: Netherlands Trial Register NL8863; https://www.trialregister.nl/trial/8863., International Registered Report Identifier (irrid): DERR1-10.2196/29467., (©Kimberley J Anneveldt, Ingrid M Nijholt, Joke M Schutte, Jeroen R Dijkstra, Geert W J Frederix, Erwin Ista, Inez M Verpalen, Sebastiaan Veersema, Judith A F Huirne, Wouter J K Hehenkamp, Martijn F Boomsma. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 24.11.2021.)

Objective: Uterine fibroids can cause a variety of symptoms in women, from heavy menstrual bleeding and dysmenorrhea to bulk symptoms. The Uterine Fibroid Symptom and health-related Quality Of Life questionnaire (UFS-QOL) is a patient-reported outcome measure developed for assessing fibroid-related symptoms in a standardised way. Our aim was to translate and validate the UFS-QOL in Dutch., Design: Validation study., Setting: Patients were recruited by a gynaecologist at the outpatient clinic., Participants: Women with uterine fibroids., Methods: The UFS-QOL was translated into Dutch (UFS-QOL NL) and validated through testing construct validity (comprising of structural validity and hypotheses testing), reliability, responsiveness and interpretability, assessing floor and ceiling effects and minimal important change. An option to answer 'not applicable' was added to the translated questionnaire., Results: 191 women with uterine fibroids completed the UFS-QOL NL at baseline, after 2 weeks and after 3 months. The questionnaire retained the same factor structure after translation (Comparative Fit Index 0.94-0.95; Tucker-Lewis fit Index 0.93-0.95; Root Mean Square Error of Approximation 0.10-0.11) and correlations to other questionnaires (RAND 36, Hospital Anxiety and Depression Scale and Golombok Rust Inventory of Sexual Satisfaction) were generally moderate, as hypothesised (Pearson's r 0.3-0.7). We found a sufficient reliability with intraclass correlation coefficients of approximately 0.8-0.9 for all subscales. Responsiveness was sufficient when testing hypotheses comparing women who had surgery with those who did not. Cronbach's alpha was higher than 0.7 for all subscales, indicating sufficient internal consistency and there were no concerns about floor or ceiling effects. Minimal important change could not be calculated due to low correlation between the different subscales and the anchor question., Conclusions: The results support the measurement properties of the Dutch UFS-QOL for assessing fibroid-related symptoms and health-related quality of life in Dutch women with uterine fibroids., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Uterine fibroids are benign tumours that cause various complaints. These complaints may significantly compromise quality of life, necessitating a clinical intervention in 25-50% of the affected women. Hysterectomy, myomectomy or embolization may offer symptomatic relief, but are costly, include a recovery period, can cause serious side-effects, sometimes fail to treat symptoms completely and are not always desired by patients. Ulipristal is a conservative long-term treatment that has a fibroid-volume decreasing effect, acceptable side-effects while preserving fertility and may be an alternative to surgical alternatives. Currently, ulipristal is investigated by the European Medicine Agency and suspended from marketing authorization because it may cause drug-induced liver injury (DILI). However, many drugs can cause severe DILI and prospective studies estimate 14-19 DILI cases/100 000 people., Methods: This overview will discuss the risk-benefit balance between ulipristal and DILI, describe the safety-efficacy balance of ulipristal and its alternative treatments and the arguments that led to the suspension of its marketing authorization., Results: Ulipristal may be associated with DILI resulting in a risk of severe liver injury in 1.5:100 000 patients and fatal liver injury in 0.1:100 000 patients. This risk needs to be weighed against the higher mortality risk of >1:1000 and higher incidence of severe complications after surgery., Conclusion: The DILI risk of ulipristal is considerably lower than that of other medicines that are not suspended, nor need additional safety measures. When evaluating drugs and drug safety, risks that apply to the alternative nonpharmacological treatment options should be taken into consideration., (© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objectives: Fibroids are the most common benign tumours found in the uterus and can cause various symptoms. In 20-50 % of the women, an intervention is required. When conservative options fail, invasive options such as hysterectomy, uterine artery embolization or myomectomy are eligible options. Ulipristal acetate (UPA) was launched as the sole available long term pharmaceutical treatment, with the potential to avoid surgery. It is suggested that UPA improves quality of life, reduces symptoms and fibroid volumes. However, UPA is an expensive medicine, is possibly associated with liver injury and has never been directly compared to surgical treatment. The aim of this trial is to compare UPA to surgical treatment on both effectiveness and cost-effectiveness. Primary outcome is the reduction in symptom severity scores (part of the Uterine Fibroid Symptom and Quality of Life questionnaire) at 24 months of follow-up compared to baseline. Secondary outcomes include quality of life, societal costs, societal participation, liver function variation, patient satisfaction and preference. Outcomes will be analysed according to intention-to-treat principle., Study Design: The MYOMEX-2 trial is an open-label, multicentre, non-inferiority randomized controlled trial. Patients are pre-menopausal women with symptomatic fibroids eligible for surgical treatment (hysterectomy, myomectomy or UAE). Fibroid symptoms may comprise (but are not limited to) heavy menstrual bleeding, bulk symptoms or pain. Patients are randomised 2:1 in a parallel group design between two treatment arms: 119 patients in the UPA group and 60 patients in the surgery group. Follow up comprises of online questionnaires, outpatient visits and phone appointments on several follow up moments, up to 24 months after surgery or start UPA., Registration Details: MYOMEX-2 trial; protocol version 4, date 22-02-2019; NTR6860; NL62638.029.18. All items from the World Health Organization Trial Registration Data Set are provided in the online supplementary file (Appendix-B)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To compare pain measured with a new electronic device - the Continuous Pain Score Meter (CPSM) - and the Verbal Rating Scale (VRS) during gynaecological procedures in an outpatient setting, and to correlate these outcomes with baseline anxiety and patient (in)tolerance to the procedure., Study Design: This prospective cohort study was undertaken in two centres: a university hospital and a large teaching hospital in The Netherlands. Patients undergoing an outpatient hysteroscopy, colposcopy or ovum pick-up procedure for in-vitro fertilization in one of the two participating hospitals with availability of the CPSM were included. Pain was measured by both the CPSM and the VRS. Patient tolerance to the procedure was reported. Various outcomes of the CPSM were compared with those of the VRS and related to baseline anxiety scores., Results: Ninety-one of 108 included patients (84 %) used the CPSM correctly during the procedure, and it was possible to analyse the CPSM scores for 87 women (81 %). The CPSM scores were all linearly related to the VRS. The peak pain score on the CPSM (CPSM-PPS) had the strongest correlation with the VRS score for all three procedures. Higher CPSM-PPS was related to patient (in)tolerance to the procedure (p = 0.03-0.002). Anxiety at baseline was not correlated with pain perception, except for VRS during colposcopy (r = 0.39, p = 0.016)., Conclusion: The majority of patients were able to use the CPSM correctly, resulting in detailed information on pain perception for each individual pain stimulus during three outpatient gynaecological procedures. The CPSM-PPS had the strongest correlation with the VRS score and patient (in)tolerance to the procedure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Uterine fibroids are the most common benign tumours in women of the reproductive age. Symptoms of heavy menstrual bleeding, abdominal discomfort and infertility may seriously affect a woman's quality of life. Uterine artery embolization is a safe and effective alternative treatment to hysterectomy or myomectomy for symptomatic uterine fibroids. Which treatment provides the highest quality of life, least complications, symptom reduction and least chance intervention, has not been established and might depend on strict patient selection. This study aims to identify which specific subgroups benefit most of each treatment by analyzing individual participant data derived from randomized controlled trials of women undergoing embolization or surgical treatment. This study will primarily assess the effectiveness of both treatment groups by evaluating the effect on quality of life of embolization in comparison to surgery on specific patient and fibroid characteristics and the possible need for re-intervention for fibroid-related symptoms., Data Sources: PubMed/MEDLINE, Embase and The Cochrane Library were searched up to August 2020., Study Eligibility Criteria: We will collect individual participant data from randomized controlled trials that studied clinical and procedural outcomes of premenopausal women with symptomatic uterine fibroids, who were randomized between uterine artery embolization and surgery., Study Appraisal and Synthesis Methods: Individual participant data from all eligible trials will be sought and analysed according to intention-to-treat principle. Risk of Bias will be done by using version 2 of the Cochrane tool for Risk of Bias in randomized trials. Subgroup analyses to explore the effect of e.g. age, fibroid characteristics and fibroid complaints will be performed, if data is available. This individual patient data meta-analysis will be analysed according to a one-stage model., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to compare the effect of ulipristal acetate (UPA) and gonadotropin-releasing hormone agonists (GnRHa) before laparoscopic myomectomy on long term secondary outcomes of the MYOMEX-trial, regarding quality of life, ultrasound characteristics, hemoglobin levels 6 weeks post-operative, sexual function and menstrual bleeding control. A cost-analysis was also performed. Short-term primary and secondary outcomes are reported elsewhere., Study Design: A double-blind, randomized, controlled, non-inferiority trial in nine hospitals in the Netherlands. Participants were randomized in a 1:1 ratio (block size of four, stratified per hospital) to either UPA or GnRHa pre-treatment. Additional placebo injections containing saline, respectively daily placebo tablets were given to both groups to ensure double-blinding. Surgery was performed within a month after the last tablet. Women were followed up until six months post-surgery., Results: A total of 55 participants were randomized: 30 to the UPA- and 25 to the GnRHa-group between May 2015 and July 2017. Uterine volume at six weeks post-operative did not differ significantly between both pre-treatment groups with 170.1 cm 3 (106.8-243.5; N = 29) vs. 152.8 cm 3 (92.3-205.6; N = 23) for the UPA- and GnRHa-group respectively (p = 0.423). Hemoglobin levels six weeks post-operatively recovered back to baseline and were not significantly different between groups with 7.7 mmol/L for the UPA- vs. 8.1 mmol/L for the GnRHa-group (p = 0.157; mean difference -0.4 (CI -0.9, 0.2). Menstrual bleeding pattern, quality of life, effects on general and sexual health showed a significant improvement compared to baseline in both groups without any differences between the treatment groups. Symptom severity scores also decreased significantly at 6 week post-operatively compared to baseline, but did not differ between the treatment groups. Fibroid characteristics at baseline (e.g. mean diameter of largest fibroid) appeared not to be a confounding factor. An exploratory cost analysis showed no significant differences in absenteeism costs, total healthcare and societal costs, after adjustment for confounding factors., Conclusion: Pre-treatment prior to laparoscopic myomectomy with UPA compared to GnRHa has similar effects on bleeding pattern, menopausal symptoms, sexual functioning, symptom severity and quality of life from baseline up to six months post-operative. Due to the small sample size, these findings should be interpreted with caution. Also, no firm conclusions on costs could be made., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Study Question: Is it feasible to perform uterus transplantations (UTx) in a tertiary centre in the Netherlands?, Summary Answer: Considering all ethical principles, surgical risks and financial aspects, we have concluded that at this time, it is not feasible to establish the UTx procedure at our hospital., What Is Known Already: UTx is a promising treatment for absolute uterine factor infertility. It is currently being investigated within several clinical trials worldwide and has resulted in the live birth of 19 children so far. Most UTx procedures are performed in women with the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a congenital disorder characterized by absence of the uterus. In the Netherlands, the only possible option for these women for having children is adoption or surrogacy., Study Design Size Duration: We performed a feasibility study to search for ethical, medical and financial support for performing UTx at the Amsterdam UMC, location VUmc., Participants/materials Setting Methods: For this feasibility study, we created a special interest group, including gynaecologists, transplant surgeons, researchers and a financial advisor. Also, in collaboration with the patients' association for women with MRKH, a questionnaire study was performed to research the decision-making in possible recipients. In this paper, we present an overview of current practices and literature on UTx and discuss the results of our feasibility study., Main Results and the Role of Chance: A high level of interest from the possible recipients became apparent from our questionnaire amongst women with MRKH. The majority (64.8%) positively considered UTx with a live donor, with 69.6% having a potential donor available. However, this 'non-life-saving transplantation' requires careful balancing of risks and benefits. The UTx procedure includes two complex surgeries and unknown consequences for the unborn child. The costs for one UTx are calculated to be around €100 000 and will not be compensated by medical insurance. The Clinical Ethics Committee places great emphasis on the principle of non-maleficence and the 'fair distribution of health services'., Limitations Reasons for Caution: In the Netherlands, alternatives for having children are available and future collaboration with experienced foreign clinics that offer the procedure is a possibility not yet investigated., Wider Implications of the Findings: The final assessment of this feasibility study is that that there are not enough grounds to support this procedure at our hospital at this point in time. We will closely follow the developments and will re-evaluate the feasibility in the future., Study Funding/competing Interests: This feasibility study was funded by the VU Medical Center (Innovation grant 2017). No conflicts of interest have been reported relevant to the subject of all authors., Trial Registration Number: n.a., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

Objective: To evaluate changes in health-related quality of life (HRQOL) the first year after laparoscopic niche resection., Study Design: Prospective cohort study in women with a large niche (residual myometrium thickness <3.0 mm) after caesarean section who underwent laparoscopic niche resection between May 2010 and January 2018. Women were included consecutively. 36-Item Short Form Survey (SF-36) was sent at baseline, three and twelve months postoperatively. All participants that filled out the questionnaire at baseline were included. Physical (PCS) and mental component summary scores (MCS) and scores for subdomains were calculated. Scores were analysed over time using Wilcoxon signed rank test., Results: 146 participants responded to the SF-36 at baseline, of which 129 (88.4 %) responded at three or twelve months follow-up. After three months, median PCS and MCS improved, compared to baseline (p = 0.014 and p = 0.008, respectively). Subdomains physical functioning, bodily pain, general health, vitality, mental health and social functioning improved significantly. At twelve months follow-up, improvement in PCS and MCS did not reach statistical significance (p = 0.053 and p = 0.063, respectively). Subdomains bodily pain (77.6-89.8, p < 0.001), mental health (76-80, p = 0.004) and social functioning (75-87.5, p = 0.016) improved significantly. Women with symptom relief as main goal of the intervention showed larger improvement in PCS than women with distorted anatomy and to restore anatomy as main goal for the intervention (p = 0.001)., Conclusion: Laparoscopic niche resection improves HRQOL in women with a large niche in physical and mental domains three and twelve months postoperatively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To investigate differences in volume and fibroid vascularity expressed in vascular index after three months of (pre-)treatment with leuprolide acetate (LPA) or ulipristal acetate (UPA)., Study Design: Prospective pilot study of 23 premenopausal women with uterine fibroids. Patients who started with LPA or UPA and had at least one fibroid with a size between 3 and 12 cm, were included consecutively. Per patient one fibroid was evaluated. The ultrasound was performed at baseline and after three months using LPA or UPA using a standardized protocol. 3D scans were evaluated using VOCAL software to calculate outcomes of volume, vascular index (VI) without shell ("shell off") and of the inner shell., Results: Four patients in the LPA group were additionally excluded from analyses due to insufficient quality of 3D scans. In the ten remaining patients (pre-)treated with LPA both volume and vascular indices of the fibroid reduced significantly after three months from a median of 224.3 cm 3 (IQR 338.0) to 124.8 cm 3 (IQR 186.1) (p = 0,05); median VI fibroid (shell off) reduced from 4.30 (IQR 4.72) to 0.93 (IQR 1.54) (p = 0,05); and VI inner capsule from 6.34 (IQR 7.51) to 1.28 (IQR 2.13) (p = 0,05). After UPA (n = 9) changes in fibroid volume and vascular indices did not reach statistical significance. Volume reduced from 248.5 cm 3 (IQR 271.9) to 140.7 cm 3 (IQR 209.4) (p > 0,05); median VI fibroid (shell off) from 2.97 (IQR 3.81) to 2.90 (IQR 4.82) (p > 0,05); and VI inner capsule from 2.56 (IQR 7.48) to 2.89 (IQR 4.83) (p > 0,05). A strong positive correlation was found between the VI of the fibroid (shell off) at baseline with the volume change after three months of LPA use (LPA r = 0.636, p = 0.048, 95% CI = -0.03 - 1.00)., Conclusion: In this pilot study we observed a consistent and statistically significant decrease in VI and fibroid volume after three months of LPA treatment in patients with uterine fibroids. The decrease in fibroid volume and VI was less consistent after UPA use. The strong correlation between the VI at baseline and volume reduction, may in theory be used to predict the volume reduction after LPA., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: Laparoscopic myomectomy can be difficult when fibroids are large and numerous. This may result in extensive intraoperative bleeding and the need for a conversion to a laparotomy. Medical pretreatment prior to surgery might reduce these risks by decreasing fibroid size and vascularization of the fibroid. We compared pretreatment with ulipristal acetate (UPA) vs gonadotropin-releasing hormone agonists (GnRHa) prior to laparoscopic myomectomy on several intra- and postoperative outcomes., Material and Methods: We performed a non-inferiority double-blind randomized controlled trial in nine hospitals in the Netherlands. Women were randomized between daily oral UPA for 12 weeks and single placebo injection or single intramuscular injection with leuprolide acetate and daily placebo tablets for 12 weeks. The primary outcome was intraoperative blood loss. Secondary outcomes were reduction of fibroid volume, suturing time, total surgery time and surgical ease., Results: Thirty women received UPA and 25 women leuprolide acetate. Non-inferiority of UPA regarding intraoperative blood loss was not demonstrated. When pretreated with UPA, median intraoperative blood loss was statistically significantly higher (525 mL [348-1025] vs 280 mL[100-500]; P = 0.011) and suturing time of the first fibroid was statistically significantly longer (40 minutes [28-48] vs 22 minutes [14-33]; P = 0.003) compared with GnRHa. Pretreatment with UPA showed smaller reduction in fibroid volume preoperatively compared with GnRHa (-7.2% [-35.5 to 54.1] vs -38.4% [-71.5 to -19.3]; P = 0.001). Laparoscopic myomectomies in women pretreated with UPA were subjectively judged more difficult than in women pretreated with GnRHa., Conclusions: Non-inferiority of UPA in terms of intraoperative blood loss could not be established, possibly due to the preliminary termination of the study. Pretreatment with GnRHa was more favorable than UPA in terms of fibroid volume reduction, intraoperative blood loss, hemoglobin drop directly postoperatively, suturing time of the first fibroid and several subjective surgical ease parameters., (© 2019 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Adenomyosis commonly occurs with abnormal uterine bleeding (AUB) and is associated with subfertility and a higher miscarriage rate. Recent evidence showed abnormal vascularization in the endometrium in patients with adenomyosis, suggesting a role of angiogenesis in the pathophysiology of AUB and subfertility in adenomyosis and providing a possible treatment target., Objective and Rationale: We hypothesized that the level of abnormal vascularization and expression of angiogenic markers is increased in the ectopic and eutopic endometrium of adenomyosis patients in comparison with the endometrium of control patients. This was investigated through a search of the literature., Search Methods: A systematic search was performed in PubMed and Embase until February 2019. Combinations of terms for angiogenesis and adenomyosis were applied as well as AUB, subfertility or anti-angiogenic therapy. The main search was limited to clinical studies carried out on premenopausal women. Original research articles focusing on markers of angiogenesis in the endometrium of patients with adenomyosis were included. Studies in which no comparison was made to control patients or which were not published in a peer-reviewed journal were excluded. A second search was performed to explore the therapeutic potential of targeting angiogenesis in adenomyosis. This search also included preclinical studies., Outcomes: A total of 20 articles out of 1669 hits met our selection criteria. The mean vascular density (MVD) was studied by quantification of CD31, CD34, von Willebrand Factor (vWF) or factor-VIII-antibody-stained microvessels in seven studies. All these studies reported a significantly increased MVD in ectopic endometrium, and out of the six articles that took it into account, four studies reported a significantly increased MVD in eutopic endometrium compared with control endometrium. Five articles showed a significantly higher vascular endothelial growth factor expression in ectopic endometrium and three articles in eutopic endometrium compared with control endometrium. The vascular and pro-angiogenic markers α-smooth muscle actin, endoglin, S100A13, vimentin, matrix metalloproteinases (MMPs), nuclear factor (NF)-kB, tissue factor (TF), DJ-1, phosphorylated mammalian target of rapamycin, activin A, folli- and myostatin, CD41, SLIT, roundabout 1 (ROBO1), cyclooxygenase-2, lysophosphatidic acid (LPA) 1,4-5, phospho signal transducer and activator of transcription 3 (pSTAT3), interleukin (IL)-6, IL-22 and transforming growth factor-β1 were increased in ectopic endometrium, and the markers S100A13, MMP-2 and -9, TF, follistatin, myostatin, ROBO1, LPA1 and 4-5, pSTAT3, IL-6 and IL-22 were increased in eutopic endometrium, compared with control endometrium. The anti-angiogenic markers E-cadherin, eukaryotic translation initiation factor 3 subunit and gene associated with retinoic-interferon-induced mortality 19 were decreased in ectopic endometrium and IL-10 in eutopic endometrium, compared with control endometrium. The staining level of vWF and two pro-angiogenic markers (NF-κB nuclear p65 and TF) correlated with AUB in patients with adenomyosis. We found no studies that investigated the possible relationship between markers of angiogenesis and subfertility in adenomyosis patients. Nine articles reported on direct or indirect targeting of angiogenesis in adenomyosis-either by testing hormonal therapy or herbal compounds in clinical studies or by testing angiogenesis inhibitors in preclinical studies. However, there are no clinical studies on the effectiveness of such therapy for adenomyosis-related AUB or subfertility., Wider Implications: The results are in agreement with our hypothesis that increased angiogenesis is present in the endometrium of patients with adenomyosis compared with the endometrium of control patients. It is likely that increased angiogenesis leads to fragile and more permeable vessels resulting in adenomyosis-related AUB and possibly subfertility. While this association has not sufficiently been studied yet, our results encourage future studies to investigate the exact role of angiogenesis in the etiology of adenomyosis and related AUB or subfertility in women with adenomyosis in order to design curative or preventive therapeutic strategies., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

Background and Purpose: The Dutch national guideline on heavy menstrual bleeding was updated and published in 2013. It recommended (for the first time) that uterine artery embolization (UAE) should be part of counseling of women with symptomatic fibroids. We aimed to evaluate the implementation of UAE for symptomatic uterine fibroids in the Netherlands and to investigate gynecologists preference and other influential factors., Methods: The primary outcome was to examine the UAE/hysterectomy ratio before and after introduction of the 2013 guideline by the use of annual hospital reports. The secondary outcome assessed factors that could influence implementation by means of a questionnaire to gynecologists., Results: A total of 29/30 (97%) UAE+ hospitals and 36/52 (69%) UAE- hospitals sent their annual reports. The UAE/hysterectomy percentages in 2012, 2013 and 2014 were 7,0%, 7.0% and 6.9%, respectively. Regarding the questionnaire, the response rates were 88% and 91%, respectively. In both groups we observed a high self-perceived tendency for UAE counseling (90% versus 70%, p = .001). Approximately 50% of gynecologists from UAE- hospitals indicate they have insufficient information about UAE for appropriate counseling and 40% doubts the effectiveness of UAE. Furthermore, in the majority of gynecologists some 'urban myths' about the effectiveness and side-effects of UAE seem to persevere., Conclusion: Adding UAE as a treatment option to the national guideline did not change the number of performed UAEs for symptomatic fibroids. It might be useful to develop an option grid in order to offer appropriate, independent counseling and encourage shared decision making.

Background: In women with abnormal uterine bleeding, fibroids are a frequent finding. In case of heavy menstrual bleeding and presence of submucosal type 0-1 fibroids, hysteroscopic resection is the treatment of first choice, as removal of these fibroids is highly effective. Hysteroscopic myomectomy is currently usually performed in the operating theatre. A considerable reduction in costs and a higher patient satisfaction are expected when procedural sedation and analgesia with propofol (PSA) in an outpatient setting is applied. However, both safety and effectiveness - including the necessity for re-intervention due to incomplete resection - have not yet been evaluated., Methods: This study is a multicentre randomised controlled trial with a non-inferiority design and will be performed in the Netherlands. Women > 18 years with a maximum of 3 symptomatic type 0 or 1 submucosal fibroids with a maximum diameter of 3.5 cm are eligible to participate in the trial. After informed consent, 205 women will be randomised to either hysteroscopic myomectomy using procedural sedation and analgesia with propofol in an outpatient setting or hysteroscopic myomectomy using general anaesthesia in a clinical setting in the operating theatre. Primary outcome will be the percentage of complete resections, based on transvaginal ultrasonography 6 weeks postoperatively. Secondary outcomes are cost effectiveness, menstrual blood loss (Pictorial blood assessment chart), quality of life, pain, return to daily activities/work, hospitalization, (post) operative complications and re-interventions. Women will be followed up to one year after hysteroscopic myomectomy., Discussion: This study may demonstrate comparable effectiveness of hysteroscopic myomectomy under procedural sedation and analgesia versus general anaesthesia in a safe and patient friendly environment, whilst achieving a significant cost reduction., Trial Registration: Dutch trial register, number NTR5357 . Registered 11th of August 2015.

Background: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility., Methods: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective., Discussion: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound., Trial Registration: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

Purpose: To perform an evaluation on safety and efficacy of uterine artery embolization (UAE) in the patients with symptomatic cervical leiomyomata., Methods: Patients with symptomatic cervical leiomyomata who underwent UAE in one specialized hospital were retrospectively analyzed, both clinically and with MR imaging. The 3-month outcomes were assessed with MR imaging and a validated questionnaire. Long-term follow-up was assessed by direct contact or file review. To determine the efficacy of UAE for cervical leiomyomata, the primary objective was to assess the clinical outcome with the UFS-QOL questionnaire, containing the health-related quality of life (HRQOL) and symptom severity score (SSS). To assess safety, the secondary objective included leiomyomata volume reduction, the infarction/complication rate and secondary interventions were needed., Results: Between 2006 and 2017, eight of 1180 patients underwent UAE and were eligible for inclusion. All embolizations were technically successful (n = 8). At 3 months, all patients showed cervical leiomyomata volume reduction with a median reduction of 41.5% (38.8 cm 3 ) compared to baseline (p = 0.012). No complications occurred. At a median follow-up of 3 months (range 1-7, n = 7), the HRQOL and SSS improved with a median difference of 13 points (range - 5 to 60, p = 0.063) and - 13 points (range - 79 to 3, p = 0.046), respectively. Long-term follow-up showed two secondary interventions (median of 43.5 months). Six patients reported no symptom recurrence., Conclusion: UAE in women with symptomatic cervical leiomyomata is effective and safe with significant improvement in symptoms and quality of life. UAE is a valuable option for women seeking a non-surgical solution.

Objective: To generate guidance for detailed uterine niche evaluation by ultrasonography in the non-pregnant woman, using a modified Delphi procedure amongst European experts., Methods: Twenty gynecological experts were approached through their membership of the European Niche Taskforce. All experts were physicians with extensive experience in niche evaluation in clinical practice and/or authors of niche publications. By means of a modified Delphi procedure, relevant items for niche measurement were determined based on the results of a literature search and recommendations of a focus group of six Dutch experts. It was predetermined that at least three Delphi rounds would be performed (two online questionnaires completed by the expert panel and one group meeting). For it to be declared that consensus had been reached, a consensus rate for each item of at least 70% was predefined., Results: Fifteen experts participated in the Delphi procedure. Consensus was reached for all 42 items on niche evaluation, including definitions, relevance, method of measurement and tips for visualization of the niche. A niche was defined as an indentation at the site of a Cesarean section with a depth of at least 2 mm. Basic measurements, including niche length and depth, residual and adjacent myometrial thickness in the sagittal plane, and niche width in the transverse plane, were considered to be essential. If present, branches should be reported and additional measurements should be made. The use of gel or saline contrast sonography was preferred over standard transvaginal sonography but was not considered mandatory if intrauterine fluid was present. Variation in pressure generated by the transvaginal probe can facilitate imaging, and Doppler imaging can be used to differentiate between a niche and other uterine abnormalities, but neither was considered mandatory., Conclusion: Consensus between niche experts was achieved regarding ultrasonographic niche evaluation. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology., (© 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)