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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.)

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., (© 2017 Royal College of Obstetricians and Gynaecologists.)

The aims of this prospective diagnostic evaluation study were (i) to estimate the inter-observer agreement and reproducibility of real-time sonoelastography and real-time gray-scale ultrasound in the measurement of uterine and fibroid volumes; (ii) to evaluate the agreement between real-time gray-scale ultrasound, sonoelastography and magnetic resonance imaging with respect to these outcomes; and (iii) to evaluate the diagnostic accuracy of sonoelastography in the diagnosis of uterine pathology on stored sonoelastography and gray-scale cine loops. Women without a history of uterine pathology and with the diagnosis intrauterine fibroids or adenomyosis were included. All participants underwent gray-scale ultrasound, sonoelastography and magnetic resonance imaging. Compression sonoelastography was found to have high inter-observer and inter-method agreement for the measurement of uterine and fibroid volumes. The addition of sonoelastography to gray-scale ultrasound seems to be useful in the differentiation between fibroids, adenomyosis and normal uteri as reflected by an increase in accuracy and diagnostic agreement., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Objective: To analyse fibroid vascularisation measured with three-dimensional (3D) power Doppler in relation to absolute fibroid volume change during 12 months of follow up and in relation to fibroid growth rate per year., Design: A prospective cohort study was performed between March 2012 and March 2014., Setting: Outpatient clinic of the VU medical centre, Amsterdam., Population or Sample: All premenopausal women diagnosed with a maximum of two fibroids with expectant management were consecutively included., Methods: Three-dimensional ultrasound including power Doppler was performed at baseline, 3, 6 and 12 months. Volume and vascular parameters were calculated using VOCAL software., Main Outcome Measures: The relationship between vascular index (VI) at baseline and fibroid volume over time was analysed using linear mixed model analyses for repeated measurements. Second, the relationship between VI at baseline and fibroid growth rate per year was calculated using linear regression analyses. Analyses were adjusted for possible confounders., Results: In all, 66 women (mean age 42 years) completed 12 months of follow up without treatment. Baseline fibroid vascularisation (VI) measured with 3D power Doppler is correlated with fibroid volume at 12 months (P = 0.02 ). An increase of 1% in VI at baseline was associated with a 7.00-cm 3 larger fibroid volume at 12 months. Furthermore, vascularisation was also associated with fibroid growth rate per year (P = 0.04)., Conclusion: In women with uterine fibroids without therapy, baseline vascularisation (VI) measured with 3D power Doppler is correlated with absolute fibroid volume change at 12 months and with fibroid growth rate per year., Tweetable Abstract: Fibroid vascularisation correlates with absolute fibroid volume change and fibroid growth rate per year., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Objective: To compare the effectiveness of a hysteroscopic niche resection versus no treatment in women with postmenstrual spotting and a uterine caesarean scar defect., Design: Multicentre randomised controlled trial., Setting: Eleven hospitals collaborating in a consortium for women's health research in the Netherlands., Population: Women reporting postmenstrual spotting after a caesarean section who had a niche with a residual myometrium of ≥3 mm, measured during sonohysterography., Methods: Women were randomly allocated to hysteroscopic niche resection or expectant management for 6 months., Main Outcome Measures: The primary outcome was the number of days of postmenstrual spotting 6 months after randomisation. Secondary outcomes were spotting at the end of menstruation, intermenstrual spotting, dysuria, sonographic niche measurements, surgical parameters, quality of life, women's satisfaction, sexual function, and additional therapy. Outcomes were measured at 3 months and, except for niche measurements, also at 6 months after randomisation., Results: We randomised 52 women to hysteroscopic niche resection and 51 women to expectant management. The median number of days of postmenstrual spotting at baseline was 8 days in both groups. At 6 months after randomisation, the median number of days of postmenstrual spotting was 4 days (interquartile range, IQR 2-7 days) in the intervention group and 7 days (IQR 3-10 days) in the control group (P = 0.04); on a scale of 0-10, discomfort as a result of spotting had a median score of 2 (IQR 0-7) in the intervention group, compared with 7 (IQR 0-8) in the control group (P = 0.02)., Conclusions: In women with a niche with a residual myometrium of ≥3 mm, hysteroscopic niche resection reduced postmenstrual spotting and spotting-related discomfort., Tweetable Abstract: A hysteroscopic niche resection is an effective treatment to reduce niche-related spotting., (© 2017 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Objective: To evaluate the effectiveness of a laparoscopic niche resection on niche-related symptoms and/or fertility-related problems, ultrasound findings and quality of life., Design: Prospective cohort study., Setting: University hospital., Population: Women with a large niche (residual myometrium <3 mm) and complaints of either postmenstrual spotting, dysmenorrhoea, intrauterine fluid accumulation and/or difficulties with embryo transfer due to distorted anatomy., Methods: Women filled out questionnaires and a validated menstrual score chart at baseline and 6 months after the laparoscopic niche resection. At baseline and between 3 and 6 months follow up niches were evaluated by transvaginal ultrasound., Main Outcome Measures: The primary outcome was reduction of the main problem 6 months after the intervention. Secondary outcomes were complications, menstrual characteristics, dysmenorrhoea, niche measurements, intrauterine fluid, surgical outcomes, satisfaction and quality of life., Results: In all, 101 women underwent a laparoscopic niche resection. In 80 women (79.2%) the main problem was improved or resolved. Postmenstrual spotting was significantly reduced by 7 days at 6 months follow up compared with baseline. Dysmenorrhoea and discomfort related to spotting was also significantly reduced. The residual myometrium was increased significantly at follow up. The intrauterine fluid was resolved in 86.9% of the women with intrauterine fluid at baseline; 83.3% of women were (very) satisfied. The physical component of quality of life increased, the mental component did not change., Conclusions: A laparoscopic niche resection reduced postmenstrual spotting, discomfort due to spotting, dysmenorrhoea and the presence of intrauterine fluid in the majority of women and increased the residual myometrium., Tweetable Abstract: Laparoscopic niche resection reduces niche-related problems and enlarges the residual myometrium., (© 2017 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Objectives: To investigate the accuracy and reliability of 3-dimensional (3D) transvaginal sonography in classifying submucous fibroids using the International Federation of Gynecology and Obstetrics PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified) classification and protrusion (percent) compared to 2-dimensional (2D) transvaginal sonography, 2D saline infusion sonography, and 3D saline infusion sonography, using hysteroscopy as a reference test., Methods: A prospective cohort pilot study was performed among 14 consecutive patients undergoing hysteroscopic surgery, preceded by routine sonography (2D transvaginal sonography, 2D saline infusion sonography, 3D transvaginal sonography, and 3D saline infusion sonography)., Results: The intraclass correlation coefficient (ICC) for 2D transvaginal sonography versus hysteroscopy was 0.69 (95% confidence interval [CI], 0.06, 0.90) compared to 0.94 (95% CI, 0.83, 0.98) for 2D saline infusion sonography. The ICCs for 3D transvaginal sonography versus hysteroscopy were 0.69 (95% CI, 0.03, 0.90 [investigator A]) and 0.55 (95% CI, -0.48, 0.86 [investigator B]). The ICCs for 3D saline infusion sonography versus hysteroscopy were 0.94 (95% CI, 0.81, 0.98 [investigator A]) and 0.87 (95% CI, 0.60, 0.96 [investigator B]). Interobserver agreement of 3D transvaginal sonography was 0.81 (95% CI, 0.43, 0.94) compared to 0.86 (95% CI, 0.56, 0.96) for 3D saline infusion sonography., Conclusions: In these preliminary data, 3D transvaginal sonography was not as accurate as 2D or 3D saline infusion sonography and was not more accurate than 2D transvaginal sonography. There was moderate interobserver agreement for 3D transvaginal sonography. There might be room for improvement, as 3D transvaginal sonography is more accurate when endometrial thickness increases. Further study is warranted to evaluate in which patients saline infusion sonography eventually can be obviated., (© 2017 by the American Institute of Ultrasound in Medicine.)

This study answers the question of whether ultrasound machine settings and the cardiac cycle can influence 3D power Doppler (3D PD) indices in the evaluation of uterine fibroid vascularisation. These parameters were reported to affect the vascular indices and cause undesired variation. 3D PD ultrasound was performed using three different gain settings: a fixed predetermined gain (50 dB), a higher gain (65 dB) and an individualised subjectively most optimal gain. Two consecutive 3D PD sweeps were taken to evaluate the effect of the cardiac cycle. A predetermined most optimal fixed gain setting was not different from the individually most optimal chosen gain in vascular assessment of fibroids. A higher gain corresponded with a significantly higher vascular index (VI). Potential variation during the cardiac cycle does not disturb the VI in fibroids.

The effect of uterine artery embolization (UAE) on symptomatic adenomyosis was evaluated in a systematic review and meta-analysis. Four groups were evaluated: short-term (< 12 months) pure adenomyosis, short-term adenomyosis with fibroids (combined adenomyosis), long-term (> 12 months) pure adenomyosis, and long-term combined adenomyosis. Improvement of symptoms occurred in 83.1% (872/1,049) of patients. Reported symptom reduction was 4.8% greater in the short-term combined group (P = .169) and 11.4% greater in the long-term combined group (P = .003). Uterine volume was reduced in all patients at 3 months. The effects of UAE on symptom improvement and uterine volume reduction in patients with adenomyosis are encouraging., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

The technique of a laparoscopic niche resection is described in ten steps and alternative steps for future studies are discussed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to assess clinical outcomes 7 years after uterine artery embolization (UAE) in the treatment of symptomatic adenomyosis., Materials and Methods: In this prospective cohort study, one specialized hospital in the Netherlands recruited patients with symptomatic adenomyosis or adenomyosis in combination with fibroids for UAE. The 7-year post-intervention outcomes were health-related quality of life (HRQOL), symptom severity scores (SSS), satisfaction, menopause and re-interventions., Results: Twenty-nine patients with adenomyosis (15 with fibroids) were treated with UAE between September 2006 and January 2010. The 7-year questionnaire was mailed in November 2016. The mean follow-up was 95 months (SD 9.0) at a mean age of 50 (SD 5.4). Questionnaires were returned by 24/29 patients (83%). The remaining five patients were contacted through telephone. One of these patients was untraceable. Seven years after treatment 5 of 28 patients (18%) underwent a secondary hysterectomy. The HRQOL and SSS scores as measured by UFS-QOL at 3 months after UAE showed significant improvement of -57 points (score: 15) and +40 points (score: 91), respectively. These scores remained comparable stable up unto 7 years. The SSS showed a significant difference of 17 points (0-100) in favor of the adenomyosis in combination with fibroids group (p = 0.020). Menopause was reported by 10/28 patients (36%). Twenty-one of 29 (72%) patients declared to be at least fairly satisfied about UAE., Conclusions: After 7 years of follow-up, in 82% of UAE-treated patients with symptomatic adenomyosis a hysterectomy was avoided.

Purpose: Since the introduction of minimally invasive gynecologic surgery, the percentage of advanced laparoscopic procedures has greatly increased worldwide. It seems therefore, timely to standardize laparoscopic gynecologic care according to the principles of evidence-based medicine. With this goal in mind-the Dutch Society of Gynecological Endoscopic Surgery initiated in The Netherlands the development of a national guideline for laparoscopic hysterectomy (LH). This present article provides a summary of the main recommendations of the guideline., Methods: This guideline was developed following the Dutch guideline of medical specialists and in accordance with the AGREE II tool. Clinically important issues were firstly defined and translated into research questions. A literature search per topic was then conducted to identify relevant articles. The quality of the evidence of these articles was rated following the GRADE systematic. An expert panel consisting of 18 selected gynecologists was consulted to formulate best practice recommendations for each topic., Results: Ten topics were considered in this guideline, including amongst others, the different approaches for hysterectomy, advice regarding tissue extraction, pre-operative medical treatment and prevention of ureter injury. This work resulted in the development of a clinical practical guideline of LH with evidence- and expert-based recommendations. The guideline is currently being implemented in The Netherlands., Conclusion: A guideline for LH was developed. It gives an overview of best clinical practice recommendations. It serves to standardize care, provides guidance for daily practice and aims to guarantee the quality of LH at an (inter)national level.

The research objective of the current systematic literature review is to classify the laparoscopic niche repair according to the IDEAL framework of 'innovation stages' and to recommend the required research setting to facilitate safe and properly timed implementation of the technique. In doing so, we are also able to evaluate the practical applicability of the IDEAL framework. A systematic search of the available literature on laparoscopic niche repair was performed in PubMed, Embase, and the Wiley/Cochrane library. Articles were classified according to the IDEAL framework and recommendations were given on additional required research before the technique can be safely implemented. Practical applicability of the IDEAL framework was also evaluated. Introduction of laparoscopic niche repair matches Idea (1) and Development (2a), according to the stages of IDEAL framework, although most studies are retrospective and complications have not been registered structurally in a considerable number of the articles. As feasibility and safety have been more or less established and surgery has been further developed we enter stage 2b (Exploration) and need prospective trials preferably comparing the effectiveness of laparoscopic niche repair to expectant management, the current standard care. Available studies were classified with the use of the IDEAL framework, achieving an overall IDEAL stage to be 2a Development. As clinical outcomes, though poorly registered, have been substantially improved, laparoscopic niche repair needs to be carried forward by more advanced study designs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Ulipristal acetate is increasingly used for several clinical indications, like emergency contraception and pre-treatment of uterine fibroids. It has mixed progesterone agonist and antagonist effects in the myometrium and endometrium. Due to its progesterone antagonistic effect, an unopposed estrogen effect could occur which could cause (pre-)malignant lesions in the endometrium. Several studies have been performed to evaluate this possible increased risk for endometrial malignancies when using ulipristal acetate. The specific spectrum of morphological changes due to ulipristal acetate, named progesterone receptor modulator associated endometrial changes (PAEC), occurs to be reversible after discontinuing ulipristal acetate. In this systematic review we provide a detailed overview of the literature on histopathological endometrial changes and imaging characteristics of the endometrium in ulipristal acetate users. We performed an extensive search in Embase.com, Wiley/Cochrane Library and PubMed in accordance with the prisma guidelines. All studies published as full papers in peer reviewed journals using ulipristal acetate reporting on endometrial changes were included, independent of clinical indication, dosage taken and duration of therapy. No language restrictions were applied. Ten studies with a total of 1450 participants were included. Seven were randomized clinical trials and three prospective cohort studies. A quality assessment of all included studies was performed. In only five of ten studies an endometrial biopsy was performed during treatment. All of these studies described specific histological non-physiological endometrial changes (PAEC) due to ulipristal acetate, varying from 41 to 78.8% of all patients. Three of these studies also performed follow-up biopsies after discontinuing ulipristal acetate. The percentage of PAEC decreased from 62% to 0%, 78.8% to 0% and from 59% to 6-7% after the treatment period. In six of 1450 women (0.4%) endometrial hyperplasia was reported during or after ulipristal acetate use. Five were simple hyperplasia, one biopsy showed simple atypical endometrial hyperplasia that resolved into benign secretory endometrium by the end of the treatment. One case of endometrial adenocarcinoma was reported, however this does not seem to be related to ulipristal acetate use, since it was already present at the baseline biopsy. In eight of ten studies a transvaginal ultrasound or MRI was performed at any moment to assess the endometrial thickness before, during and after treatment. Most studies showed a transient increase of endometrial thickness during treatment, which returned to normal within a few weeks after discontinuing ulipristal acetate. Based on the literature found in this systematic review, follow-up after a maximum of four courses of ulipristal acetate did not report any non-reversible (pre-)malignant lesions of the endometrium. Most studies focused on short term use of ulipristal acetate and their follow-up period was limited. Therefore, we believe more information concerning long term (intermittent) use is needed before it can be concluded that its use is completely safe., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: This study was designed to compare the costs and effects of epidural analgesia (EDA) to those of patient-controlled intravenous analgesia (PCA) for postintervention pain relief in women having uterine artery embolization (UAE) for systematic uterine fibroids., Methods: Cost-effectiveness analysis (CEA) based on data from the literature by constructing a decision tree to model the clinical pathways for estimating the effects and costs of treatment with EDA and PCA. Literature on EDA for pain-relief after UAE was missing, and therefore, data on EDA for abdominal surgery were used. Outcome measures were compared costs to reduce one point in visual analogue score (VAS) or numeric rating scale (NRS) for pain 6 and 24 h after UAE and risk for complications., Results: Six hours after the intervention, the VAS was 3.56 when using PCA and 2.0 when using EDA. The costs for pain relief in women undergoing UAE with PCA and EDA were 191 and 355, respectively. The costs for EDA to reduce the VAS score 6 h after the intervention with one point compared with PCA were 105 and 179 after 24 h. The risk of having a complication was 2.45 times higher when using EDA., Conclusions: The results of this indirect comparison of EDA for abdominal surgery with PCA for UAE show that EDA would provide superior analgesia for post UAE pain at 6 and 24 h but with higher costs and an increased risk of complications.