A 52-mg levonorgestrel-releasing intrauterine system vs bipolar radiofrequency nonresectoscopic endometrial ablation in women with heavy menstrual bleeding: long-term follow-up of a multicenter randomized controlled trial.

BACKGROUND: The symptom of heavy menstrual bleeding has a substantial impact on professional, physical, and social functioning. In 2021, results from a randomized controlled trial comparing a 52-mg levonorgestrel-releasing intrauterine system and radiofrequency nonresectoscopic endometrial ablation as treatments for women with heavy menstrual bleeding were published. Both treatment strategies were equally effective in treating heavy menstrual bleeding during 2-year follow-up. However, long-term results are also relevant for both patients and healthcare providers. OBJECTIVE: This study aimed to assess long-term differences in reintervention risk and menstrual blood loss in women with the symptom of heavy menstrual bleeding treated according to a strategy starting with a 52-mg levonorgestrel-releasing intrauterine system or radiofrequency nonresectoscopic endometrial ablation. STUDY DESIGN: This study was a long-term follow-up study of a multicenter randomized controlled trial (MIRA trial), in which women were allocated to either a 52-mg levonorgestrel-releasing intrauterine device (n=132) or radiofrequency nonresectoscopic endometrial ablation (n=138). Women from the original trial were contacted to fill out 6 questionnaires. The primary outcome was the reintervention rate after allocated treatment. Secondary outcomes included surgical reintervention rate, menstrual bleeding measured by the Pictorial Blood Loss Assessment Chart, (disease-specific) quality of life, sexual function, and patient satisfaction. RESULTS: From the 270 women who were randomized in the original trial, 196 (52-mg levonorgestrel-releasing intrauterine system group: n=94; radiofrequency nonresectoscopic endometrial ablation group: n=102) participated in this long-term follow-up study. Mean follow-up duration was 7.4 years (range, 6-9 years). The cumulative reintervention rate (including both medical and surgical reinterventions) was 40.0% (34/85) in the 52-mg levonorgestrel-releasing intrauterine system group and 28.7% (27/94) in the radiofrequency nonresectoscopic endometrial ablation group (relative risk, 1.39; 95% confidence interval, 0.92-2.10). The cumulative rate of surgical reinterventions only was significantly higher among patients with a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system compared with radiofrequency nonresectoscopic endometrial ablation (35.3% [30/85] vs 19.1% [18/94]; relative risk, 1.84; 95% confidence interval, 1.11-3.10). However, the hysterectomy rate was similar (11.8% [10/94] in the 52-mg levonorgestrel-releasing intrauterine system group and 18.1% [17/102] in the radiofrequency nonresectoscopic endometrial ablation group; relative risk, 0.65; 95% confidence interval, 0.32-1.34). Most reinterventions occurred during the first 24 months of follow-up. A total of 171 Pictorial Blood Loss Assessment Chart scores showed a median bleeding score of 0.0. No clinically relevant differences were found regarding quality of life, sexual function, and patient satisfaction. CONCLUSION: The overall risk of reintervention after long-term follow-up was not different between women treated according to a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system and those treated using a strategy starting with radiofrequency nonresectoscopic endometrial ablation. However, women allocated to a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system had a higher risk of surgical reintervention, which was driven by an increase in subsequent endometrial ablation. Both treatment strategies were effective in lowering menstrual blood loss over the long term. The results of this long-term follow-up study can support physicians in optimizing the counseling of women with heavy menstrual bleeding, thus promoting informed decision-making regarding choice of treatment.

Single-layer vs double-layer uterine closure during cesarean delivery: 3-year follow-up of a randomized controlled trial (2Close study).

BACKGROUND: The rising rate of cesarean deliveries has led to an increased incidence of long long-term complications, including niche formation in the uterine scar. Niche development is associated with various gynecologic complaints and complications in subsequent pregnancies, such as uterine rupture and placenta accreta spectrum disorders. Although uterine closure technique is considered a potential risk factor for niche development, consensus on the optimal technique remains elusive. OBJECTIVE: We aimed to evaluate the effect of single-layer vs double-layer closure of the uterine incision on live birth rate at a 3-year follow-up with secondary objectives focusing on gynecologic, fertility, and obstetrical outcomes at the same follow-up. STUDY DESIGN: A multicenter, double-blind, randomized controlled trial was performed at 32 hospitals in the Netherlands. Women ≥18 years old undergoing a first cesarean delivery were randomly assigned (1:1) to receive either single-layer or double-layer closure of the uterine incision. The primary outcome of the long-term follow-up was the live birth rate; with secondary outcomes, including pregnancy rate, the need for fertility treatment, mode of delivery, and obstetrical and gynecologic complications. This trial is registered on the International Clinical Trials Registry Platform www.who.int (NTR5480; trial finished). RESULTS: Between 2016 and 2018, the 2Close study randomly assigned 2292 women, with 830 of 1144 and 818 of 1148 responding to the 3-year questionnaire in the single-layer and double-layer closure. No differences were observed in live birth rates; also there were no differences in pregnancy rate, need for fertility treatments, mode of delivery, or uterine ruptures in subsequent pregnancies. High rates of gynecologic symptoms, including spotting (30%-32%), dysmenorrhea (47%-49%), and sexual dysfunction (Female Sexual Function Index score, 23) are reported in both groups. CONCLUSION: The study did not demonstrate the superiority of double-layer closure over single-layer closure in terms of reproductive outcomes after a first cesarean delivery. This challenges the current recommendation favoring double-layer closure, and we propose that surgeons can choose their preferred technique. Furthermore, the high risk of gynecologic symptoms after a cesarean delivery should be discussed with patients.

Hysterectomy and sexual function: a systematic review and meta-analysis.

BACKGROUND: Sexual function after hysterectomy can be a concern for patients, and research remains inconclusive about changes in sexual function associated with hysterectomy. AIM: We meta-analyzed studies on change in sexual function from pre- to posthysterectomy and the role of total vs subtotal hysterectomy and concomitant bilateral salpingo-oophorectomy (BSO) in differences in such change. METHODS: We searched PubMed, Embase, and Cochrane databases from inception to January 2022. Two reviewers screened and included studies if they were published in a peer-reviewed journal and reported on sexual function pre- and posthysterectomy for benign nonprolapse indication. Methodological quality was assessed with the STROBE checklist. We used random effects multilevel models to meta-analyze standardized mean differences in pre- to postoperative sexual function and the posthysterectomy Female Sexual Function Index mean across study groups in R (RStudio). OUTCOMES: Outcomes included overall sexual function, dyspareunia, desire, arousal, lubrication, and orgasm. RESULTS: Thirty-two articles were analyzed: 8 randomized controlled trials, 20 prospective studies, 2 retrospective studies, 1 cross-sectional study, and 1 secondary analysis, comprising a total of 4054 patients. Each study provided data for at least 1 outcome. Study quality was moderate, and effect sizes showed large between-study heterogeneity. Hysterectomy was not associated with significant change in overall sexual function irrespective of surgical route, with patients tending to report potentially remaining sexual dysfunction posthysterectomy. Cervix removal was not significantly associated with differences in magnitude of change. Hysterectomy without BSO was associated with significantly stronger improvement in lubrication and orgasm than hysterectomy with BSO, which was not the case for desire, arousal or overall sexual function. However, these significant differences were not replicated within studies that directly compared cases with and without BSO. CLINICAL IMPLICATIONS: Clinicians should address remaining sexual dysfunction posthysterectomy, and BSO should not be considered if not medically required. STRENGTHS AND LIMITATIONS: We analyzed a comprehensive number of trials and studied clinically relevant factors that might relate to differences in change in sexual function. Conclusions need to be interpreted with caution since many studies showed moderate methodological quality and large effect size heterogeneity. CONCLUSION: Subtotal and total hysterectomy was not associated with significant change in overall sexual function irrespective of surgical route, with patients tending to report potentially remaining sexual dysfunction posthysterectomy. Hysterectomy without BSO was associated with significantly stronger improvement in lubrication and orgasm than hysterectomy with BSO. Future research on hysterectomy should analyze predictors of sexual function change trajectories, such as different indications.

The effects of Saline Infusion Sonography on the histological quality of endometrial sampling in women with postmenopausal bleeding.

BACKGROUND: The aim of this study is to analyze the histopathological features of endometrial samples obtained by aspiration when performed before or after the saline contrast sonohysterography in women with postmenopausal bleeding and a thickened endometrium. Hypothetically, the saline infusion could disrupt the tissue and therefore affect the quality of the sample. Furthermore, we want to determine which histological features have impact on the quality of the endometrial sample. METHODS: We performed a randomized controlled trial (ESPRESSO trial) in which we analyzed the aspiration samples in two groups. Women were allocated either to saline contrast sonohysterography and subsequent endometrial sampling (SCSH-Sampling group) or to the opposite order (Sampling-SCSH group). Dedicated gyneco-pathologists retrospectively assessed the specimens and recorded the type (blood, mucus, epithelium, intact glands, stroma and tissue context) and quantity (on a scale of 0-3) of material that was found in the specimens. RESULTS: This analysis consisted of 197 samples, with 101 women in the SCSH-Sampling group and 96 women in the Sampling-SCSH group. No significant differences were found in the histological features between the two groups. All significant histological features differed significantly in the sufficient samples compared to the insufficient samples: higher amounts of blood, more endometrial epithelium, presence of intact endometrial glands, better stroma and tissue context. Oppositely, a significantly higher amount of mucus was found in the insufficient samples. CONCLUSION: This study shows that the histological features of the endometrial sample were not affected by the saline contrast sonohysterography, when performed prior to the tissue sampling. Trial registration ESPRESSO TRIAL, NTR5690, registered 16 February 2016, https://trialsearch.who.int/Trial2.aspx?TrialID=NTR5690 .

Endometrial cancer after endometrial ablation: a systematic review.

OBJECTIVE: To investigate whether a previously performed endometrial ablation is associated with the development and diagnosis of endometrial cancer. METHODS: First, a systematic review was performed of the articles reporting the incidence of endometrial cancer in patients treated with endometrial ablation. Second, a systematic review was performed to identify all individual cases of endometrial cancer after ablation to evaluate presenting symptoms, diagnostic work-up, potential risk factors, and the type and stage of the endometrial cancer. A systematic search was performed, using Medline, EMBASE, and the Cochrane Library databases, from inception through February 24, 2022. RESULTS: Based on 11 included studies, the incidence of endometrial cancer in a population of 29 102 patients with a prior endometrial ablation ranged from 0.0% to 1.6%.A total of 38 cases of endometrial cancer after ablation were identified. In 71% of cases (17 of 24 cases), vaginal bleeding was the first presenting symptom. With transvaginal ultrasound it was possible to identify and measure the endometrial thickness in eight cases. Endometrium sampling was successful in 16 of 18 described cases (89%). In 18 of 20 cases (90%) pathologic examination showed early-stage endometrioid adenocarcinoma (International Federation of Gynecology and Obstetrics stage I). CONCLUSION: Previous endometrial ablation is not associated with the development of endometrial cancer. Diagnostic work-up is not impeded by previous endometrial ablation. In addition, endometrial cancers after endometrial ablation are not detected at an advanced stage.

Endometrial ablation plus levonorgestrel releasing intrauterine system versus endometrial ablation alone in women with heavy menstrual bleeding: study protocol of a multicentre randomised controlled trial; MIRA2 trial.

BACKGROUND: It is estimated that between 12 to 25% of women who undergo an endometrial ablation for heavy menstrual bleeding (HMB) are dissatisfied after two years because of recurrent menstrual bleeding and/or cyclical pelvic pain, with around 15% of these women ultimately having a hysterectomy. The insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) immediately after endometrial ablation may inactivate residual untreated endometrium and/or inhibit the regeneration of endometrial tissue. Furthermore, the LNG-IUS may prevent agglutination of the uterine walls preventing intrauterine adhesion formation associated with endometrial ablation. In these ways, insertion of an LNG-IUS immediately after endometrial ablation might prevent subsequent hysterectomies because of persisting uterine bleeding and cyclical pelvic pain or pain that arises de novo. Hence, we evaluate if the combination of endometrial ablation and an LNG-IUS is superior to endometrial ablation alone in terms of reducing subsequent rates of hysterectomy at two years following the initial ablative procedure. METHODS/DESIGN: We perform a multicentre randomised controlled trial in 35 hospitals in the Netherlands. Women with heavy menstrual bleeding, who opt for treatment with endometrial ablation and without contraindication for an LNG-IUS are eligible. After informed consent, participants are randomly allocated to either endometrial ablation plus LNG-IUS or endometrial ablation alone. The primary outcome is the hysterectomy rate at 24 months following endometrial ablation. Secondary outcomes include women's satisfaction, reinterventions, complications, side effects, menstrual bleeding patterns, quality of life, societal costs. DISCUSSION: The results of this study will help clinicians inform women with HMB who opt for treatment with endometrial ablation about whether concomitant use of the LNG-IUS is beneficial for reducing the need for hysterectomy due to ongoing bleeding and/or pain symptoms. Trial registration Dutch Trial registration: NL7817. Registered 20 June 2019, https://www.trialregister.nl/trial/7817 .

Predictive factors of return to work after hysterectomy: a retrospective study.

PURPOSE: Although hysterectomy is one of the most frequently performed gynaecological surgeries, there is a dearth of evidence on perioperative care. The aim of the current study was to identify sociodemographic, surgical-related and work-related predictors of recovery following different approaches of hysterectomy. METHODS: Eligible patients for this retrospective cohort study were women who underwent vaginal, abdominal or laparoscopic hysterectomy for both benign and malignant gynaecological disease in 2014 in Máxima Medical Centre in the Netherlands. The main outcome measure was full return to work (RTW). Data were collected using a patient survey. Potential prognostic factors for time to RTW were examined in univariate Cox regression analyses. The strongest prognostic factors were combined in a multivariable model. RESULTS: In total 83 women were included. Median time to full return to work was 8 weeks (interquartile range [IQR] 6-12). The multivariable analysis showed that higher age (hazard ratio [HR] 1.053, 95% confidence interval [CI] 1.012-1.095) and same day removal of indwelling catheter (HR 0.122, 95% CI 0.028-0.539) were predictors of shorter duration until full RTW after hysterectomy. CONCLUSIONS: This study provided insight in the predictors of recovery after hysterectomy. By identifying patient specific factors, pre-operative counselling can be individualized, changes can be made in perioperative care and effective interventions can be designed to target those factors.

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding affects the physical functioning and social well-being of many women. The levonorgestrel-releasing intrauterine system and endometrial ablation are 2 frequently applied treatments in women with heavy menstrual bleeding. OBJECTIVE: This study aimed to compare the effectiveness of the levonorgestrel-releasing intrauterine system with endometrial ablation in women with heavy menstrual bleeding. STUDY DESIGN: This multicenter, randomized controlled, noninferiority trial was performed in 26 hospitals and in a network of general practices in the Netherlands. Women with heavy menstrual bleeding, aged 34 years and older, without a pregnancy wish or intracavitary pathology were randomly allocated to treatment with either the levonorgestrel-releasing intrauterine system (Mirena) or endometrial ablation, performed with a bipolar radiofrequency device (NovaSure). The primary outcome was blood loss at 24 months, measured with a Pictorial Blood Loss Assessment Chart score. Secondary outcomes included reintervention rates, patient satisfaction, quality of life, and sexual function. RESULTS: We registered 645 women as eligible, of whom 270 women provided informed consent. Of these, 132 women were allocated to the levonorgestrel-releasing intrauterine system (baseline Pictorial Blood Loss Assessment Chart score, 616) and 138 women to endometrial ablation (baseline Pictorial Blood Loss Assessment Chart score, 630). At 24 months, mean Pictorial Blood Loss Assessment Chart scores were 64.8 in the levonorgestrel-releasing intrauterine system group and 14.2 in the endometrial ablation group (difference, 50.5 points; 95% confidence interval, 4.3-96.7; noninferiority, P=.87 [25 Pictorial Blood Loss Assessment Chart point margin]). Compared with 14 women (10%) in the endometrial ablation group, 34 women (27%) underwent a surgical reintervention in the levonorgestrel-releasing intrauterine system group (relative risk, 2.64; 95% confidence interval, 1.49-4.68). There was no significant difference in patient satisfaction and quality of life between the groups. CONCLUSION: Both the levonorgestrel-releasing intrauterine system and endometrial ablation strategies lead to a large decrease in menstrual blood loss in women with heavy menstrual bleeding, with comparable quality of life scores after treatment. Nevertheless, there was a significant difference in menstrual blood loss in favor of endometrial ablation, and we could not demonstrate noninferiority of starting with the levonorgestrel-releasing intrauterine system. Women who start with the levonorgestrel-releasing intrauterine system, a reversible and less invasive treatment, are at an increased risk of needing additional treatment compared with women who start with endometrial ablation. The results of this study will enable physicians to provide women with heavy menstrual bleeding with the evidence to make a well-informed decision between the 2 treatments.

Endometrial sampling before or after saline contrast sonohysterography in women with postmenopausal bleeding (ESPRESSO trial): A multicenter randomized controlled trial.

INTRODUCTION: The aim of this study is to evaluate the quality of the endometrial sample obtained by office endometrial aspiration when performed before or after saline contrast sonohysterography (SCSH) in women with postmenopausal bleeding and a thickened endometrium. To conduct a complete, minimally invasive and cost-effective diagnostic workup in women with postmenopausal bleeding and a thickened endometrium, ideally both the office endometrial sampling and SCSH are performed. However, it is not known whether both tests affect each other when performed one after another. MATERIAL AND METHODS: Women with postmenopausal bleeding and an endometrial thickness >4 mm were eligible. Women were randomized into two groups: one group received endometrial aspiration before SCSH, the other group received SCSH before endometrial aspiration. The primary outcome was the proportion of sufficient endometrial samples. Reliability of the SCSH images and pain during procedures were secondary outcomes. RESULTS: During the inclusion period, 513 eligible women with postmenopausal bleeding visited the participating hospitals, 293 of whom received information about the study. Of these women, 232 (79%) agreed to participate. In the SCSH-aspiration group, 65 women (59%) had a sufficient endometrial sample compared with 70 (67%) in the aspiration-SCSH group (odds ratio 1.46, 95% CI 0.83-2.54, P = .19). The proportion of reliable sonographic images was significantly higher in the SCSH-aspiration group (n = 88, 87%) compared with the aspiration-SCSH group (n = 71, 74%) (OR 2.38, 95% CI 1.38-4.99, P = .02) in the per protocol analysis. CONCLUSIONS: This study shows that the quality of an endometrial sample in women with postmenopausal bleeding is not affected by SCSH. Both procedures can be performed in one outpatient visit to perform an optimal diagnostic workup.

The combined use of endometrial ablation or resection and levonorgestrel-releasing intrauterine system in women with heavy menstrual bleeding: A systematic review.

INTRODUCTION: Despite endometrial ablation/resection being a very successful treatment for women with heavy menstrual bleeding, re-intervention with additional surgery is needed in 12%-25% of cases. Introducing a levonorgestrel-intrauterine system (LNG-IUS) immediately after ablation could preserve the integrity of the uterine cavity and suppress the regenerated or non-ablated endometrial tissue. Therefore, this combined treatment can perhaps lower the re-intervention rate. The aim of this systematic review was to assess the impact of the combined treatment. MATERIAL AND METHODS: The MEDLINE, EMBASE, and Cochrane library were systematically searched. No language restrictions were applied. All types of studies were included reporting on the results of endometrial ablation or resection combined with immediate insertion of LNG-IUS for treatment of heavy menstrual bleeding. The primary outcome was the number of hysterectomies after the ablation procedure. Secondary outcomes included re-intervention rates, removals of LNG-IUS, bleeding pattern, patient satisfaction, adverse effects, and complications. Our protocol was registered in PROSPERO, an international prospective register of systematic reviews under registration number CRD42020151384. RESULTS: Six studies with a retrospective design and one case series with a follow-up duration varying from 6 to 55 months were included. In total, 427 women were treated with the combined treatment. The studies described a lower hysterectomy and re-intervention rate after combined treatment compared with treatment with endometrial ablation/resection alone. Hysterectomy rate varied from 0% to 11% after combined treatment compared with 9.4% to 24% after endometrial ablation/resection alone. Bleeding patterns and patient satisfaction appeared to be in favor of the combined treatment group. No intra- or post-operative complications or complications in the removal of LNG-IUS were described. The most reported adverse effects after combined treatment were weight gain, mood changes, and headaches. An additional 11 studies with only an abstract available substantiated these findings. All the included studies had poor methodological quality. CONCLUSIONS: Based on the available literature, inserting an LNG-IUS immediately after endometrial ablation/resection seems to lower the hysterectomy and re-intervention rates compared with ablation/resection alone. However, as only limited observational studies of low methodological quality are available, high-quality research is necessary to confirm the findings of this systematic review.

Risk of Hysterectomy After Endometrial Ablation: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the risk of hysterectomy after nonresectoscopic endometrial ablation in patients with heavy menstrual bleeding. DATA SOURCES: The EMBASE, MEDLINE, ClinicalTrials.gov and Cochrane databases were searched for eligible articles from inception until June 13, 2022. We used combinations of search terms for endometrial ablation and hysterectomy. METHODS OF STUDY SELECTION: Articles included in the review described the incidence of hysterectomy at a specific point in time after ablation with a minimum follow-up duration of 12 months. TABULATION, INTEGRATION, AND RESULTS: The literature search yielded a total of 3,022 hits. A total of 53 studies met our inclusion and exclusion criteria, including six retrospective studies, 24 randomized controlled trials, and 23 prospective studies. A total of 48,071 patients underwent endometrial ablation between 1992 and 2017. Follow-up duration varied between 12 and 120 months. Analyses per follow-up moment showed 4.3% hysterectomy rate at 12 months of follow-up (n=29 studies), 11.1% at 18 months (n=1 study), 8.0% at 24 months (n=11 studies), 10.2% at 36 months (n=12 studies), 7.6% at 48 months (n=2 studies), and 12.4% at 60 months (n=6 studies). Two studies reported a mean hysterectomy rate at 10 years after ablation of 21.3%. Minimal clinically relevant differences in hysterectomy rates were observed among the different study designs. Furthermore, we found no significant differences in hysterectomy rate among the different nonresectoscopic endometrial ablation devices. CONCLUSION: The risk of hysterectomy after endometrial ablation seems to increase from 4.3% after 1 year to 12.4% after 5 years. Clinicians can use the results of this review to counsel patients about the 12% risk of hysterectomy 5 years after endometrial ablation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020156281.

Preoperative CA125 Significantly Improves Risk Stratification in High-Grade Endometrial Cancer.

Patients with high-grade endometrial carcinoma (EC) have an increased risk of tumor spread and lymph node metastasis (LNM). Preoperative imaging and CA125 can be used in work-up. As data on cancer antigen 125 (CA125) in high-grade EC are limited, we aimed to study primarily the predictive value of CA125, and secondarily the contributive value of computed tomography (CT) for advanced stage and LNM. Patients with high-grade EC (n = 333) and available preoperative CA125 were included retrospectively. The association of CA125 and CT findings with LNM was analyzed by logistic regression. Elevated CA125 ((>35 U/mL), (35.2% (68/193)) was significantly associated with stage III-IV disease (60.3% (41/68)) compared with normal CA125 (20.8% (26/125), [p < 0.001]), and with reduced disease-specific-(DSS) (p < 0.001) and overall survival (OS) (p < 0.001). The overall accuracy of predicting LNM by CT resulted in an area under the curve (AUC) of 0.623 (p < 0.001) independent of CA125. Stratification by CA125 resulted in an AUC of 0.484 (normal), and 0.660 (elevated). In multivariate analysis elevated CA125, non-endometrioid histology, pathological deep myometrial invasion ≥50%, and cervical involvement were significant predictors of LNM, whereas suspected LNM on CT was not. This shows that elevated CA125 is a relevant independent predictor of advanced stage and outcome specifically in high-grade EC.

Is 2-dimensional transvaginal ultrasonography necessary 6 weeks after insertion of the levonorgestrel 52-mg intrauterine device?

BACKGROUND: In Dutch practice, gynecologists are used to assessing the position of the LNG-IUD by performing a two-dimensional transvaginal ultrasonography (TVUS) directly after insertion and do not routinely invite patients for another consultation 4-12 weeks after insertion. There is no consensus whether a TVUS six weeks after insertion is routinely needed. OBJECTIVE: This study aimed to assess the incidence of malposition using 2-dimensional transvaginal ultrasonography during routine investigation 6 weeks after insertion. In addition, we investigated the relationship between malposition of the levonorgestrel 52-mg intrauterine device and unfavorable bleeding patterns and pelvic pain. STUDY DESIGN: We performed a large prospective cohort study. Patients seeking a levonorgestrel 52-mg intrauterine device were eligible for inclusion. Transvaginal ultrasonography was performed to check position of the levonorgestrel 52-mg intrauterine device immediately after insertion and 6 weeks later. Patients filled in questionnaires about bleeding pattern and pelvic pain 6 weeks after insertion. RESULTS: From March 2015 to December 2016, we enrolled 500 patients. Data from the transvaginal ultrasonography assessment 6 weeks after insertion were available for 448 patients, and complete data (transvaginal ultrasonography and questionnaire data) were available for 363 patients (72.6%). Malposition rate was 6.3% (28/448 patients). Malposition was seen in 15 of 198 patients (7.6%) with unfavorable bleeding and/or pelvic pain and in 3 of 165 patients (1.8%) with favorable bleeding patterns and no pelvic pain (P=.03).Malposition was seen in 14 of 186 patients (7.5%) with an unfavorable bleeding pattern and in 4 of 177 patients (2.3%) with favorable bleeding patterns (P=.008). Malposition was seen in 5 of 50 patients (10%) with pelvic pain and in 13 of 313 patients (4.2%) without pelvic pain (P=.08). CONCLUSION: The malposition rate of the levonorgestrel 52-mg intrauterine device observed using transvaginal ultrasonography 6 weeks after insertion was 6.3%. If patients have no complaints of unfavorable bleeding and/or pelvic pain, the risk for malposition is low (1.8%) and a routine transvaginal ultrasonography is not necessary. However, if patients experience unfavorable bleeding, a transvaginal ultrasonography should be considered to exclude malposition, because the effect of malposition on contraceptive effectiveness is unsure. Future research should focus on cost-benefit analysis.

The effect of an informative 360-degree virtual reality video on anxiety for women visiting the one-stop clinic for abnormal uterine bleeding: A randomized controlled trial (VISION-trial).

OBJECTIVE: To evaluate the effect of an informative 360-degree virtual reality (VR) video on preoperative anxiety before visiting a one-stop clinic for abnormal uterine bleeding. STUDY DESIGN: A randomized controlled trial was performed in a teaching hospital in the Netherlands. A total of 83 women scheduled for a first consultation at the one-stop clinic between April 2017 and September 2017 were included in the analysis. All women received a standard information leaflet about the clinic. 40 women were randomized to receive a 360-degree VR-video of the clinic in addition. The primary outcome was change in the Visual Analogue Scale for Anxiety (VAS-A), measured at baseline (before randomization) and in the waiting room (before visit, after randomization). Anxiety assessed with the State-Trait Anxiety Inventory (STAI-S) was a secondary outcome. Other secondary outcomes included anxiety during the visit and the opinion of the women about the provided information. RESULTS: Only 27 out of the 40 women actually watched the VR-video. Women in the VR-group who actually watched the video reported lower levels of anxiety at baseline compared to women in the VR-group who did not watch the video. In the intention-to-treat analysis, there was no difference in change in anxiety between the VR-group and the control group (mean difference VAS-A = 0.07, 95% CI -0.96 to 1.10; mean difference STAI-S = 1.97, 95% CI -1.82 to 5.77). In the per-protocol analysis, women in the VR-group reported lower anxiety scores in the waiting room. However, the change in anxiety scores between baseline and waiting room was comparable in both groups. 31% of the women who watched the VR-video reported that the video resulted in a reduction of anxiety, 69% reported that the video is of added value and 65% would use a VR-video again in future. CONCLUSIONS: Adding the informative 360-degree VR-video to conventional information did not result in a reduction of anxiety prior to visiting the one-stop clinic. However, the majority of women who watched the video felt that it was of added value. Remarkable was that women who reported higher anxiety at baseline seemed less willing to watch the video.

Should we centralise care for the patient suspected of having ovarian malignancy?

OBJECTIVES: Outcome of ovarian cancer is better when surgery is provided by a gynaecological oncologist than by a general gynaecologist. However, when all patients with an adnexal mass have to be operated by gynaecological oncologists, this requires a change in the organisation of care, which generates additional costs. In this study, we assess the costs and effects of centralised and regular care for women with an ovarian malignancy in the Netherlands. METHODS: We performed a cost-effectiveness analysis. We considered three strategies. In the first strategy, patients were operated by a general gynaecologist (general care strategy). In the second strategy, patients were operated by a gynaecological oncologist (specialised care strategy). In the third strategy, evaluation of the adnexal mass took place prior to surgery by means of the Risk of Malignancy Index (diagnostic strategy). Patients at high risk for malignancy were supposed to be operated in a specialised care setting, whereas low risk patients were supposed to be operated in a general care setting. For each strategy we calculated life expectancy and incremental costs per life year gained (LYG). RESULTS: Mean life expectancy of a patient with an ovarian malignancy in the general strategy was 2.7 years, in the diagnostic strategy 3.0 years and in the specialised strategy 3.1 years. The incremental costs to gain one additional life year with specialised surgery as compared to the diagnostic strategy were € 61,871 per LYG. CONCLUSION: In women with an adnexal mass, a diagnostic strategy prior to the decision for surgery by a general gynaecologist or a gynaecological oncologist provides the best balance between costs and effects.

Improving preoperative diagnosis in endometrial cancer using systematic morphological assessment and a small immunohistochemical panel.

Preoperative histopathological classification determines the primary surgical approach in endometrial carcinoma (EC) patients but has only moderate agreement between preoperative and postoperative diagnosis. The aim of the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study is to determine whether histopathological assessment and a small panel of diagnostic biomarkers decreases discrepancies between preoperative and postoperative diagnosis in EC. Preoperative endometrial tissue of 378 included patients with EC was stained with 15 different antibodies. Clinically relevant discrepancies in grade or histological subtype between original preoperative and reviewed postoperative diagnosis were observed in 75 (20%) patients. Highest clinically relevant discrepancy was found in grade 2 ECs (20%), compared to 5% and 14% in respectively grade 1 and 3 endometrioid endometrial carcinomas (EECs). A practical two-biomarker panel with PR and p53 improved diagnostic accuracy (AUC = 0.92; 95%CI = 0.88-0.95) compared to solely morphological evaluation (AUC = 0.86). In preoperative high-grade EC, the diagnostic accuracy of histological subtype was improved by a three-immunohistochemical biomarker panel (PR, IMP3, and L1CAM) (AUC = 0.93; 95%CI = 0.88-0.98) compared to solely morphological evaluation (AUC = 0.81). In conclusion to improve correct preoperative diagnosis in EC, we recommend use of a panel of at least two easily accessible immunohistochemical biomarkers (PR and p53), only in grade 2 ECs. Overall, this will reduce clinically relevant discrepancies in tumor grade and subtype with postoperative diagnosis with 6% (from 20% to 14%). Addition of PR, IMP3, and L1CAM for histological subtyping in high-grade EECs resulted in a further decrease in discrepancies with 8% (from 20% to 12%).

[Labium majus enlargement in a 6-year old girl: benign or alarming?] / Zwelling van een labium majus bij een 6-jarig meisje.

A 6-year old girl was referred because she had a painless enlarged left labium majus. There were no further symptoms. Ultrasound and MRI revealed no hernias, malignancy or cystic abnormalities. We diagnosed CALME, Childhood Asymmetry Labium Majus Enlargement, a non-neoplastic expansion of normal vulvar tissue in response to hormonal changes. Expectant management is preferred.

Immediate catheter removal after laparoscopic hysterectomy: A retrospective analysis.

OBJECTIVES: All patients undergoing a laparoscopic hysterectomy receive an indwelling catheter during surgery. The optimum timing of removal of the catheter is uncertain. A possible advantage of leaving the catheter in up to 12 h after surgery is to reduce the risk of urinary retention. Possible disadvantages are patient discomfort and increased risk of urinary tract infection. Timing of removal of the catheter after laparoscopic hysterectomy has not been studied. Previous studies have assessed timing of catheter removal after abdominal hysterectomy. In these studies immediate removal seems safe and feasible after an uncomplicated hysterectomy. In 2015 immediate catheter removal after an uncomplicated hysterectomy was introduced in our clinic. We performed a retrospective analysis of all patients who underwent a laparoscopic hysterectomy. The primary objective of this study was to evaluate the rate of urinary retentions and the secondary objective was to investigate the rate of urinary tract infections when the indwelling catheter was removed immediate after surgery. STUDY DESIGN: We included all women who underwent a laparoscopic hysterectomy from April 2015 until December 2017. Informed consent was obtained from all patients. Medical records were analysed to identify baseline characteristics, surgical details and complications. General practitioners of the included patients were contacted to check for post-operative urinary tract infection up to 6 weeks after surgery. RESULTS: 325 patients underwent an uncomplicated hysterectomy between April 2015 and December 2017. After informed consent we ultimately included 242 cases in our analysis. The mean age of our study population was 50 years. In 194 (802 %) patients the catheter was removed immediately after surgery. Main reason for delayed removal of the catheter was resection of deep endometriosis (n = 21). The incidence of urinary retention was 4,6 % (95 % CI 2,3-8,3 %) in the immediate removal group. In these 9 cases, 5 (2,6 %) where solved after single catheterisation. The remaining 4 patients (2,0 %) had an indwelling catheter for 24 h after which the urinary retention resolved. The incidence of urinary tract infection was 9,3 % (95 % CI 5,8-14,0- %), when the catheter was removed immediately after surgery. The incidence of urinary retention and UTI were respectively 2,1% (95 % CI 0,1-9,8%) and 208 % (95 % CI 11,1-34,0 %) in the cases with delayed catheter removal (N = 48). CONCLUSION: Immediate removal of the urine catheter after uncomplicated hysterectomy is safe and results in low levels of urinary retention.

Ulipristal acetate versus gonadotropin-releasing hormone agonists prior to laparoscopic myomectomy (MYOMEX trial): Long term results of a double-blind randomized controlled trial.

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 cm3 (106.8-243.5; N = 29) vs. 152.8 cm3 (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.

Prognostic Factors for the Failure of Endometrial Ablation: A Systematic Review and Meta-analysis.

OBJECTIVE: To provide an overview of prognostic factors predicting failure of second-generation endometrial ablation. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched from 1988 until February 2019. The search was conducted without language restrictions using the following search terms: "endometrial ablation," "prognosis," "predict," "long term," "late onset," "outcome." METHODS OF STUDY SELECTION: The literature search provided a total of 990 studies. All types of studies reporting about prognostic factors of second-generation endometrial ablation failure were included. TABULATION, INTEGRATION, AND RESULTS: After screening for eligibility, 56 studies were included in this review, of which 21 were included in the meta-analysis. In these 56 studies, 157,830 women were included. We evaluated 10 prognostic factors: age, myomas, history of tubal ligation, body mass index, parity, preexisting dysmenorrhea, caesarean delivery, bleeding pattern, uterus position, and uterus length. Meta-analysis was performed for the primary outcome (surgical reintervention) to estimate summary treatment effects. Younger age (aged 35 years or younger, odds ratio [OR] 1.68, 95% CI 1.19-2.36; aged 40 years or younger, OR 1.58, 95% CI 1.30-1.93; aged 45 years or younger OR 1.63, 95% CI 1.28-2.07), prior tubal ligation (OR 1.46, 95% CI 1.23-1.73), and preexisting dysmenorrhea (OR 2.12, 95% CI 1.41-3.19) were associated with an increased risk of surgical reintervention. Studies investigating the prognostic factors myomas and obesity showed conflicting results. CONCLUSION: Younger age, prior tubal ligation and preexisting dysmenorrhea were found to be associated with failure of endometrial ablation. Obesity and the presence of large submucous myomas may be associated with failure, as well, though more research is necessary to estimate the influence of these factors. It is important to take the results of this review into account when counselling women with heavy menstrual bleeding. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019126247.