Reproductive and obstetrical outcomes after treatment of retained products of conception: hysteroscopic removal vs ultrasound-guided electric vacuum aspiration, a prospective follow-up study.

BACKGROUND: Traditionally, curettage has been the most widely performed surgical intervention for removing retained products of conception. However, hysteroscopic removal is increasingly performed as an alternative because of the potentially lower risk of intrauterine adhesions and higher rates of complete removal. Until recently, studies comparing curettage with hysteroscopic removal regarding reproductive and obstetrical outcomes were limited, and data conflicting. OBJECTIVE: This study aimed to assess reproductive and obstetrical outcomes in women wishing to conceive after removal of retained products of conception by hysteroscopy or ultrasound-guided electric vacuum aspiration. STUDY DESIGN: This was a prospective long-term follow-up study, conducted in 3 teaching hospitals and 1 university hospital. Patients were included from April 2015 until June 2022 for follow-up, either in a randomized controlled, nonblinded trial on the risk of intrauterine adhesions after removal of retained products of conception, or in a cohort alongside the randomized trial. Women with an ultrasonographic image suggestive of retained products of conception ranging from 1 to 4 cm were eligible. Surgical procedures in the randomized controlled trial were hysteroscopic morcellation or ultrasound-guided electric vacuum aspiration. In the cohort study, hysteroscopic treatment included hysteroscopic morcellation or cold loop resection compared with ultrasound-guided electric vacuum aspiration. RESULTS: A total of 261 out of 305 patients (85.6%) were available for follow-up after removal of retained products of conception, resulting in a cohort of 171 women after hysteroscopic removal and 90 women after removal by ultrasound-guided vacuum aspiration. Respectively, 92 of 171 women (53.8%) in the hysteroscopic removal group and 56 of 90 (62.2%) in the electric vacuum aspiration group wished to conceive (P=.192). Subsequent pregnancy rates were 88 of 91 (96.7%) after hysteroscopic removal and 52 of 56 (92.9%) after electric vacuum aspiration (P=.428). The live birth rates were 61 of 80 (76.3%) and 37 of 48 (77.1%) after hysteroscopic removal and electric vacuum aspiration, respectively (P=.914), with 8 of 88 pregnancies (9.1%) in the hysteroscopic removal group and 4 of 52 (7.7%) in the electric vacuum aspiration group still ongoing at follow-up (P=1.00). The median time to conception was 8.2 weeks (interquartile range, 5.0-17.2) in the hysteroscopic removal group and 6.9 weeks (interquartile range, 5.0-12.1) in the electric vacuum aspiration group (P=.262). The overall placental complication rate was 13 of 80 (16.3%) in the hysteroscopic removal group and 11 of 48 (22.9%) in the electric vacuum aspiration group (P=.350). CONCLUSION: Hysteroscopic removal and ultrasound-guided electric vacuum aspiration of retained products of conception seem to have no significantly different effects on subsequent live birth rate, pregnancy rate, time to conception, or pregnancy complications. Reproductive and obstetrical outcomes after removal of retained products of conception are reassuring, albeit with a high risk of placental complications.

Quantitative ultrasound measurement of uterine contractility in adenomyotic vs. normal uteri: a multicenter prospective study.

OBJECTIVE: To evaluate uterine contractility in patients with adenomyosis compared with healthy controls using a quantitative two-dimensional transvaginal ultrasound (TVUS) speckle tracking method. DESIGN: A multicenter prospective observational study took place in three European centers between 2014 and 2023. SETTING: One university teaching hospital, 1 teaching hospital and 1 specialised clinic. PATIENTS: A total of 46 women with a sonographic or magnetic resonance imaging diagnosis of adenomyosis were included. 106 healthy controls without uterine pathologies were included. INTERVENTION: Four-minute TVUS recordings were performed and four uterine contractility features were extracted using a speckle tracking algorithm. MAIN OUTCOMES MEASURES: The extracted features were contraction frequency (contractions/min), amplitude, velocity (mm/s), and coordination. Women with adenomyosis were compared with healthy controls according to the phase of the menstrual cycle. RESULTS: Throughout the different phases of the menstrual cycle, trends of increased amplitude, decreased frequency and velocity, and reduced contraction coordination were seen in patients with adenomyosis compared with healthy controls. These were statistically significant in the late follicular phase, with a higher amplitude (0.087 ± 0.042 vs. 0.050 ± 0.018), lower frequency and velocity (1.49 ± 0.22 vs. 1.68 ± 0.25 contractions/min, and 0.65 ± 0.18 vs. 0.88 ± 0.29 mm/s, respectively), and reduced contraction coordination (0.34 ± 0.08 vs. 0.26 ± 0.17), in the late luteal phase, with higher amplitude (0.050 ± 0.022 vs. 0.035 ± 0.013), lower velocity (0.51 ± 0.11 vs. 0.65 ± 0.13 mm/s), and reduced contraction coordination (0.027 ± 0.06 vs. 0.18 ± 0.07), and in the midfollicular phase, with decreased frequency (1.48 ± 0.21 vs. 1.69 ± 0.16 contractions/min) in patients with adenomyosis compared with healthy controls. During menses, a higher pain score was significantly associated with lower frequency and velocity and higher contraction amplitude. Results remained significant after correcting for age, parity, and body mass index. CONCLUSION: Uterine contractility differs in patients with adenomyosis compared with healthy controls throughout the phases of the menstrual cycle. This suggests an etiologic mechanism for the infertility and dysmenorrhea seen in patients with adenomyosis. Moreover, it presents new potential therapeutic targets and diagnostic markers.

Hysteroscopic morcellation vs. curettage for removal of retained products of conception: a multicenter randomized controlled trial.

OBJECTIVE: To study the comparison between hysteroscopic morcellation (HM) of retained products of conception (RPOC) with ultrasound (US)-guided electric vacuum aspiration in terms of intrauterine adhesion (IUA) formation, efficacy, and complications. DESIGN: A randomized controlled, nonblinded trial. SETTING: Three teaching hospitals and one university hospital from April 2015 to June 2022. PATIENTS: A total of 133 women with RPOC on US, ranging from 1-4 cm, were randomized to receive either HM or electric vacuum aspiration. INTERVENTION: Hysteroscopic morcellation was performed with the TruClear System (Medtronic, Minneapolis, MN, USA). Electric vacuum aspiration was performed using an 8- or 10-mm flexible plastic Karman cannula under US guidance. Women allocated to vacuum aspiration underwent the procedure as soon as possible. MAIN OUTCOME MEASURES: In the HM group, an office diagnostic hysteroscopy was planned a minimum of 6 weeks after the end of pregnancy, followed by retained product of conception removal at least 8 weeks after the end of the pregnancy. Postoperatively, an office second-look hysteroscopy was scheduled to assess the primary outcome of IUAs. RESULTS: Postoperative IUAs were seen in 14.3% (9/63) of patients in the HM group and 20.6% (13/64) of patients in the vacuum aspiration group (-6% [-19.1% to 7.1%]). Significantly more RPOC were removed completely by HM compared with vacuum aspiration (95.2% vs. 82.5% (-14% [-24.9% to -3.1%]), and additional operative hysteroscopy was less frequently necessary in the HM group (12.5%) compared with the vacuum aspiration group (31.3%) (-20.1% [-34.3% to -6%]). The median operating time was shorter for vacuum aspiration compared with HM (5.80 minutes vs. 7.15 minutes). No differences were observed between HM and vacuum aspiration for the occurrence of intraoperative or postoperative complications (5.5% vs. 5.0% and 2.7% vs. 1.3%, respectively). CONCLUSION: In our randomized controlled trial, no significant differences were found in the occurrence of IUAs and complications. However, the RPOC were more often completely removed by HM than vacuum aspiration, and the HM group required fewer additional hysteroscopic treatments. CLINICAL TRIAL REGISTRATION NUMBER: NTR4923 (https://trialsearch.who.int/Trial2.aspx?TrialID=NTR4923). Date of registration: November 23, 2014, date of initial participant enrollment: January 1, 2015.

Operative hysteroscopy versus ultrasound-guided electric vacuum aspiration for removal of retained products of conception: A prospective cohort study.

Objectives: To compare intrauterine adhesion (IUA) formation after hysteroscopic removal (HR) of retained products of conception (RPOC) with IUA formation after ultrasound-guided electric vacuum aspiration (EVA) and externally validate the outcomes of an RCT. Study design: This prospective cohort study was conducted from April 2015 until June 2022 in 2 Dutch teaching hospitals and one Belgian university hospital. Women opting for EVA underwent the procedure as soon as possible. In the HR group, the therapeutic hysteroscopy was performed at least eight weeks after the end of pregnancy. Postoperatively, an office second-look hysteroscopy was offered to all patients. Women were included if they had been diagnosed with RPOC ranging from 1 to 4 cm on ultrasound and did not want to participate in the RCT. EVA was performed using a Karman cannula. Operative hysteroscopy consisted either of hysteroscopic morcellation with the TruClear™ System or the Intrauterine BIGATTI Shaver or cold loop resection with a bipolar resectoscope. Results: Of 178 included women, 124 were treated with HR and 28 with EVA. Outcomes of HR and EVA did not differ significantly in terms of complications (5.6 % vs 3.6 %; p = 1.00). Second-look hysteroscopy showed IUAs in 14 of 91 women (15.4 %) after HR and in 1 of 16 (6.3 %) after EVA (p = .461). Completeness of removal was significantly higher (90.1 %) after HR than after EVA (68.8 %) (p = .035). Additional operative hysteroscopy was required in 14.3 % of the HR group versus 37.5 % in the EVA group (p = .036). Conclusion: In our cohort study, no significant differences in IUAs or complications were found. RPOC removal with HR was more often complete than removal with EVA, and additional therapeutic hysteroscopy was less frequently required after HR. These findings need to be correlated with those of RCTs. Clinical trial registration: The study was registered in de Dutch Trial Register (NTR4923). Date of registration 23-11-2014. Date of first enrollment 01-01-2015. https://trialsearch.who.int/Trial2.aspx?TrialID=NTR4923.

Clinical evaluation of a new hand-driven hysteroscopic tissue removal device, Resectr™ 5fr, for the resection of endometrial polyps in an office setting.

PURPOSE: A first clinical evaluation of a new hand-driven hysteroscopic tissue removal device, Resectr™ 5fr, for office polypectomy without any anesthesia. METHODS: Women with at least one small endometrial polyp were eligible. Hysteroscopic polypectomy was performed using the Resectr™ 5fr in an office setting, without any anesthesia. RESULTS: One hundred and two hysteroscopic polypectomies were included in the analysis. The median installation time was 1.9 min (95% confidence interval (CI) 1.6-2.1). The median time to complete polyp removal was 1.2 min (95% CI 0.8-1.6). The median surgeon's safety, practical, and comfort scores on a 5-point Likert scale were high (5 (5-5), 5 (4-5), and 5 (4-5), respectively). Women's pain score was low (median 1 (0-3)), whereas the satisfaction rate was high (median 5 (5-5)), both on a 5-point Likert scale. There were two conversions (hysteroscopic scissors (n = 1), a new Resectr™ 5fr device (n = 1)). There was one incomplete procedure (tissue hardness). CONCLUSION: Hysteroscopic removal of small polyps, using the [Formula: see text] 5fr in an office setting is feasible in terms of installation and resection time. Surgeon's practical, comfort, and safety scores are high, whereas women report low pain scores and high satisfaction rates.  TRIAL REGISTRATION: Dutch Clinical Trial Registry (NTR 7119, NL6923): https://www.trialregister.nl/trial/6923 . Date of registration: 27/03/2018.

Manual morcellation (Resectr™ 9Fr) vs electromechanical morcellation (TruClear™) for hysteroscopic polypectomy: A randomized controlled non-inferiority trial.

INTRODUCTION: Meta-analyses comparing hysteroscopic electromechanical morcellation with electrosurgical resection showed a shorter operating time for electromechanical morcellation, mainly for polypectomy. The Resectr™ 9Fr is a new hysteroscopic manual morcellator, designed to simplify this procedure. We aimed to compare manual with electromechanical morcellation for hysteroscopic polypectomy. MATERIAL AND METHODS: This two-center randomized controlled non-inferiority trial was performed from 2018 to 2021 in the Catharina Hospital and the Ghent University Hospital. The study was registered at the Dutch Trial Register (NL6922; ICTRP ID: NTR7118). One hundred and forty women with polyps (between 8 and 20 mm) scheduled for hysteroscopic removal were randomized between manual (Resectr™ 9Fr) or electromechanical (TruClear™) morcellation. The primary outcome was time (instrumentation set-up, resection, and total procedure time). RESULTS: The non-inferiority margin for the primary outcome time was 1.3. Mean instrumentation set-up time was 10% shorter with the manual compared with the electromechanical morcellator (estimated mean ratio manual/electromechanical = 0.9; 97.5% confidence interval [CI] 0.8-1.1). Mean resection time was 30% longer with the manual compared with the motor-driven system (estimated mean ratio manual/electromechanical = 1.3; 97.5% CI 0.9-1.9). Mean total procedure time was 10% longer with the manual compared with the electromechanical morcellator (estimated mean ratio manual/electromechanical = 1.1; 95% CI 0.91-1.298). The estimated odds (electromechanical/manual) of better surgeon's safety, effective and comfort scores were, respectively, 4.5 (95% CI 0.9-22.1), 7.0 (95% CI 1.5-31.9), and 5.9 (95% CI 1.1-30.3) times higher with the motor-driven compared with the manual morcellator. Conversion rates and incomplete resection rates were comparable in both groups (manual vs electromechanical) (7.6% [4/66] vs 2.9% [2/68] and 6.1% [4/66] vs 3.0% [2/66], respectively). No intraoperative and postoperative complications were registered. CONCLUSIONS: The manual morcellator was non-inferior to the electromechanical morcellator for hysteroscopic polypectomy in terms of mean instrumentation set-up time and total procedure time. Results on resection time were inconclusive. Conversion and incomplete resection rates were within the range reported in the literature. Surgeon's reported rating for both devices was high, however, in favor of the motor-driven tissue removal system.

The ADENO study: ADenomyosis and its Effect on Neonatal and Obstetric outcomes: a retrospective population-based study.

BACKGROUND: Adenomyosis is a benign gynecologic condition arising from the uterine junctional zone. Recent studies suggest a relationship between adenomyosis and adverse obstetrical outcomes, but evidence remains conflicting. There is no large-scale study investigating obstetrical outcomes in women with adenomyosis using the gold standard of histopathologic diagnosis. OBJECTIVE: This study aimed to investigate the prevalence of adverse obstetrical and neonatal outcomes in women with histopathologic adenomyosis and that of the general (Dutch) population. STUDY DESIGN: This retrospective population-based study used 2 Dutch national databases (Perined, the perinatal registry, and the nationwide pathology databank [Pathologisch Anatomisch Landelijk Geautomiseerd Archief], from 1995 to 2018) to compare obstetrical outcomes in women before histopathologic adenomyosis diagnosis to the general Dutch population without registered histopathologic adenomyosis. The adjusted odds ratios (95% confidence interval) were calculated for adverse obstetrical outcomes. The outcomes were adjusted for maternal age, parity, ethnicity, year of registered birth, induction of labor, hypertensive disorders in previous pregnancies, multiple gestation, and low socioeconomic status. RESULTS: The pregnancy outcomes of 7925 women with histopathologic adenomyosis were compared with that of 4,615,803 women without registered adenomyosis. When adjusted for confounders, women with adenomyosis had adjusted odds ratios of 1.37 (95% confidence interval, 1.25-1.50) for hypertensive disorders, 1.37 (95% confidence interval, 1.25-1.51) for preeclampsia, 1.15 (95% confidence interval, 1.07-1.25) for small-for-gestational-age infants, 1.54 (95% confidence interval, 1.41-1.68) for emergency cesarean delivery, 1.24 (95% confidence interval, 1.12-1.37) for failure to progress, 1.29 (95% confidence interval, 1.10-1.48) for placental retention, and 1.23 (95% confidence interval, 1.10-1.38) for postpartum hemorrhage. No increased risk of HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, placental abruption, or operative vaginal delivery or need for oxytocin stimulation was found. CONCLUSION: Women with a histopathologic diagnosis of adenomyosis showed an increased prevalence of hypertensive disorders of pregnancy and small-for-gestational-age infants, failure to progress in labor, and placental retention compared with the general population in previous pregnancies. This suggests that uterine (contractile) function in labor and during pregnancy is impaired in women with adenomyosis.

Uterine contractile activity in healthy women throughout the menstrual cycle measured using a novel quantitative two-dimensional transvaginal ultrasound speckle tracking method.

RESEARCH QUESTION: To explore normal uterine contractile function across the menstrual cycle using a novel quantitative ultrasound method. DESIGN: This multicentre prospective observational study took place in three European centres from 2014 to 2022. Uterine contraction frequency (contractions/minute), amplitude, direction (cervix-to-fundus, C2F; fundus-to-cervix; F2C), velocity and coordination were investigated. Features were extracted from transvaginal ultrasound recordings (TVUS) using speckle tracking. Premenopausal women ≥18 years of age, with normal, natural menstrual cycles were included. A normal cycle was defined as: regular (duration 28 ± 2 days), no dysmenorrhoea, no menometrorrhagia. Four-minute TVUS were performed during the menstrual phase, mid-follicular, late follicular phase, early luteal phase and/or late luteal phase. Of the 96 recordings available from 64 women, 70 were suitable for inclusion in the analysis. RESULTS: Contraction frequency (for the posterior wall) and velocity (for the anterior uterine wall in the F2C direction) were highest in the late follicular phase and lowest in the menstrual and late luteal phases (1.61 versus 1.31 and 1.35 contractions/min, P < 0.001 and 0.81 versus 0.67 and 0.62 mm/s, P < 0.001, respectively). No significant difference was found for contraction amplitude. Contraction coordination (simultaneous contraction of the anterior and posterior walls in the same direction) was least coordinated in the mid-follicular phase (P = 0.002). CONCLUSIONS: This is the first study to objectively measure uterine contraction features in healthy women during the natural menstrual cycle on TVUS. Likewise, it introduces contraction coordination as a specific feature of uterine peristalsis. Differences in uterine contractility across the menstrual cycle are confirmed, with highest activity seen in the late follicular phase, and lowest in the late luteal phase.

Women with combined adenomyosis and endometriosis on MRI have worse IVF/ICSI outcomes compared to adenomyosis and endometriosis alone: A matched retrospective cohort study.

STUDY OBJECTIVES: To assess the effect of adenomyosis, endometriosis and combined adenomyosis and endometriosis, diagnosed on MRI, on IVF/ICSI outcomes versus male subfertility controls. STUDY DESIGN: This single-centre matched retrospective cohort study was carried out at Catharina Hospital in Eindhoven, The Netherlands. The study group consisted of infertile women undergoing their first, fresh embryo transfer during IVF/ICSI, with adenomyosis only (N = 36), endometriosis only (N = 61), and combined adenomyosis and endometriosis (N = 93) based on MRI. The control group consisted of IVF/ICSI patients undergoing treatment due to male subfertility (N = 889). 1:2 case-control matching based on age during IVF/ICSI, parity and number of embryos transferred was performed. Odds ratios were calculated for biochemical pregnancy, ongoing pregnancy and live birth rate versus matched male subfertility controls, and were corrected for embryo quality. RESULTS: Only the combined adenomyosis and endometriosis group showed a significantly reduced OR for biochemical pregnancy (p = 0.004, OR 0.453 (95% CI :(0.284-0.791)), ongoing pregnancy (p = 0.001, OR 0.302 (95% CI: (0.167-0.608)) and live birth (p = 0.001, OR 0.309 (95% CI: (0.168-0.644)) compared to matched male subfertility controls. CONCLUSIONS: The lower (ongoing) pregnancy and live birth rates in the combined adenomyosis and endometriosis women can be attributed to more severe disease in these women, ultimately resulting in increased chances for failed implantation and miscarriage. This highlights the importance of screening for adenomyosis in endometriosis patients, and identifies these women target for additional (hormonal) treatment prior to IVF/ICSI.

Prediction models in gynaecology: Transparent reporting needed for clinical application.

The clinical application of prediction models is increasing within the field of gynaecology and obstetrics. This is mostly due to the fact that clinicians and patients prefer individualized counselling and person specific, more objective outcome assessment. To prevent using inadequate models, it is important to construct and perform prediction model studies correctly. Therefore, the TRIPOD statement (the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) was developed. The aim of this review is to obtain an overview of the existing published prediction models for benign gynaecology and to investigate to what extent these studies meet the TRIPOD criteria. We performed a literature search in the databases PubMed, Embase and Cochrane Library from inception to August 2020. Searching the cross-references of the relevant studies within our search identified additional articles. Publications were included if the aim of the study was to develop a multivariable prediction model within the field of benign gynaecology. Two independent reviewers extracted the data. Analysis of the studies was performed by using a checklist derived from the TRIPOD criteria. Based on our search, 2487 studies were selected, including potential duplications. Eventually, a total of twenty-two studies were selected. 91% of these studies handled their predictors by univariable analysis before developing a multivariable prediction model. Fifteen studies described having missing data, but not all of them (9%) handled these missing data. Four different internal validation methods were used in twenty studies. Fifteen studies (68%) had prediction models with a C-index ≥ 0.7, which indicates a good model. Half of the studies (50%) did not measure the calibration, overall performance was described in two studies (9%). External validation was performed in 9% of the studies. The correct development of a prediction model within benign gynaecology and subsequent transparent reporting of the model development is important to facilitate clinical use. Without transparent reporting, wrong assumptions can be made leading to incorrect application of a specific prediction model. This overview shows that excepting carrying out an external validation, only one article met all the criteria. Therefore, we strongly recommend use of the TRIPOD criteria for developing and validating a prediction model (study). In addition, prior to publication, content experts should critically and statistically review the prediction model. If too many criteria are not met, refusing publication should be considered.

Four year evaluation of therapeutic hysteroscopy under procedural sedation in an outpatient clinic.

OBJECTIVE: Due to the evolution of hysteroscopic instruments, therapeutic hysteroscopic procedures are increasingly performed in an outpatient, office-based setting. The most important limiting factor of performing these hysteroscopic treatments is patient discomfort. Procedural Sedation Analgesia (PSA) decreases patient discomfort and anxiety. The main goal of this study is to determine safety, feasibility and patient satisfaction of therapeutic hysteroscopy performed under procedural sedation in an outpatient clinic. Our second objective was to compare 9 mm scopes with smaller diameter scopes. STUDY DESIGN: All consecutive patients suitable for procedural sedation and scheduled for a therapeutic hysteroscopy in the outpatient clinic were prospectively included from February 2014 to November 2018 in a teaching hospital in the Netherlands. A variety of therapeutic hysteroscopies procedures was performed including myomectomy, removal of retained products of conception and endometrial ablation. Therapeutic hysteroscopes with 3.8 mm, 5 mm and 9 mm diameter were used. In all selected women procedure time, admission time, pain scores, anaesthesiologic and procedural complications were assessed. All women received a questionnaire on patient satisfaction. RESULTS: In total 455 patients underwent a therapeutic hysteroscopy. Median procedure time was 11 min (2-63 min) and median admission time was 130 min (30-480 min). Median pain score according to the visual analog scale (VAS) before, during and after procedure were respectively 0 (0-10), 0 (0-4) and 0 (0-9). Anaesthesiologic complication rate was 4.4 %, all minor. Procedural complications consisted of infection postoperatively (0.4 %), excessive blood loss during procedure (0.6 %) and perforation (0.4 %). Procedure was incomplete in 3.3 % of all procedures. Patient satisfaction was high, as 96 % of the women were satisfied. No differences were found in pain scores, VAS 0 versus 1 after the procedure, between 3.8 or 5 mm and 9 mm scopes. CONCLUSION: It is safe and feasible to perform a therapeutic hysteroscopy under procedural sedation in an outpatient setting, with low pain scores and a high degree of patient satisfaction, also when large diameter instruments are used.

Objective measures of adenomyosis on MRI and their diagnostic accuracy-a systematic review & meta-analysis.

INTRODUCTION: Magnetic resonance imaging (MRI) diagnosis of adenomyosis is considered the most accurate non-invasive technique, but remains subjective, with no consensus on which diagnostic parameters are most accurate. We aimed to systematically review the literature on how adenomyosis can be objectively quantified on MRI in a scoping manner, to review the diagnostic performance of these characteristics compared with histopathological diagnosis, and to summarize correlations between measures of adenomyosis on MRI and clinical outcomes. MATERIAL AND METHODS: We searched databases Pubmed, Embase, and Cochrane for relevant literature up to April 2020 according to PRISMA guidelines. We included studies that objectively assessed adenomyosis on MRI, and separately assessed studies investigating the diagnostic performance of MRI vs histopathology for inclusion in a meta-analysis. The QUADAS-2 tool was used for risk of bias, with many studies showing an unclear or high risk of bias. RESULTS: Eighty studies were included, of which 14 assessed the diagnostic performance of individual MRI parameters, with four included in the meta-analysis of diagnostic accuracy. Common MRI parameters were: junctional zone (JZ) characteristics, such as maximum JZ thickness-pooled sensitivity 71.6% (95% CI 46.0%-88.2%), specificity 85.5% (52.3%-97.0%); JZ differential-pooled sensitivity 58.9% (95% CI 44.3%-72.1%), specificity 83.2% (95% CI 71.3%-90.8%); and JZ to myometrial ratio-pooled sensitivity 63.3% (95% CI 51.9%-73.4%), specificity 79.4% (95% CI 42.0%-95.4%); adenomyosis lesion size, uterine morphology (pooled sensitivity 42.9% (95% CI 15.9%-74.9%), specificity 87.7%, (95% CI 37.9-98.8) and changes in signal intensity-eg, presence of myometrium cysts; pooled 59.6% (95% CI 41.6%-75.4%) and specificity of 96.1% (95% CI 80.7%-99.3%). Other MRI parameters have been used for adenomyosis diagnosis, but their diagnostic performance is unknown. Few studies attempted to correlate adenomyosis MRI phenotype to clinical outcomes. CONCLUSIONS: A wide range of objective parameters for adenomyosis exist on MRI; however, in many cases their individual diagnostic performance remains uncertain. JZ characteristics remain the most widely used and investigated with acceptable diagnostic accuracy. Specific research is needed into how these objective measures of adenomyosis can be correlated to clinical outcomes.

Hysteroscopic morcellation versus bipolar resection for removal of type 0 and 1 submucous myomas: A randomized trial.

OBJECTIVES: To compare hysteroscopic morcellation with bipolar resection for the removal of submucous type 0 and 1 myomas, in terms of procedure time (primary outcome), adverse events, tissue availability, short term effectiveness and postoperative adhesion formation (secondary outcomes). STUDY DESIGN: The study was performed from May 2011 to May 2018 in the Catharina hospital (Eindhoven, the Netherlands) and the Ghent University hospital (Ghent, Belgium). Women with type 0 and 1 submucous myomas up to 3 cm were randomized to hysteroscopic morcellation with the TruClearTM 8.0 Tissue Removal System or to bipolar resection with a rigid 8.5-mm resectoscope. Skewed time variables were log-transformed and analyzed with the Student t-test. Multiple linear regression analysis was performed to assess the effect of myoma diameter on operating time. RESULTS: Forty-five and 38 women were included in the hysteroscopic morcellation and resection group, respectively. The median operating time was significantly shorter for hysteroscopic morcellation compared with resection (9.2 min [interquartile range 5.6-14.4] versus 13.4 min [interquartile range 8.6-17.5], P = .04). In the morcellation group, operating time, corrected for the myoma diameter, was reduced by 26 % (95 % CI 5-43%; P = .02). The median setup time was significantly longer in the morcellation group (5.2 min [interquartile range 4.2-6.9] versus 3.8 min [interquartile range 3.3-5.3], P = .006). The median total procedure time was not significantly different between the two techniques (14.4 min [interquartile range 11.4-19.2] versus 17.3 [interquartile range 12.7-23.8], P = .18). Two procedures of the morcellation group were converted to bipolar resection because of the myoma hardness. Complete resection was found in 89 % of the morcellation group and 95 % of the resection group. Adverse events occurred in 3 patients of the morcellation group, namely a fluid deficit > 2500 mL with the need of potassium suppletion, an asystolic vasovagal response after conversion to resection and postoperative fever requiring antibiotics. Tissue was available for pathology analysis in all cases. Routine second-look hysteroscopy performed in one center showed no intrauterine adhesions. CONCLUSION: Overall, there is no difference in total procedure time between hysteroscopic morcellation using the TruClearTM system compared to bipolar resection for the removal of smaller type 0 and 1 submucous myomas. Although hysteroscopic morcellation is faster, its setup time is longer. Calcified myomas can be challenging and fluid deficit remains a limiting factor.

Assessment of uterine activity during IVF by quantitative ultrasound imaging: a pilot study.

RESEARCH QUESTION: Does uterine activity differ in patients who have undergone successful IVF treatment compared with patients who have undergone unsuccessful IVF treatment? DESIGN: Prospective study of 16 women who underwent fresh single embryo transfer. All patients underwent transvaginal ultrasound in three phases of the IVF treatment: ovarian stimulation 1 h before embryo transfer (ET1) and 5-7 days after embryo transfer (ET5-7). Uterine motion analysis was implemented by a dedicated speckle tracking algorithm; frequency- and amplitude-related features were extracted from the derived signals to characterize the uterine activity in relation to ongoing implantation (positive HCG after 6 weeks) and ongoing pregnancy at 11 weeks. RESULTS: Uterine activity in terms of frequency (ovarian stimulation ET1, P = 0.04; ovarian stimulation ET5-7, P = 0.002) and amplitude (ovarian stimulation ET1, P = 0.0003; ovarian stimulation ET5-7, P = 0.000008) is significantly higher in the ovarian stimulation phase compared with ET1 and ET5-7. Women with ongoing pregnancies showed significantly higher uterine contraction frequency compared with those with no ongoing pregnancies in all phases (ovarian stimulation, P = 0.006; ET1, P = 0.015; ET5-7, P = 0.007). Uterine contraction amplitude was significantly lower (P = 0.037) in women at ET5-7 in women with ongoing pregnancies. CONCLUSIONS: This study is a first step towards assessing uterine activity during IVF objectively and non-invasively. It is an essential step to understanding the previously suggested effect of contractions on IVF failure. Uterine activity after embryo transfer characterized by high frequency and low amplitude may favour embryo implantation. Research with larger patient cohorts is needed to build on current evidence and knowledge of uterine contractions during IVF.

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.

Propagation of spontaneous electrical activity in the ex vivo human uterus.

Contractions of the non-pregnant uterus play a key role in fertility. Yet, the electrophysiology underlying these contractions is poorly understood. In this paper, we investigate the presence of uterine electrical activity and characterize its propagation in unstimulated ex vivo human uteri. Multichannel electrohysterographic measurements were performed in five freshly resected human uteri starting immediately after hysterectomy. Using an electrode grid externally and an electrode array internally, measurements were performed up to 24 h after hysterectomy and compared with control. Up to 2 h after hysterectomy, we measured biopotentials in all included uteri. The median root mean squared (RMS) values of the external measurements ranged between 3.95 µV (interquartile range (IQR) 2.41-14.18 µV) and 39.4 µV (interquartile range (IQR) 10.84-105.64 µV) and were all significantly higher than control (median RMS of 1.69 µV, IQR 1.13-3.11 µV), consisting of chicken breast meat. The RMS values decreased significantly over time. After 24 h, the median RMS (1.27 µV, IQR 0.86-3.04 µV) was comparable with the control (1.69 µV, IQR 1.13-3.11 µV, p = 0.125). The internal measurements showed a comparable pattern over time, but overall lower amplitude. The measured biopotentials propagated over the uterine surface, following both a plane-wave as well as an erratic pattern. No clear pacemaker location nor a preferred propagation direction could be identified. These results show that ex vivo uteri can spontaneously generate propagating biopotentials and provide novel insight contributing to improving our understanding of the electrophysiology of the human non-pregnant uterus.

Incidence of endometrioid and clear-cell ovarian cancer in histological proven endometriosis: the ENOCA population-based cohort study.

BACKGROUND: Several studies have suggested that endometriosis is associated with an increased risk of ovarian cancer, especially for the clear-cell and endometrioid subtypes. However, previous studies lack sufficient power or diagnostic certainty. OBJECTIVE: The objective of the study was to assess the association between histologically proven endometriosis and ovarian cancer in a large population-based cohort study. STUDY DESIGN: We identified 131,450 women with a histological diagnosis of endometriosis between 1990 and 2015 from the Dutch nationwide registry of histopathology and cytopathology (PALGA). For the control cohort 132,654 women with a benign dermal nevus were matched on age and inclusion year with the endometriosis cases. Histological diagnoses of ovarian, fallopian tubes, and peritoneal cancers between January 1990 and July 2017 were retrieved. Incidence rate ratios were estimated for ovarian cancer and its subtypes for the whole follow-up period as well as for women with more than 1 person-year at risk. RESULTS: We found a crude incidence rate ratio of 4.79 (95% confidence interval, 4.33-5.31) and an age-adjusted incidence rate ratio of 7.18 (95% confidence interval, 6.17-8.36) for ovarian cancer overall. Endometrioid and clear-cell ovarian cancer had the highest age-adjusted incidence rate ratio of 29.06 (95% confidence interval, 20.66-40.87) and 21.34 (95% confidence interval, 14.01-32.51), respectively. Median age at ovarian cancer diagnosis was 56 years (interquartile range, 49-63) for the endometriosis cohort and 60 years (interquartile range, 53-67) for the nevus cohort, (P < .05). After excluding women with less than 1 person-year at risk following an endometriosis diagnosis, we found a crude incidence rate ratio of 1.04 (95% confidence interval, 0.91-1.19) and an age-adjusted incidence rate ratio of 1.08 (95% confidence interval, 0.87-1.35) for ovarian cancer overall. However, statistically significant age-adjusted incidence rate ratios of 2.29 (95% confidence interval, 1.24-4.20) for clear-cell ovarian cancer and 2.56 (95% confidence interval, 1.47-4.47) for endometrioid ovarian cancer were found. CONCLUSION: A significantly higher incidence of clear-cell and endometrioid ovarian cancer was found in women with histologically proven endometriosis. Additionally, we found an increased incidence of all ovarian cancer subtypes in histologically proven endometriosis; however, in many of these women, endometriosis and ovarian cancer were diagnosed synchronously after the average menopausal age, which may suggest that the risk of ovarian cancer in endometriosis patients remains, even when clinical endometriosis symptoms are no longer present.

Impaired implantation in endometriosis compared with couples with male subfertility after transfer of equal quality embryos: a matched cohort study.

RESEARCH QUESTION: Is implantation impaired in patients with endometriosis undergoing IVF and intracytoplasmatic sperm injection (ICSI) cycles? DESIGN: A retrospective matched cohort study was carried out on IVF/ICSI cycles with fresh single embryo transfer at the Department of Assisted Reproductive Medicine, Ghent University Hospital, Belgium, between July 2015 and August 2017 (n = 1053). A total of 118 endometriosis cases were matched 1:1 to 118 couples diagnosed with male subfertility and stratified by embryo quality (identical ALPHA grading categories), female age (±1 year) and parity (±1 delivery). Transvaginal ultrasound, magnetic resonance imaging or laparoscopy was used to diagnosed endometriosis, and the revised American Society for Reproductive Medicine score was used to classify the endometriosis into grade I/II versus grade III/IV. Male subfertility was defined in accordance with World Health Organization criteria (fifth edition). RESULTS: Compared with endometriosis cases, control couples with male subfertility had significantly higher rates of positive HCG test on day 16 (P = 0.047, OR 2.077, CI 1.009 to 4.276), ongoing implantation (defined as a positive fetal heart rate on transvaginal ultrasound at a gestational age of at least 6.5-7 weeks) (P = 0.038, OR 2.265, CI 1.048 to 4.893), ongoing pregnancy (defined by a vital pregnancy at 11 weeks) (P = 0.046, OR 2.292, CI 1.016 to 5.173) and live birth (P = 0.043, OR 2.502, CI 1.029 to 6.087). CONCLUSIONS: After matching for embryo quality, woman's age and parity, rates of positive HCG tests, ongoing implantation, ongoing pregnancy and live birth were more than twice as high in the control group compared with the endometriosis group.

Reproductive and Obstetric Outcomes After Hysteroscopic Removal of Retained Products of Conception.

STUDY OBJECTIVE: To evaluate the reproductive outcomes in women treated for retained products of conception (RPOC) by hysteroscopy (morcellation vs loop resection). DESIGN: Cohort study. SETTING: A teaching and university hospital. PATIENTS: Patients included in a previous randomized controlled trial on hysteroscopic removal of RPOC comparing morcellation (n = 46) with loop resection (n = 40). INTERVENTIONS: Hysteroscopic morcellation versus loop resection. MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were live birth and pregnancy complications (including abnormal placentation [placenta accreta/increta/percreta], placenta previa, vasa previa, retained placenta after delivery or incomplete expulsion with the need for manual removal or curettage, and RPOC), uterine rupture, and other complications (blood loss, preterm labor, preterm premature rupture of membranes, hypertensive disorders of pregnancy, and intrauterine growth restriction). The live birth rate was 88.9% in the morcellation group and 68.2% in the loop resection group (p = .09). Uterine rupture occurred in 1 patient in the morcellation group (4.2%) (p = 1.00). Placental complications were found in 20.8% and 22.2% of the hysteroscopic morcellation and loop resection groups, respectively (p = .33), and other pregnancy complications were seen in 33.3% and 16.6% of the 2 groups (p = .33). The secondary outcome was time to pregnancy. The median time to pregnancy was 14 weeks (interquartile range [IQR], 5-33 weeks) in the morcellation group and 15 weeks (IQR, 6-37 weeks) in the loop resection group (p = .96). CONCLUSION: Hysteroscopic removal of RPOC seems to have no detrimental effect on reproductive outcome and no significant effect on pregnancy rate.