Procedural sedation and analgesia versus general anesthesia for hysteroscopic myomectomy (PROSECCO trial): A multicenter randomized controlled trial.

BACKGROUND: Hysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia. However, studies evaluating safety and effectiveness of hysteroscopic myomectomy under procedural sedation are lacking. This study aims to investigate whether hysteroscopic myomectomy under procedural sedation and analgesia with propofol is noninferior to hysteroscopic myomectomy under general anesthesia. METHODS AND FINDINGS: This was a multicenter, randomized controlled noninferiority trial conducted in 14 university and teaching hospitals in the Netherlands between 2016 and 2021. Inclusion criteria were age ≥18 years, maximum number of 3 type 0 or 1 fibroids, maximum fibroid diameter 3.5 cm, American Society of Anesthesiologists class 1 or 2, and having sufficient knowledge of the Dutch or English language. Women with clotting disorders or with severe anemia (Hb < 5.0 mmol/L) were excluded. Women were randomized using block randomization with variable block sizes of 2, 4, and 6, between hysteroscopic myomectomy under procedural sedation and analgesia (PSA) with propofol or under general anesthesia (GA). Primary outcome was the percentage of complete resections, assessed on transvaginal ultrasonography 6 weeks postoperatively by a sonographer blinded for the treatment arm and surgical outcome. Secondary outcomes were the surgeon's judgment of completeness of procedure, menstrual blood loss, uterine fibroid related and general quality of life, pain, recovery, hospitalization, complications, and surgical reinterventions. Follow-up period was 1 year. The risk difference between both treatment arms was estimated, and a Farrington-Manning test was used to determine the p-value for noninferiority (noninferiority margin 7.5% of incomplete resections). Data were analyzed according to the intention-to-treat principle, including a per-protocol analysis for the primary outcome. A total of 209 women participated in the study and underwent hysteroscopic myomectomy with PSA (n = 106) or GA (n = 103). Mean age was 45.1 [SD 6.4] years in the PSA group versus 45.0 [7.7] years in the GA group. For 98/106 women in the PSA group and 89/103 women in the GA group, data were available for analysis of the primary outcome. Hysteroscopic resection was complete in 86/98 women (87.8%) in the PSA group and 79/89 women (88.8%) in the GA group (risk difference -1.01%; 95% confidence interval (CI) -10.36 to 8.34; noninferiority, P = 0.09). No serious anesthesiologic complications occurred, and conversion from PSA to GA was not required. During the follow-up period, 15 serious adverse events occurred (overnight admissions). All were unrelated to the intervention studied. Main limitations were the choice of primary outcome and the fact that our study proved to be underpowered. CONCLUSIONS: Noninferiority of PSA for completeness of resection was not shown, though there were no significant differences in clinical outcomes and quality of life. In this study, hysteroscopic myomectomy for type 0 and 1 fibroids with PSA compared to GA was safe and led to shorter hospitalization. These results can be used for counseling patients by gynecologists and anesthesiologists. Based on these findings, we suggest that hysteroscopic myomectomies can be performed under PSA in an outpatient setting. TRIAL REGISTRATION: The study was registered prospectively in the Dutch Trial Register (NTR 5357; registration date: 11 August 2015; Date of initial participant enrollment: 18 February 2016).

Incidence of ovarian cancer after bilateral salpingo-oophorectomy in women with histologically proven endometriosis.

OBJECTIVE: To assess the incidence of ovarian cancer in women with histologically proven endometriosis after bilateral salpingo-oophorectomy (BSO). DESIGN: Retrospective nationwide cohort study. SETTING: Dutch pathology database. PATIENT(S): Women with histologically proven endometriosis who had undergone BSO between 1990 and 2015 (n = 7,984). This study consists of 2 control cohorts: women with histologically proven endometriosis without BSO (n = 42,633) and women with a benign dermal nevus (n = 132,535). INTERVENTION(S): Observational study. MAIN OUTCOME MEASURE(S): Number of histologic diagnoses of (extra-)ovarian cancers. Incidence rate ratios (IRR) were estimated for (extra-)ovarian cancer. The number needed to treat was calculated. RESULT(S): We identified 9 (0.1%) (extra-)ovarian cancers in the BSO cohort and 170 (0.4%) and 444 (0.3%) ovarian cancers in the endometriosis and nevus control cohorts, respectively. We found an age-adjusted IRR of 0.34 (95% confidence interval [CI], 0.15-0.76) when the BSO cohort was compared with the endometriosis cohort. Comparing the BSO cohort with the nevus control cohort resulted in an age-adjusted IRR of 0.38 (95% CI, 0.17-0.85). The number needed to treat when the BSO cohort was compared with the endometriosis control cohort was 351 (95% CI, 272-591). CONCLUSION(S): In this nationwide study, we found that the (extra-)ovarian cancer incidence in women with histologically proven endometriosis decreased to less than the background population risk after BSO. Additionally, we found a significant reduction of the incidence of ovarian cancer when compared with women with histologically proven endometriosis without BSO. Endometriosis surgery could in the future be a preventive strategy in women with endometriosis and a high-risk profile for ovarian cancer.

Endometrial cancer prognosis in women with endometriosis and adenomyosis: A retrospective nationwide cohort study of 40 840 women.

We aim to compare endometrial cancer survival in women with or without histological proven endometriosis or adenomyosis. We identified all women with endometrial cancer between 1990 and 2015 from the Netherlands Cancer Registry (NCR). Data were linked to the Dutch pathology database (PALGA) to select all women with histological proven endometriosis/adenomyosis. Overall survival was compared between women with endometrial cancer with or without endometriosis/adenomyosis. We used multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs). We included 1701 women with endometrial cancer and endometriosis/adenomyosis, of whom 1236 (72.7%) women had adenomyosis, 320 (18.8%) had endometriosis and 145 (8.5%) had both. We compared these women to 39 139 women with endometrial cancer without endometriosis/adenomyosis. Women in the combined endometriosis/adenomyosis cohort were younger at endometrial cancer diagnosis, had earlier disease stage, more often had endometrioid endometrial cancer and low grade tumors. The 5-year survival rate in the combined endometriosis/adenomyosis cohort was 84.8% (95% CI 84.6-88.1) and 71.6% (95% CI 71.1-72.0) in the nonendometriosis/adenomyosis cohort. Univariable analysis resulted in a crude HR of 0.63 (95% CI 0.59-0.69). Significant confounding factors were age, stage, cancer subtype, histological grading, surgery and chemotherapy rate. Correction for these confounders resulted in a HR of 0.98 (95% CI 0.90-1.06). Including endometriosis/adenomyosis status as a categorical factor resulted in similar HRs. In conclusion, women with endometrial cancer and histologically proven endometriosis/adenomyosis have a better overall survival when compared to women with endometrial cancer without endometriosis/adenomyosis. This better survival was correlated to stage, grade, age and histological subtype, but not to the presence of endometriosis/adenomyosis.

Endometrial Cancer Incidence in Endometriosis and Adenomyosis.

Women with histologically proven endometriosis/adenomyosis have an increased risk of ovarian cancer. Small studies show conflicting results on the endometrial cancer risk in women with endometriosis/adenomyosis. Therefore, we assessed the incidence of endometrial cancer in women with histologically proven endometriosis or adenomyosis. We performed a population-based retrospective cohort study of 129,862 women with histologically proven endometriosis/adenomyosis, matched with 132,700 women with a nevus selected from the Dutch pathology registry between 1990 and 2015. Histology results for endometrial cancer were retrieved. Crude and age-adjusted odds ratios for endometrial cancer were estimated. In the endometriosis/adenomyosis group, 1827 (1.4%) women had a histological report on endometrial cancer, and in the nevus group, 771 (0.6%) women. The age-adjusted OR for endometrial cancer was 2.58 (95%CI 2.37-2.81). After excluding the first year of follow-up, the age-adjusted OR was 0.76 (95%CI 0.63-0.92), indicating that endometrial cancer is most often found at time of histological diagnosis of endometriosis/adenomyosis. In around 20% of the endometrial cancer cases, the endometrial cancer was not recognized until after hysterectomy. Of these women, 35% had no prior (micro)curettage or biopsy. This study shows an increased incidence of endometrial cancer in women with histologically proven endometriosis and adenomyosis.

Increased incidence of ovarian cancer in both endometriosis and adenomyosis.

OBJECTIVE: Assessing the association between endometriosis and/or adenomyosis and ovarian cancer. METHODS: We identified all women with histological proven endometriosis (51,544 women) and/or adenomyosis (85,015 women) from the Dutch pathology database (1990-2015) and matched with women with a benign dermal nevus (132,654 women). Histology results for ovarian cancer were retrieved. We estimated crude and age-adjusted incidence rate ratios (IRR) for ovarian cancer. RESULTS: We found 1017 (2.0%), 1284 (1.5%) and 471 (0.4%) ovarian cancer cases in the endometriosis, adenomyosis and nevus cohort, respectively. The age-adjusted IRRs were 19.75 (95% CI 16.70-23.35) in the endometriosis cohort and 5.93 (95% CI 4.91-7.16) in the adenomyosis cohort. The highest IRRs were found for endometrioid and clear cell ovarian cancer subtypes. Excluding the first year of follow-up did not result in a significant IRR for ovarian cancer overall but resulted in a statistically significant age-adjusted IRR of 3.92 (95% CI 2.19-7.01) for clear cell ovarian cancer and 2.39 (95% CI 1.28-4.45) for endometrioid ovarian cancer in the endometriosis cohort. Additionally, we found a statistically significant age-adjusted IRR of 2.51 (95% CI 1.29-4.90) for endometrioid ovarian cancer in the adenomyosis cohort. CONCLUSION: We found an increased ovarian cancer incidence in both histological proven endometriosis and adenomyosis. This increased incidence was largest for endometriosis. Excluding the first year of follow-up resulted in an increased incidence for endometrioid ovarian cancer in both cohorts and clear cell ovarian cancer in the endometriosis cohort. This study shows that gynecologist should also be aware of an increased ovarian cancer incidence in women with adenomyosis.

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.

Ovarian cancer prognosis in women with endometriosis: a retrospective nationwide cohort study of 32,419 women.

BACKGROUND: Contradicting results regarding ovarian cancer prognosis in women with endometriosis have been reported in the literature. Owing to the small sample size of previous studies, larger studies are required to elucidate the role of endometriosis in ovarian cancer prognosis. OBJECTIVE: This study aimed to evaluate the survival rate in women with ovarian cancer with or without histologically proven endometriosis in a Dutch population-based cohort. STUDY DESIGN: All women with ovarian cancer diagnosed between 1990 and 2015 were identified from the Netherlands Cancer Registry. We linked these women with the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief) to identify all women with histologically proven endometriosis. We compared the prognosis of patients with ovarian cancer with and without histologically proven endometriosis. Primary outcome was the overall survival with subgroup analyses stratified by histologic ovarian cancer subtype and stage. Multivariable Cox proportional hazard analysis was used to estimate hazard ratios with 95% confidence intervals. RESULTS: We included 32,419 patients with ovarian cancer, of whom 1979 (6.1%) had histologically proven endometriosis. The median age of histologic endometriosis diagnosis was 53 years (interquartile range, 46-62). Of all women with ovarian cancer and endometriosis, 81.2% received a diagnosis of synchronous endometriosis and ovarian cancer. The endometriosis cohort was younger at ovarian cancer diagnosis, had more favorable tumor characteristics, and more often had surgical treatment for ovarian cancer than the women without endometriosis. These variables were included in the multivariable model as confounders. Women with histologically proven endometriosis had a significantly better prognosis in both crude and adjusted analyses (hazard ratio, 0.46; 95% confidence interval, 0.43-0.49; P<.0005, and adjusted hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; P<.05, respectively). CONCLUSION: Women with ovarian cancer and histologically proven endometriosis had longer overall survival than women with ovarian cancer without endometriosis, even after adjustment for confounders. Future studies on ovarian cancer treatment and prognosis should consider stratifying by endometriosis status to elucidate its role. Furthermore, women diagnosed as having ovarian cancer and concurrent endometriosis should be explained the role of endometriosis in ovarian cancer survival.

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.

The (cost) effectiveness of procedural sedation and analgesia versus general anaesthesia for hysteroscopic myomectomy, a multicentre randomised controlled trial: PROSECCO trial, a study protocol.

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.

Laparoscopic Sterilization Under Local Anesthesia with Conscious Sedation Versus General Anesthesia: Systematic Review of the Literature.

Female sterilization is the most popular and common contraceptive method worldwide. Because hysteroscopic sterilization techniques are used less often due to side effects, the number of laparoscopic sterilization is increasing. A systematic overview concerning the most optimal anesthetic technique for laparoscopic sterilization is lacking. We performed a systematic review to compare conscious sedation with general anesthesia for laparoscopic sterilization procedures with respect to clinical relevant outcome measures, such as operating times, perioperative parameters and complications, patient comfort, recovery, and patient satisfaction. We searched Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE for randomized controlled trials comparing general anesthesia with conscious sedation for laparoscopic sterilization. Two authors (AGH and HAAMvV) abstracted and entered data into RevMan. Methodologic quality of the included trials was critically appraised. For our main outcome measures mean differences (continuous variables) and risk ratios (dichotomous variables) with 95% confidence intervals using random-effect models were calculated. Four randomized controlled trials were included comparing general anesthesia versus local anesthesia with conscious sedation for laparoscopic sterilization. The methodologic quality of the studies was moderate to good. Both techniques were comparable with regard to operating times, complications, and postoperative pain. However, local anesthesia with conscious sedation showed better results compared with general anesthesia with respect to recovery times, patient complaints of sore throat, and patient recovery and satisfaction. In conclusion, this systematic review about anesthetic techniques for laparoscopic sterilization showed that both general anesthesia and conscious sedation have no major anesthetic complications and may therefore be safe. Patients might benefit from conscious sedation in terms of recovery times, sore throat, and patient recovery and satisfaction, but only a few studies are included in the review and are relatively old. New research regarding this subject is needed to advise our patients most optimally in the future about the best anesthetic technique to be used when choosing for a laparoscopic sterilization procedure.

Prevalence of intrauterine adhesions after the application of hyaluronic acid gel after dilatation and curettage in women with at least one previous curettage: short-term outcomes of a multicenter, prospective randomized controlled trial.

OBJECTIVE: To examine whether intrauterine application of auto-crosslinked hyaluronic acid (ACP) gel, after dilatation and curettage (D&C), reduces the incidence of intrauterine adhesions (IUAs). DESIGN: Multicenter; women and assessors blinded prospective randomized trial. SETTING: University and university-affiliated teaching hospitals. PATIENT(S): A total of 152 women with a miscarriage of <14 weeks with at least one previous D&C for miscarriage or termination of pregnancy. INTERVENTION(S): Women were randomly assigned to either D&C plus ACP gel (intervention group) or D&C alone (control group). A follow-up diagnostic hysteroscopy was scheduled 8-12 weeks after the D&C procedure. MAIN OUTCOME MEASURE(S): The primary outcome was the number of women with IUAs and the secondary outcome was the severity of IUAs. RESULT(S): Outcomes were available for 149 women: 77 in the intervention group and 72 in the control group. The IUAs were observed in 10 (13.0%) and 22 women (30.6%), respectively (relative risk, 0.43; 95% confidence interval 0.22-0.83). Mean adhesion score and the amount of moderate-to-severe IUAs were significantly lower in the intervention group according to the American Fertility Society (AFS) and European Society of Gynecological Endoscopy classifications systems of adhesions. CONCLUSION(S): Intrauterine application of ACP gel after D&C for miscarriage in women with at least one previous D&C seems to reduce the incidence and severity of IUAs but does not eliminate the process of adhesion formation completely. Future studies are needed to confirm our findings and to evaluate the effect of ACP gel on fertility and reproductive outcomes. CLINICAL TRIAL REGISTRATION NUMBER: NTR 3120.

Hysteroscopic Tissue Removal Systems: A Randomized In Vitro Comparison.

STUDY OBJECTIVE: To compare polyp resection time and myoma resection rate using 2 hysteroscopic tissue removal systems. DESIGN: Prospective randomized in vitro trial (Canadian Task Force classification I). SETTING: Clinical skills laboratory of a non-university teaching hospital. SAMPLES: Polyp surrogate and myoma tissue. INTERVENTIONS: Hysteroscopic tissue removal with the TRUCLEAR system, using the TRUCLEAR INCISOR 2.9 (TI), TRUCLEAR INCISOR Plus (TIP), or TRUCLEAR ULTRA Plus (TUP) device, and the MyoSure system, using the MyoSure Lite (ML), MyoSure Classic (MC), or MyoSure XL (MXL) device. MEASUREMENTS AND MAIN RESULTS: Forty-two fragments of umbilical cord weighing 5 g, as a surrogate for polyps, were randomly allocated to 4 types of devices (TI, TIP, ML, and MC). Three consecutive fragments were removed using a single device. In addition, 18 pieces of myoma tissue were divided into 2 equal parts and randomly allocated to 2 types of devices (TUP and MXL). A new device was used for each fragment. Each type of device was tested at 2 vacuum settings. When removing 1 polyp, the TIP (median time, 2:33 minutes [interquartile range (IQR), 1:32-3:27 minutes]), the MC (median time, 3:15 minutes [IQR, 2:42-3:42 minutes]), and the ML (median time, 3:00 minutes [IQR, 2:16-3:25 minutes]) performed significantly faster than the TI (median time, 14:09 minutes [IQR, 13:44-14:36 minutes]), by 84%, 78%, and 82% respectively (p < .001). The TIP performed 80% faster than the TI (median time, 2:27 minutes [IQR, 1:45-2:46 minutes] vs 10:37 minutes [IQR, 8:38-13:44 minutes]; p < .001) when removing a second polyp. For removal of a third polyp, the TIP performed significantly faster (median time, 2:22 minutes [IQR, 1:32-3:07 minutes]) than the TI (median time, 8:35 minutes [IQR, 7:37-9:03 minutes]) and the ML (median time, 10:02 minutes [IQR, 9:51-10:18 minutes]), by 74% and 78%, respectively (p < .001). The performance of the ML decreased (p < .001) during removal of 3 consecutive tissue samples. For myoma tissue, the estimated mean resection rate of the TUP (2.96 g/min [95% confidence interval (CI), 2.32-3.77 g/min]) was 24% (95% CI 0.2%-52.4%) higher than the mean resection rate of the MXL (2.39 g/min [95% CI 1.87-3.05 g/min]; p = .048). The resection rate of the MXL adjusted for vacuum setting declined by 3% per unit increase in myoma volume (95% CI, -0.6% to -5.7%; p = .02). For the TUP, no linear association was found (0.4%; 95% CI, -2.1% to 3.0%; p = .72). CONCLUSION: In vitro comparison of the removal of surrogate polyps showed that although the larger TIP, MC, and ML devices were significantly faster than the TI for removal of 1 polyp, only the TIP was consistently faster than the TI for consecutive removal of polyps. The performance of the ML decreased significantly during removal of 3 consecutive tissue samples, making it slower than the TIP with a similar window size in the third run. For removal of myoma tissue, the resection rate of the TUP was significantly higher than that of the MXL, and the resection rate of the MXL decreased with increasing myoma volume. In vitro testing can provide useful information on the time and rate of hysteroscopic tissue removal.

Hysteroscopic Morcellation Versus Loop Resection for Removal of Placental Remnants: A Randomized Trial.

STUDY OBJECTIVE: To compare hysteroscopic morcellation with loop resection for the removal of placental remnants in terms of procedure time, adverse events, tissue availability, histology results, short-term effectiveness, and postoperative adhesions. DESIGN: A randomized controlled trial (Canadian Task Force classification I). SETTING: A teaching and university hospital. PATIENTS: Women with placental remnants. INTERVENTIONS: Hysteroscopic morcellation with the TRUCLEAR 8.0 Tissue Removal System (Smith & Nephew, Inc, Andover, MA) or loop resection with a rigid 8.5-mm bipolar resectoscope (Karl Storz GmbH, Tuttlingen, Germany). MEASUREMENTS AND MAIN RESULTS: Forty-six and 40 women were included in the hysteroscopic morcellation and resection groups, respectively. The median operating time was significantly shorter for hysteroscopic morcellation compared with loop resection (6.2 minutes [interquartile range, 4.0-11.2 minutes] vs 10.0 minutes [5.8-16.4 minutes], p = .023). Both operating time and total procedure time, corrected for the diameter of the placental remnants, were significantly reduced for hysteroscopic morcellation compared with loop resection, by 40% (95% confidence interval, 15%-58%; p = .005) and 22% (95% CI, 5%-37%; p = .014), respectively. No adverse events occurred during hysteroscopic removal. Perforation at dilation in 8 cases of the hysteroscopic morcellation group resulted in 2 procedure discontinuations and 1 incomplete procedure. Incomplete removal was found in 1 uncomplicated hysteroscopic morcellation procedure and 2 resection procedures. Pathology results confirmed the presence of placental remnants in 27 of 40 (67.5%) and 26 of 37 (70%) patients in the hysteroscopic morcellation and resection groups, respectively. Second-look hysteroscopy showed de novo intrauterine adhesions in 1 of 35 patients (3%) in the hysteroscopic morcellation group and 1 of 30 (3%) patients in the resection group. CONCLUSION: Hysteroscopic morcellation is a faster alternative than loop resection. Both techniques are safe and show high rates of complete removal and tissue availability and low rates of de novo intrauterine adhesions.

Removal of Endometrial Polyps: Hysteroscopic Morcellation versus Bipolar Resectoscopy, A Randomized Trial.

STUDY OBJECTIVES: To compare hysteroscopic morcellation with bipolar resectoscopy for removal of endometrial polyps, in terms of procedure time, peri- and postoperative adverse events, tissue availability, and short-term effectiveness. DESIGN: Multicenter, open label, randomized controlled trial (Canadian Task Force classification I). SETTING: Day surgery setting of a teaching and a university hospital. PATIENTS: Women with larger (≥1 cm) endometrial polyps. INTERVENTIONS: Hysteroscopic morcellation with the TRUCLEAR 8.0 Tissue Removal System or bipolar resectoscopy with a rigid 8.5-mm bipolar resectoscope. MEASUREMENTS AND MAIN RESULTS: Eighty-four women were included in the intention-to-treat analysis. Median operating time was 4.0 min (range: 2.5-7.1) and 6.0 min (range: 3.8-11.7) in the hysteroscopic morcellation and resectoscopy groups, respectively. Operating time was reduced by 38% (95% confidence interval: 5%-60%; p = .028) in the hysteroscopic morcellation group. Procedure time, which was defined as the sum of the installation and operating time, tended to be less for the hysteroscopic morcellation group (median 9.5 min [range: 7.6-12.2] vs 12.2 min [range: 8.8-16.0]; p = .072). Perforation occurred at dilation or hysteroscope (re)introduction in 3 patients of the resectoscopy group, resulting in procedure discontinuation or prolongation of hospital stay. Perforation occurred at dilation in 1 patient in the hysteroscopic morcellation group; however, the procedure was successfully completed. Postoperatively, 2 patients of the hysteroscopic morcellation group were diagnosed with a urinary tract infection. Tissue was available for pathology analysis in all patients, except for 2 patients in the resectoscopy group in whom the procedure was discontinued due to perforation. CONCLUSION: Hysteroscopic morcellation is a fast, effective, and safe alternative to bipolar resectoscopy for removal of endometrial polyps.

Immediate postpartum insertion of intrauterine device for contraception.

BACKGROUND: Women who want to start intrauterine contraception (IUC) during the postpartum period might benefit from IUC insertion immediately after delivery. Postplacental insertion greatly reduces the risk of subsequent pregnancy and eliminates the need for a return visit to start contraception. Without the option of immediate insertion, many women may never return for services or may adopt less effective contraception. OBJECTIVES: Our aim was to examine the outcomes of IUC insertion immediately after placenta delivery (within 10 minutes), especially when compared with insertion at other postpartum times. We focused on successful IUC placement (insertion), subsequent expulsion, and method use. SEARCH METHODS: We searched for trials until 1 April 2015. Sources included PubMed (MEDLINE), the Cochrane Central Register of Controlled Trials (CENTRAL), POPLINE, Web of Science, EMBASE, LILACS, ClinicalTrials.gov, and ICTRP. For the original review, the authors contacted investigators to identify other trials. SELECTION CRITERIA: We sought randomized controlled trials (RCTs) with at least one treatment arm that involved immediate IUC placement (i.e., within 10 minutes of placenta delivery). Comparison arms could have included early postpartum insertion (from 10 minutes postplacental to hospital discharge) or standard insertion (during a postpartum visit). Trials could also have compared different IUC methods or insertion techniques. Delivery may have been vaginal or cesarean. Primary outcomes were placement (insertion), subsequent expulsion, and method use at study assessment. DATA COLLECTION AND ANALYSIS: For dichotomous outcomes, we used the Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI). Earlier studies primarily reported results as life-table rates. We aggregated trials in a meta-analysis if they had similar interventions and outcome measures. A sensitivity analysis included studies with moderate or high quality evidence and sufficient outcome data. MAIN RESULTS: We included 15 trials. Seven studies reported from 2010 to 2014 were added to eight from the original 2001 review. Newer trials compared immediate postplacental insertion versus early (10 minutes to 48 hours) or standard insertion (during the postpartum visit). Of four with full reports, three were small trials. The other three studies had conference abstracts. The eight early trials examined immediate insertion of different devices or insertion techniques. Most studies were published in the 1980s, some with limited reporting.Our sensitivity analysis included trials with sufficient outcome data and moderate or high quality evidence. Four newer trials comparing insertion times met the inclusion criteria. Two studies used the levonorgestrel-releasing intrauterine system (LNG-IUS) after vaginal delivery. The other two trials placed IUC after cesarean section; one used the CuT 380A intrauterine device (IUD) and the other used the LNG-IUS.A pilot trial compared immediate insertion versus early or standard insertion. In groups comparing immediate versus early insertion (N = 30), all women had the LNG-IUS inserted. By six months, the groups had the same expulsion rate and did not differ significantly in IUC use.For immediate versus standard insertion, we conducted meta-analyses of four trials. Insertion rates did not differ significantly between study arms. However, the trial from Uganda showed insertion was more likely for the immediate group, although the estimate was imprecise. In the meta-analysis, expulsion by six months was more likely for the immediate group, but the confidence interval was wide (OR 4.89, 95% CI 1.47 to 16.32; participants = 210; studies = 4). IUC use at six months was more likely with immediate insertion than with standard insertion (OR 2.04, 95% CI 1.01 to 4.09; participants = 243; studies = 4). Study arms did not differ in use at 3 or 12 months in individual small trials. AUTHORS' CONCLUSIONS: Recent trials compared different insertion times after vaginal or cesarean delivery. Evidence was limited because studies with full reports generally had small sample sizes. Overall, the quality of evidence was moderate; abstracts and older studies had limited reporting. Ongoing trials will add to the evidence, although some are small. Trials of adequate power are needed to estimate expulsion rates and side effects.The benefit of effective contraception immediately after delivery may outweigh the disadvantage of increased risk for expulsion. Frequent prenatal visits during the third trimester provide the opportunity to discuss effective contraceptive methods and desired timing for initiation. Clinical follow-up can help detect early expulsion, as can educating women about expulsion signs and symptoms.

Vasectomy occlusion techniques for male sterilization.

BACKGROUND: Vasectomy is an increasingly popular and effective family planning method. A variety of vasectomy techniques are used worldwide, including vas occlusion techniques (excision and ligation, thermal or electrocautery, and mechanical and chemical occlusion methods), as well as vasectomy with vas irrigation or with fascial interposition. Vasectomy guidelines largely rely on information from observational studies. Ideally, the choice of vasectomy techniques should be based on the evidence from randomized controlled trials (RCTs). OBJECTIVES: The objective of this review was to compare the effectiveness, safety, acceptability and costs of vasectomy techniques for male sterilization. SEARCH METHODS: In February 2014, we updated the searches of CENTRAL, MEDLINE, POPLINE and LILACS. We looked for recent clinical trials in ClinicalTrials.gov and the International Clinical Trials Registry Platform. Previous searches also included EMBASE. For the initial review, we searched the reference lists of relevant articles and book chapters. SELECTION CRITERIA: We included RCTs comparing vasectomy techniques, which could include suture ligature, surgical clips, thermal or electrocautery, chemical occlusion, vas plugs, vas excision, open-ended vas, fascial interposition, or vas irrigation. DATA COLLECTION AND ANALYSIS: We assessed all titles and abstracts located in the literature searches. Two reviewers independently extracted data from articles identified for inclusion. Outcome measures include contraceptive efficacy, safety, discontinuation, and acceptability. Peto odds ratios (OR) with 95% confidence intervals (CI) were used for dichotomous outcomes, such as azoospermia. The mean difference (MD) was used for the continuous variable of operating time. MAIN RESULTS: Six studies met the inclusion criteria. One trial compared vas occlusion with clips versus a conventional vasectomy technique. No difference was found in failure to reach azoospermia (no sperm detected). Three trials examined vasectomy with vas irrigation. Two studies looked at irrigation with water versus no irrigation, while one examined irrigation with water versus the spermicide euflavine. None found a difference between the groups for time to azoospermia. However, one trial reported that the median number of ejaculations to azoospermia was lower in the euflavine group compared to the water irrigation group. One high-quality trial compared vasectomy with fascial interposition versus vasectomy without fascial interposition. The fascial interposition group was less likely to have vasectomy failure. Fascial interposition had more surgical difficulties, but the groups were similar in side effects. Lastly, one trial found that an intra-vas was less likely to produce azoospermia than was no-scalpel vasectomy. More men were satisfied with the intra-vas device, however. AUTHORS' CONCLUSIONS: For vas occlusion with clips or vasectomy with vas irrigation, no conclusions can be made as those studies were of low quality and underpowered. Fascial interposition reduced vasectomy failure. An intra-vas device was less effective in reducing sperm count than was no-scalpel vasectomy. RCTs examining other vasectomy techniques were not available. More and better quality research is needed to examine vasectomy techniques.

Scalpel versus no-scalpel incision for vasectomy.

BACKGROUND: Currently, the two most common surgical techniques for approaching the vas during vasectomy are the incisional method and the no-scalpel technique. Whereas the conventional incisional technique involves the use of a scalpel to make one or two incisions, the no-scalpel technique uses a sharp-pointed, forceps-like instrument to puncture the skin. The no-scalpel technique aims to reduce adverse events, especially bleeding, bruising, hematoma, infection and pain and to shorten the operating time. OBJECTIVES: The objective of this review was to compare the effectiveness, safety, and acceptability of the incisional versus no-scalpel approach to the vas. SEARCH METHODS: In February 2014, we searched the computerized databases of CENTRAL, MEDLINE, POPLINE and LILACS. We looked for recent clinical trials in ClinicalTrials.gov and the International Clinical Trials Registry Platform. Previous searches also included in EMBASE. For the initial review, we searched the reference lists of relevant articles and book chapters. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials were included in this review. No language restrictions were placed on the reporting of the trials. DATA COLLECTION AND ANALYSIS: We assessed all titles and abstracts located in the literature searches and two authors independently extracted data from the articles identified for inclusion. Outcome measures included safety, acceptability, operating time, contraceptive efficacy, and discontinuation. We calculated Peto odds ratios (OR) with 95% confidence intervals (CI) for the dichotomous variables. MAIN RESULTS: Two randomized controlled trials evaluated the no-scalpel technique and differed in their findings. The larger trial demonstrated less perioperative bleeding (OR 0.49; 95% CI 0.27 to 0.89) and pain during surgery (OR 0.75; 95% CI 0.61 to 0.93), scrotal pain (OR 0.63; 95% 0.50 to 0.80), and incisional infection (OR 0.21; 95% CI 0.06 to 0.78) during follow up than the standard incisional group. Both studies found less hematoma with the no-scalpel technique (OR 0.23; 95% CI 0.15 to 0.36). Operations using the no-scalpel approach were faster and had a quicker resumption of sexual activity. The smaller study did not find these differences; however, the study could have failed to detect differences due to a small sample size as well as a high loss to follow up. Neither trial found differences in vasectomy effectiveness between the two approaches to the vas. AUTHORS' CONCLUSIONS: The no-scalpel approach to the vas resulted in less bleeding, hematoma, infection, and pain as well as a shorter operation time than the traditional incision technique. No difference in effectiveness was found between the two approaches.

Levonorgestrel releasing intrauterine system (Mirena) versus endometrial ablation (Novasure) in women with heavy menstrual bleeding: a multicentre randomised controlled trial.

BACKGROUND: Heavy menstrual bleeding is an important health problem. Two frequently used therapies are the levonorgestrel intra-uterine system (LNG-IUS) and endometrial ablation. The LNG-IUS can be applied easily by the general practitioner, which saves costs, but has considerable failure rates. As an alternative, endometrial ablation is also very effective, but this treatment has to be performed by a gynaecologist. Due to lack of direct comparison of LNG-IUS with endometrial ablation, there is no evidence based preferred advice for the use of one of these treatment possibilities. METHOD/DESIGN: A multicenter randomised controlled trial, organised in a network infrastructure in the Netherlands in which general practitioners and gynaecologists collaborate. DISCUSSON: This study, considering both effectiveness and cost effectiveness of LNG-IUS versus endometrial ablation may well improve care for women with heavy menstrual bleeding. TRIAL REGISTRATION: Dutch trial register, number NTR2984.