Search

Objective To evaluate the costs and non‐inferiority of a strategy starting with the levonorgestrel intrauterine system (LNG‐IUS) compared with endometrial ablation (EA) in the treatment of heavy menstrual bleeding (HMB). Design Cost‐effectiveness analysis from a societal perspective alongside a multicentre randomised non‐inferiority trial. Setting General practices and gynaecology departments in the Netherlands. Population In all, 270 women with HMB, aged ≥34 years old, without intracavitary pathology or wish for a future child. Methods Randomisation to a strategy starting with the LNG‐IUS (n = 132) or EA (n = 138). The incremental cost‐effectiveness ratio was estimated. Main outcome measures Direct medical costs and (in)direct non‐medical costs were calculated. The primary outcome was menstrual blood loss after 24 months, measured with the mean Pictorial Blood Assessment Chart (PBAC)‐score (non‐inferiority margin 25 points). A secondary outcome was successful blood loss reduction (PBAC‐score ≤75 points). Results Total costs per patient were €2,285 in the LNG‐IUS strategy and €3,465 in the EA strategy (difference: €1,180). At 24 months, mean PBAC‐scores were 64.8 in the LNG‐IUS group (n = 115) and 14.2 in the EA group (n = 132); difference 50.5 points (95% CI 4.3–96.7). In the LNG‐IUS group, 87% of women had a PBAC‐score ≤75 points versus 94% in the EA group (relative risk [RR] 0.93, 95% CI 0.85–1.01). The ICER was €23 (95% CI €5–111) per PBAC‐point. Conclusions A strategy starting with the LNG‐IUS was cheaper than starting with EA, but non‐inferiority could not be demonstrated. The LNG‐IUS is reversible and less invasive and can be a cost‐effective treatment option, depending on the success rate women are willing to accept. Tweetable abstract Treatment of heavy menstrual bleeding starting with LNG‐IUS is cheaper but slightly less effective than endometrial ablation., Tweetable abstract Treatment of heavy menstrual bleeding starting with LNG‐IUS is cheaper but slightly less effective than endometrial ablation.

The enzyme type 1 17β-hydroxysteroid dehydrogenase (17β-HSD-1), responsible for generating active 17β-estradiol (E2) from low-active estrone (E1), is overexpressed in endometrial cancer (EC), thus implicating an increased intra-tissue generation of E2 in this estrogen-dependent condition. In this study, we explored the possibility of inhibiting 17β-HSD-1 and impairing the generation of E2 from E1 in EC using in vitro, in vivo, and ex vivo models. We generated EC cell lines derived from the well-differentiated endometrial adenocarcinoma Ishikawa cell line and expressing levels of 17β-HSD-1 similar to human tissues. In these cells, HPLC analysis showed that 17β-HSD-1 activity could be blocked by a specific 17β-HSD-1 inhibitor. In vitro, E1 administration elicited colony formation similar to E2, and this was impaired by 17β-HSD-1 inhibition. In vivo, tumors grafted on the chicken chorioallantoic membrane (CAM) demonstrated that E1 upregulated the expression of the estrogen responsive cyclin A similar to E2, which was impaired by 17β-HSD-1 inhibition. Neither in vitro nor in vivo effects of E1 were observed using 17β-HSD-1-negative cells (negative control). Using a patient cohort of 52 primary ECs, we demonstrated the presence of 17β-HSD-1 enzyme activity (ex vivo in tumor tissues, as measured by HPLC), which was inhibited by over 90% in more than 45% of ECs using the 17β-HSD-1 inhibitor. Since drug treatment is generally indicated for metastatic/recurrent and not primary tumor, we next demonstrated the mRNA expression of the potential drug target, 17β-HSD-1, in metastatic lesions using a second cohort of 37 EC patients. In conclusion, 17β-HSD-1 inhibition efficiently blocks the generation of E2 from E1 using various EC models. Further preclinical investigations and 17β-HSD-1 inhibitor development to make candidate compounds suitable for the first human studies are awaited. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

OBJECTIVE: The objective was to assess whether patient-perceived pain during the insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) depends on the timing during the menstrual cycle. DESIGN: A stratified two-armed non-inferiority randomised controlled trial. SETTING: Large teaching hospital in Veldhoven the Netherlands. SAMPLE: From October 2013 to May 2014 60 nulliparous and 60 multiparous women were randomised. Eight women withdrew after randomisation and before insertion took place: therefore data from 112 women were collected and analysed. METHODS: Women were randomised to the groups during menstruation (i.e. days 1-7 of menstruation) or outside menstruation (i.e. any day of the cycle after menstruation without the presence of vaginal blood loss) in a ratio of 1 : 1. MAIN OUTCOME MEASURES: The primary outcome was pain during insertion measured by the visual analogue scale (VAS 0-100 mm). Second we analysed ease of insertion bleeding pattern satisfaction pregnancy and expulsion rate. The follow-up time was 3 months. RESULTS: The mean VAS score for nulliparous women was 74 mm (95% confidence interval 95% CI 67-81) in the during menstruation group compared with 66 mm (95% CI 59-74) in the outside menstruation group (P = 0.14). The mean VAS score for multiparous women was 30 mm (95% CI 20-40) in the during menstruation group compared with 43 mm (95% CI 32-53) in the outside menstruation group (P = 0.08). There was no difference between the stratified during menstruation group and the outside menstruation group with regards to ease of insertion satisfaction bleeding pattern and median spotting and bleeding days for the use of the LNG-IUS 3 months after insertion. CONCLUSIONS: As we did not find that the level of pain perceived during insertion was higher during menstruation compared with outside menstruation we conclude that the LNG-IUS can be inserted at any time during the menstrual cycle especially in the case of nulliparous women. TWEETABLE ABSTRACT: We conducted an RCT on time of insertion of LNG-IUS. We conclude that the LNG-IUS can be inserted at any time. (c) 2016 Royal College of Obstetricians and Gynaecologists.

Objective Previously, we have reported that, at both 12 months and 5 years after treatment, bipolar endometrial ablation is superior to balloon ablation in the treatment of heavy menstrual bleeding. In this article, we evaluate the results at 10 years after these interventions. Design Ten-year follow-up of a double-blind randomised controlled trial. Setting A teaching hospital in the Netherlands. Population Premenopausal women suffering from heavy menstrual bleeding. Method A follow-up questionnaire was sent to women 10 yearsafter randomisation for bipolar ablation and balloon ablation (2 : 1 ratio). Main outcome measures Amenorrhoea rates, re-intervention and patient satisfaction. Results At 10 years of follow-up, the response rate was 69/83 (83%) in the bipolar group and 35/43 (81%) in the balloon group. Amenorrhoea rates were 50/69 (73%) in the bipolar group and 23/35 (66%) in the balloon group [relative risk, 1.1 (95% CI, 0.83–1.5)]. Further treatment following initial ablation was reported in 21 cases, 14 in the bipolar group and nine in the balloon group [relative risk, 0.9 (95% CI, 0.63–1.3)]. Eight of these women required further treatment after 5 years, including two hysterectomies. Patient satisfaction in the bipolar group was 81% (56/69) compared with 77% (27/35) in the balloon group [relative risk, 1.1 (95% CI, 0.82–1.2)]. Conclusion Ten years after treatment, the superiority of bipolarablation over balloon ablation in the treatment of heavy menstrual bleeding was no longer evident.

Department of Urology, Radboud University Nijmegen Medical Centre, The NetherlandsAims: To assess in women with stress urinary incontinence (SUI) the value of urodynamics prior to treatment.Methods: We performed a multicenter non-inferiority randomized controlled trial. Women with SUI were randomlyallocated to management based on a workup with or without urodynamics. The primary outcome was clinical reductionof complaints as measured with the Urogenital Distress Inventory urinary incontinence subscale (UDI-UI) at12 months after the onset of treatment. A mean difference in improvement of less than 8 was considered non-inferior.The study was analyzed according to intention-to-treat. Results: The trial was stopped prematurely because of slowrecruitment. We randomly allocated 59 women to a strategy with (N ¼ 31) or without (N ¼ 28) urodynamics. Themean difference in improvement on the UDI-UI was 14 in favor of the group without urodynamics (48 SD 22 vs. 34SD 22, 95% CI: 28 to 0.26), confirming non-inferiority. Addition of urodynamics did not result in a lower occur-rence of de novo overactive bladder complaints compared to a workup without urodynamics (6/31 vs. 1/28; RR 5.4, 95%CI: 0.70–42). In the group allocated to urodynamics, initial surgical management was more often abandoned comparedto the group not allocated to urodynamics (5/31 vs. 1/28; RR 4.5, 95% CI: 0.56–36). Conclusions: In this relativelysmall study, the omission of urodynamics was not inferior to the use of urodynamics in the preoperative workup ofwomen with SUI. Women with SUI undergoing urodynamics had the risk of a choice for more prudent treatment,which seemed to result in a delay until effective treatment. Neurourol. Urodynam. 31:1118–1123, 2012. 2012 Wiley Periodicals, Inc.Key words: diagnostic; outcome; surgery; stress incontinence; urodynamics

Please cite this paper as: Janssen P, Brolmann H, van Kesteren P, Bongers M, Thurkow A, Heymans M, Huirne J. Perioperative outcomes using LigaSure compared with conventional bipolar instruments in laparoscopic hysterectomy: a randomised controlled trial. BJOG 2011;118:1568–1575. Objective To compare the effects of LigaSure versus the conventional bipolar technique on operating time and blood loss during laparoscopic hysterectomy. Design A randomised controlled trial. Setting Three teaching hospitals. Population Women undergoing a laparoscopic hysterectomy for benign indications. Methods 140 women undergoing a laparoscopic hysterectomy were randomised for LigaSure or conventional bipolar instruments. Main outcome measures Primary outcome was operating time from initial skin incision till detachment of the uterus. Secondary outcome measures were total operating time (from initial skin incision till final skin closure), time to dissect the adnexal ligaments, intra-operative blood loss and subjective evaluation by the surgeon of the instrument used. Results No differences in operating time (from initial skin incision till uterine detachment and initial skin incision till final skin closure) using LigaSure versus conventional bipolar instruments: 97.6 versus 91.8 minutes (P = 0.39, 95% CI – 7.6 to 19.2), and 148.1 versus 142.1 minutes (P = 0.46, 95% CI – 10.1 to 22.3), respectively. The mean blood loss using LigaSure versus conventional bipolar was 234.1 versus 273.1 ml (P = 0.46, 95% CI -39.1 to 52.7). Various subjective efficacy and instrument handling parameters were significantly different between the two instruments and between the different participating centres. Conclusions There were no significant differences in operating time and blood loss between the use of LigaSure and the use of conventional bipolar instruments during laparoscopic hysterectomy, even after correction for potential confounders. User satisfaction parameters were assessed as significantly different by surgeons of the participating centres.

We describe the design of a randomised controlled trial to evaluate the efficacy of endometrial polyp removal in women with postmenopausal bleeding. We designed a trial in which patients with postmenopausal bleeding and endometrial thickness >4 mm undergo hysteroscopy. If during hysteroscopy an endometrial polyp was diagnosed, patients were asked to participate in this trial and after informed consent allocated to immediate removal of the polyp or expectant management. This trial suffered from lack of recruitment related both to doctors seeking for informed consent as well as to patients' unwillingness to participate in this trial. However, a randomised controlled trial on this subject is still necessary to evaluate the efficacy of uterine cavity evaluation in the diagnostic work-up of women with postmenopausal bleeding, focussing on benign pathology. Therefore, we propose an alternative design, which might be more feasible.