Cost-Effectiveness of perioperative Vaginally Administered estrogen in postmenopausal women undergoing prolapse surgery (EVA trial): study protocol for a multicenter double-blind randomized placebo-controlled trial.

BACKGROUND: Surgery for pelvic organ prolapse (POP) is associated with high recurrence rates. The costs associated with the treatment of recurrent POP are huge, and the burden from women who encounter recurrent POP, negatively impacts their quality of life. Estrogen therapy might improve surgical outcome for POP due to its potential beneficial effects. It is thought that vaginal estrogen therapy improves healing and long-term maintenance of connective tissue integrity. Hence, this study aims to evaluate the cost-effectiveness of perioperative vaginal estrogen therapy in postmenopausal women undergoing POP surgery. METHODS: The EVA trial is a multi-center double-blind randomized placebo-controlled trial conducted in the Netherlands comparing the effectiveness and costs-effectiveness of vaginal estrogen therapy. This will be studied in 300 postmenopausal women undergoing primary POP surgery, with a POP-Q stage of ≥ 2. After randomization, participants administer vaginal estrogen cream or placebo cream from 4 to 6 weeks preoperative until 12 months postoperative. The primary outcome is subjective improvement of POP symptoms at 1 year follow-up, measured with the Patient Global Impression of Improvement (PGI-I) scale. Secondary outcomes are POP-Q anatomy in all compartments, re-interventions, surgery related complications, general and disease specific quality of life, sexual function, signs and complaints of vaginal atrophy, vaginal pH, adverse events, costs, and adherence to treatment. Follow up is scheduled at 6 weeks, 6 months and 12 months postoperative. Data will be collected using validated questionnaires and out-patient visits including gynecological examination performed by an independent gynecologist. DISCUSSION: This study investigates whether perioperative vaginal estrogen will be cost-effective in the surgical treatment of POP in postmenopausal women. It is hypothesized that estrogen therapy will show a reduction in recurrent POP symptoms and a reduction in reoperations for POP, with subsequent improved quality of life among women and cost savings. Trial registrationNetherlands Trial Registry: NL6853; registered 19-02-2018, https://www.trialregister.nl/trial/6853 . EudraCT: 2017-003144-21; registered: 24-07-2017.

Dutch translation and validation of the pelvic organ prolapse/incontinence sexual questionnaire-IUGA revised (PISQ-IR).

INTRODUCTION AND HYPOTHESIS: Condition-specific sexual questionnaires are important patient-reported outcome measures. The aim of this study was to translate and validate the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-International Urogynecology Association Revised (PISQ-IR) into Dutch. METHODS: The translated PISQ-IR was linguistically validated, followed by psychometrical validation among women presenting with symptoms of pelvic floor dysfunction in urogynecology clinics. For analysis of the criterion validity, the Pelvic Floor Dysfunction Inventory-20 (PFDI-20) and Female Sexual Function Index (FSFI) were used. Descriptive statistics, floor and ceiling effects, internal consistency using Cronbach's alpha coefficient and Pearson's and Spearman's correlations were calculated for all PISQ-IR subscales. RESULTS: The PISQ-IR was completed by 220 women, of whom 61 (27.7%) considered themselves not sexually active (NSA) and 159 (72.3%) sexually active (SA). The mean age of participating women was 57 years; 49.5% reported symptoms of pelvic organ prolapse (POP), 66.8% urinary incontinence and 2.3% anal incontinence. The PISQ-IR subscales were analyzed separately for SA and NSA women with Cronbach's alpha coefficient ranging from 0.61 to 0.87. Moderate to high correlations were observed between PISQ-IR subscales and corresponding FSFI subscales and a moderate correlation between urinary distress and the condition impact (CI) subscale among NSA subjects. CONCLUSIONS: The Dutch PISQ-IR demonstrated a good internal consistency and criterion validity compared with the FSFI, but criterion validity compared with the PFDI-20 was poor except for urinary distress in NSA women and needs further attention.

Evaluation of two vaginal, uterus sparing operations for pelvic organ prolapse: modified Manchester operation (MM) and sacrospinous hysteropexy (SSH), a study protocol for a multicentre randomized non-inferiority trial (the SAM study).

BACKGROUND: Pelvic organ prolapse (POP) affects up to 40% of parous women which adversely affects the quality of life. During a life time, 20% of all women will undergo an operation. In general the guidelines advise a vaginal operation in case of uterine descent: hysterectomy with uterosacral ligament plication (VH), sacrospinous hysteropexy (SSH) or a modified Manchester operation (MM). In the last decade, renewed interest in uterus sparing techniques has been observed. Previous studies have shown non-inferiority between SSH and VH. Whether or not SSH and MM are comparable concerning anatomical and functional outcome is still unknown. The practical application of both operations is at least in The Netherlands a known cause of practice pattern variation (PPV). To reveal any difference between both techniques the SAM-study was designed. METHODS: The SAM-study is a randomized controlled multicentre non-inferiority study which compares SSH and MM. Women with symptomatic POP in any stage, uterine descent and POP-Quantification (POP-Q) point D at ≤ minus 1 cm are eligible. The primary outcome is the composite outcome at two years of absence of prolapse beyond the hymen in any compartment, the absence of bulge symptoms and absence of reoperation for pelvic organ prolapse. Secondary outcomes are hospital parameters, surgery related morbidity/complications, pain perception, further treatments for prolapse or urinary incontinence, POP-Q anatomy in all compartments, quality-of-life, sexual function, and cost-effectiveness. Follow-up takes place at 6 weeks, 12 and 24 months. Additionally at 12 weeks, 6 and 9 months cost-effectiveness will be assessed. Validated questionnaires will be used and gynaecological examination will be performed. Analysis will be performed following the intention-to-treat and per protocol principle. With a non-inferiority margin of 9% and an expected loss to follow-up of 10%, 424 women will be needed to prove non-inferiority with a confidence interval of 95%. DISCUSSION: This study will evaluate the effectiveness and costs of SSH versus MM in women with primary POP. The evidence will show whether the existing PPV is detrimental and a de-implementation process regarding one of the operations is needed. TRIAL REGISTRATION: Dutch Trial Register (NTR 6978, http://www.trialregister.nl ). Date of registration: 29 January 2018. Prospectively registered.

Hysteroscopy and removal of endometrial polyps: a Dutch survey.

OBJECTIVE: To evaluate current practice of Dutch gynecologists in polyp removal. STUDY DESIGN: All practicing gynecologists in The Netherlands in 2003 were surveyed by a mailed self-administered questionnaire about polypectomy. Gynecologists were asked about their individual performance of polypectomy: setting, form of anesthesia, method and instrument used. RESULTS: The response rate was 74% (553 of 752 gynecologists). Among the respondents, 455 (83%) stated that they removed polyps themselves. Polyps were most commonly removed in an inpatient setting (71%), under general or regional anesthesia (77%), and under direct hysteroscopic visualization (69%). Gynecologists working in a teaching hospital removed polyps more often in an outpatient setting compared to gynecologists working in a non-teaching hospital (93 (39%) versus 36 (19%) p<0.001). CONCLUSION: In the Netherlands, outpatient polyp removal is not practiced on a large scale. However, teaching hospitals are more often performing polypectomy in an outpatient setting. Therefore, we expect that there must be a tendency towards outpatient hysteroscopic removal of polyps for the future. Further research is required to assess the efficacy polyp removal.

Implementation of hysteroscopic surgery in The Netherlands.

OBJECTIVE: This study was conducted to assess the degree of diffusion of hysteroscopic surgery in gynaecological practice in The Netherlands in order to guide further implementation. The diffusion was objectified by defining the percentage of hospitals performing hysteroscopic procedures and the number of different procedures performed per gynaecologist. STUDY DESIGN: In 2003 all Departments of Gynaecology (n=102) in The Netherlands were sent a questionnaire. The questionnaire addressed the number and type of all hysteroscopic procedures that were performed in each hospital in 2002. Data from this study were compared to previously published data from 1997. RESULTS: Responses were received from 80% of all gynaecological departments in The Netherlands. Diagnostic hysteroscopy was performed in almost all hospitals in both 1997 and 2002. The percentage of hospitals that adopted polypectomy, myomectomy and endometrial ablation increased to more than 90% in 2002. The number of teaching hospitals that integrated diagnostic hysteroscopy, polypectomy and myomectomy (procedures required for graduation) into their operative spectrum increased to 100%. CONCLUSION: This survey indicates a growing trend of the diffusion of diagnostic and "basic" therapeutic hysteroscopic procedures in The Netherlands. However, figures upon more advanced hysteroscopic surgery are less optimistic.

Diagnostic hysteroscopy and saline infusion sonography in the diagnosis of intrauterine abnormalities: an assessment of patient preference.

This study was conducted to assess whether women would prefer to undergo saline infusion sonography (SIS) or office hysteroscopy for the investigation of the uterine cavity. In a randomised controlled trial, 100 patients underwent SIS or office hysteroscopy for assessing patients' pain scores. After the investigation, 92 of them were asked to fill out an anonymous questionnaire addressing their preference regarding the method of evaluation and treatment of the uterine cavity. A control group, consisting of 50 women who never underwent SIS or office hysteroscopy, was also asked to complete an identical questionnaire. The questionnaire was completed by 113 women (83.7%). Twenty-four (21.2%) women would opt for SIS, whereas 52 (46.0%) would opt for office hysteroscopy, and 37 (32.7%) had no preference. If therapy would be necessary, 48.7% of the women would opt for an outpatient treatment, whereas 33.0% of the women would prefer treatment under general anaesthesia. Despite the fact that SIS is less painful, the majority of the women prefer office hysteroscopy. Additionally, therapy in an outpatient setting is preferred to a day case setting.

The impact of alternative treatment for abnormal uterine bleeding on hysterectomy rates in a tertiary referral center.

STUDY OBJECTIVE: The purpose of this study was to estimate the influence of alternatives to hysterectomy for abnormal uterine bleeding (AUB) on hysterectomy rates. DESIGN: Retrospective cohort study. Canadian Task Force II-2. SETTING: University hospital. PATIENTS: Premenopausal patients with AUB. INTERVENTIONS: Medical records of all premenopausal patients treated for AUB in our university clinic between January 1, 1995, and December 31, 2004, were reviewed. Patients were identified based on (specific) diagnostic and therapy codes used in the registry system of the hospital. The total number of placements of levonorgestrel-releasing intrauterine device (LNG-IUD), hysteroscopic surgery, and hysterectomies performed/year was estimated. In addition, the course of treatment of each patient was assessed. MEASUREMENTS AND MAIN RESULTS: A total of 640 patients received surgery and 246 LNG-IUDs were placed. The proportion of endometrial ablations decreased significantly over time (p <.001), whereas hysteroscopic polyp or myoma removal (p =.030) and insertion of LNG-IUD (p <.001) both increased. The proportion of patients receiving hysterectomy for AUB as their first therapy decreased significantly (p =.005) from 40.6% to 31.4%, although the total number of patients receiving hysterectomy remained similar (p =.449). The 5-year intervention-free percentage for LNG-IUD was 70.6% (SD = 3.3%), for hysteroscopic polyp or myoma removal 75.5% (SD = 3.3%), and for endometrial ablation 78.0% (SD = 4.3%; p =.067). CONCLUSION: Despite the introduction of alternative therapies, the total hysterectomy rate in the management of AUB did not decrease in our clinic.

Ectopic pregnancy: a heart beating case.

Abdominal pregnancy is a rare event that occurs in western countries in 1.3% of ectopic gestations. Delayed diagnosis and attempted removal of the fetus have occasionally resulted in massive and even fatal intraperitoneal hemorrhage. We present a case of an ectopic pregnancy at the intraabdominal surface of the left diaphragm, which was removed successfully with laparoscopic hydrodissection. This case report demonstrates that awareness of this condition is important when the location of the pregnancy cannot be found in the lower abdominal cavity, especially if the patient has unexplained complaints such as shoulder pain.

Hysteroscopic morcellator for removal of intrauterine polyps and myomas: a randomized controlled pilot study among residents in training.

The purpose of this randomized controlled study was to compare conventional resectoscopy and hysteroscopic morcellation among residents in training (Canadian Task Force classification I). Sixty women with an intrauterine polyp or myoma were randomized to either hysteroscopic removal by conventional resectoscopy or hysteroscopic morcellation performed by 6 residents in training for obstetrics and gynecology (10 procedures per resident). The mean operating time for resectosocpy and morcellation was 17.0 (95% confidence interval [95% CI] 14.1-17.9, standard deviation [SD] 8.4) and 10.6 (95% CI 7.3-14.0, SD 9.5) min, respectively (p = .008). Multiple linear regression analysis showed that operating time increased significantly, for both resectoscopy and morcellator, when volume of intrauterine disorder increased. The use of the hysteroscopic morcellator reduced operating time more than 8 min in comparison to conventional resectoscopy (p < .001) when correction for volume was applied. Subjective surgeon and trainer scores for convenience of technique on a visual analog scale were in favor of the morcellator. No learning curve was observed. In conclusion, the hysteroscopic morcellator for removal of intrauterine polyps and myomas offers a good alternative to conventional resectoscopy for residents in training.

Polypectomy in premenopausal women with abnormal uterine bleeding: effectiveness of hysteroscopic removal.

STUDY OBJECTIVE: To estimate the effectiveness of hysteroscopic polypectomy in premenopausal women with abnormal uterine bleeding and to identify prognostic factors for persistence or recurrence of symptoms after polypectomy. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: University teaching hospital. PATIENTS: Premenopausal women with abnormal uterine bleeding. INTERVENTION: Hysteroscopic polypectomy, regardless of whether combined with endometrial ablation or insertion of a levonorgestrel-releasing intrauterine device. MEASUREMENTS AND MAIN RESULTS: Seventy-eight consecutive patients met the inclusion criteria and were followed over time. Data were retrieved from medical records or from additional questionnaires sent to the patients. Failure of treatment was defined as persistence or recurrence of abnormal uterine bleeding after polypectomy, requiring further treatment. The mean age was 44.2 years (SD 5.2, 95% CI 33.9-54.4 years). Intervention-free survival after polypectomy, as calculated by Kaplan-Meier survival analysis, was 41.1% (SE 8.3%, 95% CI 24.8%-57.4%) after 4 years for patients who underwent only hysteroscopic polypectomy and 54.7% (SE 13.6%, 95% CI 28.0%-81.4%) for patients who underwent a polypectomy combined with endometrial ablation or insertion of a levonorgestrel-releasing intrauterine device (p = .08). Cox regression analyses revealed no statistically significant predictors for persistence or recurrence of symptoms after polypectomy. CONCLUSION: Nearly 60% of patients required further treatment for persistence or recurrence of abnormal uterine bleeding 4 years after hysteroscopic polypectomy. Although not significant, outcome of treatment tended to improve by combining polypectomy with either an endometrial ablation or insertion of a levonorgestrel-releasing intrauterine device.

Follow-up after incomplete hysteroscopic removal of uterine fibroids.

BACKGROUND: In this observational study, we analysed whether a period of wait and see was reasonable following incomplete removal of submucous fibroids, with regard to symptoms of abnormal uterine bleeding, and whether factors predicting subsequent surgery could be identified. METHODS: In 3 affiliated hospitals, patients with incomplete removal of submucous fibroids, treated with hysteroscopic myomectomy for abnormal uterine bleeding, between January 1997 and January 2005, were followed over time. Using life-table analysis (Kaplan-Meier method), the cumulative proportion of women having surgery-free survival following incomplete removal of submucous fibroids was calculated. Cox-proportional hazard analyses were used to analyse relationships of variables with recurrence of symptoms. RESULTS: Forty-one consecutive patients met the inclusion criteria, and were followed over time. The mean age was 42.5 years (range 27-55). The majority of patients with incomplete removal of submucous fibroids were diagnosed with type 2 fibroids. Termination of the procedure before complete removal was achieved, was principally caused by reaching the maximum fluid deficit (90.2%). The surgery-free percentages were 70.2% (95%-CI: 55.3-85.1) at 1 year, 54.8% (95%-CI: 38.1-70.7) at 2 years, and 44.2% (95%-CI: 26.9-61.5) at 3 years. Size of fibroid (diameter) pre-operatively turned out to be of statistically significant influence, with a hazard ratio of 1.762 (95%-CI: 1.114-2.787) per cm increase in diameter (p=0.016). CONCLUSIONS: The results indicate that incomplete removal does not always seem to necessitate subsequent surgery. Instead of subsequent surgery immediately post-operatively, a wait and see policy is worth considering after incomplete removal.

Diagnostic hysteroscopy and saline infusion sonography: prediction of intrauterine polyps and myomas.

STUDY OBJECTIVE: To compare the positive predictive value (PPV) of diagnostic hysteroscopy (DH) and saline infusion sonography (SIS) for the detection of myomas and polyps in patients with abnormal uterine bleeding. DESIGN: All consecutive women referred to our University Hospital diagnosed with an intrauterine polyp or myoma by office DH or SIS were included in the study. Patients referred to our clinic from 1993 through 2000 underwent DH. From 2001 through 2004 SIS was performed. After hysteroscopic removal in an inpatient setting, histopathologic results were used as a gold standard to calculate PPV of SIS and DH. (Canadian Task Force classification II-3) SETTING: Tertiary referral center. INTERVENTION: Diagnostic hysteroscopy and saline infusion sonography. PATIENTS: Women in whom an intrauterine polyp or myoma was diagnosed either by DH or SIS MEASUREMENTS AND MAIN RESULTS: The PPVs of SIS and DH in the evaluation of intrauterine polyps and fibroids did not significantly differ. However, p = 0.3 is the significant difference for the PPV of SIS in premenopausal women comparing the PPV of SIS for fibroids (0.95) with the PPV of SIS for polyps (0.81). CONCLUSIONS: Diagnostic hysteroscopy and saline infusion sonography are equivalent diagnostic tools for the detection of intrauterine myomas and polyps.