Innovative and conventional "conservative" technologies for the treatment of uterine fibroids in Italy: a multidimensional assessment.

BACKGROUND: To evaluate the potential benefits of the Magnetic Resonance-guided high intensity Focused Ultrasound (MRgFUS) introduction in the clinical practice, for the treatment of uterine fibroids, in comparison with the standard "conservative" procedures, devoted to women who wish to preserve their uterus or enhance fertility: myomectomy and uterine artery embolization (UAE). METHODS: A Health Technology Assessment was conducted, assuming the payer's perspective (Italian National Healthcare Service). The nine EUnetHTA Core Model dimensions were deeply investigated, by means of i) a literature review; ii) the implementation of health economics tools (useful for uterine fibroids patients' clinical pathway economic evaluation, and budget impact analysis), to define MRgFUS economic and organizational sustainability, and iii) administration of specific questionnaires filled by uterine fibroids' experts, to gather their perceptions on the three possible conservative approaches (MRgFUS, UAE and myomectomy). RESULTS: Literature revealed that MRgFUS would generate several benefits, from a safety and an efficacy profile, with significant improvement in symptoms relief. Advantages emerged concerning the patients' perspective, thus leading to a decrease both in the length of hospital stay (p-value< 0.001), and in patients' productivity loss (p-value = 0.024). From an economic point of view, the Italian NHS would present an economic saving of - 6.42%. A positive organizational and equity impact emerged regarding the capability to treat a larger number of women, thus performing, on average, 131.852 additional DRGs. CONCLUSIONS: Results suggest that MRgFUS could be considered an advantageous technological alternative to adopt within the target population affected by uterine fibroids, demonstrating its economic and organisational feasibility and sustainability, with consequent social benefits.

Three-dimensional transvaginal sonographic assessment of uterine volume as preoperative predictor of need to morcellate in women undergoing laparoscopic hysterectomy.

OBJECTIVE: In light of recent statements from the United States Food and Drug Administration warning against the use of power morcellation of uterine leiomyomas during laparoscopy, we sought to evaluate the use of preoperative two- (2D) and three- (3D) dimensional transvaginal ultrasound (US) assessment of uterine volume to predict the need for morcellation in women undergoing laparoscopic hysterectomy (LH). METHODS: This was a prospective observational study performed between October 2008 and November 2011 in a tertiary referral laparoscopic unit. All women scheduled to undergo LH were included and underwent detailed preoperative transvaginal US. Uterine volumes were calculated using 2D-US measurements (ellipsoid formula), and using Virtual Organ Computer-aided AnaLysis (VOCAL™) having acquired 3D-US volumes of the uterus. Age, parity, need to morcellate and final uterine dry weight at histology were recorded. The estimated uterine volumes were then incorporated into a previously published logistic regression model to predict the need to morcellate for both nulliparous and parous women. The probability threshold cut-off of 0.14 (95% sensitivity) was evaluated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratios (LRs). The performance of the models incorporating 2D- and 3D-US calculations were compared with 2D- and 3D-US-generated volumes alone, using receiver-operating characteristics (ROC) curves. RESULTS: Of 76 women who underwent LH during the study period, 79% (n = 60) had complete background and 3D-US data. Their mean age was 43.7 years, 91.7% were parous and 35% underwent morcellation. The greatest uterine volume that did not require morcellation was 404 mL estimated using 3D-US, which corresponded to a uterine volume of 688.8 mL using 2D-US. The smallest uterine volume that required morcellation was 118.9 mL using 3D-US, which corresponded to a uterine volume of 123.4 mL using 2D-US. The 3D-US uterine volume for parous women with a sensitivity of 95% based on ROC-curve analysis was approximately 120 mL, which equated to a predicted probability of morcellation cut-off of 0.14. For this cut-off, specificity was 55.00%, PPV was 51.35%, NPV was 95.65%, LR+ was 2.11 and LR- was 0.09. Areas under the ROC curves for the morcellation logistic regression model were 0.769 (95% CI, 0.653-0.886) and 0.586 (95% CI, 0.419-0.753) using uterine volumes obtained by 3D-US and by 2D-US, respectively, and they were 0.938 (95% CI, 0.879-0.996) and 0.815 (95% CI, 0.681-0.948) using 3D-US and 2D-US volumes alone. CONCLUSIONS: The need to morcellate can be predicted preoperatively using 3D-US uterine volumes obtained by transvaginal US with a fair degree of accuracy. Uteri with volumes smaller than 120 mL at 3D-US are very unlikely to require morcellation. The incorporation of 3D-US-estimated uterine volume into the previously published logistic regression model does not seem to confer any significant improvement when compared with 3D-US uterine volume alone to predict the need to morcellate in women undergoing total LH. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Association between three-dimensional transvaginal sonographic markers and outcome of pregnancy of unknown location: a pilot study.

OBJECTIVE: To assess the accuracy of three-dimensional (3D) transvaginal sonographic (TVS) parameters in predicting the evolution of a pregnancy of unknown location (PUL). METHODS: This was a prospective observational study performed at the early pregnancy unit of a university hospital from September 2008 to June 2012. Women with a positive pregnancy test without any signs of intra- or extrauterine pregnancy at their first TVS examination were considered eligible and a 3D dataset containing the entire uterus was acquired. An experienced observer analyzed all 3D datasets for assessment of the following parameters: endometrial thickness, volume, mean gray-scale index and asymmetry. Women were followed until they were classified as having: (i) non-visualized pregnancy loss (NVPL); (ii) intrauterine pregnancy (IUP); or (iii) ectopic pregnancy or persistent PUL. We compared the values of the TVS parameters across the three groups. We also assessed the area under the receiver-operating characteristics curve of the 3D-TVS parameters in comparison to that for serum ß-human chorionic gonadotropin (ß-hCG) ratio (48 h/baseline) to predict PUL outcome. We then evaluated whether combining the 3D-TVS parameters with serum ß-hCG ratio improved the predictive accuracy for PUL outcome by performing a logistic regression analysis. RESULTS: During the study period 4939 consecutive pregnant women presented at the unit for their initial TVS examination and 325 (7%) were classified as having a PUL, of whom 161 women were enrolled and had a 3D scan of the uterus. However, 19 were excluded because of incomplete follow-up. Data from 142 women with PUL were therefore included in the analysis and the outcomes of these women were: NVPL in 98 (69%), IUP in 27 (19%) and ectopic pregnancy + persistent PUL in 14 + 3 = 17 (12%). Endometrial thickness, endometrial volume and the proportion of women with asymmetric endometrial shape differed significantly between the outcome groups. Endometrial thickness and volume could be used as reasonable predictors of both NVPL and IUP, whereas asymmetric endometrial shape and mean gray-scale index could be used as reasonable predictors of IUP only. The best single parameter to predict PUL outcomes was the ß-hCG ratio. Regression analysis demonstrated that endometrial volume and endometrial shape asymmetry added significantly to the ß-hCG ratio in predicting IUP but not NVPL. CONCLUSIONS: 3D-TVS markers have a low diagnostic accuracy in predicting PUL outcome. The addition of endometrial volume and shape asymmetry improves the accuracy of the ß-hCG ratio in predicting IUP. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Detection of intracavitary uterine pathology using offline analysis of three-dimensional ultrasound volumes: interobserver agreement and diagnostic accuracy.

OBJECTIVE: To estimate the diagnostic accuracy and interobserver agreement in predicting intracavitary uterine pathology at offline analysis of three-dimensional (3D) ultrasound volumes of the uterus. METHODS: 3D volumes (unenhanced ultrasound and gel infusion sonography with and without power Doppler, i.e. four volumes per patient) of 75 women presenting with abnormal uterine bleeding at a 'bleeding clinic' were assessed offline by six examiners. The sonologists were asked to provide a tentative diagnosis. A histological diagnosis was obtained by hysteroscopy with biopsy or operative hysteroscopy. Proliferative, secretory or atrophic endometrium was classified as 'normal' histology; endometrial polyps, intracavitary myomas, endometrial hyperplasia and endometrial cancer were classified as 'abnormal' histology. The diagnostic accuracy of the six sonologists with regard to normal/abnormal histology and interobserver agreement were estimated. RESULTS: Intracavitary pathology was diagnosed at histology in 39% of patients. Agreement between the ultrasound diagnosis and the histological diagnosis (normal vs abnormal) ranged from 67 to 83% for the six sonologists. In 45% of cases all six examiners agreed with regard to the presence/absence of intracavitary pathology. The percentage agreement between any two examiners ranged from 65 to 91% (Cohen's κ, 0.31-0.81). The Schouten κ for all six examiners was 0.51 (95% CI, 0.40-0.62), while the highest Schouten κ for any three examiners was 0.69. CONCLUSION: When analyzing stored 3D ultrasound volumes, agreement between sonologists with regard to classifying the endometrium/uterine cavity as normal or abnormal as well as the diagnostic accuracy varied substantially. Possible actions to improve interobserver agreement and diagnostic accuracy include optimization of image quality and the use of a consistent technique for analyzing the 3D volumes.

Effect of gel-instillation sonography on Doppler ultrasound findings in endometrial polyps.

OBJECTIVE: Saline infusion sonohysterography has been reported to suppress the color signal within the endometrium at color or power Doppler evaluation. The aim of this study was to evaluate if gel-instillation sonography (GIS) affects the power Doppler signal in patients with endometrial polyps. METHODS: Ultrasound volumes of the uterus, obtained by three-dimensional ultrasound imaging of 25 women with histologically confirmed endometrial polyps, were assessed offline by six gynecologists with a special interest in gynecological ultrasound. Each woman contributed four volumes: one gray-scale volume and one power Doppler volume before GIS, and one gray-scale volume and one power Doppler volume at GIS. Power Doppler features before and after gel infusion were compared. RESULTS: At unenhanced ultrasound a pedicle artery was seen in 27-46% of cases, whereas, after gel infusion the examiners reported a pedicle artery in 30-46% of cases (Exact McNemar's test P-values ranged from 0.50 to 1.00). The level of agreement between unenhanced ultrasound and GIS ranged from 59 to 91% (Cohen's kappa values ranged from 0.17 to 0.79). There was no tendency for a pedicle artery to be identified less often at GIS than before gel instillation. CONCLUSION: Gel infusion does not affect the power Doppler signal in patients with endometrial polyps.

Ultrasound for ovarian cancer screening: are we throwing the baby out with the bath water?

The lack of standardization in gynaecological scanning is worrying, especially with regard to the sonographic evaluation of adnexal masses. The results of ongoing trials on the use of ultrasound as a screening test for ovarian cancer are likely to be affected by this lack of standardization in terminology and classifications. The lack of high-quality gynaecological ultrasound, combined with the low prevalence of ovarian cancer, may yield to a poor performance of transvaginal ultrasound as a screening test for ovarian cancer in large trials. In order to increase the specificity of ultrasound in a screening program, thus reducing unnecessary surgeries, a uniform, reproducible and accurate method for the sonographic evaluation of ovarian masses must be implemented. This move to improve and standardize reporting in gynaecological ultrasound should negate the need to use the phrase 'complex ovarian mass'. In this paper, we will critically evaluate current terminology, newly proposed accepted morphological classification of ovarian cysts as well as the ability for ultrasound to discriminate between benign and malignant ovarian masses.

Viability of intrauterine pregnancy in women with pregnancy of unknown location: prediction using human chorionic gonadotropin ratio vs. progesterone.

OBJECTIVES: To find the best predictor of the viability of intrauterine pregnancies of uncertain viability (IPUVs). An IPUV is defined as an empty intrauterine gestational sac measuring less than 20 mm in diameter or an intrauterine gestational sac containing a fetal pole with a crown-rump length (CRL) of less than 6 mm with no fetal cardiac activity. METHODS: This was a prospective observational study comparing the following two markers for the prediction of viability in IPUVs: human chorionic gonadotropin (hCG) ratio (hCG 48 h : hCG 0 h); and serum progesterone at first presentation. All women classified with a pregnancy of unknown location (PUL) were followed up until final diagnosis: failing PUL, viable or non-viable intrauterine pregnancy (IUP), or ectopic pregnancy. Those PULs found to have an IPUV at follow-up transvaginal ultrasound scan (TVS) were included in the final analysis. Receiver-operating characteristics (ROC) curves were used to compare the performance of the hCG ratio and progesterone. Using logistic regression, the added value of combining both variables over single-variable prediction was also evaluated. Missing values were imputed using multiple imputation. RESULTS: In total, 12 572 consecutive first-trimester women were scanned. Of these, 1003 (8%) women were classified as having PULs at first scan; 379 (37.8%) PULs were confirmed as IPUVs at follow-up scan, with 82.6% (276/334) found to be viable IUPs and 17.4% (58/334) non-viable IUPs on a second follow-up scan. Forty-five PULs were lost to follow-up. For prediction of viability in IPUVs, the area under the ROC curve (AUC) for the hCG ratio was 0.756 (95% CI, 0.686-0.826) whilst that for progesterone was 0.678 (95% CI, 0.603-0.753). The difference in AUC was 0.078 (95% CI, 0.014-0.169, P = 0.098), suggesting that the hCG ratio was at least as good as initial progesterone. Furthermore, there was no clear threshold for initial progesterone, whilst for hCG a ratio of 2 was suggested (sensitivity 78%, specificity 67%). Logistic regression modeling demonstrated that progesterone did not improve the discriminatory power of the hCG ratio (AUC = 0.758). CONCLUSIONS: The hCG ratio may be preferred to single measurements of progesterone to predict the viability of IPUVs in the PUL population.

Transrectal ultrasound-guided surgical evacuation of Cesarean scar ectopic pregnancy.

OBJECTIVES: To describe a new technique for the management of Cesarean scar ectopic pregnancy (CSEP): transrectal ultrasound (TRS)-guided surgical evacuation. METHODS: All women who presented at our early pregnancy units (EPU) from November 2006 to July 2008 underwent transvaginal sonography. CSEP was diagnosed if all of the following criteria were met: absence of an intrauterine pregnancy; empty endocervical canal; presence of a gestational sac implanted within the lower anterior segment of the uterine corpus, with or without evidence of myometrial thinning. Women were offered TRS-guided surgical evacuation under general anesthesia. Successful treatment was defined as complete primary evacuation of the CSEP. The need to perform additional interventions (emergency cervical cerclage, insertion of Foley's balloon catheter, blood transfusions) was recorded. RESULTS: Of 1195 consecutive women who presented at the EPUs, seven (0.59%) were diagnosed with CSEP. Three (43%) of these were viable at the time of diagnosis. Two (29%) of the seven pregnancies followed in-vitro fertilization; six (86%) women had previously had a single Cesarean section and one had had two. One of these women had a previous tubal ectopic pregnancy, and one a previous CSEP. Three (43%) of the women were asymptomatic. Five (71%) women were treated with TRS-guided surgical evacuation as the primary treatment, whilst two (29%) were given systemic methotrexate, one of whom subsequently underwent TRS-guided aspiration because of failure of conservative management. There were no major complications. CONCLUSIONS: The best treatment for CSEP has yet to be established. TRS-guided surgical evacuation is a novel and potentially alternative treatment modality. However, in the absence of further studies we cannot draw any conclusions, and the management of such women should be individualized.

Expectant management of spontaneous first-trimester miscarriage: prospective validation of the '2-week rule'.

OBJECTIVES: To assess uptake and success of expectant management of first-trimester miscarriage for a finite 14-day period, in order to evaluate our '2-week rule' of management. METHODS: This was a prospective observational study evaluating our proposed 2-week rule of expectant management, which is based on the finding that women managed expectantly are most likely to miscarry in the first 14 days and that to wait longer than 2 weeks without intervention does not confer a greater chance of successful resolution. Eligible women diagnosed with first-trimester miscarriage were offered a choice of expectant management or surgical evacuation under general anesthesia. Inclusion criteria for expectant management were: diagnosis of incomplete miscarriage (heterogeneous tissue, with or without a gestational sac, seen on ultrasound in the uterine cavity and distorting the endometrial midline echo), missed miscarriage (crown-rump length (CRL) >or= 6 mm with absent fetal heart activity) or empty sac (anembryonic pregnancy) based on transvaginal ultrasonography. Women with complete miscarriage, missed miscarriage at the nuchal translucency scan, molar pregnancy or miscarriage >or= 3 weeks in duration (missed miscarriage in which the CRL was >or= 3 weeks smaller than the gestational age based on last menstrual period), or with signs of infection or hemodynamic instability were excluded. Expectant management consisted of weekly ultrasonography for 2 weeks. If after 2 weeks resolution was not complete, surgery was advised. RESULTS: 1062 consecutive pregnant women underwent transvaginal ultrasound examination. Of these, 38.6% (410/1062) were diagnosed with miscarriage, of whom 241 (59%) were symptomatic at the time of presentation and 282 were eligible for the study. These were offered expectant management and 80% (227/282) took up this option. 11% (24/227) were lost to follow-up; therefore, complete data were available on 203 women. Overall spontaneous resolution of miscarriage at 2 weeks was observed in 61% (124/203) of women. Rates of spontaneous resolution at 2 weeks according to the type of miscarriage were 71% for incomplete miscarriage, 53% for empty sac and 35% for missed miscarriage. The incidence of unplanned emergency dilatation and curettage due to gynecological infection or hemorrhage was 2.5% (5/203). CONCLUSIONS: Expectant management based on the 2-week rule is a viable and safe option for women with first-trimester miscarriage. Women with an incomplete miscarriage are apparently the most suitable for expectant management.

Management of women referred to an acute gynecology unit: impact of an ultrasound-based model of care.

OBJECTIVE: To assess the impact of the introduction of an ultrasound-based model of care for women with acute gynecological complications. METHODS: This was a prospective comparative study of women attending an ultrasound-based acute gynecology unit (AGU) at the Nepean Hospital during a 6-week period 4 months after the unit's inception (new model of care), and a group of women presenting at the hospital during a similar period 6 months immediately prior to the unit's inception (traditional model). In the new model of care, ultrasound was performed at the time of the initial assessment by a senior clinician. The main outcome measures were admission rates and occupied bed days. RESULTS: The study included 290 consecutive women with complete data, 133 before and 157 after the introduction of the AGU. Compared with the group presenting before establishment of the AGU, the group who attended the AGU had significantly lower admission rate (7% vs. 36%, P < 0.0001) and significantly shorter time to see a trainee gynecologist (mean, 172 vs. 205 min, P = 0.00089), time to ultrasound examination (mean, 199 vs. 533 min, P < 0.0001), length of stay as an outpatient (mean, 45 vs. 248 min, P < 0.0001), fewer occupied bed days (total, 30 vs. 85 days, P < 0.0001) and lower surgical intervention rates (12% vs. 29%, P = 0.00025). They also had significantly higher expectant management rate (26 vs. 8%, P = 0.00023). The extrapolated annual reduction in occupied bed days represented a total financial saving of $ 257 617 Australian dollars. CONCLUSIONS: In the AGU, the availability of ultrasound carried out by a senior clinician with an interest in gynecological emergencies may lead to a reduction in admissions and improved outcomes.

Does tubal ectopic pregnancy with hemoperitoneum always require surgery?

OBJECTIVE: Hemoperitoneum is accepted as an indication for surgery in women with tubal ectopic pregnancy. The aim of this pilot study was to evaluate the feasibility of managing such women non-surgically. METHODS: This was a prospective observational study. Women with tubal ectopic pregnancy and hemoperitoneum detected on transvaginal sonography (TVS) were managed as inpatients either expectantly or with methotrexate (MTX). Inclusion criteria for conservative management were: compliance, clinical stability, absence of acute abdomen, stable hemoglobin level on two measurements (0 and 12-24 h apart), serum human chorionic gonadotropin (hCG) < 5000 IU/L, absence of fetal cardiac activity on TVS and absence of significant hemoperitoneum, defined as blood above the level of the uterine fundus and/or in Morison's pouch (hepatorenal space). Subsequent management was based upon the hCG ratio at 48 h. All the women were managed as inpatients until the abdominal pain settled and the serum hCG levels were falling. RESULTS: Forty-one women with tubal ectopic pregnancy presented between November 2006 and March 2008. Eight women (20%) fulfilled the entry criteria. The median gestational age at diagnosis was 49 (interquartile range, 38-52.5) days. All women presented with lower abdominal pain/right iliac fossa or left iliac fossa pain. Hemoglobin levels ranged from 11.2 to 14.2 g/dL at presentation and from 12.0 to 14.8 g/dL after 12-24 h. 6/8 (75%) women were managed expectantly and 2/8 (25%) received MTX. All women had resolution of their ectopic pregnancy within 3 weeks with no complications. CONCLUSIONS: This pilot study suggests that the finding of hemoperitoneum on ultrasound examination may not be an absolute contraindication to conservative management of tubal ectopic pregnancy.