Marco Angiolucci

In the use of ‘tenderness-guided’ transvaginal ultrasound, is the diagnostic accuracy of three-dimensional (3D) ultrasonography better than two-dimensional (2D) ultrasonography in the identification of deep endometriosis? Three-dimensional ultrasonography has a significantly higher diagnostic accuracy in the diagnosis of posterior locations of deep endometriosis without intestinal involvement, such as the uterosacral ligaments, vaginal and rectovaginal endometriosis. The only previous study of the diagnosis of posterior compartment endometriosis reported an poor sensitivity of 3D ultrasonography for uterosacral and sigmoid colon involvement. This diagnostic test study included 202 patients scheduled for surgery because of clinical suspicion of deep pelvic endometriosis and was carried out between January 2009 and September 2012. Modified transvaginal ultrasonography was performed on all of the women by a single examiner. Two locations of deep endometriosis were considered: intestinal involvement and other posterior lesions (including vaginal location, rectovaginal septum and uterosacral ligaments). Once the 2D ultrasonography had been performed, the 3D acquisition was performed and the obtained volume was stored. To avoid the risk of recall bias, the same operator evaluated the 3D volumes 6 months after the last examination using virtual navigation to provide a presumptive diagnosis of the presence and localization of deep endometriosis. In addition, to evaluate the reproducibility of 3D, two operators with different levels of expertise performed a retrospective review of 3D volumes from a random sample of 35 patients, twice, 1 week apart to also assess intraobserver agreement. The diagnostic performance of both tests was expressed as area under the receiver-operating characteristics curve (AUC), sensitivity, specificity, positive and negative predictive values, positive (LR+) and negative (LR−) likelihood ratios, with their respective 95% confidence interval (CI). Reproducibility was evaluated using kappa statistics. Surgery revealed deep endometriosis in 129 patients. The AUCs for endometriosis of intestinal location were similar for both ultrasound techniques. The AUCs for endometriosis of other posterior locations were significantly different (0.891, 95% CI 0.839–0.943 for 3D versus 0.789, 95% CI 0.720–0.858 for 2D; P = 0.0193). For the intestinal involvement, the specificity, sensitivity, positive and negative predictive value, and LR+ and LR− were 93% (89−95%), 95% (88–98%), 89% (83–92%), 97% (93–99%), 13, and 0.06, respectively, for 2D ultrasound and 97% (93–99%), 91% (84–94%), 95% (88–98%), 95% (91–96%), 25, and 0.09, respectively, for 3D ultrasound. For other posterior locations, the specificity, sensitivity, positive and negative predictive value, and LR+ and LR− were 88% (82–93%), 71% (64–77%), 83% (75–90%), 79% (74–83%), 6.10, 0.32, respectively, for 2D ultrasound and 94% (89–97%), 87% (81–91%), 92% (86–96%), 90% (85–93%), 14.0, 0.14, respectively, for 3D ultrasound. Intraobserver agreement was substantial for both examiners (kappa 0.8754, for operator A and 0.7087, for operator B, respectively). Interobserver agreement was also substantial. The disadvantages of 3D ultrasound to be considered are the necessity of newer ultrasonographic equipment and that fewer sonographers completely know the 3D technique. There are also some limitations within this study. First, an expert examiner performed the real-time ultrasound and 3D volume acquisitions. Second, the same operator also performed the 3D evaluations but at least 6 months after the last acquisition to avoid a possible recall bias. The diagnostic performance obtained in the present study is superior to the accuracy reported in other studies of 3D ultrasonography, but not superior to all other published articles of 2D ultrasonography. The reported high diagnostic accuracy of 3D ultrasound could be widely generalizable because good reproducibility was demonstrated even with an operator with less expertise. This study was supported in part by the Regione Autonoma della Sardegna (project code CPR-24750).

Introduction: Progesterone (P), and its receptors (PRs), play a key role in uterine leiomyoma growth. Selective progesterone receptor modulators exert mixed antagonist and agonist effects on the PRs. Mifepristone, a PR-antagonist, reduces leiomyoma volume and related symptoms. Ulipristal acetate (UPA) exerts a potent antiprogestin activity, with less antiglucocorticoid activity compared to mifepristone. This property provides potential advantages for long-term use. Areas covered: This paper focuses on the effect of UPA on leiomyoma's growth and related symptoms in women. The authors also evaluate UPA's efficacy in reducing leiomyoma's size and menorrhagia in Phase II/III trials. Expert opinion: In the authors' opinion, UPA (5 mg/day) over 3 months can be used to plan the surgery in women with symptomatic leiomyomas. The tolerability and the safety of treatment over a period longer than 3 months have to be evaluated. The results of the follow-up treatment suggest that further studies could successfully evaluate the efficacy and the tolerability of intermittent 3-month courses of treatment.

Objectives: To identify the abnormal transvaginal ultrasound (TVS) findings typical of aneuploidic pregnancies that end with early pregnancy loss (EPL).Methods: This was a prospective clinical trial over a 2½‐year period from January 2004 to June 2006 at the University Hospital of Cagliari, Italy. One hundred and fifty‐six singleton pregnancies with EPL were evaluated by TVS, both before and at the moment of EPL diagnosis. Fetal karyotyping was performed on products of conception using microsatellite analysis to exclude maternal contamination in 46,XX cases. The proportions of abnormal karyotypes were compared among different groups of EPLs characterized by different morphological features.Results: Six morphological types were identified in EPLs, one normal and five abnormal (small gestational sac, small embryo/fetus, early symmetrical arrested growth, enlarged yolk sac and empty sac). The highest rate of chromosomal abnormalities was observed in the early symmetrical arrested growth group (100%), followed by small embryo/fetus (94.1%), enlarged yolk sac (93.3%) and empty sac (72.2%) groups. The majority of cases of trisomy 22 (92.3%) were in the enlarged yolk sac group and the majority of cases with a 45,X karyotype were in the small embryo/fetus group (77.8%).Conclusions: There is an association in EPLs between some abnormal karyotypes and some morphological types. The demonstration by TVS of abnormalities in the development of early pregnancy structures could be helpful for predicting aneuploidy in EPLs. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Adnexal masses can be classified in ovarian, paraovarian or tubal. In the present review we analyzed the diagnostic performance of transvaginal ultrasonography in identifying simple ultrasonographic findings of benign adnexal pathology but also the role of color Doppler in the differential diagnoses between benign and malignant masses and in the preoperative triage. Because of many kinds of adnexal masses have usually a typical ultrasound appearance, the results of the studies present in literature showed a good and sufficient diagnostic accuracy. Unfortunately some cases with uncertain findings are present and in these cases the addition of color Doppler can be useful as demonstrated by several authors. Using the location of flow evaluated using color Doppler as main parameter a mass should be graded as malignant if flow is shown centrally within the excrescences or solid areas. The same approach should be used to triage the patients with adnexal masses to the most appropriate surgical approach with an increase of less invasive surgery.

Objective. The aim of this prospective study was to investigate the accuracy of B‐mode transvaginal sonography alone and combined with color Doppler imaging and cancer antigen 125 (CA 125) plasma concentrations in differentiating peritoneal cysts from other adnexal masses. Methods. Between September 1999 and September 2003, 213 adnexal masses underwent transvaginal sonography combined with power Doppler evaluation. Plasma concentrations of CA 125 were measured before surgery. The sonographic suspicion of peritoneal cysts (the presence of a bizarre lump‐shaped cyst with a thin wall and fine internal septations with or without an ovary suspended among adhesions) was then compared with the surgical diagnosis. The overall agreement between the sonographic test results and the surgical findings was calculated by the κ index. The diagnostic value of each test was also evaluated with likelihood ratios (LRs). Results. Thirteen of 213 patients were found to have peritoneal cysts. Specificity and sensitivity of B‐mode sonography for differentiating peritoneal cysts from other adnexal masses were 96% (95% confidence interval, 94%–97%) and 62% (95% confidence interval, 35%–83%), respectively. The value of the negative LR (0.40) indicated a good clinical test, whereas the positive LR (15) indicated an excellent test. Power Doppler imaging did not seem to increase the accuracy of B‐mode transvaginal sonography (κ = 0.51 and 0.52, respectively), nor did the association of CA 125 plasma concentration (κ = 0.34). Conclusions. Transvaginal sonography alone is a useful method for detection of peritoneal cysts.

OBJECTIVE: Several effects of melatonin are modulated by gonadal steroids and are reduced in ageing women. Administration of melatonin reduces internal carotid artery pulsatility index (PI), and blood pressure in young individuals. Whether these effects are conserved in postmenopausal women and are influenced by hormone replacement therapy (HRT), was herein investigated.DESIGN: Randomised, double‐blind placebo controlled study.PATIENTS: Twenty‐three postmenopausal women of which 11 were unreplaced with HRT and 12 on the oestrogenic phase of continuous transdermal estradiol (50 µg/day) plus cyclic medroxyprogesterone acetate (5 mg/day × 12 days every 28 days).MEASUREMENTS: Internal carotid PI, by colour Doppler, and supine blood pressure were evaluated 90, 180 and 240 minutes following the oral administration of melatonin (1 mg) or placebo. Levels of nitrites/nitrates (NOx), the stable derivatives of nitric oxide, were also evaluated in samples collected 90 minutes following the administration of placebo or melatonin.RESULTS: In women not on replacement therapy melatonin was ineffective. In HRT‐treated women, melatonin reduced internal carotid artery PI (P = 0·005). The effect was maximal within 90 minutes, and maintained for at least 240 minutes, with melatonin levels in the nocturnal physiological range. Systolic and diastolic blood pressures were reduced of 8 mmHg (P = 0·038) and 4 mmHg (P = 0·045), respectively, while NOx levels were significantly increased (P = 0·024).CONCLUSIONS: The circulatory response to melatonin is conserved in postmenopausal women with but not without hormone replacement therapy. Maintenance of the cardiovascular response to melatonin, may be implicated in the reduced cardiovascular risk of postmenopausal women with hormone replacement therapy.

In young men and women, melatonin influences vascular reactivity and reduces blood pressure and norepinephrine levels. Herein, we investigated whether these effects are conserved in postmenopausal women without and with hormone replacement therapy (HRT). Oral melatonin (1 mg) or placebo was randomly and in double blind fashion administered to 18 untreated and 13 postmenopausal women who were treated continuously with transdermal estradiol (50 μg/day) plus cyclic medroxyprogesterone acetate (5 mg/day×12 days every 28 days). Internal carotid artery pulsatility index (PI), an index of downstream resistance to blood flow, blood pressure and catecholamine levels were evaluated. In untreated postmenopausal women, melatonin was ineffective, while in HRT‐treated women, studied during the only estrogenic phase, melatonin reduced, within 90 min, systolic (−8.1±9.9 mmHg; P=0.054), diastolic (−5.0±7.0 mmHg; P=0.049) and mean (−6.0±6.6 mmHg; P=0.037) blood pressure. Norepinephrine (−50.1±66.7 pg/mL; P=0.019), but not epinephrine levels, were also significantly reduced. Similarly, resistance to blood flow in the internal carotid artery, as evaluated by the PI, decreased (−0.190±0.15; P=0.0006) in a way that was linearly related to pre‐existing PI values (r²=0.5; P=0.0059). These data show that the circulatory response to melatonin is conserved in postmenopausal women on HRT but not in untreated postmenopausal women. Possible physiological and pharmacological implications of these data on the cardiovascular risk of postmenopausal women can be envisioned.

To evaluate the short- and long-term effect on the uterus, endometrium, and vascular reactivity of uterine arteries of sequential transdermal estradiol (50 microg/day) and norethisterone (0.25 mg/day in the last 14 days of each cycle). An intravaginal ultrasound evaluation was performed in 48 postmenopausal women before and at the 3rd and 12th month of treatment, during the last 3 days of both estradiol alone and estradiol plus norethisterone. An endometrial biopsy was also performed before and at the end of treatment. In 11 participants, intravaginal ultrasound and endometrial biopsy were repeated after 48 months of treatment. Uterine volume (33.7 +/- 3.3 cm3 to 56.8 +/- 3.7 cm3; p = 0.001) and endometrial thickness (3.07 +/- 0.48 mm to 5.74 +/- 0.41 mm; p = 0.001) increased within 3 months, with no further increases. Thickness was similar in the estradiol and estradiol-norethisterone phase. Endometrial hyperplasia was found in one participant at 12 months of treatment. A significant decrease (p = 0.002) in the pulsatility index of uterine arteries was observed only during the estradiol phase. After 48 months of treatment, the pulsatility index of uterine arteries was lower than at baseline (2.78 +/- 0.24 vs. 2.23 +/- 0.33; p = 0.044) even when evaluated in the combined phase. The transdermal administration of sequential estradiol and norethisterone reduces uterine artery resistance and induces a self-limiting growth of the uterus and endometrium.