Association between different morphological types and abnormal karyotypes in early pregnancy loss.

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.

Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy.

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 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 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.

Different circulatory response to melatonin in postmenopausal women without and 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 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 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.

Transdermal administration of estradiol and norethisterone: effect on the uterus and uterine arteries.

OBJECTIVE: 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). DESIGN: 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. RESULTS: 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. CONCLUSIONS: The transdermal administration of sequential estradiol and norethisterone reduces uterine artery resistance and induces a self-limiting growth of the uterus and endometrium.

Oral contraceptives and vascular reactivity of great vessels in women.

Blood pressure and great vessel vascular reactivity, evaluated by color Doppler ultrasound, were investigated in users of third-generation oral contraceptives (n = 18) compared to non-users, who were studied either in the follicular (n = 8) or in the luteal (n = 10) phase of the menstrual cycle. Blood pressure measured at rest in the supine position, evaluated both in the follicular phase and in the luteal phase, was similar between oral contraceptive users and non-users. The pulsatility index (an indirect index of resistance to blood flow) of both the internal carotid artery and the axillary artery was similar in control women studied in the follicular phase and in the luteal phase. By contrast, in users of oral contraceptives, pulsatility index values of the internal carotid artery tended to be higher, whilst those of the axillary artery were significantly higher, than those of women in either the follicular phase (p < 0.01) or the luteal phase (p < 0.025). In conclusion, new third-generation oral contraceptives do not have a significant impact on blood pressure control, but still tend to increase vascular resistance to blood flow, particularly in areas more involved in the regulation of blood pressure, for example the axillary artery.

Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men.

In this study it was investigated whether the oral administration of melatonin (1 mg) in comparison to placebo was able to reduce blood pressure, vascular reactivity, and catecholamines in men, as previously reported in young women. The administration of melatonin significantly reduced blood pressure, the pulsatility index in the internal carotid artery, and catecholamines levels within 90 minutes. The effect of melatonin on the artery pulsatility index was related to baseline values, being greater in men with higher baseline values. The present data indicate that melatonin may blunt the activity of the cardiovascular system and may have both physiopathologic and clinical implications.

Diagnosis of adnexal malignancies by using color Doppler energy imaging as a secondary test in persistent masses.

The purpose of this prospective study was to compare the accuracy of B-mode transvaginal ultrasonography alone and in combination with color Doppler energy (or power Doppler) imaging in differentiating benign from malignant adnexal masses. A total of 192 consecutive persistent adnexal masses (159 benign, 33 malignant) were studied before surgery by B-mode transvaginal ultrasonography with and without color Doppler energy. In addition, CA-125 plasma levels were determined and spectral Doppler analysis was performed. By color Doppler energy imaging, a mass was considered malignant when arterial flow was visualized in an echogenic portion of a mass defined as malignant by B-mode. Intratumoral arterial blood flow could be readily detected by color Doppler energy imaging in all malignant tumors and in 94% of the benign tumors. The combined use of transvaginal B-mode ultrasonography and color Doppler energy imaging has greater accuracy in the diagnosis of ovarian malignancies than transvaginal ultrasonography alone (value of kappa: 0.81 and 0.63, respectively), reducing the number of false-positive results. The use of spectral Doppler analysis was of limited diagnostic value, with a kappa value of 0.17 for the pulsatility index (< 1) and of 0.41 for the resistance index (< 0.4). Also, the association with CA-125 increased the number of false-negative results. In conclusion, the use of color Doppler energy imaging seems to be a useful secondary test when a mass is suspected to be malignant by B-mode ultrasonography.

Influences of melatonin administration on the circulation of women.

The cardiovascular effects induced by the daytime administration of melatonin (1 mg) were compared with those of placebo in 17 young, healthy, early follicular-phase women. Compared with placebo, the administration of melatonin modified, within 90 min, the pulsatility index (PI), evaluated by color Doppler ultrasound, of the internal carotid artery, abdominal aorta, and axillary artery. The effect was linearly related to baseline PI, higher baseline PI being associated with greater PI declines. Melatonin administration significantly decreased mean PI of internal carotid artery (P < 0.02), systolic and diastolic blood pressure (P < 0.01), and norepinephrine levels evaluated after 5 min of standing position (P < 0.02). Heart rate and supine catecholamine levels were not modified. These data indicate that in young, healthy women the administration of 1 mg of melatonin greatly influences artery blood flow, decreases blood pressure, and blunts noradrenergic activation. Clinical implications of present data are worthy to be fully explored.

Effect of desogestrel-containing oral contraceptives on vascular reactivity and catecholamine levels.

The modifications induced by new oral contraceptives (OC) on blood pressure, great vessel vascular reactivity by color Doppler, and catecholamine levels were investigated. Young healthy women not taking OC (n = 22; controls) or receiving, for > or = 6 months, OC containing desogestrel with either 30 micrograms (n = 14) or 20 micrograms of EE (n = 8) were enrolled. Blood pressure measured at rest in supine position was similar between controls and OC users. The pulsatility index (PI), an indirect index of resistance to blood flow, of axillary artery was significantly higher (p < 0.05) in 30 micrograms than in 20 micrograms EE OC users or controls. A similar trend, albeit not significant, was observed for the internal carotid artery PI. Norepinephrine (p < 0.01) and dopamine (p < 0.05) but not epinephrine levels, were lower in 30 micrograms EE OC users than in 20 micrograms EE OC users or controls. Thus, both 20 micrograms and 30 micrograms EE OC had no negative effect on blood pressure, but the 30 micrograms EE OC tended to increase great vessel resistance to blood flow, independently of catecholamine levels.

PIP: The effects on blood pressure of oral contraceptives (OCs) containing desogestrel plus either 20 or 30 mcg of ethinyl estradiol were investigated in 22 women who had been using one of these formulations for 6 months or more and 22 matched controls. There were no significant differences between both groups of cases and controls in blood pressure measured at rest in supine position. However, subtle differences were recorded in vascular reactivity, as evaluated by color Doppler ultrasound investigation. Compared to controls and users of OCs containing 20 mcg of ethinyl estradiol, cases taking OCs consisting of 30 mcg of ethinyl estradiol had a significantly higher pulsatility index in the axillary artery, indicating increased vessel resistance to blood flow. A similar, although not significant, trend was found in the internal carotid artery pulsatility index. On the other hand, catecholamine (dopamine and norepinephrine) levels were reduced by both OCs in a dose-dependent manner. Overall, these findings suggest that third-generation OCs, especially those containing 20 mcg of ethinyl estradiol, exert minimal effects on circulatory parameters. It is hypothesized that the cardiovascular effects of catecholamine reduction are antagonized by other mechanisms, among them the stimulus on the renin-angiotensin system.

Color Doppler energy imaging in the diagnosis of fetal intracranial hemorrhage in the second trimester.

Unlike conventional color Doppler imaging; color Doppler energy (or power Doppler) displays the intensity of the returning Doppler signal, is less dependent on the orientation of the blood vessel, and is therefore better able to detect low blood velocities. For these reasons it could be useful in some investigations which are difficult to perform, such as transvaginal evaluation of fetal brain vessels. We report a case of a fetal intracranial hyperechoic lesion detected at 26 weeks by transabdominal sonography in a severely growth-retarded fetus. There was absence of diastolic flow in the umbilical artery and low impedance to diastolic flow in the middle cerebral arteries. The fetus was further investigated by transvaginal sonography for the evaluation of the nature and localization of the lesion and an intraventricular hemorrhage in the right brain parenchyma with disorganized supratentorial brain structure was observed. As color Doppler energy imaging is more sensitive to slow flow, it was more reliable than conventional Doppler imaging in confirming the absence of flow within and around the hyperechoic lesion in contrast to the normal vascularity of the contralateral ventricular system. After informed parental counselling, the mother, for psychological reasons, asked to be delivered by Cesarean section. The fetus died 24 h after birth. The autopsy corroborated the ultrasonographic diagnosis. This case report confirms the accuracy of transvaginal ultrasonography in the diagnosis of intracranial hemorrhage and suggests a specific role for color Doppler energy imaging.

Transvaginal ultrasound and computed tomography combined with clinical parameters and CA-125 determinations in the differential diagnosis of persistent ovarian cysts in premenopausal women.

The purpose of this prospective study was to compare the accuracy of computed tomography (CT) and transvaginal ultrasonography in the differential diagnosis of persistent cystic ovarian lesions. The candidates for this study were 161 premenopausal non-pregnant women with an adnexal mass. After a 3-month follow-up, 83 masses persisted and were examined by both techniques before surgery. We also evaluated the CA-125 plasma levels. The CT and ultrasonographic diagnoses were then compared with the histopathological diagnosis. The overall agreement between the test results and the actual outcome was calculated by means of the kappa statistic. Transvaginal ultrasonography has a closer accuracy in the diagnosis of serous cysts and serous cystadenoma, ovarian carcinoma and endometrioma (value of kappa: 0.78, 0.73 and 0.80, respectively) than CT, even if the latter is associated with clinical and biochemical parameters such as patient's age and CA-125 plasma levels. Only in the diagnosis of cystic teratoma, is transvaginal ultrasonography less accurate than CT. In conclusion, in premenopausal women, transvaginal ultrasonography remains a cost-effective method in the diagnosis of most cystic ovarian lesions.

Potentially beneficial cardiovascular effects of melatonin administration in women.

The cardiovascular effects induced by the daytime administration of melatonin (1 mg) were compared to those of placebo in 12 young women. In order to eliminate cardiovascular effects due to fluctuating endogenous sex steroids, all women were taking a fixed dose of monophasic contraceptive pill. In comparison to placebo, the administration of melatonin reduced, within 90 min, the pulsatility index of the internal carotid artery, evaluated by color Doppler ultrasound (P < 0.01), as well as both systolic and diastolic blood pressure evaluated in supine position (P < 0.01). Supine catecholamine levels were not significantly modified, but norepinephrine levels evaluated after 5 min of standing position were significantly reduced (P < 0.02). These data suggest that in women the administration of 1 mg of melatonin may exert beneficial effects on blood vessels.

Tumor markers and transvaginal ultrasonography in the diagnosis of endometrioma.

OBJECTIVE: To evaluate the accuracy of CA 19.9 plasma levels (with or without CA 125 levels) combined with transvaginal ultrasonography in the differential diagnosis of endometrioma. METHODS: One hundred eighteen consecutive premenopausal nonpregnant women had laparoscopy or laparotomy between November 1994 and November 1995 because of the presence of a persistent adnexal mass. They underwent transvaginal ultrasonography and measurement of CA 19.9 and CA 125 plasma levels within 2 days before surgery. The ultrasonographic impression and the tumor marker values were compared with the histopathologic diagnosis. The overall agreement between the test result and the actual outcome was calculated using the kappa statistic. RESULTS: Transvaginal ultrasonography had a strong agreement between test result and surgery (kappa value 0.84), whereas the combined methods were associated with a lower kappa value (range 0.24-0.80). CONCLUSION: Transvaginal ultrasonography used alone is the most cost-effective method in the preoperative differential diagnosis of endometrioma.

Transvaginal ultrasonography combined with CA-125 plasma levels in the diagnosis of endometrioma.

OBJECTIVE: To assess the role of transvaginal ultrasonography combined with CA-125 plasma levels in the diagnosis of endometrioma. DESIGN: Prospective study with pathological confirmation of the diagnosis. SETTING: Department of Obstetrics and Gynecology of the University of Cagliari, Italy. PATIENTS: One hundred one consecutive premenopausal nonpregnant women submitted to laparoscopy or laparotomy, from November 1993 to October 1994, because of the presence of an adnexal mass. INTERVENTIONS: Within 2 days before surgery all patients underwent transvaginal ultrasonography and evaluation of CA-125 plasma levels. The ultrasonographic impression and the CA-125 value were then compared with the histopathological diagnosis. MAIN OUTCOME MEASURE: The overall agreement between the test result and the actual outcome was calculated using the kappa index for the transvaginal ultrasonography used alone and for the combination of transvaginal ultrasonography and CA-125 values, for each chosen cutoff and range. RESULTS: Transvaginal ultrasonography has a strong agreement between test and surgery (kappa value 0.76) whereas the combined use of the two methods is associated with a lower kappa index, ranging from 0.40 to 0.69. CONCLUSION: Transvaginal ultrasonography used alone has a better predictive capacity in differentiating endometrioma from other adnexal masses than combined methods.

Transvaginal ultrasonography in the diagnosis of cystic teratoma.

OBJECTIVE: To assess prospectively the role of transvaginal ultrasonography in screening for cystic teratoma and in differentiating cystic teratoma from other ovarian masses. METHODS: Three hundred seventy-six premenopausal non-pregnant women underwent transvaginal ultrasonography 1 week before undergoing laparotomy or laparoscopy. The visualization of localized or diffuse echogenicity was chosen as the characteristic ultrasonographic finding of cystic teratoma. Endosonographic diagnosis was compared with surgical and pathologic findings. RESULTS: Sensitivity and specificity for the ultrasonographic screening were 57.9 and 99.7%, respectively, calculated for each visualized ovary (n = 659), and 84.6 and 98.2%, respectively, for differentiating cystic teratoma from other ovarian masses, calculated for each visualized cyst (n = 123). CONCLUSION: Transvaginal ultrasonography has a better predictive ability for differentiating cystic teratoma from other ovarian masses (kappa value 0.84) than in screening for cystic teratomas (kappa value 0.69).

The role of endovaginal ultrasound in differentiating endometriomas from other ovarian cysts.

Endometriomas have a prevalence of 24% among all ovarian cysts. Various sonographic features have been proposed to identify endometriomas. Although the visualization of ovarian masses with low-level internal echoes is suggestive for the endometriotic origin of the cyst, no data are yet available on the specificity of endovaginal ultrasonography in differentiating endometriomas from other ovarian masses. To address this issue, the sensitivity, specificity, negative and positive predictive values of endovaginal ultrasonography in comparison with pathology were calculated for each visualized cyst. The study population (n = 251) consisted of all premenopausal non pregnant women submitted to laparotomy or laparoscopy between May 1991 and March 1993 at the Department of Obstetrics and Gynecology of the University of Cagliari. Within one week before surgery, all patients underwent endovaginal ultrasonography and 93 ovarian cysts were visualized. After the scan, the physician gave prospective impressions as to the presence of endometriomas using the visualization of round-shaped homogeneous hypoechoic "tissue" of low-level echoes within the ovary as characteristic ultrasonographic finding. Ultrasonographic impression was compared with histopathological diagnosis. Out of 93 adnexal masses detected by ultrasound, 31 were suspected to be endometriomas and the diagnosis was confirmed in 24. The sensitivity and the specificity of endovaginal ultrasonography in differentiating endometriomas from other ovarian cysts were 83% and 89%, respectively. This specificity (89%) is comparable with that obtainable with magnetic resonance imaging (91%).

Role of goserelin-depot in the clinical management of uterine fibroids.

On 30 women suffering from uterine fibroids, the monthly subcutaneous administration of goserelin depot (3.6 mg) for 6 (n = 22) or 12 months (n = 8) induced an about 50% shrinkage of uterus and fibroid volume, and within 3 months, an increase in the haematocrit value, with no metabolic side effects or detectable bone demineralization, evaluated by single photon absortiometry at distal radius. Both uterine and fibroid volumes reversed to pretreatment values after 3 months of goserelin depot withdrawal. In comparison with untreated subjects, on another 10 patients a three month administration of goserelin depot reduced the loss of blood during the surgical removal of the uterus or fibroids. Present data indicate that goserelin depot is effective and relatively safe in the medical management of uterine fibroids. Although, goserelin depot cannot yet be proposed as a definite medical therapy, it may represent a useful instrument in the presurgical management of uterine fibroids.

The efficiency of transvaginal ultrasonography in the diagnosis of endometrioma.

OBJECTIVE: To assess the efficiency of transvaginal ultrasonography in the screening of endometriomas and in differentiating endometriomas from other ovarian masses. DESIGN: Prospective study with surgical and pathological confirmation of the sonographic diagnosis. SETTING: Department of Obstetrics and Gynecology at the University of Cagliari, Cagliari, Italy. PATIENTS: All premenopausal nonpregnant women (n = 236) submitted to laparotomy or laparoscopy from May 1991 to December 1992. INTERVENTIONS: Transvaginal ultrasonographic examinations were done within 1 week before surgery. Ultrasonographic diagnosis was compared with surgical and histopathological findings. MAIN OUTCOME MEASURE: The visualization of round-shaped homogeneous hypoechoic "tissue" of low-level echoes within the ovary was chosen as characteristic ultrasonographic finding of endometrioma. Sensitivity, specificity, and predicted values were calculated for each visualized ovary (group A) to assess the efficiency in the screening, and for each visualized cyst (group B) to assess the efficiency in differentiating endometriomas from other ovarian masses. RESULTS: Four hundred twenty-three of 466 ovaries were visualized. Of the 82 visualized cysts, 27 were suspected to be endometriomas, and the diagnosis was confirmed by pathology in 21. The sensitivity and the specificity were 75% and 99%, respectively, in group A, and 84% and 90%, respectively, in group B. CONCLUSION: The study demonstrates that transvaginal ultrasonography has an efficiency of 88% in differentiating endometriomas from other ovarian masses with a specificity of 90%.