Bruno Cacciatore

Diagnosis of ectopic pregnancy by vaginal ultrasonography in combination with a discriminatory serum hCG level of 1000 IU/1 (IRP)

Summary. The diagnostic value of vaginal sonography in combination with a discriminatory serum hCG level of 1000 iu/1 (International Reference Preparation) was tested prospectively in 200 pregnant women suspected of having an ectopic pregnancy. An ectopic pregnancy was diagnosed in 68 women (34%), a miscarriage in 56 (28%) and a normal pregnancy in 76 (38%). On admission, an intrauterinc sac was seen in 89% of the intrauterinc pregnancies, but in none of the ectopic pregnancies. Detection of an adnexal mass separate from the ovaries was diagnostic of ectopic pregnancy with a sensitivity of 93%, a specificity of 99%, a positive predictive value of 98% and a negative predictive value of 96%. Tn 19 patients (9%) the initial sonogram was non‐diagnostic and the final diagnosis was obtained after a repeated scan within 6 days. Five of these women had an ectopic pregnancy, 12 a miscarriage and two a normal pregnancy. On admission the hCG level exceeded 1000 iu/1 in 77% of all patients and in 67% of those with ectopic pregnancies. In patients with an initial level exceeding 1000 iu/1, an intrauterine sac was found in all the intrauterine pregnancies but in none of the ectopic pregnancies. The use of this threshold in combination with sonographic detection of an adnexal mass was diagnostic of ectopic pregnancy with a sensitivity of 97%, a specificity of 99%, a positive predictive value of 98% and a negative predictive value of 98%.

Polycystic ovaries and levels of gonadotrophins and androgens in recurrent miscarriage: prospective study in 50 women

Objective To compare the serum levels of gonadotrophins and androgens, as well as ovarian morphology, in 50 women with a history of recurrent miscarriage and in 20 healthy controls.

Transvaginal sonography and hysteroscopy in postmenopausal bleeding

We compared transvaginal sonography and hysteroscopy with dilatation and curettage findings in 45 women with atypical postmenopausal bleedings. The histological diagnosis was atrophy in eight (17.8%) women. hormonal effects in 14 (31.1%), endometrial polyp in 19 (42.2%) xnd adenocarcinoma in four (8.8%). Hysteroscopy detected 16 (78.9%) of the 19 cases wirh polyps and two of the four with carcinoma. Sensitivity and specificity for endometrial pathology were 86.9% and 91.7% respectively. A polyp was directly diagnosed by transvaginal sonography in 13 (57.9%) women and an infiltrative endometrial cancer in two. Sensitivily and specificity for endometrial pathology were 73.9%) and 95.7% respectively. All but one case of endometrial pathology were found when the endometrium (both layers) was thicker than 5 mm. Thus, an endometrial thickness of ≥ 5 mm had a sensitivity of 95.7%, a specificity of 45.5% and a positive predictive value of 64.7% for endometrial pathology. This study shows that transvaginal scanning allows detection of an endometrial pathology in the vast majority of cases and it may be used as the first diagnostic step in the investigation of women with atypical postmenopausal bleeding.

Transvaginal Doppler study of uterine artery blood flow in in vitro fertilization-embryo transfer cycles

OBJECTIVE To verify whether uterine artery impedance, measured as pulsatility index and resistance index is related to the outcome of in IVF-ET cycles. DESIGN Prospective study of infertile women participating in an IVF-ET program. SETTING University Hospital. PATIENTS Two hundred women (24 to 40 years of age), who had one to three good quality embryos transferred to the uterus after a standardized IVF cycle. INTERVENTION Transvaginal color Doppler and a blood sample on the day of ET. MAIN OUTCOME MEASURES Uterine artery pulsatility index and resistance index, endometrial thickness, serum E2 and P concentrations, clinical pregnancy rate (PR). RESULTS Pulsatility indices and resistance indices were lower in conception (2.45 +/- 0.54 and 0.85 +/- 0.04, respectively) than in nonconception cycles (2.66 +/- 0.39 and 0.87 +/- 0.04, respectively), although the overlap of the values is considerable. Overall PR was 35% per ET, and it decreased significantly when pulsatility index was > 3.0 (15%) and resistance index > 0.92 (13%), being lowest when pulsatility index was > 3.3 and resistance index > 0.95 (10%). Such a high impedance was detected in 9% of nonconception cycles. CONCLUSION In IVF-ET cycles the uterus is likely to be unreceptive when uterine artery pulsatility index is > 3.3 and resistance index > 0.95 before ET, but this occurs only in 9% of the cycles.

Early screening for ectopic pregnancy in high-risk symptom-free women

We screened 225 symptom-free pregnant women at increased risk for ectopic pregnancy with transvaginal sonography and human chorionic gonadotropin (hCG) assays. Among 55 (24.4%), who proved to have an ectopic pregnancy, 46 (84%) cases were diagnosed at the initial screening at a median of 37 days of gestation, and the rest at repeated scans. The false-positive rate was 1.2%. Early diagnosis prevented tubal rupture, substantial haemorrhage, and the need for emergency care, allowing elective treatment. Such early surveillance reduced the risk of complications and facilitated treatment, and should be offered to at-risk women.

The long-term effects of oral and transdermal postmenopausal hormone replacement therapy on nitric oxide, endothelin-1, prostacyclin, and thromboxane.

OBJECTIVE Oral postmenopausal hormone replacement therapy (HRT) decreases the risk of cardiovascular disorders, but the mechanisms of this protection are largely unknown. We compared the long-term effects of sequential oral HRT and transdermal HRT on vasodilatory nitric oxide and prostacyclin as well as vasoconstrictive endothelin- and thromboxane A2, all of which may be factors in the protective effect of HRT against cardiovascular disorders. DESIGN Prospective, randomized study. SETTING Department of Obstetrics and Gynecology at a university hospital. PATIENT(S) Fifty-two healthy postmenopausal female nonsmokers (n = 42) or smokers (n = 10) who had climacteric symptoms. INTERVENTION(S) The women received either oral HRT (2 mg of estradiol on days 1-12, 2 mg of estradiol plus 1 mg of norethisterone acetate on days 13-22, and 1 mg of estradiol on days 23-28; n = 21) or transdermal HRT (50 microg/d of estradiol on days 1-28 followed by 250 microg/d of norethisterone acetate on days 14-28; n = 21) for 1 year. Ten female smokers received transdermal HRT for 1 year. MAIN OUTCOME MEASURE(S) Plasma levels of nitrate as an index of nitric oxide production, endothelin-1, and urinary output of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha) and that of the thromboxane A2 metabolite (2,3-dinorthromboxane B2) were measured before and during the combined phases of the 2nd, 6th, and 12th treatment months. RESULT(S) Both regimens increased plasma estradiol levels and alleviated vasomotor symptoms. Neither regimen caused significant changes in nitrate, endothelin-1, prostacyclin, or thromboxane A2 in nonsmoking women. Female smokers had significantly higher levels of endothelin-1, which were significantly reduced by transdermal HRT at 6 months of treatment. CONCLUSION(S) Nitric oxide, endothelin-1, prostacyclin, and thromboxane A2 are not of primary importance in the protective effect of sequential oral HRT against cardiovascular disorders in otherwise healthy nonsmoking postmenopausal women. In this regard, transdermal HRT appears comparable to oral HRT. Postmenopausal female smokers have high levels of endothelin-1 that are reduced by transdermal HRT.

Preoperative sonographic evaluation of endometrial cancer

Preoperative sonography was performed in 93 patients with a histologic diagnosis of endometrial cancer. Uterine volume was enlarged (mean, 164 +/- 143.7 cm3; range, 25 to 800) but did not significantly correlate with the degree of myometrial invasion. Endometrial echoes were identified in 93.5% of the cases. A significant correlation (p less than 0.01, Newman-Keuls test) was found between endometrial echoes volume and myometrial invasion. Myometrial invasion was correctly predicted by sonography in 80% of the cases. Polypoid intraluminal growth was the most common factor affecting sonographic accuracy. Sonographic staging was accurate in 91% of the cases. Sonography appears to be an efficient, economic, and practical tool for clinical staging of endometrial cancer.

Suspected ectopic pregnancy: ultrasound findings and hCG levels assessed by an immunofluorometric assay

Summary. One hundred suspected ectopic pregnancies were assessed by ultrasound on the basis of the following criteria: (A) viable intrautcrine fetus, intrauterine pregnancy is certain; (B) intrauterine double sac or eccentric ring, intrauterine pregnancy is probable; (C) empty uterus or central ring but no adnexal mass or cul‐de‐sac fluid, ectopic pregnancy is possible; (D) empty uterus or central ring and an adnexal mass or cul‐de‐sac fluid, ectopic pregnancy is probable; (E) viable ectopic fetus, ectopic pregnancy is certain. Serum human chorionic gonadotrophin (S‐hCG) was detected by an immunofluorometric assay (sensitivity 0.2 i.u./l, cut‐off level 10 i.u./l). All the 51 patients in groups A and B had an intrauterine pregnancy. Normal gestational sacs were found also at S‐hCG levels of <3600 i.u./l, the lowest level being 894 i.u./l. Ectopic pregnancy was confirmed in 29 of the 30 women in groups D and E. In the 19 women categorized into group C serial hCG assay and repeated sonography diagnosed ectopic pregnancy in 12 and miscarriage of an intrauterine pregnancy in the other seven. Ectopic pregnancy was always found when no gestational sac was seen by sonography and the hCG level was > 1000 i.u./l.

Effects of ospemifene, a novel Serm, on vascular markers and function in healthy, postmenopausal women

ObjectiveOspemifene, a novel selective estrogen receptor modulator (SERM), shows promise for bone preservation in postmenopausal women. This study examined the effects of ospemifene on different vascular surrogate markers. DesignA double-blinded study was conducted in 160 healthy, postmenopausal women who used, in a randomized order, ospemifene (at daily doses of 30, 60, or 90 mg) or placebo for 3 months. ResultsAlthough ospemifene caused falls from basal levels in total cholesterol, low-density lipoprotein cholesterol, oxidized low-density lipoprotein cholesterol, and a rise in high-density lipoprotein cholesterol, the only statistically significant difference between ospemifene and placebo was an increase of triglyceride levels (11.3%) in the 90-mg group. Ospemifene caused no significant effect on endothelial markers or homocysteine. Of the markers reflecting coagulation and fibrinolysis, plasma fibrinogen was significantly reduced in the 60- and 90-mg groups of ospemifene (8.7% and 8.5%, respectively) when compared with the placebo group. No changes were seen in generation of thrombin or degradation of crosslinked fibrin D-dimer. The uterine or carotid arteries and 24-h ambulatory blood pressure were not affected by ospemifene. Ospemifene caused no changes in basal insulin or in a 2-h glucose tolerance test, suggesting unaltered insulin sensitivity. ConclusionsNeutral effects of short-term use of ospemifene on vascular surrogate markers imply no effect for ospemifene on the risk for cardiovascular disorders in healthy, postmenopausal women.

Prospective study on gynaecological effects of two antioestrogens tamoxifen and toremifene in postmenopausal women

To assess and compare the gynaecological consequences of the use of 2 antioestrogens we examined 167 postmenopausal breast cancer patients before and during the use of either tamoxifen (20 mg/day, n = 84) or toremifene (40 mg/day, n = 83) as an adjuvant treatment of stage II–III breast cancer. Detailed interview concerning menopausal symptoms, pelvic examination including transvaginal sonography (TVS) and collection of endometrial sample were performed at baseline and at 6, 12, 24 and 36 months of treatment. In a subgroup of 30 women (15 using tamoxifen and 15 toremifene) pulsatility index (PI) in an uterine artery was measured before and at 6 and 12 months of treatment. The mean (±SD) follow-up time was 2.3 ± 0.8 years. 35% of the patients complained of vasomotor symptoms before the start of the trial. This rate increased to 60.0% during the first year of the trial, being similar among patients using tamoxifen (57.1%) and toremifene (62.7%). Vaginal dryness, which was present in 6.0% at baseline, increased during the use of tamoxifen (26.2%) and toremifene (24.1%). Endometrial thickness increased from baseline (3.9 ± 2.7 mm) to 6.8 ± 4.2 mm at 6 months (P< 0.001), and no difference emerged between the 2 regimens in this regard. Before the start of the antioestrogen regimen, the endometrium was atrophic in 71 (75.5%) and proliferative in 19 of 94 (20.2%) samples; 4 patients had benign endometrial polyps. During the use of antioestrogen altogether 339 endometrial samples were taken (159 in tamoxifen group, 180 in toremifene group). The endometrium was proliferative more often in the tamoxifen group (47.8%) than in the toremifene group (32.2%) (P< 0.0001). 20 patients had a total of 24 polyps (17 in tamoxifen and 9 in toremifene group, P< 0.05) during the use of antioestrogens. One patient in the toremifene group developed endometrial adenocarcinoma at 12 months, and one patient had breast cancer metastasis on the endometrium. Tamoxifen failed to affect the PI in the uterine artery, but toremifene reduced it by 15.0% (P< 0.05) by 12 months. In conclusion, tamoxifen and toremifene cause similarly vasomotor and vaginal symptoms. Neither regimen led to the development of premalignant endometrial changes. Our data suggest that so close endometrial surveillance as used in our study may not be mandatory during the first 3 years of use of antioestrogen treatment.