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Postmenopausal breast cancer patients who were treated with tamoxifen and progestogens showed a uniform decidual reaction of the endometrium. It is well established that progestogens antagonize the estrogen effect on the endometrium by reducing its receptors in the endometrium. To assess in vivo such a possible effect of progestogens on endometrium primarily exposed to tamoxifen, we analyzed estrogen and progesterone receptors (ER, PR) on endometrial specimens showing decidualization from nine postmenopausal breast cancer patients on tamoxifen and progestogen treatment and on endometrial polyps with areas of decidualization from two other similar patients. ER was weakly detected in the endometrial glands of four (36.4%) patients and in the endometrial stroma of one (9.1%) patient. PR was detected in the endometrial gland of only one (9.1%) patient. No PR was detected in the endometrial stroma. There was no correlation between the length of tamoxifen treatment, the tamoxifen dosage, or the length of progestogen treatment and the ER or PR content, although progestogens were administered for more than 3 consecutive months in all patients. This relatively very low ER and PR content may be attributed to the antagonistic effect of progestogens on the "priming" estrogen-like effect of tamoxifen on the endometrium.

A prospective study was performed to assess the efficacy of sonohysterography (SHG) in identifying endometrial pathologies among asymptomatic, postmenopausal breast cancer patients treated with tamoxifen. In this study the uterine cavity of 68 such patients with endometrial thickness of > or = 8 mm was prospectively evaluated by SHG. Forty-six (67.6%) patients in whom SHG did not identify any findings in the uterine cavity (negative group) were followed by diagnostic hysteroscopy. Another 22 (32.4%) who were identified by SHG to have abnormal endometrial findings, such as an echogenic or polypoid mass (positive group), were followed by operative hysteroscopy and by postoperative SHG. In the positive group the basal transvaginal sonogram revealed an endometrial echogenic mass in only 10 (45.5%). In the remaining 12 (54.5%) patients, the transvaginal sonogram identified only thick endometrium. In these latter 12 patients, histological assessment confirmed endometrial polyps in 8 (66.7%) and fibroid in 1 (8.3%). Four (18.2%) patients in the positive group had no histological endometrial pathology. Two (50%) of them had a uterine septum as diagnosed during hysteroscopy, in one (25%) operative hysteroscopy failed to resect the endometrial polyp, and in another (25%) there was a false-positive SHG diagnosis. Overall, SHG accurately diagnosed endometrial and/or other intrauterine pathology in 95.5% of these patients. In the 46 patients with "negative" basal SHG features, diagnostic hysteroscopy confirmed this diagnosis. Thus, there was no SHG false-negative diagnosis. Comparing the results of the basal SHG with those of operative hysteroscopy and/or the histopathological findings in the positive group, the sensitivity of SHG was 1.0, the specificity 0.0, positive predictive value 95.5%, and negative predictive value 0.0. It is suggested that SHG is a useful diagnostic tool for the assessment of specific endometrial pathologies in asymptomatic postmenopausal breast cancer patients treated with tamoxifen who were diagnosed by transvaginal sonography to have thick endometrium.

Background: Postmenopausal breast cancer patients treated with tamoxifen have been found to have a high incidence of ovarian tumors. Transvaginal ultrasonography is an accurate and reliable method for measuring ovarian size. The purpose of this study was to establish normal values for basal ovarian volume in postmenopausal tamoxifen-treated patients and compare them with those established for healthy, postmenopausal women in the same population with no exposure to hormone treatment., Methods: In a prospective open pilot study, the ovaries of 65 postmenopausal breast cancer patients treated for at least 6 months with tamoxifen were measured by transvaginal ultrasonography. From the same population, 311 healthy postmenopausal women with no exposure to hormone therapy were examined and served as controls. After matching for menopausal age, ovarian volume was compared between groups., Results: Mean ovarian volume of postmenopausal tamoxifen-treated patients was persistently low through the menopause, whereas the mean ovarian volume of the controls was large, gradually decreasing up to the 10th menopausal year (8.6 +/- 2.3 and 2.8 +/- 2.1 cm3, respectively). Mean ovarian volume of the tamoxifen-treated patients was significantly lower than that of the controls during the initial menopausal years., Conclusions: An ovarian volume that is considered within normal range for a specific menopausal age in a healthy postmenopausal woman is abnormal for a postmenopausal tamoxifen-treated patient.

Atretic demise rather than ovulation is the ultimate fate of the vast majority of ovarian follicles in mammals, affecting 70-99.9% of the follicles in various species. Recent studies have established that atretic degeneration of follicles is an apoptotic process, heralded by endonuclease degradation of DNA at internucleosomal sites, which generates DNA fragments in size multiples of 185-200 bp that are seen as distinct ladder bands after agarose gel electrophoresis. Using the well-characterized model of inducing atresia of preovulatory follicles in vivo by hypophysectomy and analyzing DNA fragmentation by autoradiography of size-fractionated DNA labeled at the 3' ends by [12P] dideoxy-ATP, we have examined the timing of atretic changes. DNA degradation was related to morphological signs of atresia, ovulability, and changes in follicular steroidogenesis. Rats were hypophysectomized on the morning of the day of proestrus, after which largest follicles were collected at various times. DNA fragmentation was analyzed in groups of five follicles. The increase in DNA fragments of low molecular weight up to 4 h after hypophysectomy was negligible (101 +/- 10%; 0 h time = 100%) but progressed 8, 12, 24, 48, and 72 h after hypophysectomy (143 +/- 20%, 168 +/- 27%, 235 +/- 29%, 3299 +/- 1075%, and 2249 +/- 805%, respectively; p < 0.03, n = 5). At 48 and 72 h, the extent of DNA degradation was higher than that observed in follicles cultured in a serum-free medium for 24 h. Likewise, staining of DNA by 4',6-diamido-2-phenylindole hydrochloride revealed apoptotic nuclei at 8 h after hypophysectomy (p < 0.01), and the percentage of such nuclei progressively increased afterwards. Thus, the increase in DNA fragmentation appeared concomitantly with atretic changes observed in previous studies (a decrease in ovulability at 6 h, and a spontaneous increase in progesterone accumulation and decrease in androgen and estrogen in follicles explanted 6 h after hypophysectomy) and preceded atresia detectable by morphological changes at 24 h. Detection of internucleosomal DNA degradation in preovulatory follicles early in the atretic cascade underscores the central role of apoptosis in ovarian follicle atresia.

Objective: To evaluate the role of Doppler flow in the diagnostic process of ovarian torsion., Methods: Twenty-two patients who displayed the clinical symptoms of abdominal pain concomitant with an ovarian mass and were scheduled for explorative laparoscopy were enrolled in the study. The cohort was divided into 3 groups: (A) 8 patients with clinical and sonographic evidence of torsion; (B) 8 patients with abdominal pain and sonographic diagnosis of hemorrhagic cyst; and (C) 6 patients with a simple cystic mass who had undergone explorative surgery due to abdominal pain., Results: After Doppler flow imaging, Group A displayed no blood flow within the mass, and surgery confirmed the diagnosis of ovarian torsion. Seven of the 8 group B patients showed ovarian vascular flow (RI = 0.472 +/- 0.067). Only 2 of the 6 Group C patients displayed vascular flow (RI = 0.680 +/- 0.129) within an untwisted cyst, confirmed by laparoscopy., Conclusions: The combination of Doppler flow imaging with the morphologic assessment improves the diagnostic accuracy of ovarian torsion.

Background: The purpose of our study was to determine whether ovarian volume, as measured by transvaginal ultrasound and plotted on the nomogram of normal postmenopausal ovarian volume, could assist in the diagnosis of ovarian neoplasia., Methods: A retrospective study was undertaken, in which the ovaries of 85 postmenopausal women were examined by transvaginal ultrasonography prior to laparotomy. Three dimensions of each ovary were measured and ovarian volume was calculated. The results were plotted on the nomogram of normal postmenopausal ovarian volume., Results: Eighty-five ovarian tumors were diagnosed. The range of the mean ovarian volume varied between 98.15 cm3 to 161.81 cm3 from perimenopausal age to > 15 postmenopausal years, as compared to 2.2 +/- 1.4 - 8.6 +/- 2.8 cm in the normal postmenopausal women. The deviation from the normal volume was more striking in the malignant tumors group (100%) than in the benign group (86%). When plotted on the nomogram, these values showed significant deviation (above 2 s.d.) from the norm for each group of neoplasms in every menopausal age., Conclusions: Sonographic detection of abnormal postmenopausal ovarian volume and the demonstration of the deviation from the ovarian volume nomogram, could assist the physician in early diagnosis of ovarian neoplasia. Ovarian volume measurements can serve as the primary method leading to diagnosis of ovarian cancer.

Routine vaginal ultrasonographic evaluation of pelvic organs was performed in asymptomatic postmenopausal women to evaluate the diagnostic significance of sonographic findings of endometrial fluid collections in the presence of a thin endometrium in postmenopausal women. The study included nine women aged 61 to 79 years who had been postmenopausal for 7 to 30 years, and in whom endometrial fluid collections were incidently demonstrated. Endometrial samplings followed the ultrasonographic examinations in all nine patients, and the correlation between the histologic report and the endometrial ultrasonographic thickness was evaluated. The diameter of the endometrial fluid collections varied from 3 to 12 mm. The thickness of the endometrium surrounding the fluid ranged from 1 to 3 mm. Of the nine endometrial samples examined, five revealed atrophic endometrium, three had insufficient material for histologic evaluation, and one specimen revealed well-differentiated adenocarcinoma. The woman in whom endometrial carcinoma was diagnosed underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and lymph node sampling. The pathologic examination confirmed the previous histologic finding, and deep penetration into the myometrium was noticed with intact lymph nodes. Endometrial fluid collections found in asymptomatic postmenopausal patients still may be associated with endometrial malignancy, even in the presence of thin endometrium.

We present a 46-year-old patient who underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy for persistent trophoblastic disease. Single-agent chemotherapy with alternate methotrexate 1 mg/kg/day and leucovorin 0.1 mg/kg for 8 days was instituted on the first postoperative day. Various adverse symptomatology developed, culminating in a unique side effect, polyserositis. To the best of our knowledge, the wide spectrum of side effects, the short time lapse after onset of chemotherapy, and their severity are uncommon in a patient receiving her first chemotherapeutic treatment with MTX.

Various endometrial lesions were more frequent among asymptomatic postmenopausal breast cancer patients who were treated with tamoxifen for > 48 consecutive months (30.8%) when compared with similar patients who were treated for 6-24 months or for 25-48 months (20.8% and 12.5%, respectively). However, this difference was not statistically significant. There were also no significant differences in the frequency of the various endometrial lesions between these three groups, although endometrial polyps were more frequently found among those treated for > 48 months. Overall, 20.7% of the 164 tamoxifen-treated patients in the study had an endometrial pathology. It can be concluded that there is a slight tendency among those postmenopausal patients who have been treated for > 48 consecutive months to have a higher frequency of endometrial lesions.

Objective: Our purpose was to assess and clarify the mechanism of whether an early progesterone rise in cycles with gonadotropin-releasing hormone agonist (GnRH-a) is associated with an impairment of IVF outcome., Methods: Seven hundred eighty-six cycles were induced with GnRH-a and human menopausal gonodotropin (hMG) ("long protocol"). Plasma progesterone (PP) levels on the day of human chorionic gonadotropin (hCG) administration were divided into three groups: < 0.9 ng/ml (Group A), 1-2 ng/ml (Group B), and > 2 ng/ml (Group C). We also analyzed the pregnancies achieved in our egg donation protocol in relation to the PP levels of each donor on the day of hCG administration., Results: Group A involved 525 cycles, Group B had 223, and Group C had 38. The overall pregnancy rate per egg transfer was 19.2%, with the highest for Group A (22.3%), declining for Groups B (14.3%) and C (7.9%) (A = B = C; P < 0.005). The embryo implantation rate was found to be negatively correlated with the PP levels on the day of hCG administration. In contrast, there was an opposite trend between PP levels and the chance of conception in 30 pregnancies achieved by egg donation., Conclusion: Since premature luteinization is very unlikely to occur under the conditions of this study, our findings suggest that an early PP rise has a negative impact on endometrial receptivity but not on egg and embryo quality.

Incorporation of maternal serum unconjugated estriol into the calculation of risk may increase the yield of serum screening performed during pregnancy for detection of fetal chromosomal and structural anomalies. The differential diagnosis of very low and undetectable levels of unconjugated estriol in maternal serum is discussed, with special emphasis on the prenatal diagnosis of X-linked ichthyosis. The prenatal detection of these findings dictates skilled genetic counseling, targeted sonographic evaluation and examination of fetal karyotype and fetal cDNA for Xp 22.32 with amniotic fluid levels of cortisol, STS, and ASC.

Four cases of complete (three) and partial (one) agenesis were evaluated ultrasonographically. The frontal lobe/biparietal diameter ratio were evaluated in 113 normal fetuses and compared with those ratios in fetuses with corpus callosum agenesis. In the presence of the classic ultrasonographic features of agenesis of the corpus callosum, frontal lobe shortening, along with absence of the cavum septi pellucidi, might contribute to the diagnosis of complete agenesis of the corpus callosum and distinguish it from partial agenesis.

We evaluated the feasibility of retrospective genetic testing for numerical chromosomal aberrations by applying the FISH technique to formalin-fixed fetal tissue. Fetal tissue from 10 old cases with known aneuploidy and from 13 cases with known fetal malformations, were tested with specific DNA probes for pericentromeric repeat regions of chromosomes 13/21, 18, X and Y. FISH diagnosis concurred with karyotype in all nine cases with sufficient cells. Numerical aberration was diagnosed in six out of 13 cases with fetal malformations.

From September 1, 1989, to November 30, 1994, 175 menopausal breast cancer patients treated with tamoxifen were followed at the authors' institutions. During this period. 16 (9.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, for various indications. Of these, 10 (62.5%) had either uni- or bilateral ovarian tumors. The analysis of surgical findings showed an incidence of 5.7% (10/175) ovarian tumors among all the patients. In 2 (20%), the ovarian masses displayed enlargement over a relatively short period while on treatment. In 5 (50%) patients, the findings were bilateral. All tumors were detectable by ultrasonography, except four serous cystadenomas found in 3 women. The mean duration of tamoxifen treatment was 36.6 +/- 24.9 (range 9-86) months. The rate of 5.7% for ovarian tumors, in this selected group of patients, is four to five times higher than that reported for similar pathologic conditions detected by general screening with ultrasonographic scans among nonselected, asymptomatic, and untreated postmenopausal women. Two possibilities should be considered in the development of ovarian tumors coinciding with tamoxifen treatment; (1) women with breast malignancy are prone to develop benign or malignant ovarian tumors in relation to genetic factors, regardless of tamoxifen treatment; and (2) tamoxifen may stimulate enlargement of such tumors and may even cause them.

While heparin has been the standard treatment in established deep vein thrombosis (DVT), it carries associated potential hazards of hemorrhage and induction of thrombocytopenia. Enoxaparin (Rhone-Poulenc Rorer Pharm. Inc., France) is a low molecular weight heparin which has antithrombotic properties, and has been demonstrated effective in prophylaxis of DVT, apparently without severe treatment related bleeding complications. Six patients with genital malignancies, presenting with Doppler sonography confirmed deep venous thrombosis, were treated with Enoxaparin. A uniform dosage of 2 mg/kg/day in two divided doses was administered subcutaneously for 10 days during hospitalization and then continued on an out-patient basis. The clinical symptoms of venous thromboses diminished in all six patients. Enoxaparin represents an effective treatment of DVT, with the potential advantage of a lessening hemorrhagic complications. With administration of low molecular heparin, the activated partial thromboplastin time (aPTT) is not dramatically altered, making laboratory monitoring unnecessary. Our clinical findings demonstrate an easily applied therapy for gynecologic oncology patients, which is potentially safer to use, less costly, and less dependent on laboratory monitoring than the normal regimen.

Objective: To assess the validity of transvaginal color Doppler flow in the prediction of malignancy in the uterine cervix., Study Design: Sixteen women with cervical pathology (14 with invasive carcinoma and 2 with cervical intraepithelial neoplasia III) were examined using transvaginal sonography as well as transvaginal color Doppler with measurements of the resistance index of tumor blood flow. Twenty-four women with histologically proven normal cervices served as a control group., Results: Resistance index (RI) was significantly lower in the study group [0.493; 0.475-0.511 (mean + 95% CI)] than in control group [0.643; 0.627-0.659] (P < 0.0001) (t'). There was no statistically significant difference between the carcinoma group and the CIN III cases (P = 0.067) (t'). Only two cases with cervical carcinoma showed dense vascularity with color Doppler. A RI cutoff less than or equal to 0.573 showed a sensitivity of 81% with a specificity of 93%, a positive predictive value of 93%, and a negative predictive value of 81%., Conclusion: Color Doppler flow evaluation of RI in cervix vessels may aid in the early diagnosis and management of cervical carcinoma and in differentiating benign from malignant tumors. The validity of this technique as a screening program for diagnosis is limited.

In order to assess endometrial reaction to the combined treatment of tamoxifen and progestogens in asymptomatic postmenopausal breast cancer patients, we evaluated all such patients by vaginal ultrasonography and by histological examination of endometrial samplings. All patients were initially treated with tamoxifen, and progestogens were then added when metastases became evident. Of 12 patients included in the study, eight (66.66%) showed evidence of strong endometrial stromal decidualization, while three (25%) had decidual reactions in endometrial polyps. Overall, 11 (91.66%) of the patients had decidual reactions, and all were treated with progestogens for > or = 3 consecutive months. One patient, treated with progestogens for 1 months, had an inactive endometrium. All but three had thickened endometria (> 10 mm) on ultrasonographic evaluation. These data show that postmenopausal breast cancer patients who received progestogens for < or = 3 months, and who concomitantly took tamoxifen, had a uniform decidual reaction in all uteri.

Chronic Q fever has been associated with endocarditis, granulomatous hepatitis, and osteomyelitis but only rarely with pregnancy. The apparent predilection of Coxiella burnetii, the organism causing Q fever, for the human placenta suggests that chronic Q fever of pregnancy is due to placentitis. We describe a patient with chronic, clinically apparent Q fever in pregnancy and a successful outcome. The diagnosis was made both by serology and by isolation of C. burnetii from the patient's serum and placenta. Therapy with erythromycin and rifampin contributed to the delivery of a healthy baby. The mother's infection was clinically cured by subsequent therapy with doxycycline and rifampin.

Objective: Our objective was to evaluate retrospectively the influence of different types of anesthesia on the outcome of ovum retrieval., Methods: Sedation combined with local anesthesia was used on 120 occasions (Group I), epidural block in 139 ovum retrievals (Group II), and general anesthesia in 173 cycles (Group III)., Results: No differences were found in embryo yield or number or the quality of the embryo transferred. Of 99 pregnancies achieved, 66 live deliveries were recorded. Significantly lower clinical pregnancy rates were found in Group III (14.5%) compared with Group II (23.7%; P = 0.018) or Group I (25.8%; P = 0.0074). Highly significant differences were found in the delivery rates between Group III (8.7%), Group II (20.11%; P = 0.0017), and Group I (19.2%; P = 0.0043)., Conclusion: The use of general anesthesia, especially nitrous oxide, for oocyte retrieval has an adverse effect on IVF outcome. This deleterious effect manifests itself only after embryo transfer and leads to lower pregnancy and delivery rates.

Transvaginal ultrasonography and color flow imaging, performed to investigate whether there is any diagnostic advantage, were assessed over a 3 year period in 217 patients with adnexal masses prior to explorative laparotomy. Gray scale sonography and color Doppler flow were performed 1 day prior to surgery. Benign tumors were found in 165 patients and flow was detectable in 82 (49.7%); 14 patients had tumors of low malignant potential, 12 (85.7%) of whom showed detectable flow, and 38 had malignant tumors, in 25 (65.8%) of whom flow was detectable. Blood flow velocity was evaluated by the calculation of the resistance index prior to surgery. Mean resistive index was 0.39 +/- 0.05 for malignant tumors, compared with 0.49 +/- 0.06 and 0.55 +/- 0.07 for the low malignant potential and benign tumors, respectively. These differences were statistically significant (P < 0.01). When a resistive index of 0.47 was considered the cut-off value, the sensitivity was 88% and the specificity was calculated to be 85% (using color Doppler flow as the only diagnostic method). With our large cohort of patients, we demonstration the contribution of color Doppler flow examination in differentiating benign from malignant ovarian tumors prior to surgery.

Prenatal brain hemorrhages are associated with considerable morbidity and mortality in neonates. They appear predominantly as bleeding into periventricular germinal matrix with subsequent hemorrhages into lateral ventricles and subarachnoid space. Other patterns of brain hemorrhage are not widely documented in second trimester fetuses. We report a case of hemorrhage presenting as extensive hemosiderin deposits in leptomeninges and adjacent brain parenchyma, as observed in superficial hemosiderosis. The lesion was associated with substantial tissue damage. Clinically, it was diagnosed during the second half of second trimester by successive ultrasound examinations. If differs from germinal matrix hemorrhage and other forms of hemorrhage in origin, pathogenesis, morphology, and probably in clinical manifestations.

Ovarian torsion is often difficult to diagnose due to non-specific clinical and clinical and ultrasonographic findings. We demonstrated the use of color Doppler for the early diagnosis of ovarian torsion and for post-operative follow-up until the normalization of the preserved ovary was confirmed by subsequent viable pregnancy. Color Doppler flow assessment can be useful as both a diagnostic tool and for evaluating the recovery of the affected ovary after conservative surgical treatment.

Repeated attempts with oral oestrogens and injectable progesterone failed to induce secretory endometrium in a woman with 17-alpha-hydroxylase deficiency. The insertion of s.c. 17-beta-oestradiol implants dramatically improved the endometrial response and enabled the establishment of endometrial maturation. A viable pregnancy was achieved after the uterine transfer of in-vitro fertilized donated eggs.

Between September 1, 1989 and October 31, 1994, 173 postmenopausal breast cancer women on tamoxifen treatment were followed up in the authors' institutions. During this period, 14 (8.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for various indications. Eight (57.1%) were found to have adenomyosis, of whom one had a large fundal adenomyotic lump and the other seven patients had two to four small microscopic foci of adenomyosis. In this study, the rate of adenomyosis described among those postmenopausal breast cancer patients treated with tamoxifen is nearly three to four times higher than the rate reported in the literature for pre- and postmenopausal women. There is no previous reported increased incidence of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen. Thus, it is suggested that the prolonged and unopposed estrogen-like stimulation by tamoxifen may play a causal role rather than be a casual factor in the development of this pathologic entity.

We present the first case of ovarian endometrioid carcinoma and endometriosis in a postmenopausal patient who was treated with tamoxifen for breast cancer. The association with prolonged unopposed estrogen-like stimulation with tamoxifen as a possible factor in the development of ovarian endometrioid carcinoma is discussed.

A study was performed to evaluate the outcome of pregnancies in which the decision was not to repeat cerclage in women with a doubtful indication for the previous one. Thirty-five women with a history of at least one previous McDonald cerclage were followed prospectively. Pregnancy complications and outcome were compared to those in the previous pregnancy with a cerclage. These patients had 58 pregnancies with a cerclage and 52 pregnancies without. The pregnancies without a cerclage had fewer complications, were longer and resulted in the delivery of significantly larger infants (P < .05). Whereas all 52 cumulative pregnancies without a cerclage had a favorable outcome, there were nine perinatal losses in the 58 pregnancies with a cerclage (P < .05). The decision not to repeat a cervical cerclage, when the grounds for the previous procedure are doubtful, is a safe one.

Adjuvant tamoxifen therapy for breast cancer patients has been found to be associated with various endometrial pathologic conditions, including endometrial cancer. This preliminary case control study evaluated whether prolonged and continuous exposure to tamoxifen in the menopause may aggravate existing endometrial pathologies. Two vaginal ultrasound evaluations of endometrial thickness and histologic findings of two endometrial biopsies, performed 18 months apart, were evaluated for 25 asymptomatic, postmenopausal breast cancer patients who were continuously treated with tamoxifen. In the first endometrial biopsy, 4 patients (16.0%) were found to have endometrial pathologies: 2 patients had proliferative endometrium, 1 had hyperplastic endometrium, and 1 had an endometrial polyp. In the second endometrial biopsy, none of these patients showed any endometrial pathologies. Another patient (4.0%) with no endometrial pathology in the first visit had endometrial hyperplasia in the second visit. None of the patients developed endometrial cancer, and generally there was no increase in ultrasonographically-measured endometrial widths. The results of this preliminary study may suggest that there is no increased risk of development of endometrial pathologies during an additional 18 months of continuous tamoxifen therapy nor is there aggravation of already existing endometrial pathologies.

Two patients, who developed anaphylaxis to cisplatin, are described. This phenomenon was preceded by mild allergic symptoms, which were overlooked, in previous treatment courses. Intradermal skin tests were both sensitive and specific in the diagnosis of cisplatin allergy. Pretreatment with antihistamines and corticosteroids was ineffective in preventing recurrent anaphylaxis. Thus, a trial of desensitization is mandatory among those patients whose disease responds to the administration of this agent.

A prospective pilot study was conducted to evaluate the usefulness of uterine artery blood flow in the detection of various pathologic endometrial conditions in 39 asymptomatic postmenopausal breast cancer patients who were treated with tamoxifen. No specific pattern was seen for the uterine artery pulsatility index values in the tamoxifen-treated patients that could be related to any specific endometrial lesions, nor were any specific changes observed in the pulsatility index value with increasing severity of the pathologic endometrial conditions. Similarly, no correlation was found between ultrasonographically measured endometrial widths and uterine artery pulsatility index values. Thus, although pulsed Doppler flow ultrasonography has been shown previously to be effective in the detection of uterine cancer in non-tamoxifen-treated post-menopausal patients, it probably does not contribute to the assessment of endometrial lesions in post-menopausal breast cancer patients treated with tamoxifen.

Objective: Corpus luteum steroidogenesis is lower for in vivo ectopic pregnancy than for intrauterine pregnancy. There is a progesterone hallmark level distinguishing between viable intrauterine pregnancy and nonviable or ectopic pregnancy. This study attempts to answer whether this is also true for in vitro fertilization-treated patients., Study Design: Using information retrieved from a computerized database, we compared the plasma 17 beta-estradiol (E2) and progesterone during the luteal phase and for every 2 to 3 days for several weeks during early pregnancy between those patients with proven ectopic pregnancies and those with singleton and multiple intrauterine pregnancies. Vaginal ultrasonography to detect an intrauterine gestational sac was performed from day 19. A total of 73 pregnancies resulted from the replacement of fresh embryos in our in vitro fertilization-embryo transfer program., Results: Only at day 10 post embryo transfer did those patients with ectopic pregnancy show statistically lower mean (SD) serum levels of E2 [2257 (SD, 2351) pmol/L] and plasma progesterone [PP; 221 (SD, 283) nmol/L] compared with patients with intrauterine pregnancy, whose mean E2 was 8846 (SD, 5871) pmol/L and mean PP was 805 (SD, 582) nmol/L (P = 0.008). For the rest of the follow-up until surgery was performed in ectopic pregnancy, there were no differences of statistical significance between extrauterine pregnancy and the intrauterine pregnancy groups. Furthermore, only on day 10 post embryo transfer, did we find a discriminatory zone (confidence interval, 95%) for E2 levels (903 to 3502 pmol/L for EP vs 6116 to 9493 pmol/L for a singleton and 4875 to 9493 pmol/L for multiple pregnancies). PP levels were 26 to 283 nmol/L for ectopic pregnancy versus 496 to 1096 nmol/L for both singleton and multiple pregnancies. An intrauterine gestational sac was visualized at a mean of 23.2 (SD, 4) days after embryo transfer. On this day, the mean P levels were 982.6 (SD, 286.2) nmol/L for intrauterine and 804.5 (SD, 502.4) nmol/L for ectopic pregnancies (P = NS)., Conclusions: Except for day 10 post embryo transfer, the steroidogenesis in ectopic pregnancy after in vitro fertilization treatment does not differ from successful intrauterine pregnancy. This observation negates an impaired steroidogenesis for ectopic pregnancy after in vitro fertilization and makes the PP level irrelevant in the diagnosis of pregnancy implantation.

Endometrial thickness, as evaluated by vaginal ultrasonography, and endometrial histologic findings, as well as demographic characteristics, health habits, and risk factors for endometrial cancer, were compared between 93 asymptomatic postmenopausal breast cancer patients who had been on tamoxifen treatment and 20 patients who had not. The mean ultrasonographic endometrial thickness in the women on tamoxifen treatment was 13.1 +/- 10.4 mm, which was significantly thicker than the 4.0 +/- 3.2 mm found in the nontreated women (P = 0.001). The frequency of endometrial pathological findings was remarkably high (35.5%) among the tamoxifen-treated patients, compared with nontreated patients (20.0%), with a P value of 0.058 and an odd ratio of 4.6. Thus, it is suggested that the remarkably high prevalence of pathological endometrial changes was due to the continuous and unopposed exposure of the endometrium to tamoxifen.

Objective: To establish the predictive role of preovulatory ovarian ultrasonography in the occurrence of multiple pregnancy after hMG and hCG treatment for anovulatory infertility., Design: Prospective., Setting: Outpatient Infertility Clinic., Patients: Ninety-five anovulatory women who conceived after gonadotropin therapy., Intervention: Induction of ovulation by hMG and hCG monitored by plasma E2 measurements and ovarian ultrasonography., Main Outcome Measures: All follicles visualized on the day of hCG administration were recorded and divided into the following four groups: group I, 10 to 12 mm; group II, 13 to 15 mm; group III, 16 to 18 mm; and group IV, 19 mm and larger. The sonographic findings were statistically evaluated to 80 singletons and 45 multiple pregnancies., Results: No statistical correlation was found to exist between the number of follicles from the different groups and the number of fetuses., Conclusions: The number and sizes of follicles visualized on the day of hCG administration have no predictive value regarding the occurrence of a multiple pregnancy.

A 60-year-old woman presented with progressive hirsutism and elevated serum testosterone levels. Selective bilateral ovarian and adrenal vein catheterization demonstrated mild elevated testosterone and androstenedione levels in the right ovarian vein, which increased considerably 15 minutes following intravenous injection of 5000 IU human chorionic gonadotrophin. Androgen levels decreased remarkably after administration of gonadotrophin hormone releasing hormone-agonist (GnRH-a). On histological examination, diffuse stromal hyperplasia of both ovaries was noted, with a small Sertoli-Leydig cell tumour in the right ovary. This is the first report of preoperative, direct selective diagnosis of a small Sertoli-Leydig cell tumour with such a hormonal expression. Ovarian Sertoli-Leydig cell tumours are rare sex cord stromal tumours that exhibit testicular-like structure and differentiation. These tumours are potentially malignant, can cause progressive virilization (Young & Scully, 1985), and are often clinically manifested as palpable pelvic masses and virilization (Meldrum & Abraham, 1979; Friedman et al., 1985). We describe a patient with postmenopausal virilization due to Sertoli-Leydig cell tumour, in whom a remarkable increase in androgens was detected following intravenous human chorionic gonadotrophin injection, during adrenal and ovarian selective vein blood sampling. A remarkable decrease in the serum androgen level was noticed following an injection of gonadotrophin hormone releasing hormone-agonist (GnRH-a).

Objective: The aim of this study was twofold: firstly to evaluate and compare the diagnostic precision of the microhysteroscopy (MH) and endometrial biopsy in a group of menopausal women in whom D&C had failed to obtain an adequate endometrial sample, and secondly to quantitate the value of a hysteroscopy in determining endometrial sampling in these patients., Methods: A Hamou type II CO2 microhysteroscope (MH) was used to evaluate the endocervical canal and the uterine cavity, followed by endometrial sampling., Results: Thirty-nine women were assessed using MH and endometrial biopsy. Histopathology results were available for diagnosis in 29 of them (74.3%). In the remaining ten patients, the MH diagnosis was atrophic endometrium. Biopsy results corroborated with MH in 86.2% (25/29) of the patients with tissue samples. The analysis (r) of this concordance rate was statistically significant (r = 0.96). Sample results for patients with MH determined pathological and normal endometrium corroborated in 83% and 91%, respectively, inclusive of three cases of endometrial adenocarcinoma. The sensitivity, specificity and predictive values for MH alone were 93.7%, 76.9% and 83.3%, respectively., Conclusions: These significant results are indicative that this simplified endoscopic method surpasses all blind hospital or office endometrial sampling methods. Therefore, we suggest that MH and endometrial sampling should be the initial assessment tool for any type of indication requiring endometrial and uterine cavity assessment.

Objective: To investigate the relationship between the embryo number and morphology in conception cycles and the incidence of multiple pregnancies., Design: The study is based on information received from a computerized data base., Setting: In Vitro Fertilization Unit, Sapir Medical Center, Kfar Saba, Israel., Patients: A total of 117 consecutive pregnancies resulted from replacement of fresh embryos in our IVF-ET program., Main Outcome Measures: The impact of embryo quality, as assessed by morphological parameters, on the multiple pregnancy rate (PR)., Results: Implantation rates positively correlated with the number and the quality of transferred embryos. However, no multiple pregnancies occurred when only two embryos were replaced. There were no multiple pregnancies when only embryos of low quality (grades 1 and 2) were transferred. Furthermore, there was no correlation between the number of replaced embryos of poor quality and the rate of implantation. The multiple PR increased from 10% when a mixture of high and low quality embryos were transferred to 30.76% when only embryos of highest quality were transferred., Conclusion: The implantation rate of transferred embryos is directly correlated with the morphological scoring. The results of the study suggest that the number of embryos transferred should be balanced against their morphological quality to reduce the rate of multiple pregnancies.

Objective: To evaluate whether risk factors, other than tamoxifen, can be identified for the development of endometrial pathologies in postmenopausal breast cancer patients treated with tamoxifen., Design: A cross-sectional study., Setting: Department of Obstetrics and Gynaecology and Oncology Clinic, Sapir Medical Center, Kfar Saba, Israel., Subjects: 77 asymptomatic postmenopausal women, treated with tamoxifen for breast cancer. Of these, 55 had no endometrial tissue and 22 had endometrial tissue obtained by biopsy., Main Outcome Measures: Demographic characteristics, health habits, risk factors, vaginal ultrasonographic evaluations of endometrial thickness and texture, and histologic evaluations of endometrial biopsies., Results: Overall, there was a high rate (29%) of endometrial pathological change among the 77 asymptomatic postmenopausal women. There were no significant statistical differences in the features tested between the two groups., Conclusion: It is impossible to predict which postmenopausal women will develop pathological endometrial changes after treatment with tamoxifen and thus a routine periodic endometrial sampling-follow up is suggested for all postmenopausal women being treated with this agent.

We present the first case of heterologous mixed mesodermal tumor that developed 9 years following tamoxifen therapy in a climacteric woman with no previous pelvic irradiation and was initially treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy. She continued tamoxifen therapy for 2 years, following the initial treatment, until the diagnosis of a recurrent tumor by laparotomy. The patient died of the disease 5 months subsequent to the second surgery. The association of prolonged unopposed estrogenic stimulation, with tamoxifen as a possible etiologic factor in the development of endometrial sarcomas, is discussed.

Seventy-two asymptomatic, postmenopausal women treated with tamoxifen for breast cancer were studied prospectively with vaginal ultrasonography, followed by endometrial sampling. Seventy-one patients demonstrated an endometrial echo of more than 5 mm, and one displayed an endometrial echo of less than 5 mm. No patient with an endometrial echo of less than 5 mm displayed any endometrial pathology. Different endometrial pathologic conditions were found when the endometrial echo was over 5 mm. When classifying those patients whose ultrasonic endometrial widths were wider than 5 mm, on the basis of different endometrial histologic findings, no obvious correlation was found between the various pathologic endometrial findings and endometrial thickness. Thus, a "thicker" endometrial sonographic image did not necessarily correlate with pathologic endometrial findings. When ultrasonic endometrial thickness of 5 mm was considered the upper limit of normal, the sensitivity of ultrasonography in correlating to positive histologic findings was 91% and the specificity was 96%. These findings suggest that there is good correlation between endometrial width measured by ultrasonographic assessment and histologic findings.

Placenta accreta, a rare but life-threatening complication of pregnancy, is generally treated by hysterectomy and is histologically proven. We report a case that was managed conservatively and the diagnosis was confirmed by ultrasound and magnetic resonance imaging.

Uterine leiomyomata develop during the reproductive years and may interfere with fertility through mechanisms as yet not fully understood. A developing intramural or large submucosal leiomyoma causes hypertrophy of the myometrium. Conservative myomectomy, as opposed to hysterectomy, is the preferred surgical procedure for patients who wish to preserve their fertility. Ten patients were ultrasonographically evaluated at monthly intervals following myomectomy and the changes in uterine (myometrial) volume were assessed. There was a gradual decrease in uterine volume in all patients during the six months following removal of intramural and submucosal leiomyomata. The most remarkable decrease in size occurred during the initial two to three months for the majority of the patients. The impact of this process on fertility should be further evaluated. One of the intriguing questions is whether the period of uterine shrinkage represents the time of the healing process during which conception should be prevented.