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Improved sensitivity and specificity of a single measurement of serum progesterone over serial quantitative beta-human chorionic gonadotrophin in screening for ectopic pregnancy.

The sensitivity and specificity of a single serum progesterone measurement was compared against two beta-human chorionic gonadotrophin (HCG) measurements 48 h apart in screening for abnormal pregnancy, i.e. ectopic pregnancy, completed or incomplete abortion. Of 1120 patients in the first trimester presenting with a positive urinary pregnancy test, 116/1120 (10.4%) had an ectopic pregnancy, 755/1120 (67.4%) had ultrasonographically confirmed intra-uterine pregnancies, and 249/1120 (22.2%) had abnormal intra-uterine pregnancies documented as complete, incomplete or missed abortions. Of the ectopic pregnancies, 113/116 (97.4%) had a serum progesterone level less than 25 ng/ml while 516/755 (68.3%) viable intra-uterine pregnancies had a serum progesterone level greater than or equal to ng/ml. Of the 1120 patients screened, 402 (35.9%) had both a serum progesterone and two HCG measurements and were eligible for inclusion in this study. Setting a cut-off of 25 ng/ml, the sensitivity and specificity of a single serum progesterone measurement was then compared against two serial HCG measurements, utilizing receiver operating characteristic curves. This analysis demonstrated that a single serum progesterone measurement was significantly more sensitive (P less than 0.05) than two HCG measurements in screening for an abnormal pregnancy. In some patients, a single serum progesterone makes possible the diagnosis of ectopic pregnancy 2 days earlier than two HCG determinations because a second blood sample was not required. We conclude that a single serum progesterone measurement should be added to serial HCG determinations as a standard diagnostic screening test for ectopic pregnancy.

Chorionic Gonadotropin↗

Analysis of the risk factors with regard to the occurrence of ectopic pregnancy after medically assisted procreation.

In a retrospective study (1985-1989) based on data from the Centre for Reproductive Medicine in Brussels, a total of 23 ectopic pregnancies (2.24%) occurred after 3800 embryo, zygote or gamete transfers. This number was low compared with the data published elsewhere. Tubal damage was a major risk factor towards developing an ectopic pregnancy after in-vitro fertilization and embryo transfer. The number of ectopic pregnancies after the association of clomiphene citrate and human menopausal gonadotrophin (HMG) was significantly higher in patients with tubal (7.8%) and non-tubal indications (2.1%) compared with those stimulated with gonadotrophin-releasing hormone (GnRH) and HMG (2.18% and 0.84%, respectively). The number of replaced embryos was not associated with the rate of ectopic pregnancy and neither did transfer technique (intra-uterine or intra-Fallopian transfer) influence the ectopic pregnancy rate.

Adult↗

Incidence of ectopic pregnancy. First results of a population-based register in France.

A population-based register of ectopic pregnancy was established in 1992 for two French departments, with the primary aim of monitoring the trend in ectopic pregnancy over a prolonged period. In this paper, data collected during the first year of registration (1992) are analysed. The rate of ectopic pregnancy was 20.2 per 1000 live births, 15.8 per 1000 reported pregnancies and 9.5 per 10,000 women aged 15-44 years. The ectopic pregnancy rate per 1000 live births increased steeply after the age of 30 years and especially after the age of 35 years, whereas rates per 10,000 women of reproductive age steadily increased until the age of 35 years and decreased thereafter. The rates of ectopic pregnancy were lower in spring and summer than autumn and winter. These results are discussed and comparisons with similar studies conducted in the USA and Scandinavia are attempted.

Adolescent↗

Medical management of the patient with an ectopic pregnancy.

Ectopic pregnancies are the leading cause of pregnancy-related death during the first trimester. Historically, the treatment for an ectopic pregnancy was emergency laparotomy, which included salpingectomy. In 1987, research began at the Regional Medical Center at Memphis, in conjunction with the University of Tennessee, examining early detection and medical treatment for ectopic pregnancy. Pharmacologic management of an unruptured, size-appropriate ectopic pregnancy is now an established standard of care. The present protocol recommends single-dose methotrexate. This form of methotrexate has proven to be a successful, cost-effective alternative to traditional surgical management of ectopic pregnancies.

Decision Trees↗

Suprasellar adrenocorticotropic hormone-secreting ectopic pituitary adenoma: case report and literature Review.

OBJECTIVE AND IMPORTANCE: Functional ectopic pituitary adenomas are rare and can be misdiagnosed as extensions of pituitary adenomas when they are located in the vicinity of the normal gland. In this report, we present a case of an ectopic adrenocorticotropic hormone-secreting suprasellar pituitary adenoma that caused Cushing's disease. A literature review of previously reported ectopic pituitary adenomas is included to illustrate the diverse clinical manifestations of this disease entity. CLINICAL PRESENTATION: An 11-year-old boy was noted to have hirsutism, a buffalo hump, and unexplained weight gain consistent with Cushing's syndrome. Laboratory investigations revealed that the boy had elevated adrenocorticotropic hormone and serum cortisol levels unsuppressed by dexamethasone. Magnetic resonance imaging scans were suggestive of a pituitary adenoma with suprasellar extension. INTERVENTION: The initial transsphenoidal approach failed to achieve complete surgical resection. A repeat operation in which the pterional approach was used revealed a suprasellar pituitary adenoma without association with intrasellar contents. The patient's cushingoid symptoms improved significantly 3 months after surgery. CONCLUSION: Ectopic pituitary adenomas should be considered in the differential diagnosis for all patients with Cushing's syndrome. Furthermore, surgical approaches should be chosen carefully once the diagnosis of ectopic pituitary adenoma is made.

ACTH Syndrome, Ectopic↗

Ectopic pregnancy rate and treatment utilization in a large managed care organization.

OBJECTIVE: To estimate the ectopic pregnancy rate at Kaiser Permanente, Northern California, during 1997-2000. METHODS: Computerized data systems covering inpatient, outpatient, and pharmacy records were reviewed for evidence of ectopic pregnancies during the study period. Denominator data were calculated from computerized utilization and membership data for the same period. RESULTS: We identified 2,617 ectopic pregnancies that occurred between 1997 and 2000 among 126,451 reported pregnancies for an annual rate of 20.70 per 1,000 reported pregnancies and 1.03 per 1,000 women 15-44 years old. There was no evidence of a trend over time in these data. The rate increased with increasing age. Approximately 35% of these women were medically treated, and we observed an increase over time in the proportion of women who were medically treated. CONCLUSION: Using computerized data systems in a large integrated health delivery system, we found that the rate of ectopic pregnancy in 1997-2000 was similar to the national rate in 1990-1992, when national data were last available. These data suggest that the ectopic pregnancy rate is not increasing, although differences in the study populations need to be kept in mind. Medical treatment seems to be increasing over time.

Abortion, Induced↗

A six-year audit of the management of ectopic pregnancy.

OBJECTIVE: To audit the management of ectopic pregnancy at National Women's Hospital over a six-year period to monitor changes in practice and assess adherence to hospital protocols. STUDY DESIGN: A retrospective audit of the management of women with a discharge diagnosis of ectopic pregnancy from 1996-2001 at National Women's Hospital, Auckland, New Zealand. Information was collected regarding the demographics, risk factors for ectopic pregnancy, delay in diagnosis, management undertaken and failure and complications of initial treatment. RESULTS: Over a six-year period a total of 673 women had a discharge diagnosis of ectopic pregnancy. Surgery was the most frequent method of management but there was increasing utilisation of systemic methotrexate. The proportion of women who met the criteria for methotrexate varied from 27-54% over the six year period although the highest proportion who received methotrexate in any given year was only 24% (2001). The proportion of women who met the criteria for receiving methotrexate and had the option of methotrexate discussed with them increased from 12% in 1996 to 91% in 2001. Over the six year period 74 women received methotrexate and 14 (18.9%) failed and required surgical management. Surgical management was performed in 537 women and 30 (5.6%) required either further surgery or methotrexate or a combination of both. A laparoscopic procedure was performed in 86.5% (465/533) and 10.9% (51/465) converted to laparotomy CONCLUSIONS: Although there is evidence that methotrexate is an effective and safe option for a proportion of women with ectopic pregnancy, the majority of women still undergo surgical management.

Abortifacient Agents, Nonsteroidal↗

Diagnosis and management of ACTH-dependent Cushing's syndrome: comparison of the features in ectopic and pituitary ACTH production.

The clinical features, diagnosis and management of 16 consecutive patients with ectopic ACTH production are described and biochemical data are compared with those of 48 consecutive patients with pituitary-dependent Cushing's disease. In 10 cases the ectopic ACTH secreting tumour was completely occult to routine clinical and radiological investigation, and no basal or dynamic investigation of adrenal-pituitary function was able clearly to differentiate these patients from those with Cushing's disease. High dose dexamethasone suppression testing assessed by plasma cortisol was usually helpful but unexpected responses were seen in both diagnostic groups; the metyrapone test yielded no useful information and should now be abandoned. Hypokalaemia was seen in all patients with ectopic ACTH production but in only 10% of those with Cushing's disease who were not on diuretics at presentation. Successful diagnosis and tumour localization was most frequently achieved by a combination of CT scanning of the chest and abdomen and venous catheter sampling for ACTH. All patients in whom the ectopic ACTH-secreting tumour was obvious at presentation died of their primary tumour within 8 months, whereas seven of the 10 patients with occult tumours at presentation are alive 1.5-16.5 years later, and appear cured. Occult ectopic ACTH secretion may be impossible to distinguish from pituitary Cushing's disease. Multiple and repeated investigations are often required to make this differential diagnosis, essential for appropriate therapy.

ACTH Syndrome, Ectopic↗

Accuracy in diagnosis of ectopic pregnancy by transvaginal ultrasonography.

Forty patients suspected to have ectopic pregnancy by transvaginal ultrasonography had surgery. 77.5% were confirmed to have ectopic pregnancy and 10% had other abnormal pelvic findings. The transvaginal approach appears to enable us to diagnose ectopic pregnancy at an earlier date, with the earliest diagnosis made at 4 weeks 0 days of amenorrhoea. In cases of confirmed ectopic pregnancy, the presence of a complex adnexal mass was the most common feature seen on transvaginal ultrasound and its predictability of ectopic pregnancy is enhanced by a concomitant finding of an empty uterus (95%) or free fluid in the Pouch of Douglas (94%) in the presence of a positive hCG test. The significance of transvaginal ultrasound features, and the advantages of transvaginal over transabdominal ultrasound, are discussed.

Female↗

Chronic ectopic pregnancy: a clinical analysis of 62 cases.

Chronic ectopic pregnancy is a form of tubal pregnancy in which salient minor ruptures or abortions of an ectopic pregnancy instead of a single episode of bleeding, incites an inflammatory response often leading to the formation of a pelvic mass. Its clinical features are often confusing, and laboratory evaluations are often misleading. Surgery for chronic ectopic pregnancy is frequently difficult since chronic inflammatory changes and adhesions distort the normal anatomy. In the present retrospective study, its incidence was found to be 20.3% (n = 62) in a series of 305 ectopic pregnancies. A pelvic mass of varying sonographic appearance, mostly with a nonhomogenous echo pattern, was demonstrated in all 55 patients in whom transvaginal sonographic evaluation was performed preoperatively. Although most of the patients [91.9% (n = 57)] had a positive serum beta HCG value, 5 patients had a negative test value. Laparotomy resulted in 40 salpingectomies, 19 salpingo-oophorectomies, and 3 total abdominal hysterectomies with salpingo-oophorectomies. One patient had a incidental cystotomy and 2 an incidental colotomy. We conclude that chronic ectopic pregnancy is not rare although little is mentioned about it as a clinical entity in the gynaecological literature. With increased awareness of its mildly symptomatic and protracted clinical course, and with proper interpretation of laboratory evaluations, a preoperative diagnosis can be made in the majority of the cases.

Adolescent↗

Ectopic pregnancy.

One out of every 100 to 300 pregnancies is ectopic, and the prevalence is increasing. The classic triad of symptoms; amenorrhea, abdominal pain, and abnormal bleeding, varies greatly among individuals, and ectopic pregnancies frequently are confused with other conditions, such as ovarian cyst, pelvic inflammatory disease, and spontaneous abortion. Ruptured ectopic pregnancies cause hemorrhage and shock and are the leading cause of maternal mortality in the first trimester. Although conservation surgery and tuboplasty have improved the fertility outlook of the ectopic patient, only one-third of such women will be delivered of a live baby. In this overview of ectopic pregnancy, the etiology, symptoms, physical findings, and management/treatment are presented.

Female↗

The predictive value of endometrial stripe thickness in patients with suspected ectopic pregnancy who have an empty uterus at ultrasonography.

UNLABELLED: Prior research suggests that, in patients with empty uteri at ultrasonography, endometrial stripe thickness may be predictive of ectopic pregnancy or the likelihood of obtaining chorionic villi after a dilatation and evacuation procedure (D+E). However, it is unclear whether the predictive value of endometrial stripe thickness is confined to patients with low beta-human chorionic gonadotropin (beta-hCG) values. OBJECTIVE: To determine whether endometrial stripe thickness is predictive of the risk of ectopic pregnancy or the likelihood of obtaining chorionic villi after D+E in patients with beta-hCG values >1,000 mIU/mL or < or =1,000 mIU/mL. METHODS: In an urban academic ED, the authors conducted a retrospective chart review of consecutive ED patients from August 1991 to August 1997 with abdominal pain or vaginal bleeding, a positive beta-hCG value, and an empty uterus by transvaginal ultrasound examination. Patients were divided into four groups-group 1: endometrium thin, beta-hCG value < or =1,000 mIU/mL; group 2: endometrium thick, beta-hCG value < or =1,000 mIU/mL; group 3: endometrium thin, beta-hCG value >1,000 mIU/ mL; and group 4: endometrium thick, beta-hCG value >1,000 mIU/mL. The secondary analysis was limited to patients who had a D+E performed within 48 hours of the ED visit. The risks of ectopic pregnancy and the likelihoods of obtaining chorionic villi after D+E were compared using chi-square or Fishers' exact test where appropriate, with a p-value of 0.05 being significant. RESULTS: 224 patients were enrolled in the initial analysis. Intergroup differences in the frequency of ectopic pregnancy were of borderline significance (p = 0.08). However, when the comparison was limited to the groups with beta-hCG values < or =1,000 mIU/mL, the predictive value of endometrial stripe thickness reached statistical significance (group 1: 27/99 [27%], group 2: 2/28 [7%], p = 0.05). 79 patients had a D+E performed. Intergroup differences in the rate of obtaining chorionic villi were significant (p = 0.002). Group 1 had the lowest frequency of having chorionic villi identified (4/26 [15%]) and was the only group in which villi were obtained in fewer than 50% of cases. CONCLUSION: Endometrial stripe thickness may be predictive of the risk of ectopic pregnancy and the likelihood of obtaining chorionic villi at D+E. However, its predictive value appears to be confined to patients with beta-hCG values < or =1,000 mIU/mL.

Academic Medical Centers↗

Emergency department right upper quadrant ultrasound is associated with a reduced time to diagnosis and treatment of ruptured ectopic pregnancies.

OBJECTIVE: To determine whether the time to diagnosis and treatment of patients with ruptured ectopic pregnancy is significantly less for patients who had emergency department (ED) right upper quadrant (RUQ) ultrasound (US) compared with those who had US in the radiology department. METHODS: The authors conducted a retrospective review of eligible patients presenting to an urban ED between January 1990 and December 1998. Patients were included in the study if they were seen in the ED, had a discharge diagnosis of ruptured ectopic pregnancy, were brought immediately to the operating room after a definitive diagnosis of ectopic pregnancy rupture was made, and had more than 400 mL of intraperitoneal blood found at the time of surgery. The ED, hospital, radiology, and operative records were reviewed to determine presenting vital signs, intraperitoneal blood loss, time to diagnosis, time to treatment, and type of US performed. RESULTS: There were 37 patients enrolled; 16 received ED RUQ US (group I) and 21 had a formal US in radiology (group II). The ages, pulses, systolic blood pressures, and volumes of hemoperitoneum were similar between the two groups. The average time to diagnosis from ED arrival was 58 minutes for group I (SD = 57; 95% CI = 28 to 87) and 197 minutes for group II (SD = 82; 95% CI = 162 to 232) (p < or = 0.0001). The average time to operative treatment was 111 minutes (group I) (SD = 86; 95% CI = 69 to 153) and 322 minutes (group II) (SD = 107; 95% CI = 270 to 364) (p < or = 0.0001), respectively. CONCLUSIONS: Patients with ruptured ectopic pregnancy, who were selected to have RUQ US performed in the ED by emergency physicians, had an average decrease in time to diagnosis of two and a quarter hours, and an average decrease in time to treatment of three and a half hours, compared with those having a formal pelvic US in the radiology department. Further prospective investigation is needed to determine whether ED RUQ US can safely expedite care of patients with suspected ectopic pregnancy.

Adult↗

The incidence of ectopic pregnancy in Hordaland County, Norway 1976-1993.

OBJECTIVE: To gain longterm knowledge of incidence rates of ectopic pregnancy, as a basis for analysing risk factors. MATERIAL: The incidence of ectopic pregnancy was studied in the county of Hordaland, Western Norway, through 18 years, 1976-1993. The protocols of 1821 cases of ectopic pregnancy were registered. Population data of the county, the number of births and legal abortions were available. RESULTS: There was considerable increase in crude numbers of ectopic pregnancies throughout the period. Grouping the cases in three six-year periods showed an increased crude incidence rate per 100,000 women from 95 during 1976-81 to 154 during 1988-93. The corresponding rates per 1000 births increased from 13.6 to 22.2 and the rates per 1000 reported pregnancies from 11.2 to 18.0. All rates increased also in women aged 40-44 years. During the years 1979-1993 the rates per 1000 reported pregnancies increased by 25%, from 9.4 to 11.8 in age groups below 30 years, while the rates for women over 35 years increased by 98%, from 20.7 to 40.9. Compared to the age group 15-19, women over 35 years had an eightfold risk during the last period. In addition they also contributed to higher numbers of reported pregnancies by 58%. CONCLUSION: The rates of ectopic pregnancy increased in age groups older than 20 years during 1976-93, moderately in younger age groups, but considerably in older age groups, who also contributed with higher total rates of pregnancy. More older women, with presumably accumulated risk factors getting pregnant, thus explain part of the increased rates of this disease.

Adolescent↗

Vascular cell adhesion molecule-1 in normal, failed, and ectopic pregnancy.

PROBLEM: Vascular cell adhesion molecule-1 (VCAM-1) is involved in early pregnancy establishment. This study sought to determine whether soluble VCAM-1 (sVCAM-1) serum levels differ among normal, failed, and ectopic pregnancy, its capacity to serve as a marker for pregnancy viability or ectopic pregnancy, and its correlation with serum progesterone and beta human chorionic gonadotrophin (PHCG) levels. METHOD OF STUDY: Maternal serum samples were obtained from 20 women with ectopic, 10 with normal, and 10 with failed intra-uterine pregnancy, all of comparable gestational age. Samples were assayed for sVCAM-1, progesterone, and betaHCG by specific assays. RESULTS: The median serum level of sVCAM-1 was comparable between the three pregnancy types (normal: 578.3 ng/mL, range 434.4-699.5 ng/mL; failed: 567.8 ng/mL, range 401.9 669.5 ng/mL; and ectopic: 470.7ng/mL range, 328.2-1151.1 ng/mL). Serum levels sVCAM-1 were not significantly correlated with betaHCG or progesterone levels. CONCLUSION: sVCAM-1 is not appropriate to serve as a marker for pregnancy viability or ectopic pregnancy.

Abortion, Spontaneous↗

The double sac sign of early intrauterine pregnancy: use in exclusion of ectopic pregnancy.

Pelvic sonograms from 61 consecutive patients with suspected ectopic pregnancy and an additional 17 proved ectopic pregnancy cases were reviewed retrospectively. Special attention was given to the appearance of the uterus and intrauterine fluid collections in the absence of a fetal pole. Criteria for the exclusion of an ectopic pregnancy were established, based on a specific morphologic appearance of the decidua seen in early normal intrauterine pregnancy. A "double sac" appearance of two concentric echogenic rims was consistently identified early in normal intrauterine pregnancies before the appearance of a fetal pole, and served as a good morphologic discriminator for the decidual cast of ectopic pregnancy. We think the double sac appearance is a helpful indicator for differentiating an ectopic pregnancy from an early normal intrauterine pregnancy.

Diagnosis, Differential↗

Treatment of ectopic pregnancy: is a human chorionic gonadotropin level of 2,000 mIU/mL a reasonable threshold?

PURPOSE: To determine whether a human chorionic gonadotropin (hCG) level of 2,000 mIU/mL is a reasonable threshold for diagnosing ectopic pregnancy in the absence of ultrasound (US) findings of intrauterine pregnancy (IUP) and thus to prevent inappropriate treatment that will result in the loss of an otherwise normal pregnancy in women with early IUPs. MATERIALS AND METHODS: The authors reviewed the medical records of and US scans obtained in 676 patients in whom ectopic pregnancy was clinically suspected between January 1, 1994, and December 31, 1995. RESULTS: Five hundred forty-eight patients had evidence of a normal or abnormal IUP. Fifty-one (40%) of the 128 patients without evidence of an IUP had an hCG level of more than 2,000 mIU/mL. Of these 51 patients, 15 (29%) were treated for ectopic pregnancy; 17 (33%) were not immediately treated for ectopic pregnancy and had a normal IUP at follow-up US. CONCLUSION: An hCG level of 2,000 mIU/mL without US findings of IUP, while suggestive of an abnormal pregnancy, is not diagnostic. Per the results of recent studies, it is reasonable to closely follow up rather than treat many of these early, stable cases of ectopic pregnancy.

Adult↗

Tumor necrosis factor alpha is elevated in the peritoneal fluid from women with ruptured ectopic pregnancies.

The purpose of this study was to determine whether exposure of the peritoneum to fetal tissue is associated with elevated tumor necrosis factor alpha (TNF alpha) levels in the peritoneal cavity. We measured TNF alpha levels in the peritoneal fluids and serum from women with ruptured ectopic, unruptured ectopic and intrauterine pregnancies, as well as nonpregnant women undergoing tubal ligation. The results showed that patients with ruptured ectopic pregnancies were more likely to have TNF alpha levels in the peritoneal fluid greater than 40 units/ml (68%), compared with women with unruptured ectopic or intrauterine pregnancies (21%) (p less than 0.05, Fisher exact test). No elevation of peritoneal fluid TNF alpha levels was found in nonpregnant patients. Because TNF alpha is primarily a product of activated macrophages, it is likely that elevated TNF alpha levels in the peritoneal fluid of women with ruptured ectopic pregnancies reflects activation of peritoneal macrophages.

Adolescent↗