A positive urine pregnancy test (UPT) with adnexal mass; ectopic pregnancy is not the ultimate diagnosis.

A positive urine pregnancy test (UPT) with adnexal mass in ectopic pregnancy is not the ultimate diagnosis. The incidence of ectopic pregnancy is about 27 per 1000 pregnancies [1]. On average, about 6-16% will present to an emergency department with first-trimester bleeding and abdominal pain [2]. On presenting with these symptoms with the simultaneous presence of an adnexal mass and an empty uterus, a UPT is of paramount importance to determine whether the symptoms are pregnancy related or not. When the UPT is positive, an ectopic pregnancy is not the only diagnosis as the rare entity of non-gestational ovarian choriocarcinoma (NGOC) should be considered. Here we present two case reports of NGOC, which were initially diagnosed as ectopic pregnancy. The first case is a 16-year-old girl, with vaginal bleeding and an adnexal mass due to an ovarian choriocarcinoma, She underwent unilateral oophorectomy and received multiple courses of chemotherapy. She is disease free without evidence of recurrence or metastasis after 12 months of follow-up. The second patient is also 16 years old and presented with an acute abdomen. She was diagnosed as a ruptured luteal cyst and underwent partial oophorectomy. When the pathologist diagnosed a choriocarcinoma she received multiple courses of chemotherapy, but thereafter an advanced disease was diagnosed with evidence of distant metastasis.

Cornual ectopic pregnancy in a female with initial negative ultrasound.

Cornual pregnancies are a rare form of ectopic pregnancy that can be misdiagnosed as an intrauterine pregnancy via ultrasound. We report a 16-year-old adolescent girl with a cornual ectopic pregnancy and subsequent rupture in the emergency department.

Evaluation of a urinary test as a diagnostic tool of a nonprogressive pregnancy.

OBJECTIVE: To evaluate the performance of a one-step test detecting intact hCG and free ß-hCG isoforms in the urine of pregnant women to diagnose an abnormal pregnancy. DESIGN: Prospective study. SETTING: Emergency gynecology departments in teaching hospitals. PATIENT(S): Five hundred twenty-six patients were enrolled, 272 who were not pregnant and 254 who were pregnant. INTERVENTION(S) AND MAIN OUTCOME MEASURE(S): Semiquantitative determination of intact urinary hCG of supposedly not pregnant and pregnant women with vaginal bleeding and/or vaginal pain between 5 and 8 weeks of amenorrhea. RESULT(S): The sensitivity and specificity of the urine test for diagnosing nonpregnancy were, respectively, 100% (252/252) and 100% (272/272). The sensitivity and specificity of the urine test for diagnosing ectopic pregnancy (EP) were, respectively, 97% (32/33) and 83% (142/171). The negative predictive value is 99.3% (142/143). The sensitivity and specificity or the urine test for diagnosing miscarriage were, respectively, 89.6% (43/48) and 83% (142/171). The negative predictive value is 96.6% (142/147). CONCLUSION(S): Abnormal pregnancy, such as an EP or a miscarriage, can be rapidly detected with the one-step test for intact hCG and free ß-hCG isoforms. If ultrasound cannot confirm the localization and/or evolution of a pregnancy, using this test reduces medical supervision and repeated quantification of hCG.

Clinical effectiveness of urinary human chorionic gonadotropin related protein (hCGRP) quantification for diagnosis of ectopic pregnancy.

We detected pregnancy related new molecule, human chorionic gonadotropin related protein (hCGRP) in the urine of a pregnant women by using a monoclonal antibody against the human chorionic gonadotropin (hCG). This study examined the effectiveness of urinary hCGRP quantification in diagnosing ectopic pregnancy. This study included 40 normal pregnant women and 25 patients with ectopic pregnancy. Patients' serum and urinary intact whole hCG (i-hCG) and hCGRP concentrations were measured using sandwich ELISA and the ratio of hCGRP to i-hCG was calculated. Statistical analysis was performed using statistical package for social sciences (SPSS) 10.0. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the cut-off value to discriminate ectopic pregnancies from normal intrauterine pregnancies. Urinary hCGRP and hCGRP/i-hCG ratio in ectopic pregnancy group (14 +/- 6.6 ng/mL, 4.6 +/- 1.9%, respectively) were significantly lower than those of normal pregnancy group (149 +/- 10.2 ng/mL, 29.7 +/- 1.9%, respectively; p<0.001). Based on ROC curve analysis, a cut-off point of urinary hCGRP/i-hCG ratio <16.2% discriminated between ectopic pregnancy and normal pregnancy with a sensitivity, specificity, positive predictive value and negative predictive value of 92.0%, 90.0%, 32.6%, and 99.5%, respectively. Urinary hCGRP/i-hCG ratio measurement may be effective in diagnosing ectopic pregnancy.

Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy.

BACKGROUND: Early diagnosis of ectopic pregnancy uses ultrasound with serial measurements of total human chorionic gonadotropin (hCG). The objective of this study was to explore the possibility that an isolated measurement of hCG isoforms/subunits rather than total hCG could be used as a single test for ectopic pregnancy. METHODS: Total and intact hCG, free hCG beta- and alpha-subunits (hCGbeta and -alpha), and hCG beta-core fragment were measured by RIA and IRMA in the serum and urine of 76 women presenting at outpatient emergency departments with a positive pregnancy test, lower abdominal pain, and/or vaginal bleeding. Final diagnoses were based on outcomes of pregnancies and tissue histology. RESULTS: Twenty-seven of the 76 women were subsequently diagnosed with viable pregnancies, 37 with spontaneous miscarriage, and 12 with ectopic pregnancy. Concentrations of all forms of hCG were lower in cases of ectopic pregnancy and spontaneous miscarriage than in viable pregnancies. Serum samples gave better results than urine samples. The free hCGbeta isoform (P <0.0001) had 100% sensitivity at a specificity of 79% at a 281 pmol/L (6.5 micro g/L) cutoff. Total hCG (P = 0.005) had comparable ROC characteristics with a 100% sensitivity and 68% specificity at a cutoff value of 1053 pmol/L (375 IU/L). Neither hCGbeta (P = 0.7) nor total hCG (P = 0.4) could distinguish ectopic pregnancies from spontaneous miscarriage. CONCLUSION: Measurement of serum free hCGbeta at the time of presentation can identify women with a high probability of ectopic pregnancy who may benefit from closer surveillance, reducing the risk of tubal rupture.

Evaluation of nicked human chorionic gonadotropin content in clinical specimens by a specific immunometric assay.

We report the development and characterization of an IRMA for the direct measurement of nicked human chorionic gonadotropin (hCGn) in blood and urine. hCGn derived from a reference preparation of hCG used as an immunogen elicits monoclonal antibodies (mAbs) with enhanced recognition of human luteinizing hormone epitopes. The most specific assay for pregnancy hCGn is an IRMA composed of one mAb to choriocarcinoma-derived hCGn (C5) and a second mAb developed from immunization with normal-pregnancy hCGn. This assay was used to evaluate hCGn profiles in normal, in vitro fertilization, Down syndrome, and ectopic pregnancies. In all pregnancies, hCGn was usually present in much lower concentrations than the non-nicked hCG isoform. Our results suggest that some form of physical separation from the overwhelming quantities of non-nicked hCG present in clinical specimens will be required before accurate immunochemical estimations of hCGn can be made.

The shape of the endometrium evaluated with three-dimensional ultrasound: an additional predictor of extrauterine pregnancy.

The objective of this prospective follow-up study was to evaluate the potential utility of three-dimensional (3D) ultrasound to differentiate intrauterine from extrauterine gestations. Fifty-four pregnancies with a gestational age <10 weeks and with an intrauterine gestational sac <5 mm in diameter formed the study group. The configuration of the endometrium in the frontal plane of the uterus was correlated to eventual pregnancy outcome. After exclusion of three patients with a poor 3D-image quality the endometrial shape was asymmetrical with regard to the median longitudinal axis of the uterus in 84% of intrauterine pregnancies, whereas the endometrium showed a symmetry in the frontal plane in 90% of extrauterine pregnancies (P = 0.0000001). Intrauterine fluid accumulation may distort the uterine cavity, thus being responsible for false-positive as well as false-negative results. The evaluation of the endometrial shape in the frontal plane appears to be a useful additional means to distinguish intrauterine from extrauterine pregnancies, especially when a gestational sac is not clearly demonstrated with conventional ultrasound.

Urine beta-core fragment, a potential screening test for ectopic pregnancy and spontaneous abortion.

The incidence of ectopic pregnancy in the United States has risen 6-fold in the last three decades. It now accounts for about 2% of reported pregnancies. Tests are now needed to identify ectopic pregnancy before it is clinically evident. We evaluated human chorionic gonadotropin beta-core fragment as a test to predict ectopic pregnancy and spontaneous abortion. Urine samples were collected from women with in vitro fertilized pregnancies, 2 1/2-5 weeks after embryo transfer. Fifty samples were collected from those later shown to have normal intrauterine pregnancies, samples from 13 women subsequently found (at 5-9.3 weeks) to have ectopic gestations, and 15 from those with impending spontaneous abortion. Beta-Core fragment levels were determined by immunoassay, and results normalized to creatinine concentration. Median beta-core fragment levels at 2 1/2-3, 3-4, and 4-5 weeks after embryo transfer, were 6.7, 91 and 737 microg/g for unaffected pregnancies, 1.0, 5.9 and 0.6 microg/g for impending ectopic pregnancies (0.15, 0.065 and 0.0008, multiples of the unaffected pregnancy median, MoM), and 0.75, 6.8 and 12 microg/g for impending spontaneous abortions (0.11, 0.07 and 0.016 MoM). A gestation-linked curve was modeled to discriminate unaffected pregnancy from impending ectopic gestation or spontaneous abortion. Plotted beta-core fragment levels were below this curve in 12 of 13 (92%) women with impending ectopic pregnancy, in 10 of 15 (67%) with spontaneous abortion outcome, and in 2 of 50 (4%) with intrauterine pregnancy and term outcome. Measurement of urine beta-core fragment at 2 1/2-5 weeks after embryo transfer (4 1/2-7 weeks after last menstrual period) might be useful for identifying failing pregnancies. Over three quarters (predictive value positive 76%) of those with low beta-core fragment levels have ectopic pregnancy or spontaneous abortion. On the contrary, 95% (predictive value negative) of those with normal range test values may be predicted to have a nonfailing term pregnancy. Diagnosis of ectopic pregnancy could be confirmed by transvaginal ultrasound, and ectopic pregnancy terminated early by nonsurgical methods, with minimal mortality or fertility loss. Major fetal defects that cause spontaneous abort pregnancies may also be recognized by transvaginal ultrasound. In such cases, chorionic villous sampling or possibly termination may be considered.

Transvaginal sonography in the management of ectopic pregnancy.

During a 3-year period, 525 women referred to our department with abdominal pain and/or vaginal bleeding in the first trimester of pregnancy were evaluated by transvaginal sonography. Ectopic pregnancy was suspected and laparoscopy done when sonography showed an empty uterus or pseudosac together with free pelvic fluid and/or a tubal mass. Fifty-seven patients fulfilled these criteriae. Among these patients, sonography showed an empty uterus in 48, pseudosac in five, a non-diagnostic intrauterine echo in four, a tubal mass in 45 and free pelvic fluid in 54. Laparoscopy confirmed ectopic pregnancy in 53 patients (93.0%). There were only five tubal ruptures. Pelvic blood was found in all of the 54 patients with free fluid on sonography; i.e. in 51 of 53 patients with ectopic pregnancy and in three with miscarriage. Forty-nine patients with ectopic pregnancy were managed by laparoscopy and four by laparotomy. All were hemodynamically stable. The diagnostic sensitivity and specificity of vaginal sonography for ectopic pregnancy was 96.2% and 99.4%, respectively, for the finding of free pelvic fluid, and 81.1% and 99.6% for a tubal mass. All patients with ectopic pregnancy were correctly selected for laparoscopic management. Transvaginal sonography is a valuable tool in the early diagnosis of ectopic pregnancy.

First-trimester rapid semiquantitative assay for urine pregnanediol glucuronide predicts gestational outcome with the same diagnostic accuracy as serial human chorionic gonadotropin measurements.

OBJECTIVE: The purpose of this study was to compare a single urine pregnanediol glucuronide measurement with serial human chorionic gonadotropin titers for the prediction of abnormal early gestations. STUDY DESIGN: We analyzed multiple urine pregnanediol glucuronide levels in 19 spontaneously conceived pregnancies during the first 49 days of gestation. A semiquantitative measurement was made by rapid enzyme immunoassay (Phase Check) at different urinary dilutions. To establish the reliability of semiquantitative urine pregnanediol glucuronide assay to detect abnormal gestation, this test was compared with human chorionic gonadotropin doubling times derived from a previously described normal population. A receiver-operator characteristic curve was constructed for each test, and areas under the curve with corresponding SEs were calculated. The critical-ratio z test was used to compare the two assays. RESULTS: The receiver-operator characteristic curves indicate that both urine pregnanediol glucuronide and human chorionic gonadotropin doubling can predict early gestational complications (p < 0.05). The area under the curve for human chorionic gonadotropin doubling time was 0.809 +/- 0.048, and urine pregnanediol glucuronide had an area of 0.702 +/- 0.072. Comparison of the area under the curve revealed that the ability of urine pregnanediol glucuronide to predict early gestational failure was indistinguishable from that of human chorionic gonadotropin doubling times (p > 0.05). A 1:2 dilution of urine gave the best results in the semiquantitative urine pregnanediol glucuronide test (Phase Check). CONCLUSIONS: On the basis of receiver-operator analysis, semiquantitative urine pregnanediol glucuronide measurements predict abnormal early gestations as well as serial human chorionic gonadotropin measurements do. The ability of a single urine semiquantitative assay (Phase Check) to predict early gestational complications offers a convenient screening tool that may identify women with abortive or ectopic pregnancies before the onset of symptoms.

Urine hCG beta-subunit core fragment, a sensitive test for ectopic pregnancy.

hCG is a glycoprotein hormone composed of 2 dissimilar subunits, alpha and beta, joined non-covalently. hCG and its free beta-subunit are the principal hCG beta immunoreactivities in pregnancy serum samples, and the same plus beta-core fragment (beta-subunit residues 6-40 disulfide-linked to residues 55-92) in urine samples. Ectopic or tubal pregnancy is difficult to diagnose in emergency rooms. With the objective of finding better hCG-related assays for differentiating tubal and normal pregnancies, we tested 2 hCG, 1 free beta-subunit and 2 beta-core fragment immunoassays. Twelve urine samples were collected in the emergency room from women later shown by surgery to have tubal pregnancy. All were 38 to 80 days since last period. A further 36 urine samples were collected from the same period from those with normal intrauterine pregnancies. Using the 2 hCG assays the median level in tubal pregnancy samples was 1/38th and 1/48th of normal pregnancy concentrations. With the free beta-subunit assay tubal pregnancy levels were 1/28th of normal levels. Using 2 beta-core fragment assays (Ciba-Triton UGP kit and B204-FBT11 scavenger test), however, tubal levels were most different from intrauterine pregnancy, 1/149th and 1/800th of normal levels. A cut-off level of 100 micrograms/L was considered for the B204-FBT11 beta-core fragment test, at which a predictive value of > 98% was suggested for ectopic pregnancy. In an additional patient, levels were measured 15 days prior to the diagnosis of tubal pregnancy. At this time, results from the 2 hCG tests were 1/97th and 1/126th, from the free beta-subunit test was 1/8th and the 2 beta-core assays were 1/413th and 1/240th of median normal intrauterine pregnancy levels. While hCG levels are reduced in tubal pregnancy, beta-core fragment are reduced much further. beta-core fragment measurements may offer a major improvement over hCG in diagnosing tubal pregnancy in the Emergency Room, and in screening for this life threatening disease.

Early detection of ectopic pregnancy. Use of a sensitive urine pregnancy test and transvaginal ultrasonography.

We performed a prospective study to evaluate the reliability of a rapid monoclonal antibody urine pregnancy test with a sensitivity limit of 20 mIU/mL combined with transvaginal ultrasonography in the early diagnosis of ectopic pregnancy in 116 women with subacute pelvic pain and a stable general condition. The diagnosis of tubal pregnancy was confirmed with laparoscopy in 100 of the 103 women with positive sensitive urine pregnancy tests and no intrauterine gestational sac at transvaginal ultrasonography. Laparoscopy revealed a hemorrhagic corpus luteum in four of the eight subjects with negative monoclonal antibody pregnancy tests and no intrauterine gestational sac, an ovarian cyst in three and a normal pelvis in one. Of the five women with a positive pregnancy test and an intrauterine gestational sac, two had a hemorrhagic corpus luteum, two a normal pelvis and one a tubal pregnancy at laparoscopy. The sensitivity of a monoclonal antibody urine pregnancy test and transvaginal ultrasonography combined for the diagnosis of ectopic pregnancy was 99%, and the specificity was 80%, with positive and negative predictive values of 97% and 92%, respectively.

Rapid one step urine test for human chorionic gonadotrophin in evaluating suspected complications of early pregnancy.

OBJECTIVE: To determine the ability of a sensitive one step urine test to detect human chorionic gonadotrophin in women with suspected complications of early pregnancy. DESIGN: Test on women presenting to accident and emergency department with gynaecological problems over six months. Results were validated using a quantitative assay for human chorionic gonadotrophin in serum and urine. SETTING: Accident and emergency department and gynaecology wards of a university teaching hospital. SUBJECTS: 130 unselected women. MAIN OUTCOME MEASURES: Detection of human chorionic gonadotrophin by one step test, presence of ectopic pregnancy, and results of quantitative analysis of chorionic gonadotrophin in serum and urine. RESULTS: 79 women had a positive urine test result and 51 a negative result. All 12 women with ectopic pregnancy had a positive test result, although urinary concentration varied from 191 IU/l to 47,800 IU/l. Only one woman, who had a faintly positive result, was found not to be pregnant on subsequent examination. The sensitivity and negative predictive values of the urine test were 100% respectively. 33 women were sent home from the accident and emergency department with normal clinical findings after a negative urine test result. All these women had undetectable concentrations of chorionic gonadotrophin in matched samples of urine and serum. CONCLUSIONS: A simple, rapid one step test for chorionic gonadotrophin should be available for the initial evaluation of emergency gynaecological problems. The additional cost of the test is offset by not admitting those patients whose clinical findings are normal and who have a negative urine test result and by reducing the number of women requiring quantitative assays of chorionic gonadotrophin.

Conservative treatment of ectopic pregnancy with local injection of hyperosmolar glucose solution or prostaglandin-F2 alpha: a prospective randomised study.

In a prospective randomised study, 31 patients with an unruptured tubal pregnancy were treated either with local and systemic prostaglandins or with local instillation of a hyperosmolar glucose solution. Prostaglandin therapy was successful in 13 of 15 patients and glucose therapy in 16 of 16. 9 women treated with prostaglandins had cramping abdominal pains postoperatively. No side-effects were noted in those treated with glucose. At subsequent hysterosalpingography 5 of 6 patients treated with prostaglandins and 7 of 8 treated with glucose had normal tubal configuration and patency. 3 patients treated with glucose later had a normal intrauterine pregnancy, demonstrably through the affected tube in 1 case. These results suggest that local instillation of hyperosmolar glucose solution is an option in the laparoscopic management of unruptured tubal pregnancies.

Random urinary pregnanediol glucuronide measurements in pregnancy: lack of utility for evaluation of first-trimester vaginal bleeding.

Progesterone and its urinary metabolite pregnanediol-3 alpha-glucuronide (PDG) are generally lower in women with abnormal pregnancies compared to those with normal intrauterine gestations. We evaluated the ability of random urinary PDG measurements determined by enzyme immunoassay (EIA) to differentiate normal from abnormal pregnancies. Patients with first-trimester vaginal bleeding (n = 104) were evaluated. Eventual outcomes indicated 39 women had viable intrauterine pregnancies (IUPs), 54 had spontaneous abortions (SABs) and 11 had ectopic pregnancies (EPs). Urinary PDG was significantly lower in SAB and EP compared to IUP patients. However, a wide range of values in IUP patients was noted (3.2-93.3 micrograms/ml), due to varying degrees of patient hydration at presentation. Hence, random measures of urinary PDG demonstrated poor specificity (32.8%) in correctly differentiating normal from abnormal gestations, thus limiting its clinical usefulness.

The value of endovaginal sonography and urinary human chorionic gonadotropin tests for differentiation between intrauterine and ectopic pregnancy.

Effectiveness of vaginal sonography combined with urinary human chorionic gonadotropin (hCG) for identification of ectopic pregnancy (EP) was studied in 107 pregnant women. Eighty-nine women had clinical symptoms suspicious of EP. It was suggested that 18 women carried an increased risk for developing EP. In 63 women endovaginal sonography showed no evidence of intrauterine pregnancy. Fifty-eight of these turned out to be pathological pregnancies. In 44 women endovaginal ultrasonography revealed intrauterine pregnancies. Thirty-two of these turned out to be viable, 10 were not viable and resulted in spontaneous abortions, and 2 turned out to be EP. The sensitivity of vaginal sonography to identify a viable intrauterine pregnancy thus was 81% and its specificity was 97%. The sensitivity and the specificity for endovaginal ultrasonography for identifying EP was 96% and 71%, respectively. Endovaginal ultrasonography demonstrated an intrauterine gestational sac in 54% of the women with urinary HCG as low as 40 IU/L to 500 IU/L. These results show that endovaginal ultrasonography is a sensitive instrument for identifying both early normal intrauterine pregnancies as well as pathological pregnancies.