Abnormal Intrauterine Pregnancy Research Articles

Serum vascular endothelial growth factor as a marker for tubal pregnancy.

SUMMARYOBJECTIVE:The objective of this study was to evaluate whether a single measurement of vascular endothelial growth factor could distinguish between intrauterine pregnancy and ectopic pregnancy and to correlate the levels of vascular endothelial growth factor with serum levels of progesterone andβ-human chorionic gonadotropin in each subgroup.METHODS:Ninety patients with a positive human chorionic gonadotropin test and either abdominal pain or vaginal bleeding were selected; pregnancies were singletons, spontaneously conceived, 42–56 days of gestational age. All patients had a transvaginal ultrasound examination and were divided into three subgroups: abnormal intrauterine pregnancy, tubal pregnancy, and normal intrauterine pregnancy. Tubal pregnancies were surgically treated and histologically confirmed. Blood samples were collected for the determination of β-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor and their concentrations were compared in each subgroup. Receiver operating characteristic curve was calculated by comparing the subgroup of tubal pregnancy to the other groups. A Fisher discriminant function analysis was performed. The level of significance was 5%.RESULTS:One-way analysis of variance revealed a significant correlation between the different subgroups and β-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor serum levels (p<0.001). Vascular endothelial growth factor concentration was significantly higher for patients with tubal pregnancy than for other subgroups (p<0.05). β-Human chorionic gonadotropin and progesterone levels were higher in the subgroup with normal intrauterine pregnancies compared with the subgroups with tubal and abnormal intrauterine pregnancies (p<0.05). Serum vascular endothelial growth factor level >188.7 ng/mL predicted tubal pregnancy with 96.7% sensitivity, 95.0% specificity, 90.6% positive predictive value, and 98.3% negative predictive value.CONCLUSIONS:Serum vascular endothelial growth factor could be a marker in discriminating intrauterine pregnancy from tubal pregnancy; its levels are increased in women with ectopic pregnancy compared with women with normal and abnormal intrauterine pregnancies.

An intrauterine genomic classifier reliably delineates the location of nonviable pregnancies

To compare the intrauterine gene expression signatures of women with surgically confirmed ectopic pregnancy (ECT) and those of women with miscarriage to inform the development of a genomic classifier for the reliable delineation of pregnancy location in women with clinically nonviable pregnancies of unknown location (NV-PULs). Discovery-based prospective cohort study. Academic medical center. Women with clinically nonviable early pregnancy to include abnormal intrauterine pregnancy (AIUP), ECT, or NV-PUL. Endometrial (EM) pipelle sampling of the uterus was conducted at the time of scheduled surgery for clinically nonviable early pregnancy (dilation and curettage, manual vacuum aspiration, or laparoscopy). All pregnancy locations were surgically and/or histologically confirmed as intrauterine or ectopic. Gene expression profiles as determined by array hybridization, quantitative real-time polymerase chain reaction, and nCounter technology. Intrauterine samples were obtained by EM pipelle from 27 women undergoing surgery for a clinically nonviable early pregnancy. Comparison of array-based global gene expression signatures from women with histologically confirmed ECT versus AIUP revealed 61 differentially expressed genes from which the 5 most informative were included in the pregnancy location classifier. All 5 genes (C20orf85, LRRC46, RSPH4A, WDR49, and ZBBX) were cilia-associated and showed increased expression in pipelle samples from women with ECT relative to expression in samples from women with AIUP. The 5-gene classifier demonstrated an average area under the receiver operator characteristic curve of 0.97 for the detection of ECT. In an external test set composed of publicly available EM pipelle-based gene expression data from a study with similar ECT and AIUP cohorts (n = 19), the classifier revealed an average area under the receiver operator characteristic curve of 0.84. Consistently increased expression of cilia-associated genes in the uterine cavity of women with ECT provides a reliable molecular signal for the delineation of pregnancy location in women with clinically assessed NV-PUL. A classifier consisting of the 5 most informative cilia-associated genes demonstrated 91% (42/46) accuracy in predicting the pregnancy location.

Auricular acupressure and auricular acupuncture as an adjunct for pain management during first trimester aspiration abortion: A randomized, double-blinded, three-arm trial

ObjectivesTo measure pain and anxiety during first trimester uterine aspiration when using auricular acupressure or acupuncture as an adjunct to usual care. MethodsThis randomized, double-blinded, three-arm trial enrolled patients undergoing an aspiration procedure for an induced abortion, a miscarriage, or other abnormal intrauterine pregnancy. Trial participants received auricular acupressure, auricular acupuncture, or placebo immediately prior to their procedures. The study began with 1:1:1 randomization, but later overenrolled into the acupressure group after providing retraining for greater fidelity to that intervention. All participants received ibuprofen and a paracervical block. Participants reported pain and anxiety levels via visual analog scores (0–100). Our analysis compared pain scores of those receiving acupressure versus placebo, and those receiving acupuncture versus placebo. ResultsWe randomized 177 participants over nine months and excluded data from four participants. We analyzed data from 70 participants who received acupressure, 51 who received acupuncture, and 52 who received placebo. The groups had similar baseline characteristics, including baseline pain and anxiety scores. For acupressure, acupuncture, and placebo groups, respectively, immediate post-procedure median pain scores were 50, 55, 47.5 (p = 0.88); maximum pain scores during the procedure were 77, 79, 79.5 (p = 0.96); postprocedure anxiety scores were 26, 28, and 21 (p = 0.47). The acupressure group results were similar before and after retraining. ConclusionsReceiving auricular acupressure or acupuncture did not result in lower pain or anxiety scores among women undergoing vacuum aspiration compared to a placebo group. ImplicationsThe results of this trial were null, thus differing from our previous study that had shown a benefit from auricular acupuncture. Given the conflicting results, incorporating these acupuncture techniques into abortion practice would be premature.

Pitfalls and tips in the diagnosis of ectopic pregnancy.

Women of reproductive age with pelvic pain, vaginal bleeding, and a positive pregnancy test often require evaluation with pelvic ultrasound. In these situations, the primary role of pelvic ultrasound is to differentiate an ectopic pregnancy from either a normal or abnormal intrauterine pregnancy. While an accurately performed and interpreted pelvic ultrasound results in rapid diagnosis and management, numerous diagnostic pitfalls can lead to negative outcomes. Therefore, familiarity with the appropriate laboratory tests, sonographic technique, and imaging features of ectopic pregnancy is essential for all radiologists. We present a review of ectopic pregnancy cases from our institution with attention to common pitfalls and troubleshooting tips for physicians who perform and interpret pelvic ultrasounds. We also present recently published literature to aid in the management of first trimester pregnancy.

“Negative” serum hCG can fail to diagnose ectopic and abnormal intrauterine pregnancy at levels between 1.0-5.0mIU/ml

“Negative” serum hCG can fail to diagnose ectopic and abnormal intrauterine pregnancy at levels between 1.0-5.0mIU/ml

Ectopic Pregnancy (EP) or Abnormal Intrauterine Pregnancy after Embryo Transfer (ET) with a First Post-Transfer Quantitative Serum-hCG(s-hCG)

Limited data exists on the accuracy of a negative s-hCG after embryo transfer. Here we report five cases of women with first post-ET s-hCG <5mIU/mL and subsequent diagnosis of EP or abnormal intrauterine pregnancy. To demonstrate limitations of s-hCG evaluation in identification of early abnormal pregnancies at first post-ET testing. Patients were seen at a large university-based infertility practice. First post-ET s-hCG assays were performed 12 days after cleavage-stage ET or 10 days after blastocyst ET. In-house assays were performed using Siemens IMMULITE 2000. S-hCG<5mIU/mL were considered negative. One patient's s-hCG was analyzed at a commercial laboratory whose published negative value is <5.3mIU/mL. In September 2013, policy was changed to report all numeric values >1mIU/mL, rather than “<5mIU/mL”. Five women, ages 25-33, underwent ET from November 2011-September 2013. Three were multiparous and two were nulligravid. The index cycles included antagonist, microflare, frozen donor-egg, frozen ET and gestational carrier protocols. Three had multi-cellular ET and two had blastocyst ET. All five first post-ET s-hCG results were <5mIU/mL. Two patients had positive s-hCG (1644mIU/mL and 4255mIU/mL) at the subsequent cycle's baseline visit (29 and 30 days after negative s-hCG). Both were later diagnosed with an EP. One received methotrexate 32 days after negative s-hCG. The other presented 35 days after negative s-hCG with a ruptured EP and underwent laparoscopic salpingectomy. A third patient presented to a hospital overseas 34 days after negative s-hCG with a ruptured EP and underwent laparoscopic salpingectomy. A fourth patient presented to our hospital 18 days after negative s-hCG with hemorrhage, hemodynamic instability, s-hCG=898mIU/mL and hemoglobin=5.9g/dL. We performed suction curettage, diagnostic laparoscopy and administered blood products. Curettage pathology demonstrated chorionic villi, consistent with an incomplete abortion. Subsequent review of these reported negative s-hCG results revealed values ranging 2.0-3.77mIU/mL. A fifth patient underwent ET after reporting policy changed. First post-ET s-hCG=3.8mIU/mL. S-hCG was repeated every 48 hours and increased for eight days. S-hCG peaked at 79.9mIU/mL and subsequently declined. No further treatment was indicated. Quantitative s-hCG is a critical diagnostic tool. Here we report failure of a standard threshold (<5mIU/mL) to accurately diagnose early abnormal pregnancies. These findings are particularly important to post-ET patients who are at increased risk for EP and receive early s-hCG testing. We propose that first post-ET s-hCG results between 2mIU/mL and 5mIU/mL are not necessarily negative and require subsequent serial s-hCG monitoring.

Culdocentesis Followed by Saline Solution–Enhanced Ultrasonography: Technique for Evaluation of Suspected Ectopic Pregnancy

Study Objective To evaluate the use of a technique consisting of culdocentesis followed by saline solution–enhanced pelvic ultrasonography in cases suspect for ectopic pregnancy in which an accurate diagnosis could not be made using routine transvaginal ultrasound. Design Retrospective clinical study (Canadian Task Force classification III). Setting Academic medical center. Patients Twenty patients with an initial diagnosis of pregnancy of unknown location. Interventions In 20 patients with symptoms of early pregnancy and serum quantitative human chorionic gonadotropin concentration, ectopic pregnancy could not be confirmed or ruled out. Transvaginal ultrasound-guided culdocentesis was performed, and 300 to 400 mL of normal saline solution was injected into the posterior cul-de-sac and pelvis. Transvaginal ultrasound was repeated with particular attention to the floating fallopian tubes Measurements and Main Results Using this technique, a tubal pregnancy was visualized in 15 of 20 patients, and ectopic pregnancy was ruled out in 5 patients. In all patients, appropriate management was provided according to the final diagnosis, and consisted of either methotrexate, laparoscopic salpingostomy or salpingectomy, or expectant management in patients with abnormal intrauterine pregnancies. Conclusion Ultrasound-guided culdocentesis followed by saline solution–enhanced pelvic ultrasound can be considered as a diagnostic tool in patients with suspected ectopic pregnancy in whom other methods fail to demonstrate this diagnosis.

Change in quantitative human chorionic gonadotropin after manual vacuum aspiration in women with pregnancy of unknown location

To determine whether the change in human chorionic gonadotropin after manual vacuum aspiration is predictive of an early abnormal intrauterine pregnancy in women with pregnancy of unknown location. This is a prospective cohort study of 23 clinically stable patients with an early abnormal pregnancy who had abnormally rising human chorionic gonadotropins and absence of sonographic evidence of an intrauterine pregnancy or ectopic pregnancy. The change in human chorionic gonadotropin within 24 hours after manual vacuum aspiration was compared with the pathologic diagnosis and the ultimate clinical diagnosis. Ten patients had > or = 50% decrease (mean, 74%; range, 58-80%) in human chorionic gonadotropin after manual vacuum aspiration with confirmed chorionic villi on pathology results. Two patients had a > 50% drop in human chorionic gonadotropin but absence of chorionic villi, clinically consistent with complete spontaneous abortion. The remaining 10 patients who had either rising or < 50% decrease in human chorionic gonadotropin post manual vacuum aspiration all had no chorionic villi on pathology results. The sensitivity, specificity, positive predictive value, and negative predictive value of a > or = 50% decrease in human chorionic gonadotropin after manual vacuum aspiration in predicting an abnormal intrauterine pregnancy were 92% (95% confidence interval [CI], 0.62-0.99), 100% (95% CI, 0.62-1.0), 100% (95% CI, 0.70-1.0), and 90% (95% CI, 0.54-0.99), respectively. A > or = 50% decrease in human chorionic gonadotropin within 24 hours after manual vacuum aspiration is predictive of an abnormal intrauterine pregnancy, thereby excluding an ectopic pregnancy and expediting the management of women with pregnancy of unknown location.

Ultrasound Criteria for Diagnosis of Early Pregnancy Failure and Ectopic Pregnancy

Early pregnancy failure and ectopic pregnancy are common clinical diagnoses for which ultrasound can provide useful information. This review explores the use of ultrasound to diagnose early pregnancy failure and ectopic pregnancy. By documenting the developmental milestones of early normal pregnancy using ultrasound, clinicians can distinguish normal from abnormal intrauterine pregnancies. An early pregnancy failure can be diagnosed by the absence of a visible yolk sac with a mean sac diameter of 13 mm; the absence of a visible embryo with a mean sac diameter of 20 [corrected] mm; the absence of cardiac motion with an embryo measuring 5 mm or more in maximal length; or the presence of an empty amnion. In most settings, documentation of a normal intrauterine pregnancy effectively eliminates the possibility of ectopic pregnancy. The presence of an adnexal mass in the absence of an intrauterine gestational sac may indicate an ectopic pregnancy.

O-43: Early hCG dynamics after IVF help distinguish ectopic implantation from normal and abnormal intrauterine pregnancies

Ectopic pregnancy (ECT) is a potentially catastrophic outcome of IVF that often requires early medical or surgical intervention. Biochemical pregnancies (BIO) and spontaneous abortions (SAB) are also adverse IVF events, however, the sequelae of these pregnancies are generally not life threatening, and expectant management can usually be provided. We hypothesized that initial β-hCG levels may be helpful in distinguishing between ECT implantations and either BIO or SAB, and thus could be helpful in expediting the clinical management of IVF patients.

1058: Bleeding during and after pregnancy

Bleeding in pregnancy can occur in normal or abnormal intra-uterine pregnancy, an ectopic or heterotopic pregnancy. First trimester loss rate without bleeding is 11.5% when just a gestational sac is seen and decreases to 2% to 3%. Bleeding in the first trimester has a 45% chance of having a failed gestation identified at the first imaging exam. If a live embryo is seen between six to 12 weeks, there is still a 15% chance of failure depending on the volume of blood passed. Larger amount will result in failure 10% of the time compared with 5% in spotting.

The value of a single combined measurement of VEGF, glycodelin, progesterone, PAPP-A, HPL and LIF for differentiating between ectopic and abnormal intrauterine pregnancy

To evaluate whether serum concentrations of the non-placental markers vascular endothelial growth factor (VEGF), glycodelin (GLY) and progesterone (P) and the novel placental markers pregnancy-associated plasmaprotein A (PAPP-A), human placental lactogen (HPL) and leukaemia inhibiting factor (LIF) differ in ectopic pregnancy (EP) when compared with abnormal intrauterine pregnancy (aIUP). A prospective clinical study was conducted at the University Hospital of Larissa, Greece. The study included 50 patients admitted with failed pregnancy and suspected ectopic pregnancy that were treated with curettage or laparoscopy and classified as histologically confirmed EPs (n = 27) or histologically confirmed aIUPs (n = 21) (mean gestational age of 7.15 and 7.3 weeks, respectively). Two suspected EPs proved to be normal IUPs and were excluded. VEGF, GLY, P, beta-HCG, PAPP-A, HPL and LIF were measured by enxyme-linked immunosorbent assay (ELISA) methods in a single pre-operative blood sample. The median VEGF concentration was 227.2 pg/ml in the EP group versus 107.2 pg/ml in the aIUP group (P < 0.001), with a suggested threshold value of 174 pg/ml for their differential diagnosis. LIF, P, PAPP-A, HPL and GLY serum measurements did not differ significantly between EP and aIUP. VEGF serum levels might be a useful marker in differentiating between EPs and aIUPs.

Frozen section examination of endometrial curettings in the diagnosis of ectopic pregnancy

Background. The aim of our study was to determine the accuracy and validity of frozen section analysis of endometrial curettings in differentiating between abnormal intrauterine and ectopic pregnancies. Methods. A retrospective analysis of the database of the Department of Obstetrics and Gynecology in our institute was performed from January 1998 to September 1999. In 70 women with a suspected ectopic pregnancy a diagnostic curettage was sent for frozen section examination because products of conception could not be identified macroscopically in the curettings. Routine paraffin fixation specimens were also prepared from the endometrial curettings. A frozen section diagnosis was considered correct if it concurred with the final pathologic diagnosis, and incorrect if it differed. The sensitivity, specificity, positive predictive value and negative predictive value of a frozen section in identification of conception products were calculated. Results. Of the 70 frozen section studies the diagnosis was correct in 63 (90%), and incorrect in 7 (10%) cases. Of 50 specimens interpreted as negative on frozen sections (no products of conception noted), 6 (12%) were found to contain conception products on final pathologic review. One of the 20 (5%) specimens interpreted as positive by a frozen section failed to demonstrate products of conception on a final pathologic section. The sensitivity of frozen sections in the diagnosis of ectopic pregnancy was 76%, specificity 97.8%; positive predictive value 95%; negative predictive value 88% and accuracy 90%. Conclusions. Frozen section examination is a rapid and accurate method for identifying products of conception in endometrial curettings, and may reduce delay in the diagnosis of an ectopic pregnancy and in the institution of therapy.

Frozen section examination of endometrial curettings in the diagnosis of ectopic pregnancy

The aim of our study was to determine the accuracy and validity of frozen section analysis of endometrial curettings in differentiating between abnormal intrauterine and ectopic pregnancies. A retrospective analysis of the database of the Department of Obstetrics and Gynecology in our institute was performed from January 1998 to September 1999. In 70 women with a suspected ectopic pregnancy a diagnostic curettage was sent for frozen section examination because products of conception could not be identified macroscopically in the curettings. Routine paraffin fixation specimens were also prepared from the endometrial curettings. A frozen section diagnosis was considered correct if it concurred with the final pathologic diagnosis, and incorrect if it differed. The sensitivity, specificity, positive predictive value and negative predictive value of a frozen section in identification of conception products were calculated. Of the 70 frozen section studies the diagnosis was correct in 63 (90%), and incorrect in 7 (10%) cases. Of 50 specimens interpreted as negative on frozen sections (no products of conception noted), 6 (12%) were found to contain conception products on final pathologic review. One of the 20 (5%) specimens interpreted as positive by a frozen section failed to demonstrate products of conception on a final pathologic section. The sensitivity of frozen sections in the diagnosis of ectopic pregnancy was 76%, specificity 97.8%; positive predictive value 95%; negative predictive value 88% and accuracy 90%. Frozen section examination is a rapid and accurate method for identifying products of conception in endometrial curettings, and may reduce delay in the diagnosis of an ectopic pregnancy and in the institution of therapy.

The Vascular Endothelial Growth Factor (VEGF)/VEGF Receptor 2 Pathway Is Critical for Blood Vessel Survival in Corpora Lutea of Pregnancy in the Rodent

The vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR-2) pathway regulates proliferation, survival, and permeability of vasculature. This pathway is active during the formation of a corpus luteum, a highly vascularized, endocrine organ with a short life span during the nonpregnant state. In the pregnant state, the life span of corpora lutea is much longer because they play a critical role in supporting pregnancy development. We hypothesized that the VEGF/VEGFR-2 pathway plays a critical role in regulating angiogenic events in the corpora lutea of pregnancy. Injection of the neutralizing anti-VEGFR-2 antibody DC101 (ImClone Systems, Inc., New York, NY) on embryonic d 3.5 (preimplantation) or 6.5 (postimplantation) disrupts function of the corpora lutea of pregnancy in CD1 mice, as evidenced by a decrease in organ size, regression of luteal vessels, and a fall in progesterone secretion within 24 h postinjection. Inhibition of the VEGFR-2 caused removal of endothelial cells, mostly through endothelial cell detachment from the vascular basement membrane. Luteal steroid-producing epithelial cells were eliminated through apoptosis secondary to vasculature becoming dysfunctional. Disruption of luteal function caused arrest of embryonic development. The effect of antibody is specific to the ovary, because pregnancy progresses normally in ovariectomized, progesterone-replaced animals treated with anti-VEGFR-2 antibody. Embryonic blood vessels were not affected directly by the antibody, because it did not reach the embryo. Administration of an antibody against VE-cadherin (E4G10), which specifically blocks endothelial proliferation, did not disrupt luteal function and pregnancy development. Thus, VEGFR-2-mediated endothelial cell signals are critical to maintain functionality of luteal blood vessels during pregnancy. Potential clinical applications of inhibitors of the VEGF/VEGFR-2 pathway include emergency contraception and medical treatment of ectopic and abnormal intrauterine pregnancies.

Maternal serum vascular endothelial growth factor (VEGF) levels discriminate between ectopic and intrauterine pregnancies following IVF treatment

Objective: To determine serum levels of VEGF in women with normal intrauterine pregnancy (IUP), abnormal IUP (SAB), biochemical pregnancy (BC) and ectopic pregnancy (EP) following IVF therapy and evaluate the capacity of VEGF to serve as a marker for the diagnosis of ectopic pregnancy. Design: Retrospective analysis. Materials and Methods: During the period from January 1999 to December 2002, all patients who had IVF therapy in our center leading to the establishment of a pregnancy underwent blood sampling at 11 days after a 3-day embryo transfer for possible serum VEGF measurements. These patients were asymptomatic. Samples were centrifuged and the supernatants were stored at -80°C until assayed. VEGF concentrations were measured collectively from 108 women who subsequently were diagnosed to have an EP, a BC, an abnormal IUP and a normal IUP (27 women in each category). All patients were matched by age and stimulation results. SAB and BC were diagnosed by means of serial β-hCG measurements and transvaginal sonography. EP was confirmed by laparoscopy or by sonographic visualization. Serum VEGF was measured in duplicate by commercial ELISA. The sensitivity of the assay was < 9 pg/ml. In addition to VEGF, serum β-hCG and progesterone levels were also measured for all patients. The data were analyzed using analysis of variance with the Bonferroni post hoc test, non-parametric testing and Chi-square testing where appropriate. P < 0.05 was considered statistically significant. Data are presented as mean ± standard error of the mean. Results: Serum β-hCG and progesterone levels were significantly higher in women with normal and abnormal IUP than the other two groups. The serum concentrations of VEGF among women with EP and BC were higher than in those with normal IUP and SAB, but did not reach statistical significance (Table I). VEGF levels were higher in ectopic gestations than in known intra-uterine gestations (604.4±73.4 pg/ml vs. 455.4±27.7 pg/ml; P= 0.02). Furthermore, when a cut-off concentration of > 700 pg/ml for VEGF was used, an EP could be distinguished from an IUP with a specificity of 93%, and a positive predictive value of 63%. Tabled 1 Conclusion: Maternal serum levels of VEGF are higher in women with ectopic than intrauterine IVF pregnancies, as early as 11 days following embryo transfer. This difference in VEGF concentrations provides the ability to discriminate ectopic from intrauterine IVF pregnancies, and thus may be used as an additional potential marker for an ectopic pregnancy.

Beta‐Human Chorionic Gonadotropin Levels and the Likelihood of Ectopic Pregnancy in Emergency Department Patients with Abdominal Pain or Vaginal Bleeding

AbstractStrategies for diagnosing ectopic pregnancy that defer endovaginal ultrasound in women with suggestive symptoms and serum beta‐human chorionic gonadotropin (β‐hCG) levels less than 1,500 mIU/mL ignore the increased risk of ectopic pregnancy in these patients. Objective: To quantify this increased risk by establishing and comparing the β‐hCG distributions of symptomatic women with ectopic pregnancies, abnormal intrauterine pregnancies, and normal intrauterine pregnancies. Methods: The authors reviewed the records of a cohort of women who visited an urban emergency department (ED) during a 34‐month period with abdominal pain or vaginal bleeding and non‐zero quantitative β‐hCG levels. Explicit criteria were used to determine whether the pregnancy ultimately turned out to be intrauterine and normal, intrauterine and abnormal, or ectopic. Probability distributions were compared using frequency distributions, receiver operating characteristic (ROC) curves, and likelihood ratios. Results: Of 730 ED patients included in the analysis, 96 (13%) had ectopic pregnancies, 253 (35%) had abnormal intrauterine pregnancies, and 381 (52%) had normal intrauterine pregnancies. The β‐hCG distributions of patients with ectopic pregnancies and abnormal intrauterine pregnancies were similar and much lower than the β‐hCG distribution of patients with normal intrauterine pregnancies. A β‐hCG level less than 1,500 mIU/mL more than doubled the odds of ectopic pregnancy (likelihood ratio = 2.24). Of the 158 patients with β‐hCG below 1,500 mIU/mL, 40 (25%; 95% confidence interval [CI] = 19% to 32%) had ectopic pregnancies, and only 25 (16%; CI = 11% to 22%) had normal intrauterine pregnancies. Conclusions: In women with pain or bleeding and serum β‐hCG levels less than 1,500 mIU/mL, the risk of ectopic pregnancy is substantially increased, while the likelihood of normal intrauterine pregnancy is low.

Beta-human chorionic gonadotropin levels and the likelihood of ectopic pregnancy in emergency department patients with abdominal pain or vaginal bleeding.

Strategies for diagnosing ectopic pregnancy that defer endovaginal ultrasound in women with suggestive symptoms and serum beta-human chorionic gonadotropin (beta-hCG) levels less than 1500 mIU/mL ignore the increased risk of ectopic pregnancy in these patients. To quantify this increased risk by establishing and comparing the beta-hCG distributions of symptomatic women with ectopic pregnancies, abnormal intrauterine pregnancies, and normal intrauterine pregnancies. The authors reviewed the records of a cohort of women who visited an urban emergency department (ED) during a 34-month period with abdominal pain or vaginal bleeding and non-zero quantitative beta-hCG levels. Explicit criteria were used to determine whether the pregnancy ultimately turned out to be intrauterine and normal, intrauterine and abnormal, or ectopic. Probability distributions were compared using frequency distributions, receiver operating characteristic (ROC) curves, and likelihood ratios. Of 730 ED patients included in the analysis, 96 (13%) had ectopic pregnancies, 253 (35%) had abnormal intrauterine pregnancies, and 381 (52%) had normal intrauterine pregnancies. The beta-hCG distributions of patients with ectopic pregnancies and abnormal intrauterine pregnancies were similar and much lower than the beta-hCG distribution of patients with normal intrauterine pregnancies. A beta-hCG level less than 1500 mIU/mL more than doubled the odds of ectopic pregnancy (likelihood ratio = 2.24). Of the 158 patients with beta-hCG below 1500 mIU/mL, 40 (25%; 95% confidence interval [CI] = 19% to 32%) had ectopic pregnancies, and only 25 (16%; CI = 11% to 22%) had normal intrauterine pregnancies. In women with pain or bleeding and serum beta-hCG levels less than 1500 mIU/mL, the risk of ectopic pregnancy is substantially increased, while the likelihood of normal intrauterine pregnancy is low.

Vascular endothelial growth factor (VEGF) and discrimination between abnormal intrauterine and ectopic pregnancy.

This study evaluated serum vascular endothelial growth factor (VEGF) levels in women with abnormal intrauterine and ectopic pregnancies (EP) at 6 weeks gestation. We conducted a prospective case-control study comparing serum VEGF concentrations among 84 women with abnormal intrauterine and EP matched for gestational age (42 women in each group). We analysed whether serum VEGF levels >200 pg/ml would discriminate between abnormal intrauterine pregnancies and EP at 6 weeks gestation, and we calculated sensitivity, specificity and positive predictive values. Serum VEGF concentrations did not show statistically significant differences between women with abnormal intrauterine pregnancies (median, 198.5 pg/ml; range, 0-701.6) and EP (median, 211.2 pg/ml; range 0-628.8). When threshold concentrations of a serum VEGF level >200 pg/ml were used, abnormal intrauterine pregnancy could be distinguished from EP with a sensitivity of 56%, a specificity of 51%, and a positive predictive value of 53%. VEGF does not discriminate ectopic from abnormal intrauterine pregnancies at 6 weeks gestation, and thus should not be used in clinical management.

Progesterone as a predictor of ectopic pregnancy when the ultrasound is indeterminate

The objective of this study was to evaluate a progesterone cutpoint of 5.0 ng/mL ability to identify abnormal pregnancy (abnormal intrauterine pregnancy and ectopic pregnancy) as well as ectopic pregnancy alone in 2 subclasses of indeterminate ultrasounds. This was a prospective observational study of emergency department patients with abdominal pain or vaginal bleeding and an indeterminate transvaginal ultrasound. Two subclasses of indeterminate ultrasounds were eligible: those with an empty uterus and a β-human chorionic gonadotropin value <3,000 mIU/mL and those with a nonspecific fluid collection. Patients were enrolled if a progesterone assay was collected the day of the emergency department visit. Patients were excluded if lost to follow-up. One hundred sixty patients were enrolled. Of these, 24 were diagnosed with ectopic pregnancy. The sensitivity and specificity of progesterone identifying abnormal pregnancy were 84% and 97%, respectively. The sensitivity and specificity of progesterone identifying ectopic pregnancy were 88% and 40%, respectively. In the 2 subclasses, the progesterone cutpoint was both sensitive and specific in identifying abnormal pregnancy and was sensitive but only moderately specific for identifying ectopic pregnancy. (Am J Emerg Med 2002;20:575-579. Copyright 2002, Elsevier Science (USA). All rights reserved.)