Compare TVUS with -hcg level in the evaluation of embryo in early pregnancy.

Transcription

1 1. Hasan R, Baird DD, Herring AH, Olshan AF, Jonsson Funk ML, Hartmann KE. Patterns and predictors of vaginal bleeding in the first trimester of pregnancy. Ann Epidemiol 2010; 20(7): Bree RL, Edwards M, Bohm-Velez M, Beyler S, Roberts J, Mendelson EB. Transvaginal sonography in the evaluation of normal early pregnancy: correlation with HCG level. AJR 1989; 15(1): Bradley WG, Fiske CE, Filly RA. The double sac sign of early intrauterine pregnancy: use in exclusion of ectopic pregnancy. Radiology 1982; 1(1): Parvey HR, Dubinsky TJ, Johnston DA, Maklad NF. The chorionic rim and lowimpedance intrauterine arterial flow in the diagnosis of early intrauterine pregnancy: evaluation of efficacy. AJR 1996; 167(6): Type,59 patients 5 patients; 75 TVUS examinations 50 suspected ectopic pregnancy patients; 17 proved ectopic cases 169 with early IUP; 69 with ectopic Objective (Purpose of ) To characterize the patterns and predictors of early pregnancy bleeding, setting aside bleeding episodes that occur at the time of miscarriage. Compare TVUS with -hcg level in the evaluation of embryo in early pregnancy. Retrospective review of pelvic sonograms to determine the usefulness of double sac sign in differentiating ectopic pregnancy from early IUP. Review sonograms to determine whether sonographic imaging of an intrauterine chorionic rim or arterial flow can help diagnose an early IUP. Results Approximately one-fourth of participants (n=1,207) reported bleeding (n=1,656 episodes), but only 8% of women with bleeding, reported heavy bleeding. Of the spotting and light bleeding episodes (n=1,555), 28% were associated with pain. Among heavy episodes (n=100), 5% were associated with pain. Most episodes lasted less than days, and most occurred between gestational weeks % of women with bleeding and 1% of those without experienced miscarriage. Maternal characteristics associated with bleeding included fibroids and prior miscarriage. Consistent with the hypothesis that bleeding is a marker for placental dysfunction, bleeding is most likely to be seen around the time of the luteal-placental shift. -hcg level of 1000 miu/ml - gestational sac was seen sonographically in each patient. - hcg level of 7200 miu/ml - yolk sac was seen in every patient. 10/22 patients with - hcg between 1000 and 7200 miu/ml had a visible yolk sac. Every patient with -hcg level >10,800 miu/ml had a visible embryo with a heartbeat. Results support other studies that TVUS can define pregnancy as early as 2 days and at -hcg levels as low as 1000 miu/ml. Double sac appearance is a useful indicator for differentiating an ectopic pregnancy from an early normal IUP. 126/28 patients had Doppler examination. Chorionic rim and double decidual sac had sensitivities of 80% and 6%, respectively, and specificities of 97% and 100%, respectively. Intrauterine arterial flow with either peak systolic velocity 15 cm/sec or resistive index 0.55 had a sensitivity of 70% and a specificity of 95%. Page 1

2 5. Laing FC, Brown DL, Price JF, Teeger S, Wong ML. Intradecidual sign: is it effective in diagnosis of an early intrauterine pregnancy? Radiology 1997; 20(): Yeh HC, Goodman JD, Carr L, Rabinowitz JG. Intradecidual sign: a US criterion of early intrauterine pregnancy. Radiology 1986; 161(2): Chiang G, Levine D, Swire M, McNamara A, Mehta T. The intradecidual sign: is it reliable for diagnosis of early intrauterine pregnancy? AJR 200; 18(): Mehta TS, Levine D, Beckwith B. Treatment of ectopic pregnancy: is a human chorionic gonadotropin level of 2,000 miu/ml a reasonable threshold? Radiology 1997; 205(2): Nyberg DA, Filly RA, Mahony BS, Monroe S, Laing FC, Jeffrey RB, Jr. Early gestation: correlation of HCG levels and sonographic identification. AJR 1985; 1(5): Type 102 patients observers 6 patients with IUP; 5 patients with ectopic 15 patients with IUP; patients with ectopic; observers Objective (Purpose of ) Retrospective study to determine if the intradecidual sign at sonography is effective in the diagnosis of early IUP. To determine the accuracy of the intradecidual sign (a feature on sonograms) in the detection of early IUP. Retrospective study to determine if intradecidual sign is accurate for the diagnosis of IUP and the exclusion of ectopic pregnancy. 676 patients Review medical records and US scans to determine whether hcg level of 2,000 miu/ml is a reasonable threshold for diagnosing ectopic pregnancy in the absence of US findings of IUP in order to prevent inappropriate treatment. 9 patients Compare hcg levels with US findings in patients with normal early IUP to determine the discriminatory level of β-hcg. Results Sensitivity for diagnosis of an IUP was %- 66%, specificity was 55%-7%, accuracy was 8%-65%, PPV was 91%-9%, and NPV was 12%-16%. Intradecidual sign was more sensitive (91.7% vs 6.9%) and specific (100% vs 60%) than the double decidual sac sign in the detection of early IUP. Patients with IUP had sensitivity of 70%. Ectopic pregnancies had specificity of 100% for the intradecidual sign; the accuracy rate was 75%, PPV 100%, and NPV %. Sensitivity for diagnosis of an IUP increases when -hcg levels are 2,000 miu/ml or the mean sac diameter mm. 58 patients had evidence of a normal or abnormal IUP. 51 (0%) of the 128 patients without evidence of an IUP had an hcg level >2,000 miu/ml. Of 51 patients, 15 (29%) were treated for ectopic pregnancy; 17 (%) were not immediately treated for ectopic pregnancy and had a normal IUP at follow-up US. hcg level of 2,000 miu/ml without US findings of IUP is not diagnostic. A gestational sac was always visible when the hcg level was 1800 miu/ml in 6 cases and 57 mlu/ml in one case. Comparison of serum hcg levels with US detection is useful for evaluating early pregnancy. 2 2 Page 2

3 10. Doubilet PM, Benson CB. Further evidence against the reliability of the human chorionic gonadotropin discriminatory level. J Ultrasound Med 2011; 0(12): Levi CS, Lyons EA, Lindsay DJ. Early diagnosis of nonviable pregnancy with endovaginal US. Radiology 1988; 167(2):8-85. Type Objective (Purpose of ) 202 patients To determine whether a woman with a β-hcg above 2000 miu/ml and no intrauterine fluid collection on TVUS can subsequently be found to have a live intrauterine gestation and, if so, what the prognosis is for the pregnancy. 62 patients Retrospective analysis of prospectively accumulated data to determine first trimester nonviability at endovaginal US on the basis of gestational sac size and the presence or absence of a yolk sac or embryo. Results 162 (80.2%) women had β-hcg levels below 1000 miu/ml on the day of the initial scan showing no intrauterine fluid collection, 19 (9.%) with levels of 1000 to 199, 12 (5.9%) 1500 to 1999, and 9 (.5%) above 2000 miu/ml. There was no significant relationship between initial β-hcg level and either first-trimester outcome or final pregnancy outcome (P>.05, logistic regression analysis and Fisher exact test). The highest β- hcg was 6567 miu/ml, and the highest value that preceded a liveborn term baby was 6 miu/ml. The hcg discriminatory level should not be used to determine the management of a hemodynamically stable patient with suspected ectopic pregnancy, if sonography demonstrates no findings of intrauterine or ectopic pregnancy. 59 patients with gestation sacs 8 mm; absence of a yolk sac predicted a nonviable pregnancy with sensitivity of 67%, specificity of 100%. 5 patients with gestation sacs 16 mm; absence of embryo predicted a nonviable pregnancy with sensitivity of 50% and specificity of 100%. Combining gestation sac size; demonstration of yolk sac, embryo and/or cardiac pulsations) helped in the diagnosis of a nonviable pregnancy with endovaginal US. Page

4 12. Abdallah Y, Daemen A, Kirk E, et al. Limitations of current definitions of miscarriage using mean gestational sac diameter and crown-rump length measurements: a multicenter observational study. Ultrasound Obstet Gynecol 2011; 8(5): Type 1,060 consecutive women Objective (Purpose of ) cross-sectional study to define the false-positive rate for the diagnosis of miscarriage associated with different CRL and MSD measurements with or without a yolk sac in a large study population of patients attending early pregnancy clinics. The authors also aimed to define cut-off values for CRL and MSD that, on the basis of a single measurement, can definitively diagnose a miscarriage and so exclude possible inadvertent termination of pregnancy. Results Of the 1,060 women with a diagnosis of IUP of uncertain viability, 7 remained viable and 587 were non-viable by the time of the 11-1-week scan. In the absence of both embryo and yolk sac, the false-positive rate for miscarriage was.% when an MSD cutoff of 16 mm was used and 0.5% for a cut-off of 20 mm. There were no false-positive test results for miscarriage when a cut-off of MSD 21 mm was used. If a yolk sac was present but an embryo was not, the false-positive rate for miscarriage was 2.6% for an MSD cut-off of 16 mm and 0.% for a cut-off of 20 mm, with no false-positive results when a cut-off of MSD 21 mm was used. When an embryo was visible with an absent heartbeat, using a CRL cut-off of mm the false-positive rate for miscarriage was 8.%, and for a CRL cutoff of 5 mm it was also 8.%. There were no false-positive results using a CRL cut-off of 5. mm. These data show that some current definitions used to diagnose miscarriage are potentially unsafe. An MSD cut-off of >25 mm and a CRL cut-off of >7 mm could be introduced to minimize the risk of a falsepositive diagnosis of miscarriage. Page

5 1. Rowling SE, Coleman BG, Langer JE, Arger PH, Nisenbaum HL, Horii SC. First-trimester US parameters of failed pregnancy. Radiology 1997; 20(1): Type 2,655 firsttrimester US scans in 2,285 patients Objective (Purpose of ) Retrospective review of US scans to test the reliability of established US parameters in predicting the outcome of first-trimester pregnancy. Results 0 (22%) of 15 patients without yolk sacs and with an 8 mm mean sac diameter developed live embryos: 2 had normal follow-up or delivery; six were lost to followup. 5(8%) of 59 patients with no depiction of embryos and with a 16 mm mean sac diameter developed live embryos: Two delivered, one spontaneously aborted, one had death of one twin embryo before being lost to follow-up, and one was lost to follow-up. 17 (0.7%) of 2,285 patients had early oligohydramnios: 6 (5%) had normal follow-up scans or delivery, two (12%) spontaneously aborted, and nine (5%) were lost to follow-up. Established parameters predictive of early pregnancy failure potentially result in misdiagnosis of nonviability or poor prognosis when applied to a large, unselected patient population. Close follow-up is necessary in cases with borderline abnormal findings. Page 5

6 1. Pexsters A, Luts J, Van Schoubroeck D, et al. Clinical implications of intra- and interobserver reproducibility of transvaginal sonographic measurement of gestational sac and crown-rump length at 6-9 weeks' gestation. Ultrasound Obstet Gynecol 2011; 8(5): Type Objective (Purpose of ) 5 patients To assess intra- and interobserver agreement of routinely performed measurements CRL and MSD for assessing the likelihood of miscarriage in the first trimester of pregnancy using TVUS. Results 5 patients were included in the study, with measurements obtained by both observers in of these. Intra- and interobserver intraclass correlation coefficient were high for CRL measurements, with values of and 0.99 for intraobserver agreement and 0.99 for interobserver agreement. For the MSD, the interobserver intraclass correlation coefficient was Limits of agreement were ± 8.91 and ± 11.7% for intraobserver agreement of CRL and ± 1.6% for interobserver agreement of CRL. For MSD, the interobserver limits of agreement were ± 18.78%. For an MSD measurement of 20 mm by the first observer, the prediction interval for the second observer was mm. For a CRL measurement of 6 mm, the prediction interval for the second observer was mm. For dating purposes, there is reasonable reproducibility of CRL measurements using TVUS at 6-9 weeks' gestation. When diagnosing miscarriage based on measurements of CRL care must be taken for values close to any decision boundary. The higher interobserver variability that was observed for MSD has implications for the diagnosis of miscarriage based on this measurement in the absence of a visible embryo or yolk sac. Page 6

7 15. Abdallah Y, Daemen A, Guha S, et al. Gestational sac and embryonic growth are not useful as criteria to define miscarriage: a multicenter observational study. Ultrasound Obstet Gynecol 2011; 8(5): Doubilet PM, Benson CB. Embryonic heart rate in the early first trimester: what rate is normal? J Ultrasound Med 1995; 1(6):1-. Type 1,060 consecutive intrauterine pregnancies of uncertain viability 1,185 first trimester sonograms Objective (Purpose of ) To establish cut-off values for MSD and CRL growth that could be definitively associated with either viability or miscarriage, and to establish the relationship between growth in MSD and appearance of embryonic structures in the gestational sac. Evaluate sonograms to determine prognosis of first trimester pregnancy as a function of heart rate, and to establish normal heart rate of gestational age. Results The study included 59 pregnancies in which a gestational sac with or without embryo was identified at the follow-up scan 7-1 days later. Of these, 192 were viable and 167 nonviable at the 11-1-week scan. MSD growth was significantly higher in viable than nonviable pregnancies (mean 1.00 vs 0.50 mm/day; P<0.001, 95% CI of difference ). A difference in CRL growth was found between the two groups (mean 0.67 vs 0.18 mm/day; P<0.001, 95% CI of difference ). MSD growth of 0.6 mm/day was associated with specificity for diagnosing miscarriage of 90.1%, a sensitivity of 61.7% and 19 false-positive test results. A cut-off of CRL growth rate of 0.2 mm/day gave a sensitivity of 76.% and there were no false-positive test results for miscarriage. On repeat scan the failure of either a yolk sac or embryo to be visualized was always associated with miscarriage. There is an overlap in MSD growth rates between viable and non-viable intrauterine pregnancies of uncertain viability. No cut-off exists for MSD growth below which a viable pregnancy could be safely excluded. A cut-off value for CRL growth of 0.2 mm/day was always associated with miscarriage. These data suggest that criteria to diagnose miscarriage based on growth in MSD and CRL are potentially unsafe. However, finding an empty gestational sac on two scans more than 7 days apart is highly likely to indicate miscarriage, irrespective of growth. Lower limit of normal is 100 beats per minute (bpm) up to 6.2 weeks gestation and 120 bpm at weeks. Page 7

8 17. Hertzberg BS, Mahony BS, Bowie JD. First trimester fetal cardiac activity. Sonographic documentation of a progressive early rise in heart rate. J Ultrasound Med 1988; 7(10): Benson CB, Doubilet PM. Slow embryonic heart rate in early first trimester: indicator of poor pregnancy outcome. Radiology 199; 192(2): Doubilet PM, Benson CB. Outcome of first-trimester pregnancies with slow embryonic heart rate at 6-7 weeks gestation and normal heart rate by 8 weeks at US. Radiology 2005; 26(2): Bromley B, Harlow BL, Laboda LA, Benacerraf BR. Small sac size in the first trimester: a predictor of poor fetal outcome. Radiology 1991; 178(2): Acharya G, Morgan H. First-trimester, three-dimensional transvaginal ultrasound volumetry in normal pregnancies and spontaneous miscarriages. Ultrasound Obstet Gynecol 2002; 19(6): Horrow MM. Enlarged amniotic cavity: a new sonographic sign of early embryonic death. AJR 1992; 158(2): McKenna KM, Feldstein VA, Goldstein RB, Filly RA. The empty amnion: a sign of early pregnancy failure. J Ultrasound Med 1995; 1(2): Type 12 first trimester fetuses Objective (Purpose of ) Determine heart rates of fetuses with real-time sonography and analyze with regard to gestational age. 7 patients Examine US scans to determine the outcome of early first-trimester pregnancies with slow embryonic heart rates. 2,97 patients first trimester outcome known; 567 patients met all criteria 16 patients 52 controls Retrospective study to determine the outcome of pregnancies with slow embryonic heart rate at 6-7 weeks gestation and normal heart rate by 8 weeks at US. Prospective study to determine the predictive value of a small gestational sac (mean sac size) minus CRL <5 mm in patients weeks gestation, and to compare with a group of control patients with normal sac size. 111 patients Cross-sectional observational study to correlate D US volumetry of intrauterine contents in normal and failed pregnancies with conventional 2D measurements. 25 normal gestations; 10 cases of embryonic death Compare the size of the amniotic cavity with the CRL and the size of the chorionic cavity to determine if enlarged amniotic cavity correlated with embryonic death. 15 patients Retrospective review to determine whether the empty amnion (visualization of an amnion but no identifiable embryonic pole) is a sign of early pregnancy failure. Results Mean embryonic heart rate increased from 101 bpm at menstrual weeks to 1 bpm at weeks. After nine weeks, the rate reached a plateau, ranging from 17-1 bpm. Slower heart rates are normal early in the first trimester. An embryonic heart rate 90 bpm in the first trimester has a high likelihood of fetal loss before the end of the first trimester. Loss occurred in all embryos with heart rates <70 bpm. When a slow embryonic heart rate is detected at weeks, likelihood of subsequent first-trimester loss is high although heart rate is normal at follow-up. Follow-up scan in late first trimester is needed in these pregnancies. 15/16 patients (9%) with first-trimester small sacs had spontaneous abortions. /52 control patients (8%) with normal sac sizes had spontaneous abortions. D US volumetry of intrauterine contents in normal and failed pregnancies correlates well with conventional 2D measurements. Volumetric assessment does not improve diagnosis of miscarriage. Further research is needed. Amniotic cavity that is enlarged relative to the CRL and the size of the chorionic cavity is a proof of embryonic death. Empty amnion sign is useful in confirming early pregnancy failure. Page 8

9 2. Yegul NT, Filly RA. The expanded amnion sign: evidence of early embryonic death. J Ultrasound Med 2009; 28(10): Lindsay DJ, Lovett IS, Lyons EA, et al. Yolk sac diameter and shape at endovaginal US: predictors of pregnancy outcome in the first trimester. Radiology 1992; 18(1): Type Objective (Purpose of ) 806 patients Retrospective study was performed to assess the PPV for confirming early embryonic death in the clinical scenario wherein an embryo is identified without a visible heartbeat, but the embryonic CRL is 5 mm. 86 women Evaluate women who had endovaginal sonography with fetuses <10 weeks menstrual age to establish the normal size and shape of the secondary yolk sac and to assess the value of yolk sac measurement in predicting pregnancy outcome in the first trimester. Results Among the cohort of 806 cases, 520 (6.5%) had an identifiable embryo, and 255 of those with an identifiable embryo had a visible amnion (9.0%). 116/255 with a visible amnion and an identifiable embryo without a heartbeat had a CRL that measured 5 mm (5.5%). The CRL of these embryos ranged from 1.7 to 5. mm (ie, when rounded to the nearest millimeter, these embryos would be 5 mm) with the breakdown as follows: those measuring. mm (n=28), those measuring.5 to. mm (n=5), and those measuring.5 to 5. mm (n=). Eight of these 116 patients did not have any documented followup. In the remaining 108 patients, pregnancy failure was confirmed. Authors conclude that any embryo that is surrounded by an amnion and that also lacks a heartbeat has unfortunately but definitively died. This is equally true for embryos measuring <5 mm in CRL. Yolk sac diameter >2 standard deviations above the mean when compared with the MSD allowed prediction of an abnormal pregnancy outcome with sensitivity of 15.6%, a specificity of 97.%, and PPV of 60.0%. Yolk sac diameter >2 standard deviations below the mean allowed prediction of an abnormal outcome with a sensitivity of 15.6%, specificity of 95.%, and PPV of.%. Page 9

10 26. Odeh M, Tendler R, Kais M, Grinin V, Ophir E, Bornstein J. Gestational sac volume in missed abortion and anembryonic pregnancy compared to normal pregnancy. J Clin Ultrasound 2010; 8(7): Bennett GL, Bromley B, Lieberman E, Benacerraf BR. Subchorionic hemorrhage in first-trimester pregnancies: prediction of pregnancy outcome with sonography. Radiology 1996; 200(): Mbugua Gitau G, Liversedge H, Goffey D, Hawton A, Liversedge N, Taylor M. The influence of maternal age on the outcomes of pregnancies complicated by bleeding at less than 12 weeks. Acta Obstet Gynecol Scand 2009; 88(1): Levine D. Ectopic pregnancy. Radiology 2007; 25(2): Lin EP, Bhatt S, Dogra VS. Diagnostic clues to ectopic pregnancy. Radiographics 2008; 28(6): Frates MC, Visweswaran A, Laing FC. Comparison of tubal ring and corpus luteum echogenicities: a useful differentiating characteristic. J Ultrasound Med 2001; 20(1):27-1; quiz. Type 11 normal pregnancies and 82 anembryonic abortions Objective (Purpose of ) To compare gestational sac volume between normal pregnancies and missed abortions and anembryonic pregnancies and to determine at what gestational age differences in gestational sac volume become evident. 516 patients Retrospective review of US images to assess risk of spontaneous abortion relative to size of subchorionic hemorrhage, age of patient, and time of presentation. 18 women To assess the effect of maternal age on the outcome of pregnancies complicated by bleeding at <12 weeks. N/A To review and illustrate the sonographic findings of ectopic pregnancy. Results Gestational sac volume was significantly larger in normal pregnancies than in missed or anembryonic abortion: / cm() and 8.0 +/ cm(), respectively (P<0.001). When stratified by weeks, statistically significant differences were found beginning at 7 weeks, while gestational sac volume measurements were not significantly different between the normal and abnormal pregnancies from 6 to 6(+6) weeks. Gestational sac volume in missed abortion and anembryonic pregnancies is significantly smaller than in normal pregnancies, starting at 7 weeks of gestational age. This finding may be helpful in the diagnosis of missed abortion or anembryonic pregnancies in selected cases. Spontaneous abortion rate was higher in large hemorrhages, older women (over 5 years) and earlier pregnancies (<8 weeks). Outcome measures were pregnancy loss, fetal abnormalities, preterm delivery, low birth weight and cesarean delivery. Age over 5 years was significantly associated with reduced live-birth and increased miscarriage rates. Women over 5 years of age had higher cesarean section and pregnancy loss rates than the younger women. The combination of bleeding in early pregnancy and advanced age increases risk of pregnancy loss even after US has confirmed fetal heart pulsation. Sonography is useful is making the right diagnosis is ectopic pregnancies. N/A Review diagnosis of ectopic pregnancy. Hormonal assays and pelvic US are used for the initial evaluation of ectopic pregnancy. 26 patients with tubal rings; 5 control patients with To compare the echogenicity of the tubal ring of an ectopic pregnancy and the corpus luteum with that of the ovary for improved detection of early ectopic pregnancy. Tubal ring is usually more echogenic than ovarian parenchyma, and the corpus luteum is usually equal to or less echogenic than the ovary. Echogenicity of an adnexal mass may help differentiate tubal ring from a corpus IUP luteum. Page 10

11 2. Stein MW, Ricci ZJ, Novak L, Roberts JH, Koenigsberg M. Sonographic comparison of the tubal ring of ectopic pregnancy with the corpus luteum. J Ultrasound Med 200; 2(1): Dart R, McLean SA, Dart L. Isolated fluid in the cul-de-sac: how well does it predict ectopic pregnancy? Am J Emerg Med 2002; 20(1):1-.. Nyberg DA, Hughes MP, Mack LA, Wang KY. Extrauterine findings of ectopic pregnancy of transvaginal US: importance of echogenic fluid. Radiology 1991; 178(): Wachsberg RH, Levine CD. Echogenic peritoneal fluid as an isolated sonographic finding: significance in patients at risk of ectopic pregnancy. Clin Radiol 1998; 5(7): Frates MC, Brown DL, Doubilet PM, Hornstein MD. Tubal rupture in patients with ectopic pregnancy: diagnosis with transvaginal US. Radiology 199; 191(): Type Objective (Purpose of ) 79 women Retrospective review of TVUS to compare the value of different sonographic features in distinguishing tubal ring from corpus luteum. 1 ST Group - 8 patients with cul-desac fluid; 2 nd Group - 52 patients with indeterminate US 22 patients: Group 1 68 patients with proved ectopic gestation; Group 2 8 patients with reliable evidence of IUP; Group 81 patients with no evidence of pregnancy at initial US 12 consecutive symptomatic patients 12 consecutive patients Retrospective cohort study to examine the risk of ectopic pregnancy among patients with isolated abnormal cul-de-sac fluid at TVUS. Moderate volume of anechoic fluid was compared with either a large volume of anechoic fluid or any echogenic fluid. Prospective study of TVUS studies to determine the significance of different extrauterine findings, including echogenic fluid in the cul-de-sac in patients with positive serum pregnancy tests considered to be at risk for ectopic pregnancy. Retrospective study of patients with positive pregnancy test in whom sonography revealed echogenic fluid as an isolated finding without evidence of IUP. Retrospective review of US scans and medical records to determine whether sonography can help diagnose tubal rupture in patients with ectopic pregnancy. Results Sonographic features for distinguishing tubal ring from corpus luteum include decreased wall echogenicity compared with the endometrium and an anechoic texture, which suggests a corpus luteum. Ectopic pregnancy was diagnosed in 16/8: 2% (95% CI: 26%-59%) of patients with isolated cul-de-sac fluid, 5/2: 22% (95%. CI: 7%-2%) of patients with moderate amount of anechoic fluid, and 11/15: 7% (95%, CI: 5%-92%) of patients with a large volume of fluid or any echogenic fluid. Patients with isolated abnormal cul-de-sac fluid are at moderate risk for ectopic pregnancy. The risk increases if the fluid is echogenic or the volume is large. Intraperitoneal fluid was detected in (6%) group 1 patients and in 81 (1%) group patients. Echogenic fluid was the only abnormal finding at US in 10 (15%) group 1 patients and added confidence to the diagnosis of ectopic pregnancy in many others. Echogenic fluid correlated with hemoperitoneum at the time of surgery. Presence of echogenic fluid shows a high risk for ectopic pregnancy. Small-to-moderate amount of echogenic fluid noted as an isolated finding may not be highly predictive of ectopic pregnancy. Findings at TVUS cannot reliably determine whether tubal rupture is present. Page 11

12 7. Ackerman TE, Levi CS, Dashefsky SM, Holt SC, Lindsay DJ. Interstitial line: sonographic finding in interstitial (cornual) ectopic pregnancy. Radiology 199; 189(1): Jafri SZ, Loginsky SJ, Bouffard JA, Selis JE. Sonographic detection of interstitial pregnancy. J Clin Ultrasound 1987; 15(): Jurkovic D, Hillaby K, Woelfer B, Lawrence A, Salim R, Elson CJ. Firsttrimester diagnosis and management of pregnancies implanted into the lower uterine segment Cesarean section scar. Ultrasound Obstet Gynecol 200; 21(): Ushakov FB, Elchalal U, Aceman PJ, Schenker JG. Cervical pregnancy: past and future. Obstet Gynecol Surv 1997; 52(1):5-59. Type Objective (Purpose of ) 12 patients Retrospective study to evaluate the with relationship of the endometrial canal and interstitial decidua vera to the interstitial gestational sac ectopic and to determine if this relationship can be pregnancy; used to increase the predictive value of US in 0 patients the diagnosis of interstitial ectopic pregnancy. with different diagnoses 11 patients Review sonographic findings in 11 cases of proven interstitial pregnancy and compare with previous 12 cases. 18 diagnosed cesarean section scar pregnancies 117 cases from literature cases from authors department Describe first-trimester US diagnosis and management of pregnancies implanted into uterine cesarean section scars. Review cases of cervical pregnancy in English literature from 1978 and cases performed in the authors department. Results Interstitial line had better sensitivity (80%) and specificity (98%) than eccentric gestational sac location (sensitivity 0%; specificity 88%) and myometrial thinning (sensitivity, 0%; specificity, 9%) for the diagnosis of interstitial ectopic pregnancy. Ierstitial line sign is a useful diagnostic sign of interstitial ectopic pregnancy. An ectopic pregnancy was diagnosed in all cases, and an interstitial location was suspected in 5 cases preoperatively. Most common findings were eccentrically located gestational sac surrounded by an asymmetric myometrial mantle and a separate empty uterine cavity with endometrial echoes. Laparoscopy is recommended when interstitial pregnancy is suspected by sonography. Surgical treatment was successful in all 8 cases. The respective success rates of medical treatment and expectant management were 5/7 (71%) and 1/ (%). 5 (28%) required blood transfusion and one woman (6%) had a hysterectomy. Cesarean section scar pregnancies are common. If diagnosis is made in the first trimester the prognosis is good and the risk of hysterectomy is relatively low. Sonography improved pretreatment diagnosis up to 81.8%. Early diagnosis of cervical pregnancy allowed for treatment by chemotherapy in 2 cases, with an 81. % success rate. Serial -hcg levels and TVUS with color Doppler are used to monitor therapy. Page 12

13 1. Malinowski A, Bates SK. Semantics and pitfalls in the diagnosis of cornual/interstitial pregnancy. Fertil Steril 2006; 86(6):176 e Talbot K, Simpson R, Price N, Jackson SR. Heterotopic pregnancy. J Obstet Gynaecol 2011; 1(1): Filhastre M, Dechaud H, Lesnik A, Taourel P. Interstitial pregnancy: role of MRI. Eur Radiol 2005; 15(1): Jung SE, Byun JY, Lee JM, Choi BG, Hahn ST. Characteristic MR findings of cervical pregnancy. J Magn Reson Imaging 2001; 1(6): Type Objective (Purpose of ) 1 patient To clarify the respective definitions of cornual and interstitial pregnancy and to explore the difficulties in diagnosing these entities, particularly in the context of Müllerian fusion defects. N/A Review diagnosis and management of heterotopic pregnancy. 2 patients Case report to examine role of MRI in interstitial pregnancy. 12 patients To assess characteristic MR findings of cervical pregnancy. Results Correct diagnosis and eventual termination of cornual pregnancy and identification of a uterine anomaly were achieved. The process led to the development of an enhanced understanding of diagnostic modalities and their limitations with regard to the entities under discussion. Accurate diagnosis of an interstitial pregnancy requires that those reading and reporting US use consistent, precise nomenclature. Clinicians must remain cognizant of the limitations of US in distinguishing cornual (intrauterine) from interstitial (ectopic) pregnancies and the influence of uterine anomalies on this distinction. In the majority (71%) of cases reviewed, risk factors for a heterotopic pregnancy were present. However, in several instances (%), previous sonographic reports of a normal IUP gave false reassurance. These results highlight the complexity of diagnosis. In addition, the findings were compared with two previous reviews covering cases from 1971 to 200. This comparison highlighted two important trends: first, the increasing role of US in the definitive diagnosis of a heterotopic pregnancy, and second, the development of conservative approaches to management. MRI was able to localize the ectopic pregnancy by showing a gestational structure surrounded by a thick wall in the upper part of the uterine wall separated from the endometrium by an uninterrupted junctional zone in both cases. Typical MR finding for cervical pregnancy is heterogeneous hemorrhagic mass with densely enhancing papillary solid components. Page 1

14 5. Coulier B, Malbecq S, Brinon PE, Ramboux A. MDCT diagnosis of ruptured tubal pregnancy with massive hemoperitoneum. Emerg Radiol 2008; 15(): Pham H, Lin EC. Adnexal ring of ectopic pregnancy detected by contrast-enhanced CT. Abdom Imaging 2007; 2(1): Barnhart K, van Mello NM, Bourne T, et al. Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome. Fertil Steril 2011; 95(): Condous G, Timmerman D, Goldstein S, Valentin L, Jurkovic D, Bourne T. Pregnancies of unknown location: consensus statement. Ultrasound Obstet Gynecol 2006; 28(2): Green CL, Angtuaco TL, Shah HR, Parmley TH. Gestational trophoblastic disease: a spectrum of radiologic diagnosis. Radiographics 1996; 16(6): Type Objective (Purpose of ) 1 patient Present a case report on diagnosis of ruptured tubal pregnancy with MDCT. 1 patient Case report to examine role of contrastenhanced CT in a woman with acute right lower quadrant abdominal pain. N/A N/A N/A To improve the interpretation of future studies in women who are initially diagnosed with a pregnancy of unknown location, the authors proposed a consensus statement with definitions of population, target disease, and final outcome. Panel of gynecologists with expertise in early pregnancy and US was convened by the International Society of Ultrasound in Obstetrics and Gynecology to discuss the role of US and biochemistry in the diagnosis and management of women with a pregnancy of unknown location. Review diagnosis of GTD with emphasis on the unique information provided by different diagnostic tools. Results Diagnosis was made using contrast-enhanced MDCT. The radiologist must be aware of the key signs (massive hemoperitoneum with fresh blood clots in the hypogastric area, active free peritoneal extravasation of intravascular contrast material and dramatic peripheral enhancement). Contrast-enhanced CT showed ring enhancing cystic structure in the right adnexa corresponding to tubal ring sign of ectopic pregnancy seen on subsequent pelvic US. Right tubal ectopic pregnancy was confirmed at surgery. Careful definition of populations and classification of outcomes should optimize objective interpretation of research, allow objective assessment of future reproductive prognosis, and hopefully lead to improved clinical care of women initially identified to have a pregnancy of unknown location. Consensus can be achieved in both the diagnostic approach and management of women with pregnancy of unknown location. The panel agreed that because most pregnancy of unknown location are at low risk of being an ectopic pregnancy, provided that the US examiner is sufficiently skilled and uses an US system with acceptable image quality, future efforts should concentrate on minimizing follow-up. Although US is recommended for initial diagnosis, radiography, angiography, CT, and MRI all play a role in determining the presence of GTD and the extent of its complications. US shows molar gestations as alternating cystic and solid tissue that fills the entire uterus. CT and MRI are useful in detecting myometrial invasion, parametrial extension, and metastasis. Page 1

15 50. Zhou Q, Lei XY, Xie Q, Cardoza JD. Sonographic and Doppler imaging in the diagnosis and treatment of gestational trophoblastic disease: a 12-year experience. J Ultrasound Med 2005; 2(1): Hou JL, Wan XR, Xiang Y, Qi QW, Yang XY. Changes of clinical features in hydatidiform mole: analysis of 11 cases. J Reprod Med 2008; 5(8): Type 55patients 11 cases of hydatidiform mole Objective (Purpose of ) Retrospective analysis of cases of GTD in two hospitals to evaluate the clinical utility of sonography with Doppler examination in the diagnosis and treatment of GTD. Retrospective study to investigate the changes of the clinical features of hydatidiform mole. Results 106/55 cases had hydatidiform mole, had a partial hydatidiform mole, 18 had an invasive hydatidiform mole, and 2 had choriocarcinoma. US showed abnormal molar tissue confined to the endometrial cavity in all cases of hydatidiform mole. Doppler waveforms showed resistive indices of 0.55 for hydatidiform mole, 0.56 for partial hydatidiform mole, 0.28 for invasive hydatidiform mole, 0.25 for choriocarcinoma, and 0.66 for normal pregnancies. Sonography and Doppler imaging were helpful in diagnosing GTD, in determining whether invasive disease was present, in detecting recurrence of disease, and in following the effectiveness of chemotherapy. Vaginal bleeding remains the most common presenting symptom, occurring in 9/11 cases (8.2%). Of 11 cases, 52 (6%) presented with excessive uterine size. Preeclampsia, hyperemesis, hemoptysis and theca lutein cysts occurred in /11 (.5%), 12/11 (10.6%), /11 (.5%) and 19/11 cases (16.8%), respectively. The incidence of postmolar trophoblastic neoplasia was 21% (2/11). Compared to historic data, the incidence of vaginal bleeding and preeclampsia were statistically lower (P<0.005). The incidence of postmolar gestational trophoblastic neoplasia was increased moderately without statistical significance compared to historic data. Because of the wide use of US and serum hcg test, current patients with hydatidiform mole have been diagnosed earlier in gestation and the clinical features have changed. Patterns of medical practice should be changed as well. Page 15

16 52. Barton JW, McCarthy SM, Kohorn EI, Scoutt LM, Lange RC. Pelvic MR imaging findings in gestational trophoblastic disease, incomplete abortion, and ectopic pregnancy: are they specific? Radiology 199; 186(1): Type Objective (Purpose of ) 9 patients To determine whether findings at MRI are specific for primary molar disease, persistent GTD, incomplete abortion, or ectopic pregnancy. Results Among the three groups (persistent GTD, incomplete abortion, or ectopic pregnancy) the only significant differences were a higher prevalence of endometrial distention in the group with incomplete abortion (P<.005) and the absence of junctional zone disruption in the group with ectopic pregnancy (P<.05). In the group with primary molar disease, total intrauterine volume was significantly increased (P<.001), and endometrial distention and presence of an endometrial mass had a significantly higher prevalence than that in the persistent GTD groups with (P<.0) or without (P<.001) metastases. Myometrial or extrauterine disease was identified in 65% of the patients with persistent disease and a -hcg level greater than 500 miu/ml (500 IU/L). Thus, although MRI findings in persistent GTD, incomplete abortion, and ectopic pregnancy are relatively nonspecific, MRI can depict invasive disease that may alter therapeutic management in patients with documented GTD. Page 16

17 5. Rufener SL, Adusumilli S, Weadock WJ, Caoili E. Sonography of uterine abnormalities in postpartum and postabortion patients: a potential pitfall of interpretation. J Ultrasound Med 2008; 27(): Kwon JH, Kim GS. Obstetric iatrogenic arterial injuries of the uterus: diagnosis with US and treatment with transcatheter arterial embolization. Radiographics 2002; 22(1): Degani S, Leibovitz Z, Shapiro I, Ohel G. Expectant management of pregnancyrelated high-velocity uterine arteriovenous shunt diagnosed after abortion. Int J Gynaecol Obstet 2009; 106(1):6-9. Type Objective (Purpose of ) 29 patients To identify misleading imaging features that leads to inclusion of a uterine AVM in the differential diagnosis of a uterine abnormality because consideration of this diagnosis can potentially alter patient treatment. 2 patients Retrospective review to determine value of US in detection and diagnosis of uterine vascular abnormalities and the value of transcatheter arterial embolization in treating these conditions. 12 patients To assess sonographic and clinical outcome in women with pregnancy-related uterine AVMs diagnosed after abortion. Results Interobserver agreement was as follows: the presence of a uterine mass, 90%; myometrial involvement, 8%; the presence of an associated vascular abnormality, 72%; and inclusion of a uterine AVM in the differential diagnosis, 86%. Myometrial involvement showed a statistically significant relationship to inclusion of a uterine AVM in the differential diagnosis (P<.05). Final pathologic diagnoses included retained products of conception (n=26), an endometrial polyp (n=1), chronic endometritis (n=1), and an exogenous progestational effect (n=1). No uterine AVMs were found. Despite high interobserver agreement in characterizing uterine abnormalities on sonography, readers still include uterine AVMs in the differential diagnosis of uterine masses that are ultimately proven to be retained products of conception. A myometrial location of a uterine mass is a particularly misleading imaging feature of retained products of conception. Color and duplex Doppler US is recommended for detection and diagnosis and follow-up of patients after embolization. Transcatheter arterial embolization is a safe and effective method. 9 asymptomatic patients were managed expectantly for to 10 weeks without further complications. None of the 12 required aggressive interventions such as transcatheter arterial embolization, and 6 had uncomplicated pregnancies after resolution of the lesions. Expectant management is an option in many women with pregnancyrelated uterine AVMs. Page 17

18 Evidence Table Key Category Definitions Category 1 The study is well-designed and accounts for common biases. Category 2 The study is moderately well-designed and accounts for most common biases. Category There are important study design limitations. Category The study is not useful as primary evidence. The article may not be a clinical study or the study design is invalid, or conclusions are based on expert consensus. For example: a) the study does not meet the criteria for or is not a hypothesis-based clinical study (e.g., a book chapter or case report or case series description); b) the study may synthesize and draw conclusions about several studies such as a literature review article or book chapter but is not primary evidence; c) the study is an expert opinion or consensus document. Dx = Diagnostic Tx = Treatment Abbreviations Key AVM = Arteriovenous malformation -hcg = Beta human chorionic gonadotropin CI = Confidence interval CRL = Crown-rump length CT = Computed tomography GTD = Gestational trophoblastic disease IUP = Intrauterine pregnancy MDCT = Multidetector computed tomography MRI = Magnetic resonance imaging MSD = Mean gestational sac diameter NPV = Negative predictive value PPV = Positive predictive value TVUS = Transvaginal ultrasound US = Ultrasound ACR Appropriateness Criteria Evidence Table Key