European Journal of Obstetrics & Gynecology and Reproductive Biology 106 (2003) 203208

Assessment of uterine circulation in ectopic pregnancy by transvaginal color Doppler

n Szabo *, La szlo Csabay, Zora n Belics, Tibor Fekete, Zolta n Papp Istva
First Department of Obstetrics and Gynecology, Semmelweis University, Baross Utca 27, P.O. Box 104, Budapest H-1442, Hungary Received 22 March 2002; received in revised form 21 May 2002; accepted 23 May 2002

Abstract Objective: The aim of our study was to determine the effect of abnormal implantation on uterine circulation and to evaluate whether the assessment of uterinal blood ow can provide additional information for the diagnosis of tubal pregnancies. Methods: Forty-nine patients with ectopic pregnancy were examined by transvaginal color Doppler immediately before surgery. Resistance and pulsatility indices of blood ow in the uterine and tubal arteries were measured. Results: The blood ow parameters of the uterine and tubal arteries did not change with gestational age. There was a signicant increase in blood ow on the side with the tubal gestation. Differences between sides were higher in the tubal arteries than in the main uterine arteries and showed no dependence on gestational age. Conclusion: The abnormal implantation and tubal trophoblast invasion in ectopic pregnancy (EP) can cause more marked blood ow changes in the adjacent supplying vessels than in the main uterine arteries. # 2002 Published by Elsevier Science Ireland Ltd.
Keywords: Ectopic pregnancy; Transvaginal color Doppler ultrasonography; Uterine and tubal artery blood ow

1. Introduction Transvaginal ultrasound has made a dramatic impact on the diagnosis of normal, complicated and ectopic pregnancy (EP) by allowing early detection of intrauterine pregnancy and by improving the visibility of the adnexa [13]. Recently, Doppler and transvaginal color imaging has provided the possibility for assessment of pelvic vascularity and evaluation of the blood ow characteristics in normal and abnormal implantation [46]. The detection of blood ow in the ectopic trophoblast has previously been introduced as a more accurate method for diagnosing early tubal gestation [68]. The aim of our study was to determine the effect of abnormal implantation and tubal trophoblast invasion on uterine circulation and to evaluate whether the assessment of tubal or uterinal blood ow can provide additional information for the diagnosis of tubal pregnancies. 2. Materials and methods Forty-nine patients with tubal EPs were recruited into the study. The diagnosis of EP was made by transvaginal 2D, color and pulsed Doppler scans and by quantitative serum
* Corresponding author. Tel.: 36-1-266-0473; fax: 36-1-317-6174. ). E-mail address: szabo@noi1.sote.hu (I. Szabo

hCG level measurements. All patients underwent surgery (laparoscopy or laparotomy) at the First Department of Obstetrics and Gynecology of Semmelweis University, between 1 January 1997 and 31 December 1999. The diagnosis of EP was conrmed by histopathology. The study was approved by the hospital committee. We excluded patients with severe pain, profuse haemorrhage, or acute abdomen requiring emergency intervention. The mean age of the patients was 29 years (range 1736). Sixteen of them were primigravida and 33 of them were multigravida. None of them had undergone previous tubal surgery or ovulation induction therapy. The gestational ages, calculated from the last menstrual period, ranged from 32 to 71 days, with a mean ( standard deviation) of 50 10 days. The b-hCG levels ranged from 242 to 20,500 mIU/ml with a mean of 6234 mIU/ml. Serum hCG concentrations were estimated using a Microparticle Enzyme Immunoassay (AXSYM Total b-hCG, Abbot Laboratories, Abbot Park, IL, USA) calibrated according to the WHO Third International Standard (75/537), which is equal to the First International Reference Preparation. The intra- and inter-assay coefcients of variation for this assay are 12 and 23%, respectively, at concentrations above 2 mIU/ml. All sonograms were performed by same specialist (I.Sz.) with an ATL Ultramark 9 (Advanced Technology Laboratories,

0301-2115/02/$ see front matter # 2002 Published by Elsevier Science Ireland Ltd. PII: S 0 3 0 1 - 2 1 1 5 ( 0 2 ) 0 0 2 3 5 - X

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Seattle, WA, USA) scanner with 5 MHz convex electronic vaginal transducer which is suitable for 2D, color and pulse Doppler examinations. The characteristics of this instrument and the execution of the 2D, color and pulse Doppler examinations have been described in great detail in a previous paper [9]. Color and pulsed Doppler parameters, including high pass lter, sample volume size and velocity scale were optimised for detection of slow ow. The spatial peak temporal average intensity at the maximum amplitude and minimum gate in simultaneous color and pulsed Doppler mode was less than 100 mW/cm2, according to the manufacturer's specication. Using the empty-bladder technique, longitudinal and transverse scans were performed by B-mode ultrasound. The morphology of the uterus and the adnexa as well as the accumulation of uid in the cul-de-sac was evaluated rst. Then the size of the uterus and the o.d. of the tubal pregnancy were measured in two dimensions. The adnexal masses were classied into six categories, according to their morphological characteristics: ectopic sac with live embryo, sac with embryonic echo with no heart action, sac with visible yolk sac, empty sac, haematocele and solid tubal mass. Color Doppler was used to depict uterine vascularity and to image the main uterine and tubal arteries. The main uterine artery was identied at the level of the internal o.s. The pulsed Doppler gate was placed over the vessel and ow velocity waveforms were recorded. The transducer was positioned so that the angle between the pulsed Doppler beam and the vessel was close to 0. The mean resistance index (RI) and pulsatility index (PI) were calculated for both uterine arteries when at least ve sequential, good quality waveforms were obtained. The tubal branch of the ascending arch of the uterine artery was visualised at the region adjacent to the isthmic zone of the Fallopian tube. Flow velocity waveforms were obtained by pulsed Doppler and the RI and PI calculated on both sides. Also, color Doppler was used to demonstrate the intratubular vascular branches that were supplying the ectopic sac. Once an area of neovascularity at the periphery of the sac was identied as ``trophoblastic ow'' the examination was completed using pulsed Doppler. For computer analysis of the data the program package Statgraphics Version 4.0 (Statistical Graphics Corp., Rockville, USA) was used. Simple regression analysis was used

to describe changes in Doppler indices with the length of gestation. The Student's t-test was used to compare the differences in blood ow impedance indices in the tubal and main uterine arteries between the two sides. A difference was considered signicant when, using the Student's two samples t-test, P was less than 0.05. 3. Results The results of the transvaginal 2D scans are summarised in Table 1. In 9 of 49 EP cases (18%), a live embryo was seen within the ectopic sac. In 12 cases (25%), an embryo with absence of heart action was identied, whereas 13 ectopic sacs (27%) contained only a yolk sac. Nine patients (18%) had an empty sac. A hematocele was seen in four cases (8%) and solid tubal thickening in two cases (4%). The mean diameter of the tubal pregnancies was 11.5 mm, with a range of 9.138 mm. The measurements of the smallest detectable tubal gestation sac were 5:3 mm 8:4 mm. Free uid in the cul-de-sac was detected by ultrasound in 18 of 49 cases (37%). Both uterine arteries were identied in all patients with an EP. Comparisons between the artery on the side of the EP and the contralateral side demonstrated signicant differences both in the RI and PI (Table 2). Lower RI and PI were detectable on the EP side than on the contralateral side. There was a subjective impression that the highest differences between sides were seen in intact tubal pregnancies with a live embryo within the ectopic sac. There were no signicant changes of Doppler indices with gestation and

Table 1 Classification of tubal ectopic pregnancy by transvaginal sonographic appearence Ectopic pregnancy Ectopic sac with live embryo Sac with embryonic echo with no heart action Sac with visible yolk sac Empty sac Haematocele Solid tubal mass Total n 9 12 13 9 4 2 49

Table 2 Resistance index (RI) and pulsatility index (PI) values (mean S:D:) in the uterine circulation Impedance indices Uterine arteries Ectopic pregnancy side (n 49) 0.79 0.07 1.96 0.56 P <0.05 <0.05 Contralateral side (n 49) 0.88 0.06 2.78 0.61 Tubal arteries Ectopic pregnancy side (n 47) 0.67 0.11 1.29 0.53 P <0.05 <0.05 Contralateral side (n 38) 0.91 0.08 3.14 1.13

RI PI

S.D.: standard deviation.

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Fig. 1. Pulsatility indices of the uterine arteries in EPs. Simple regression analysis (lines represent mean of the pulsatility indices on the ectopic side and on the contralateral side).

differences between sides showed no dependence on gestational age (Fig. 1). Color ow in the trophoblast was detected in 46 of 49 adnexal masses (94%) suggestive of tubal pregnancy. The mean RI of these low low-resistance ows was 0:4 0:06 with a range of 0.300.56. The mean PI was 0:59 0:11 with a range of 0.400.90. The three lowest serum b-hCG levels were between 862 and 1180 mIU/ml when trophoblastic ow was detectable with the color and pulsed sensitivity of our equipment (serum b-hCG levels were between 242 and 612 mIU/ml in the three cases with undetectable trophoblast ow). Tubal arteries were identied and optimal ow velocity waveforms were recorded in 47 of 49 cases (96%) on the EP side and in 38 of 49 cases (78%) on the contralateral side (Fig. 2). Recording failure was determined by unfavourable visualisation of the tubal artery (retrovertedretroexed uterus) and inadequate insonation angel to the correct measurements. The mean values of RI and PI were found

to be signicantly lower on the tubal pregnancy side than on the contralateral side (Table 2). Differences between sides were signicantly higher in the tubal arteries than in the uterine arteries (Table 3). There were no signicant changes of Doppler indices with gestation, and differences between sides showed no dependence on gestational age (Fig. 3). 4. Comment Histologic studies have shown that in tubal gestations the development of the placenta replicates that seen in intrauterine pregnancy [10]. Invasion of maternal blood vessels within the tube also occurs in the same way as in the uterus. Although the structure of vessels in the tubal wall differs markedly from that of the spiral arteries, the sequence of change is similar. The Doppler characteristics of the vascular supply to the gestational sac are almost identical in patients with intrauterine or extrauterine pregnancy [11].

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Fig. 2. Typical picture of a Doppler flow analysis of the tubal arteries in ectopic pregnancy: (a) the ectopic pregnancy side; (b) contralateral side.

This nding applies to both the appearance and location of ow at the periphery of the sac and the ow velocity waveform characteristics. In color imaging, the trophoblastic ow is easily demonstrated as a ring of color around the gestational sac, and in the Doppler mode it is dened by a waveform with low pulsatility and a continuous end-diastolic component. Furthermore, a good correlation between the impedance indices of trophoblastic ows and the b-hCG level has been found [6,7,12]. In cases of EP in which color ow could be demonstrated, the b-hCG levels were found to be more than

8001000 mIU/ml [6,7,12]. In the present study, color ow in the trophoblastic tissue was detected in 46 of 49 tubal pregnancies (94%) and all cases with detectable trophoblastic ow had b-hCG levels above 862 mIU/ml. Trophoblastic ow, whether intrauterine or ectopic, is a necessity for viable gestation [6,7,11,13]. This low impedance ow can alter the hemodynamic characteristic of the uterine circulation. Jurkovic et al. detected color ow at the periphery of the adnexal mass in 18 of 19 EPs (94%) [11]. They found no signicant change in Doppler indices of the uterine artery with gestation, either on the EP side or the contralateral side. In comparing the uterine artery on the side of the EP and the contralateral side, they found no signicant differences in the peak systolic velocity or RI. Tekay and Jouppila detected color ow in the trophoblast in 50% of all adnexal masses suggestive of tubal pregnancy [7]. Their results showed that ectopic trophoblast alter the pulsatility of the waveform of the ipsilateral uterine artery. The PIs of the ipsilateral uterine arteries were found to be signicantly lower in patients with trophoblastic ow than in those without it, but they found no signicant relationship between the location of the tubal pregnancy and the PIs of the ipsilateral or contralateral uterine artery. In the present study, we found a relatively high percentage of intact tubal pregnancies with detectable trophoblastic ow. These ndings can explain the signicant differences in blood ow parameters between the contralateral uterine arteries. Predominance of hormonal events in regulating blood ow in these vessels can not oppose to a local reduction in ow impedance caused by placentation in intact tubal pregnancy. It seems that viable ectopic trophoblast activity can result in more marked blood ow changes in the adjacent supplying vessels. Tekay et al. found a decrease of 34 and 47% in the PI of the ipsilateral tubal artery compared to the contralateral side in two cases of EP [14]. Stefanovic et al. measured blood ow in the tubal arteries on both sides in 46 woman with early ectopic pregnancy, and compared the impedance indices of the tubal artery ow on the tubal pregnancy side to the contralateral side [15]. They found lower RI and PI values in the tubal pregnancy side, 70 and 61%, respectively, than the contralateral side, but the difference was not statistically signicant. Kirchler et al. hypothesised that the invasion of the trophoblast increases blood ow in the tubal artery involved in ectopic pregnancy [16]. They found an increase in tubal blood ow on the ectopic pregnancy side, and the mean difference in tubal

Table 3 Mean side differences of impedance indices in the uterine and tubal arteries in the investigated study group Impedance indices Uterine arteries, mean S:D: side difference between the EP side and contralateral side 0.10 0.07 0.89 0.59 P Tubal arteries, mean S:D: side difference between the EP side and contralateral side 0.24 0.14 1.58 0.70

RI PI S.D.: standard deviation.

<0.05 <0.05

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Fig. 3. Pulsatility indices of the tubal arteries in EPs. Simple regression analysis (lines represent mean of the pulsatility indices on the ectopic side and on the contralateral side).

blood ow between sides was 20.45% in 101 ectopic pregnancies. The percentage of the difference in tubal blood ow between sides was found to be independent of gestational age. Our results clearly support these previous observations. In the present study, we found a 26% mean difference in resistance indices of tubal blood ow between sides and the percentage of the difference in tubal blood ow between sides was also found to be independent of gestational age. Transvaginal color Doppler ultrasound enables us to extend our knowledge of the hemodynamic alterations involved in tubal gestation [1118]. According to our results, the abnormal implantation and tubal trophoblast invasion in EP causes more marked blood ow changes in the adjacent supplying vessels than in the main uterine arteries. The assessment of tubal blood ow can provide supplementary information for correct and prompt diagnosis of tubal pregnancy. References
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