- Email: [email protected]
Power Doppler flow mapping and four-dimensional ultrasound for evaluating tubal patency compared with laparoscopy
European Journal of Obstetrics & Gynecology and Reproductive Biology 195 (2015) 83–87
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Power Doppler flow mapping and four-dimensional ultrasound for evaluating tubal patency compared with laparoscopy Amr A. Soliman a,b,1,*, Waleed Shaalan a,1, Tamer Abdel-Dayem a, Elsayed Elbadawy Awad a, Yasser Elkassar a, Do¨rte Lu¨dders b, Eduard Malik b, Hassan N. Sallam a a
University of Alexandria, Department of Obstetrics and Gynecology, El Shatby Maternity University Hospital, Port-Said Street, 21526 El-Shatby, Alexandria, Egypt Carl von Ossietzky University Oldenburg, Department of Obstetrics and Gynecology, Oldenburg University Women’s Hospital, Rahel-Straus-Straße 10, 26133 Oldenburg, Germany b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 9 March 2015 Received in revised form 16 June 2015 Accepted 25 September 2015
Objectives: To study the accuracy of four-dimensional (4D) ultrasound and power Doppler flow mapping in detecting tubal patency in women with sub-/infertility, and compare it with laparoscopy and chromopertubation. Study design: A prospective study. The study was performed in the outpatient clinic and infertility unit of a university hospital. The sonographic team and laparoscopic team were blinded to the results of each other. Women aged younger than 43 years seeking medical advice due to primary or secondary infertility and who planned to have a diagnostic laparoscopy performed, were recruited to the study after signing an informed consent. All of the recruited patients had power Doppler flow mapping and 4D hysterosalpingo-sonography by injecting sterile saline into the fallopian tubes 1 day before surgery. Registering Doppler signals, while using power Doppler, both at the tubal ostia and fimbrial end and the ability to demonstrate the course of the tube especially the isthmus and fimbrial end, while using 4D mode, was considered a patent tube. Results: Out of 50 recruited patients, 33 women had bilateral patent tubes and five had unilateral patent tubes as shown by chromopertubation during diagnostic laparoscopy. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for two-dimensional power Doppler hysterosalpingography were 94.4%, 100%, 100%, 89.2%, and 96.2%, respectively and for 4D ultrasound were 70.4%, 100%, 100%, 70.4%, and 82.6%, respectively. Conclusions: Four-dimensional saline hysterosalpingography has acceptable accuracy in detecting tubal patency, but is surpassed by power Doppler saline hysterosalpingography. Power Doppler saline hysterosalpingography could be incorporated into the routine sub-/infertility workup. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Tubal patency Tubal factor infertility Power Doppler Saline hysterosalpingography
Introduction Tubal factor infertility is the main cause in 29–34% of infertile women seeking pregnancy, regardless of the reproductive age [1]. Diagnostic laparoscopy with chromopertubation is currently considered as the ‘‘gold standard’’ method for evaluating tubal factor infertility. Sonographic evaluation of tubal patency is currently being investigated as a non-invasive method with varied accuracy.
* Corresponding author at: Klinikum Oldenburg, University Women’s Hospital (Carl von Ossietzky University Oldenburg), Rahel-Straus-Straße 10, 26133 Oldenburg, Germany. Tel.: +49 441 403 2288; fax: +49 441 403 3068. E-mail address: [email protected] (A.A. Soliman). 1 Both authors contributed equally to the manuscript. http://dx.doi.org/10.1016/j.ejogrb.2015.09.039 0301-2115/ß 2015 Elsevier Ireland Ltd. All rights reserved.
Hysterosalpingo-contrast sonography (HyCoSy) is an ultrasound technique in which a contrast agent is injected into the uterine cavity and through the fallopian tubes to obtain real-time images of its hyperechoic flow through the fallopian tubes. One of the limitations of using a contrast agent is that its ultrasonic hyperechoic characteristics are usually lost within 5 min [2,3]. Other limitation is the price and the commercial availability of the contrast agent [4], which may be an obstacle using it in low resource setting. Moreover, the inability to examine the whole course of the fallopian tube in one scanning plane is another limitation [5]. One of the contrast agents used for HyCoSy is Echovist-2001. This contrast material is a fine suspension of galactose micro-particle granules. These are soluble in distilled water and air particles are bonded to them [3]. A currently used contrast agent is Sonovue1 which was applied to demonstrate
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tubal patency using conventional B-mode ultrasound [4] and 3D ultrasound [6] as well. Sonovue is a sulfur hexafluoride sonographic contrast agent, is able to respond with harmonic signals at a low acoustic pressure [7]. Another available agent is ExEm1 foam and gel. It is a combination of glycerol, hydroxyethyl cellulose and purified water. The gel is used for uterine cavity distension while the foam is used to test for tubal patency with no reported side effect [8]. The same hyperechoic effect of a contrast agent can be attained by injecting a mixture of saline and air into the fallopian tubes [9,10]. This technique is however highly operator-dependant and has lower accuracy [4,10]. The limitation that the whole tubal course cannot be examined in one scanning plane was overcome by using 3D and 4D ultrasound examination to depict the whole tubal length in one volume assessment [7,11]. Regardless of whether a contrast agent or a mixture of saline and air is used, recognition of tubal patency is enabled by the positive pressure flow of echogenic contrast from the uterine cavity and into the pelvis through patent fallopian tubes. Antibiotic prophylaxis is indicated sometimes before such procedures as recommended by the American college of obstetrics and gynecology (ACOG) [12]. Color Doppler evaluation of tubal patency has a sensitivity of 76.2% and a specificity of 81.4%, as well as a positive (PPV) and negative predictive value (NPV) of 66.7% and 87.5%, respectively [13]. In a previous study, blood flow was mapped along the tubal path and the tube was designated as patent when blood flow was recognized at the proximal and distal parts of the tube [13]. Additionally, the absence of blood flow either proximally or distally indicated that the tubes were occluded [13]. With further advancement of ultrasound technologies, three-dimensional (3D) power Doppler HyCoSy was examined and compared with laparoscopy for detecting tubal patency. The sensitivity, specificity, PPV, and NPV of this method for detecting tubal patency compared with laparoscopy and chromopertubation were 100%, 99.1%, 99.2%, and 100%, respectively [11]. Four-dimensional (4D) ultrasound offers high precision in examining the target volumes of tissues, exactly like a 3D ultrasound however in real time, so that a 4D ultrasound can be considered actually as a live 3D ultrasound examination. 4D ultrasound may help in detecting tubal motility during an examination. However, the role of 4D ultrasound in examining tubal patency has rarely been reported in the literature. Therefore, this study aimed to examine the accuracy of 4D ultrasound and that of power Doppler flow mapping in detecting tubal patency in women with sub-/infertility. We compared these techniques with laparoscopy and chromopertubation, which is the current standard method of evaluating tubal patency. Methods This was a prospective study at the outpatient infertility clinic at El Shatby University Hospital, Alexandria, Egypt. We recruited all of the women who planned to have diagnostic laparoscopy because of either primary or secondary infertility, with normal semen analysis of their male partner and normal ovarian function. The age of the recruited women was 43 years, with absence of known uterine anomalies. Women with active uterine bleeding, recent tubal or uterine surgery, and vulvar, vaginal, or cervical pathology were excluded. Obstetric and medical history were documented. They received a general, as well as a gynecological, examination. A transvaginal ultrasound routine scan was performed to exclude any uterine, cervical, endometrial, or ovarian pathology, using a Sonoace X81 (Samsung Medison, Seoul, South Korea). A prerequisite for recruiting women to this study was signing a consent after being thoroughly informed about the procedure and its possible risks, as stated in the institutional review board approval that was obtained before beginning the
study. The internal review board registration number for this study is 11/12/14224. The recruitment period extended from March 2013 to March 2014. The women participating in the study were recruited in the mid-follicular phase of the menstrual cycle (i.e., days 7–10) to avoid dispersion of menstrual debris into the peritoneal cavity, if recruited earlier. All of the recruited women, with history of pelvic inflammatory disease (PID) were given antibiotic prophylaxis according to the recommendations of the American College of Obstetrics and Gynecology [12]. The recruited women were booked to have diagnostic laparoscopy and chromopertubation on the day following the procedure. To prepare for power Doppler and a 4D ultrasound examination (live-3D examination), the patient voided and assumed the lithotomy position on a gynecological examination chair. A Graves speculum was then inserted into the vagina and positioned so that the entire cervix was visualized with the os being easily accessible. The cervix and the vagina were then thoroughly scrubbed with Betadine1 (Purdue Products L.P., Stamford, CT, USA) solution. A multi-toothed vulsellum forceps was placed on the anterior lip of the cervix. A Foley catheter size F12 was then inserted into the uterine cavity through the cervical os, and the balloon was inflated with 2.0-mL saline solution for stabilization and occlusion of the internal cervical os. After removal of the vulsellum, the 4D transvaginal probe (3D4-9ES) of the SonoaceX81 ultrasound machine (Samsung Medison, Seoul, South Korea) was gently introduced into the posterior fornix of the vagina. We then searched for the uterine cornua and the ovaries. When these were found, we identified the coronal plane where the cornua and the corresponding ovary could be seen together. At this point, sterile saline was slowly injected into the Foley catheter under sonographic control. Ten milliliters of normal saline (NaCl 0.9%) was instilled into the uterine cavity in three incremental boluses of 2, 3, and 5 mL, with a short period of time between each injection. The injections were repeated while examining the other side. At this stage, we could observe the morphology of the uterine cavity, and could also detect the flow of saline by power Doppler in the corresponding tube (right or left). In case no flow was detected, another 10 mL of saline was injected, for each possibly blocked tube, but two 5-mL injections were administered instead of the incremental manner used at the first injection. Directly after the Doppler examination had finished, another sonographer took over, and the volume mode was initiated. The scanning plane was based on a coronal section of the uterus with part of the ovary in the targeted side, right or left, being demonstrated in the scanned area. The region of interest was set as wide as possible so that the whole length of the fallopian tube could be detected. The saline injection was repeated in the same incremental manner (i.e., 2, 3, and 5 mL), where 10 mL were injected to demonstrate each tube. In case the tube could be not detected, another 10 mL of saline was injected, for each possibly occluded tube, using two 5-mL injections instead of the incremental manner used at the first injection. We could observe the morphology of the uterus (i.e., full contours of the uterus) and the endometrial lining using the 4D transvaginal probe, as well as tubal structure. We used two criteria for determining tubal patency on power Doppler: detection of steady flow signals in a segment of the tube for at least 5 s and detection of spill at the fimbrial end. Both criteria were needed for a tube to be considered patent. A tube was considered patent in 4D volume analysis if the contour of the tube, especially at the uterine cornua and fimbrial end, was clearly demonstrated. Otherwise, the tube was considered as occluded. Injecting 20 mL saline per tube without demonstrating patency by either method indicated that the tube was not patent. Power Doppler hysterosalpingography was performed by a single sonographer (TA), while the 4D ultrasound was performed by another sonographer (EA). Both are qualified and experienced ultrasonographers. Both of the sonographers
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were blinded from the results of each other. Injecting the saline was performed by another team member, other than the sonographer. A patent tube was considered as a positive test for the evaluation methods. Laparoscopy was performed by another team (WS and YE), which was blinded from the results of the ultrasound examinations. The data obtained was tabulated using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) and analyzed using SPSS for Microsoft Windows, version 13.0 (SPSS, Chicago, IL, USA). Data is expressed as means, medians, standard deviations, and percentages. For continuous data, Student’s t-test was used for analysis, while for categorical data, the x2 test was used. A p value <0.05 was considered statistically significant. Results During the recruitment period, 50 infertile women were enrolled after meeting the inclusion criteria. One hundred fallopian tubes were examined. The age range of the recruited women was 25–42 years, with a median age of 29 years. Nineteen (38%) women had primary infertility. A total of 20 (40%) women were pregnant once, nine (18%) were pregnant twice, and two (4%) were pregnant more than two times. Among those who were pregnant, 15 never gave birth, while 12 of them gave birth once and four of them gave birth twice. Among the 16 women who gave birth, the mode of delivery was by cesarean section in 11 and normal vaginal delivery in five. With regard to the women who never gave birth but were able to achieve pregnancy, 11 of them had an abortion and two had an ectopic pregnancy. Accordingly, we recruited 19 (38%) women with primary infertility and 31 (63%) women with secondary infertility. The duration of infertility was from 1 to 13 years, with a mean (SD) of 4.30 2.86 years and a median of 3.5 years. Twenty (40%) women complained of abdominal pain during insertion of Foley’s catheter and/or the injections of saline. Mild pain spontaneously resolved in 19 women and it required oral medication in one woman. There were no post-procedural infections in our cohort. In this study, 33 women had confirmed bilateral patent tubes, five had unilateral patent tubes and 12 had bilateral blocked tubes as shown by chromopertubation during diagnostic laparoscopy. There were 71 patent tubes and 29 blocked tubes. Power Doppler hysterosalpingography showed tubal patency bilaterally in 31 women and unilaterally in five, with a total of 67 patent tubes and 33 blocked tubes. The other two women whose tubes were confirmed as patent laparoscopically, but not patent sonographically, showed increased resistance to injecting the blue dye during laparoscopy. Fig. 1 shows a power Doppler hysterosalpingography of a patent tube. Twenty-three women had bilaterally patent tubes using 4D ultrasound and four had unilateral patent tubes, with a total of 50 patent tubes and 50 occluded ones. Fig. 2 shows 4D saline hysterosalpingography and demonstrate patent tubes. Sensitivity, specificity, PPV, NPV, and accuracy for two-dimensional power Doppler hysterosalpingography were 94.4%, 100%, 100%, 89.2%, and 96.2% respectively. Sensitivity, specificity, PPV, NPV, and accuracy for 4D ultrasound were 70.4%, 100%, 100%, 70.4%, and 82.6%, respectively. The time required for power Doppler examination from the moment the vaginal probe was inserted until deciding whether the tube was patent (including the time involved in finding the correct plane to scanning using the power Doppler flow mode) was compared to the time required for the 4D saline hysterosalpingography examination from the moment that the second sonographer took over until deciding whether the tube was patent (including the time involved in scanning the endometrial outline and the cavity, and finding the correct plane to perform the tubal patency scan). The 4D saline hysterosalpingography method
Fig. 1. Power Doppler flow mapping showing the flow in the cavity, proximal and distal parts of one tube while showing the flow in the distal part of the other tube.
Fig. 2. 4D examination depicting the course of both tubes (arrows).
required a significantly longer time to be performed than power Doppler hysterosalpingography (p < 0.001, t = 40.34, at 95% CI), see Table 1. The patients who were subjected to each of the examination methods received 20, 30, or 40 mL of injected saline. The 4D saline hysterosalpingography examination required significantly more saline compared with power Doppler hysterosalpingography (p = 0.002), see Table 1. The patients who were shown to have patent tubes with power Doppler hysterosalpingography received a median of 20 mL of saline injections compared with 40 mL for those with blocked tubes. Patients with patent tubes on 4D saline
Table 1 Comparison between power Doppler and 4D saline hysterosalpingography as regards time needed to finish the examination and the average amount of saline needed to perform the test.
Time interval needed to finish the examination in seconds (mean SD) Average amount of saline needed to perform the test
Power Doppler
4D saline hysterosalpingography
p value
214.54 53.43
289.7 50.78
p < 0.001
30
40
p = 0.002
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hysterosalpingography examinations received a median of 30 mL of saline injections compared with 40 mL for those with blocked tubes.
incorporated into routine sub-/infertility workup because of its high accuracy, lower cost, and shorter duration of examination. Authors’ contribution
Comment Evaluating tubal factor infertility is pivotal in managing couples presenting with sub-/infertility. Offering diagnostic laparoscopy with chromopertubation for every patient presenting for infertility evaluation is not practical. X-ray hysterosalpingography used to be a standard procedure for evaluating tubal patency. but because of the risk of exposure to ionizing radiation and advancement in ultrasound machines and techniques, hysterosalpingography is not as popular as it once was. HyCoSy is a sonographic technique used for evaluating tubal patency that showed a reasonable accuracy and is now considered state of the art for tubal patency testing. The reported sensitivity and specificity of this technique is 76.1–100% and 73.1–100%, respectively [14–17]. The main disadvantage of HyCoSy is the rapid degradation of contrast material and the inability to depict the whole course of the tube because of its tortuosity. Van Shoubroeck et al. used ExEm1 gel foam kit to examine the tubal patency in 20 patients by means of real-time conventional B-mode ultrasound and compared it to tubal chromopertubation during diagnostic laparoscopy. They reported 100% agreement between their technique and laparoscopic findings using chromopertubation [18]. Sladkevicius and co-workers used sonographic contrast material (Echovist-2001) to compare 3D power Doppler to conventional HyCoSy. They reported distal tubal flow in 91% of the tubes using 3D power Doppler HyCoSy compared with 46% of the tubes using conventional HyCoSy [19]. They reported using 4–6 mL of contrast agent for the 3D power Doppler compared with 9–15 mL for conventional HyCoSy [19]. This amount is much lower than that required in our study. This can be explained by the use of normal saline in our study with lower echogenic properties compared with sonographic contrast material. Chan et al. reported a sensitivity, specificity, and concordance of 78%, 60%, and 74%, respectively, for 3D HyCoSy using sonographic contrast material and comparing it with laparoscopy [20]. In our study, 4D saline hysterosalpingography did not provide better sensitivity or specificity than the currently available techniques. Power Doppler hysterosalpingography provided acceptable sensitivity, specificity, PPV, NPV, and accuracy. The predictive values in our study showed that power Doppler hysterosalpingography and 4D saline hysterosalpingography are good positive tests, but not as good for negative results, especially 4D saline hysterosalpingography. He and coworkers studied 192 tubes of 96 sub-/infertile women using 4D HyCoSy and reported a sensitivity, specificity, PPV, and NPV of 81.8%, 90.5%, 81.8%, and 90.5%, respectively for this technique [7]. One drawback of this previous study is that only 16 patients received laparoscopy, whereas the concordance of 4D HyCoSy and laparoscopy was 87.5% [7]. In contrast to our study, they injected sonographic contrast material (Sonovue1) instead of saline. This may be the reason for the better test parameters in their study compared with our results. They injected substantially lower amounts of contrast material and required almost one tenth of the time needed for the examination in comparison to the amount of saline we injected and the time we required for the examination. This can be explained that we included the time required to study the uterine cavity, the time required to find the accurate plane, and the time required to examine tubal patency in our calculations. We conclude that 4D saline hysterosalpingography is a novel technique for examining tubal patency, with acceptable accuracy. However, 4D saline hysterosalpingography is surpassed by power Doppler saline hysterosalpingography, which could be
All authors contributed to study design and idea formulation. TA and EA performed the ultrasound examinations. WS and YE performed the laparoscopy with chromopertubation. AS, WS, DL and EM contributed to statistical analysis and data editing. All authors contributed to manuscript writing, revision and finalizing in its current form. Conflict of interest The authors declare no conflicts of interest for this manuscript. Acknowledgements This work was funded through internal research resources of the Department of Obstetrics and Gynecology, University of Alexandria, Egypt, and no external sources of funding were involved. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.ejogrb.2015.09.039. References [1] Miller J, Weinberg R, Canino N, Klein N, Soules M. The pattern of infertility diagnoses in women of advanced reproductive age. Am J Obstet Gynecol 1999;181(4):952–7. [2] Campbell S, Bourne T, Tan S, Collins W. Hysterosalpingo contrast sonography (HyCoSy) and its future role within the investigation of infertility in Europe. Ultrasound Obstet Gynecol: Off J Int Soc Ultrasound Obstet Gynecol 1994;4: 245–53. [3] Tamasi F, Weidner A, Domokos N, Bedros RJ, Bagdany S. ECHOVIST-200 enhanced hystero-sonography: a new technique in the assessment of infertility. Eur J Obstet Gynecol Reprod Biol 2005;121(2):186–90. [4] Sladkevicius P, Zannoni L, Valentin L. B-flow ultrasound facilitates visualization of contrast medium during hysterosalpingo-contrast sonography. Ultrasound Obstet Gynecol: Off J Int Soc Ultrasound Obstet Gynecol 2014;44(2): 221–7. [5] Exacoustos C, Di Giovanni A, Szabolcs B, Binder-Reisinger H, Gabardi C, Arduini D. Automated sonographic tubal patency evaluation with three-dimensional coded contrast imaging (CCI) during hysterosalpingo-contrast sonography (HyCoSy). Ultrasound Obstet Gynecol: Off J Int Soc Ultrasound Obstet Gynecol 2009;34(5):609–12. [6] Zhou L, Zhang X, Chen X, et al. Value of three-dimensional hysterosalpingocontrast sonography with SonoVue in the assessment of tubal patency. Ultrasound Obstet Gynecol: Off J Int Soc Ultrasound Obstet Gynecol 2012;40(1): 93–8. [7] He Y, Geng Q, Liu H, Han X. First experience using 4-dimensional hysterosalpingo-contrast sonography with SonoVue for assessing fallopian tube patency. J Ultrasound Med: Off J Am Inst Ultrasound Med 2013;32(7):1233–43. [8] Exalto N, Stassen M, Emanuel MH. Safety aspects and side-effects of ExEm-gel and foam for uterine cavity distension and tubal patency testing. Reprod Biomed Online 2014;29(5):534–40. [9] Chenia F, Hofmeyr G, Moolla S, Oratis P. Sonographic hydrotubation using agitated saline: a new technique for improving fallopian tube visualization. Br J Radiol 1997;70(836):833–6. [10] Ahinko-Hakamaa K, Huhtala H, Tinkanen H. The validity of air and saline hysterosalpingo-contrast sonography in tubal patency investigation before insemination treatment. Eur J Obstet Gynecol Reprod Biol 2007;132(1):83–7. [11] Kupesic S, Plavsic BM. 2D and 3D hysterosalpingo-contrast-sonography in the assessment of uterine cavity and tubal patency. Eur J Obstet Gynecol Reprod Biol 2007;133(1):64–9. [12] ACOG. ACOG practice bulletin no. 104: antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol 2009;113:1180–9. [13] Demir B, Kocak M, Beydilli G, Kaplan M, Gelisen O, Haberal A. Diagnostic accuracy and efficacy of color Doppler mapping for tubal patency. J Obstet Gynaecol Res 2011;37(7):782–6. [14] Radic V, Canic T, Valetic J, Duic Z. Advantages and disadvantages of hysterosonosalpingography in the assessment of the reproductive status of uterine cavity and fallopian tubes. Eur J Radiol 2005;53(2):268–73.
A.A. Soliman et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 195 (2015) 83–87 [15] Hamilton J, Larson A, Lower A, Hasnain S, Grudzinskas J. Evaluation of the performance of hysterosalpingo-contrast sonography in 500 consecutive, unselected, infertile women. Hum Reprod 1998;13:1519–26. [16] Hamed H, Shahin A, Elsamman A. Hysterosalpingo-contrast sonography versus radiographic hysterosalpingography in the evaluation of tubal patency. Int J Gynaecol Obstet: Off Organ Int Fed Gynaecol Obstet 2009;105(3): 215–7. [17] Deichert U, Schlief R, van de Sandt M, Ines Juhnke I. Transvaginal hysterosalpingo-contrast-sonography (Hy-Co-Sy) compared with conventional tubal diagnostics. Hum Reprod 1989;4:418–24.
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[18] Van Schoubroeck D, Van den Bosch T, Meuleman C, Tomassetti C, D’Hooghe T, Timmerman D. The use of a new gel foam for the evaluation of tubal patency. Gynecol Obstet Invest 2013;75(3):152–6. [19] Sladkevicius P, Ojha K, Campbell S, Nargund G. Three-dimensional power Doppler imaging in the assessment of Fallopian tube patency. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 2000;16:644–7. [20] Chan C, Ng E, Tang O-S, Chan K, Ho P-C. Comparison of three-dimensional hysterosalpingo-contrast-sonography and diagnostic laparoscopy with chromopertubation in the assessment of tubal patency for the investigation of subfertility. Acta Obstet Gynecol Scand 2005;84:909–13.
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Power Doppler flow mapping and four-dimensional ultrasound for evaluating tubal patency compared with laparoscopy Amr A. Soliman a,b,1,*, Waleed Shaalan a,1, Tamer Abdel-Dayem a, Elsayed Elbadawy Awad a, Yasser Elkassar a, Do¨rte Lu¨dders b, Eduard Malik b, Hassan N. Sallam a a
University of Alexandria, Department of Obstetrics and Gynecology, El Shatby Maternity University Hospital, Port-Said Street, 21526 El-Shatby, Alexandria, Egypt Carl von Ossietzky University Oldenburg, Department of Obstetrics and Gynecology, Oldenburg University Women’s Hospital, Rahel-Straus-Straße 10, 26133 Oldenburg, Germany b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 9 March 2015 Received in revised form 16 June 2015 Accepted 25 September 2015
Objectives: To study the accuracy of four-dimensional (4D) ultrasound and power Doppler flow mapping in detecting tubal patency in women with sub-/infertility, and compare it with laparoscopy and chromopertubation. Study design: A prospective study. The study was performed in the outpatient clinic and infertility unit of a university hospital. The sonographic team and laparoscopic team were blinded to the results of each other. Women aged younger than 43 years seeking medical advice due to primary or secondary infertility and who planned to have a diagnostic laparoscopy performed, were recruited to the study after signing an informed consent. All of the recruited patients had power Doppler flow mapping and 4D hysterosalpingo-sonography by injecting sterile saline into the fallopian tubes 1 day before surgery. Registering Doppler signals, while using power Doppler, both at the tubal ostia and fimbrial end and the ability to demonstrate the course of the tube especially the isthmus and fimbrial end, while using 4D mode, was considered a patent tube. Results: Out of 50 recruited patients, 33 women had bilateral patent tubes and five had unilateral patent tubes as shown by chromopertubation during diagnostic laparoscopy. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for two-dimensional power Doppler hysterosalpingography were 94.4%, 100%, 100%, 89.2%, and 96.2%, respectively and for 4D ultrasound were 70.4%, 100%, 100%, 70.4%, and 82.6%, respectively. Conclusions: Four-dimensional saline hysterosalpingography has acceptable accuracy in detecting tubal patency, but is surpassed by power Doppler saline hysterosalpingography. Power Doppler saline hysterosalpingography could be incorporated into the routine sub-/infertility workup. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Tubal patency Tubal factor infertility Power Doppler Saline hysterosalpingography
Introduction Tubal factor infertility is the main cause in 29–34% of infertile women seeking pregnancy, regardless of the reproductive age [1]. Diagnostic laparoscopy with chromopertubation is currently considered as the ‘‘gold standard’’ method for evaluating tubal factor infertility. Sonographic evaluation of tubal patency is currently being investigated as a non-invasive method with varied accuracy.
* Corresponding author at: Klinikum Oldenburg, University Women’s Hospital (Carl von Ossietzky University Oldenburg), Rahel-Straus-Straße 10, 26133 Oldenburg, Germany. Tel.: +49 441 403 2288; fax: +49 441 403 3068. E-mail address: [email protected] (A.A. Soliman). 1 Both authors contributed equally to the manuscript. http://dx.doi.org/10.1016/j.ejogrb.2015.09.039 0301-2115/ß 2015 Elsevier Ireland Ltd. All rights reserved.
Hysterosalpingo-contrast sonography (HyCoSy) is an ultrasound technique in which a contrast agent is injected into the uterine cavity and through the fallopian tubes to obtain real-time images of its hyperechoic flow through the fallopian tubes. One of the limitations of using a contrast agent is that its ultrasonic hyperechoic characteristics are usually lost within 5 min [2,3]. Other limitation is the price and the commercial availability of the contrast agent [4], which may be an obstacle using it in low resource setting. Moreover, the inability to examine the whole course of the fallopian tube in one scanning plane is another limitation [5]. One of the contrast agents used for HyCoSy is Echovist-2001. This contrast material is a fine suspension of galactose micro-particle granules. These are soluble in distilled water and air particles are bonded to them [3]. A currently used contrast agent is Sonovue1 which was applied to demonstrate
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tubal patency using conventional B-mode ultrasound [4] and 3D ultrasound [6] as well. Sonovue is a sulfur hexafluoride sonographic contrast agent, is able to respond with harmonic signals at a low acoustic pressure [7]. Another available agent is ExEm1 foam and gel. It is a combination of glycerol, hydroxyethyl cellulose and purified water. The gel is used for uterine cavity distension while the foam is used to test for tubal patency with no reported side effect [8]. The same hyperechoic effect of a contrast agent can be attained by injecting a mixture of saline and air into the fallopian tubes [9,10]. This technique is however highly operator-dependant and has lower accuracy [4,10]. The limitation that the whole tubal course cannot be examined in one scanning plane was overcome by using 3D and 4D ultrasound examination to depict the whole tubal length in one volume assessment [7,11]. Regardless of whether a contrast agent or a mixture of saline and air is used, recognition of tubal patency is enabled by the positive pressure flow of echogenic contrast from the uterine cavity and into the pelvis through patent fallopian tubes. Antibiotic prophylaxis is indicated sometimes before such procedures as recommended by the American college of obstetrics and gynecology (ACOG) [12]. Color Doppler evaluation of tubal patency has a sensitivity of 76.2% and a specificity of 81.4%, as well as a positive (PPV) and negative predictive value (NPV) of 66.7% and 87.5%, respectively [13]. In a previous study, blood flow was mapped along the tubal path and the tube was designated as patent when blood flow was recognized at the proximal and distal parts of the tube [13]. Additionally, the absence of blood flow either proximally or distally indicated that the tubes were occluded [13]. With further advancement of ultrasound technologies, three-dimensional (3D) power Doppler HyCoSy was examined and compared with laparoscopy for detecting tubal patency. The sensitivity, specificity, PPV, and NPV of this method for detecting tubal patency compared with laparoscopy and chromopertubation were 100%, 99.1%, 99.2%, and 100%, respectively [11]. Four-dimensional (4D) ultrasound offers high precision in examining the target volumes of tissues, exactly like a 3D ultrasound however in real time, so that a 4D ultrasound can be considered actually as a live 3D ultrasound examination. 4D ultrasound may help in detecting tubal motility during an examination. However, the role of 4D ultrasound in examining tubal patency has rarely been reported in the literature. Therefore, this study aimed to examine the accuracy of 4D ultrasound and that of power Doppler flow mapping in detecting tubal patency in women with sub-/infertility. We compared these techniques with laparoscopy and chromopertubation, which is the current standard method of evaluating tubal patency. Methods This was a prospective study at the outpatient infertility clinic at El Shatby University Hospital, Alexandria, Egypt. We recruited all of the women who planned to have diagnostic laparoscopy because of either primary or secondary infertility, with normal semen analysis of their male partner and normal ovarian function. The age of the recruited women was 43 years, with absence of known uterine anomalies. Women with active uterine bleeding, recent tubal or uterine surgery, and vulvar, vaginal, or cervical pathology were excluded. Obstetric and medical history were documented. They received a general, as well as a gynecological, examination. A transvaginal ultrasound routine scan was performed to exclude any uterine, cervical, endometrial, or ovarian pathology, using a Sonoace X81 (Samsung Medison, Seoul, South Korea). A prerequisite for recruiting women to this study was signing a consent after being thoroughly informed about the procedure and its possible risks, as stated in the institutional review board approval that was obtained before beginning the
study. The internal review board registration number for this study is 11/12/14224. The recruitment period extended from March 2013 to March 2014. The women participating in the study were recruited in the mid-follicular phase of the menstrual cycle (i.e., days 7–10) to avoid dispersion of menstrual debris into the peritoneal cavity, if recruited earlier. All of the recruited women, with history of pelvic inflammatory disease (PID) were given antibiotic prophylaxis according to the recommendations of the American College of Obstetrics and Gynecology [12]. The recruited women were booked to have diagnostic laparoscopy and chromopertubation on the day following the procedure. To prepare for power Doppler and a 4D ultrasound examination (live-3D examination), the patient voided and assumed the lithotomy position on a gynecological examination chair. A Graves speculum was then inserted into the vagina and positioned so that the entire cervix was visualized with the os being easily accessible. The cervix and the vagina were then thoroughly scrubbed with Betadine1 (Purdue Products L.P., Stamford, CT, USA) solution. A multi-toothed vulsellum forceps was placed on the anterior lip of the cervix. A Foley catheter size F12 was then inserted into the uterine cavity through the cervical os, and the balloon was inflated with 2.0-mL saline solution for stabilization and occlusion of the internal cervical os. After removal of the vulsellum, the 4D transvaginal probe (3D4-9ES) of the SonoaceX81 ultrasound machine (Samsung Medison, Seoul, South Korea) was gently introduced into the posterior fornix of the vagina. We then searched for the uterine cornua and the ovaries. When these were found, we identified the coronal plane where the cornua and the corresponding ovary could be seen together. At this point, sterile saline was slowly injected into the Foley catheter under sonographic control. Ten milliliters of normal saline (NaCl 0.9%) was instilled into the uterine cavity in three incremental boluses of 2, 3, and 5 mL, with a short period of time between each injection. The injections were repeated while examining the other side. At this stage, we could observe the morphology of the uterine cavity, and could also detect the flow of saline by power Doppler in the corresponding tube (right or left). In case no flow was detected, another 10 mL of saline was injected, for each possibly blocked tube, but two 5-mL injections were administered instead of the incremental manner used at the first injection. Directly after the Doppler examination had finished, another sonographer took over, and the volume mode was initiated. The scanning plane was based on a coronal section of the uterus with part of the ovary in the targeted side, right or left, being demonstrated in the scanned area. The region of interest was set as wide as possible so that the whole length of the fallopian tube could be detected. The saline injection was repeated in the same incremental manner (i.e., 2, 3, and 5 mL), where 10 mL were injected to demonstrate each tube. In case the tube could be not detected, another 10 mL of saline was injected, for each possibly occluded tube, using two 5-mL injections instead of the incremental manner used at the first injection. We could observe the morphology of the uterus (i.e., full contours of the uterus) and the endometrial lining using the 4D transvaginal probe, as well as tubal structure. We used two criteria for determining tubal patency on power Doppler: detection of steady flow signals in a segment of the tube for at least 5 s and detection of spill at the fimbrial end. Both criteria were needed for a tube to be considered patent. A tube was considered patent in 4D volume analysis if the contour of the tube, especially at the uterine cornua and fimbrial end, was clearly demonstrated. Otherwise, the tube was considered as occluded. Injecting 20 mL saline per tube without demonstrating patency by either method indicated that the tube was not patent. Power Doppler hysterosalpingography was performed by a single sonographer (TA), while the 4D ultrasound was performed by another sonographer (EA). Both are qualified and experienced ultrasonographers. Both of the sonographers
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were blinded from the results of each other. Injecting the saline was performed by another team member, other than the sonographer. A patent tube was considered as a positive test for the evaluation methods. Laparoscopy was performed by another team (WS and YE), which was blinded from the results of the ultrasound examinations. The data obtained was tabulated using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) and analyzed using SPSS for Microsoft Windows, version 13.0 (SPSS, Chicago, IL, USA). Data is expressed as means, medians, standard deviations, and percentages. For continuous data, Student’s t-test was used for analysis, while for categorical data, the x2 test was used. A p value <0.05 was considered statistically significant. Results During the recruitment period, 50 infertile women were enrolled after meeting the inclusion criteria. One hundred fallopian tubes were examined. The age range of the recruited women was 25–42 years, with a median age of 29 years. Nineteen (38%) women had primary infertility. A total of 20 (40%) women were pregnant once, nine (18%) were pregnant twice, and two (4%) were pregnant more than two times. Among those who were pregnant, 15 never gave birth, while 12 of them gave birth once and four of them gave birth twice. Among the 16 women who gave birth, the mode of delivery was by cesarean section in 11 and normal vaginal delivery in five. With regard to the women who never gave birth but were able to achieve pregnancy, 11 of them had an abortion and two had an ectopic pregnancy. Accordingly, we recruited 19 (38%) women with primary infertility and 31 (63%) women with secondary infertility. The duration of infertility was from 1 to 13 years, with a mean (SD) of 4.30 2.86 years and a median of 3.5 years. Twenty (40%) women complained of abdominal pain during insertion of Foley’s catheter and/or the injections of saline. Mild pain spontaneously resolved in 19 women and it required oral medication in one woman. There were no post-procedural infections in our cohort. In this study, 33 women had confirmed bilateral patent tubes, five had unilateral patent tubes and 12 had bilateral blocked tubes as shown by chromopertubation during diagnostic laparoscopy. There were 71 patent tubes and 29 blocked tubes. Power Doppler hysterosalpingography showed tubal patency bilaterally in 31 women and unilaterally in five, with a total of 67 patent tubes and 33 blocked tubes. The other two women whose tubes were confirmed as patent laparoscopically, but not patent sonographically, showed increased resistance to injecting the blue dye during laparoscopy. Fig. 1 shows a power Doppler hysterosalpingography of a patent tube. Twenty-three women had bilaterally patent tubes using 4D ultrasound and four had unilateral patent tubes, with a total of 50 patent tubes and 50 occluded ones. Fig. 2 shows 4D saline hysterosalpingography and demonstrate patent tubes. Sensitivity, specificity, PPV, NPV, and accuracy for two-dimensional power Doppler hysterosalpingography were 94.4%, 100%, 100%, 89.2%, and 96.2% respectively. Sensitivity, specificity, PPV, NPV, and accuracy for 4D ultrasound were 70.4%, 100%, 100%, 70.4%, and 82.6%, respectively. The time required for power Doppler examination from the moment the vaginal probe was inserted until deciding whether the tube was patent (including the time involved in finding the correct plane to scanning using the power Doppler flow mode) was compared to the time required for the 4D saline hysterosalpingography examination from the moment that the second sonographer took over until deciding whether the tube was patent (including the time involved in scanning the endometrial outline and the cavity, and finding the correct plane to perform the tubal patency scan). The 4D saline hysterosalpingography method
Fig. 1. Power Doppler flow mapping showing the flow in the cavity, proximal and distal parts of one tube while showing the flow in the distal part of the other tube.
Fig. 2. 4D examination depicting the course of both tubes (arrows).
required a significantly longer time to be performed than power Doppler hysterosalpingography (p < 0.001, t = 40.34, at 95% CI), see Table 1. The patients who were subjected to each of the examination methods received 20, 30, or 40 mL of injected saline. The 4D saline hysterosalpingography examination required significantly more saline compared with power Doppler hysterosalpingography (p = 0.002), see Table 1. The patients who were shown to have patent tubes with power Doppler hysterosalpingography received a median of 20 mL of saline injections compared with 40 mL for those with blocked tubes. Patients with patent tubes on 4D saline
Table 1 Comparison between power Doppler and 4D saline hysterosalpingography as regards time needed to finish the examination and the average amount of saline needed to perform the test.
Time interval needed to finish the examination in seconds (mean SD) Average amount of saline needed to perform the test
Power Doppler
4D saline hysterosalpingography
p value
214.54 53.43
289.7 50.78
p < 0.001
30
40
p = 0.002
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hysterosalpingography examinations received a median of 30 mL of saline injections compared with 40 mL for those with blocked tubes.
incorporated into routine sub-/infertility workup because of its high accuracy, lower cost, and shorter duration of examination. Authors’ contribution
Comment Evaluating tubal factor infertility is pivotal in managing couples presenting with sub-/infertility. Offering diagnostic laparoscopy with chromopertubation for every patient presenting for infertility evaluation is not practical. X-ray hysterosalpingography used to be a standard procedure for evaluating tubal patency. but because of the risk of exposure to ionizing radiation and advancement in ultrasound machines and techniques, hysterosalpingography is not as popular as it once was. HyCoSy is a sonographic technique used for evaluating tubal patency that showed a reasonable accuracy and is now considered state of the art for tubal patency testing. The reported sensitivity and specificity of this technique is 76.1–100% and 73.1–100%, respectively [14–17]. The main disadvantage of HyCoSy is the rapid degradation of contrast material and the inability to depict the whole course of the tube because of its tortuosity. Van Shoubroeck et al. used ExEm1 gel foam kit to examine the tubal patency in 20 patients by means of real-time conventional B-mode ultrasound and compared it to tubal chromopertubation during diagnostic laparoscopy. They reported 100% agreement between their technique and laparoscopic findings using chromopertubation [18]. Sladkevicius and co-workers used sonographic contrast material (Echovist-2001) to compare 3D power Doppler to conventional HyCoSy. They reported distal tubal flow in 91% of the tubes using 3D power Doppler HyCoSy compared with 46% of the tubes using conventional HyCoSy [19]. They reported using 4–6 mL of contrast agent for the 3D power Doppler compared with 9–15 mL for conventional HyCoSy [19]. This amount is much lower than that required in our study. This can be explained by the use of normal saline in our study with lower echogenic properties compared with sonographic contrast material. Chan et al. reported a sensitivity, specificity, and concordance of 78%, 60%, and 74%, respectively, for 3D HyCoSy using sonographic contrast material and comparing it with laparoscopy [20]. In our study, 4D saline hysterosalpingography did not provide better sensitivity or specificity than the currently available techniques. Power Doppler hysterosalpingography provided acceptable sensitivity, specificity, PPV, NPV, and accuracy. The predictive values in our study showed that power Doppler hysterosalpingography and 4D saline hysterosalpingography are good positive tests, but not as good for negative results, especially 4D saline hysterosalpingography. He and coworkers studied 192 tubes of 96 sub-/infertile women using 4D HyCoSy and reported a sensitivity, specificity, PPV, and NPV of 81.8%, 90.5%, 81.8%, and 90.5%, respectively for this technique [7]. One drawback of this previous study is that only 16 patients received laparoscopy, whereas the concordance of 4D HyCoSy and laparoscopy was 87.5% [7]. In contrast to our study, they injected sonographic contrast material (Sonovue1) instead of saline. This may be the reason for the better test parameters in their study compared with our results. They injected substantially lower amounts of contrast material and required almost one tenth of the time needed for the examination in comparison to the amount of saline we injected and the time we required for the examination. This can be explained that we included the time required to study the uterine cavity, the time required to find the accurate plane, and the time required to examine tubal patency in our calculations. We conclude that 4D saline hysterosalpingography is a novel technique for examining tubal patency, with acceptable accuracy. However, 4D saline hysterosalpingography is surpassed by power Doppler saline hysterosalpingography, which could be
All authors contributed to study design and idea formulation. TA and EA performed the ultrasound examinations. WS and YE performed the laparoscopy with chromopertubation. AS, WS, DL and EM contributed to statistical analysis and data editing. All authors contributed to manuscript writing, revision and finalizing in its current form. Conflict of interest The authors declare no conflicts of interest for this manuscript. Acknowledgements This work was funded through internal research resources of the Department of Obstetrics and Gynecology, University of Alexandria, Egypt, and no external sources of funding were involved. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.ejogrb.2015.09.039. References [1] Miller J, Weinberg R, Canino N, Klein N, Soules M. The pattern of infertility diagnoses in women of advanced reproductive age. Am J Obstet Gynecol 1999;181(4):952–7. [2] Campbell S, Bourne T, Tan S, Collins W. Hysterosalpingo contrast sonography (HyCoSy) and its future role within the investigation of infertility in Europe. Ultrasound Obstet Gynecol: Off J Int Soc Ultrasound Obstet Gynecol 1994;4: 245–53. [3] Tamasi F, Weidner A, Domokos N, Bedros RJ, Bagdany S. ECHOVIST-200 enhanced hystero-sonography: a new technique in the assessment of infertility. Eur J Obstet Gynecol Reprod Biol 2005;121(2):186–90. [4] Sladkevicius P, Zannoni L, Valentin L. B-flow ultrasound facilitates visualization of contrast medium during hysterosalpingo-contrast sonography. Ultrasound Obstet Gynecol: Off J Int Soc Ultrasound Obstet Gynecol 2014;44(2): 221–7. [5] Exacoustos C, Di Giovanni A, Szabolcs B, Binder-Reisinger H, Gabardi C, Arduini D. Automated sonographic tubal patency evaluation with three-dimensional coded contrast imaging (CCI) during hysterosalpingo-contrast sonography (HyCoSy). Ultrasound Obstet Gynecol: Off J Int Soc Ultrasound Obstet Gynecol 2009;34(5):609–12. [6] Zhou L, Zhang X, Chen X, et al. Value of three-dimensional hysterosalpingocontrast sonography with SonoVue in the assessment of tubal patency. Ultrasound Obstet Gynecol: Off J Int Soc Ultrasound Obstet Gynecol 2012;40(1): 93–8. [7] He Y, Geng Q, Liu H, Han X. First experience using 4-dimensional hysterosalpingo-contrast sonography with SonoVue for assessing fallopian tube patency. J Ultrasound Med: Off J Am Inst Ultrasound Med 2013;32(7):1233–43. [8] Exalto N, Stassen M, Emanuel MH. Safety aspects and side-effects of ExEm-gel and foam for uterine cavity distension and tubal patency testing. Reprod Biomed Online 2014;29(5):534–40. [9] Chenia F, Hofmeyr G, Moolla S, Oratis P. Sonographic hydrotubation using agitated saline: a new technique for improving fallopian tube visualization. Br J Radiol 1997;70(836):833–6. [10] Ahinko-Hakamaa K, Huhtala H, Tinkanen H. The validity of air and saline hysterosalpingo-contrast sonography in tubal patency investigation before insemination treatment. Eur J Obstet Gynecol Reprod Biol 2007;132(1):83–7. [11] Kupesic S, Plavsic BM. 2D and 3D hysterosalpingo-contrast-sonography in the assessment of uterine cavity and tubal patency. Eur J Obstet Gynecol Reprod Biol 2007;133(1):64–9. [12] ACOG. ACOG practice bulletin no. 104: antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol 2009;113:1180–9. [13] Demir B, Kocak M, Beydilli G, Kaplan M, Gelisen O, Haberal A. Diagnostic accuracy and efficacy of color Doppler mapping for tubal patency. J Obstet Gynaecol Res 2011;37(7):782–6. [14] Radic V, Canic T, Valetic J, Duic Z. Advantages and disadvantages of hysterosonosalpingography in the assessment of the reproductive status of uterine cavity and fallopian tubes. Eur J Radiol 2005;53(2):268–73.
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