Qi Cheng*, Sha-sha Wang, Xian-sheng Zhu, and Fan Li

Department of Ultrasonography, Guangzhou General Hospital of Guangzhou Military Command of People’s Liberation Army, Guangzhou 510010, China

ORIGINAL ARTICLE

Evaluation of Tubal Patency with Transvaginal Threedimensional Hysterosalpingo-contrast Sonography△

Qi Cheng*, Sha-sha Wang, Xian-sheng Zhu, and Fan Li

Department of Ultrasonography, Guangzhou General Hospital of Guangzhou Military Command of People’s Liberation Army, Guangzhou 510010, China

contrast-enhanced sonography; three-dimensional construction; oviduct; infertility

Objective To investigate diagnostic efficacy of transvaginal three-dimensional hysterosalpingo-contrast sonography (3D-HyCoSy) in assessing tubal patency with chromolaporoscopy.

Methods A total of 157 infertile women underwent 3D-HyCoSy to evaluate tubal patency. Among these patients, 39 patients were also examined by chromolaporoscopy. The concordance of the two clinical assessment methods was analyzed by the Kappa coefficient test.

Results Among the 306 oviducts examined by 3D-HyCoSy, 99 (32.4%) were patent, 126 (41.2%) partially obstructed, and 81 (26.5%) completely obstructed. Diagnostic results with 3D-HyCoSy were not statistically different from those obtained in the 39 women (78 oviducts) who also underwent chromolaporoscopy, and the two methods showed a high concordance (κ=0.747, p=0.000). The 3D-HyCoSy procedure had a sensitivity of 84.8% (28/33), a specificity of 96.2% (25/26), and positive and negative predictive values of 93.3% (28/30) and 86.2% (25/29) respectively.

Conclusion Transvaginal 3D-HyCoSy can accurately reveal the spatial path and morphology of the oviduct and is a safe and effective method to evaluate tubal patency.

Chin Med Sci J 2015; 30(2)：70-75

INFERTILITY is one of the most common gynecological disorders, and the incidence of tubal infertility increases markedly with age. Morphological and functional changes of the oviducts, such as obstruction, distortion, stiffness, and peristaltic incongruity arising from various diseases, account for 25%-30% of all cases of infertility.1 Transvaginal hysterosalpingo-contrast sonography (HyCoSy) is a noninvasive, safe, and costeffective method for screening tubal patency. Threedimensional (3D) HyCoSy is a novel technique that can make clear and anatomically precise stereo pictures of the entire oviduct.2,3In this study, 3D-HyCoSy was compared with chromolaporoscopy for the evaluation of tubal patency.

PATIENTS AND METHODS

Patients

A total of 157 infertile women examined at the Gynecological Clinic and Assisted Reproductive Center of GuangzhouGeneral Hospital of Guangzhou Military Command from September 2009 to June 2011 were enrolled in this study. The average age was 29.6±4.7 (range, 21-41) years and the average duration of infertility was 4.2±3.1 (range, 0.5-15) years. The study group included 69 patients with primary infertility and 88 patients with secondary infertility. Among the 88 patients with secondary infertility, 8 patients had a history of single ectopic pregnancy. Patients with dysendocrinia, pelvic and genital tumors, and acute inflammation were excluded from this study. Examinations were performed three to seven days after menstrual bleeding stopped. No sexual intercourse took place during the examination period. All patients provided informed consent. In addition to 3D-HyCoSy, 39 patients were also examined by chromolaparoscopy within three months. This study was approved by the Ethics Committee of the Liuhuaqiao Hospital of Guangzhou (Guangzhou General Hospital of Guangzhou Military Command of People’s Liberation Army).

Instruments

Voluson E8 and E6 ultrasound systems (GE Medical Systems Kretztechnik GmbH & Co., OHG, Austria) equipped with RIC5-9-D probes were used for clinical examinations. The central frequency was 5.0 to 9.0 MHz and the mechanical index was 0.14. The sonographic equipment had coded contrast imaging capability.

Contrast agent

The contrast agent used was sulfur hexafluoride microbubbles (SonoVue, BARCO Acquired Fimi, Lombardy, Italy). Every bottle of contrast agent was dissolved in 5 ml of sterile normal saline. Before injection, 2.0 ml of this contrast agent solution was diluted in 18 ml of normal saline. A 5 ml volume of saline was slowly injected into the uterine cavity through a catheter before imaging.

Procedures

Patients were treated in the lithotomy position. After conventional sterilization and draping, a no. 12 Foley’s catheter was inserted into the pelvic cavity and 1.5 to 2.0 ml normal saline was injected into the air sac. The catheter was then adjusted to obstruct the cervical internal opening. The positions of the uterus and ovaries, the internal echo, and the presence of hydrops in the rectouterine pouch were observed by transvaginal sonography. The saline was then injected into the uterus to observe intrauterine adhesion and occupancy, and to determine the intrauterine pressure.

Before 3D-HyCoSy, 3D pre-scanning was performed for spatial positioning, and then the volume frame, acquisition scope, and angle were adjusted for contrast imaging. The contrast agent was then slowly injected into the uterine cavity. Three to five consecutive volume data sets were acquired and stored. Tubal morphology and overflow of the contrast agent (from the fimbriated extremity, around the oviduct, and into the uterine cavity) were observed in two-dimensional (2D) and dynamic modes under contrast enhancement. Countercurrent flow of contrast agent in the muscular layer was also observed under contrast-enhanced 2D and dynamic imaging modes. The backflow volume of the contrast agent, bolus injection pressure, and each patient’s report of pain were recorded.

Criteria for tubal patency as revealed by 3D-HyCoSy

In all patients, patency was evaluated by two experienced sonographic physicians. Oviducts were judged as patent, partially obstructed, or completely obstructed based on the flow of the contrast agent.

In patients with tubal patency, there was no resistance or backflow when contrast agent was injected. The entire oviduct appeared anatomically smooth. Contrast agent could reach the fimbriated extremity and into the uterine cavity (Fig. 1). Ovaries were surrounded by ring-shaped strong echo zones and contrast agent was uniformly dispersed in the uterine cavity.

If the tubes were partially obstructed, there was resistance to injection of the contrast agent and a volume of backflow was observed. The flow of the gas bubbles into the uterine cavity was slower than in patients with tubal patency. Oviducts were thin that in some sections and thickened in others, and showed significant circuity or numerous inflections (Fig. 2). Only a small volume of contrastagent eventually flowed out from the fimbriated extremity. Ovaries were surrounded with semi-ring strong echo zones and contrast agent dispersed non-uniformly in the uterine cavity.

Figure 1. A 39-year-old patient with 11 years of infertility. Three-dimensional transvaginal hysterosalpingocontrast sonography (3D-HyCoSy) shows normal uterine cavity and unobstructed bilateral oviducts.

When the oviducts were completely obstructed, there was a strong resistance when contrast agent was injected and no fluid backflow when injection was stopped. The uterine cavity was plump, the oviduct was invisible, no contrast agent flowed outward from the fimbriated extremity (Fig. 3), and no contrast was observed around the ovaries and the pelvic cavity.

Figure 2. A 26-year-old patient with 8 years of infertility. 3D-HyCoSy shows the left oviduct is partially obstructed and has a cornuted invagination, and the right oviduct has a filling defect due to proximal obstruction and hydrotubation. The proximal segment of the left oviduct is slender, the middle segment is angled and sinuous, and the distal segment slightly swollen. The filling defects (arrow) in the uterine cavity indicate endometrial polyps.

Figure 3. A 22-year-old patient with 5 years of infertility. 3D-HyCoSy shows her bilateral oviducts are obstructed and expanded at the distal end. Uterine is enlarged and the diameter of bilateral tubes widened, and no contrast agent spills out at the oviduct fimbria.

Criteria for tubal patency as revealed by chromolaparoscopy

Tubal patency was evaluated by two experienced obstetrician-gynecologists. Patent oviducts showed copious methylthioninium chloride outflow during injection of this agent (10 to 20 ml). If oviducts were partially obstructed, there was a slight resistance during injection of methylthioninium chloride. When clamping the root of the unilateral oviduct, a small volume of methylthioninium chloride flowed outward from the fimbriated extremity after increasing the injection pressure. If oviducts were completely obstructed, strong resistance was felt when injecting methylthioninium chloride and overflow was observed. The uterus exhibited high tension. A blue bulge in the uterine horn or a widened oviduct lumen was often observed, and no methylthioninium chloride flowed outward from the fimbriated extremity.

Statistical analysis

The SPSS 13.0 statistical package was used for analysis. Numerical data were compared using analysis of variance or rank sum tests in cases of heterogeneity of variance. Categorical data were compared using the χ2test. The concordance of the two clinical assessment methods was analyzed by the Kappa coefficient test. A value of P<0.05 was considered statistically significant.

RESULTS

Complications

All 157 patients were examined by 3D-HyCoSy. No severe complications were occurred. The majority of patients (111/157, 70.7%) experienced only mild pain, while 17.2% (27/157) reported moderate pain and 4.5% (7/157) reported severe pain.

3D-HyCoSy results

Tubal patency: Of the 157 patients examined, 6 had undergone unilateral salpingectomy and 2 had unicornuate uterus. Of 306 oviducts examined, 99 (32.4%) were patent, 126 (41.2%) partially obstructed, and 81 (26.5%) completely obstructed.

Uterine cavity morphology: In both cases of unicornuate uterus, the uterine cavity appeared as a tilted column. The uterine cavity was also column-shaped in 1 didelphic uterus patient. A concave in the uterine cavity was observed in 2 cases of uterus septus and in all 8 cases of uterus arcuatus. Filling defects, local depressions, or protuberances were observed among 7 cases of uterinepolyps (Fig. 2). The uterine cavity was irregular with burry filling defects in 11 patients with metrosynizesis. After intrauterine development, images of 45 cases with myometrium countercurrent displayed hyperechoic irregularshaped areas adjacent to the uterine cavity, like "fine mesh" or "tousle”, which extended outward and gradually converged; strong hyperechoic areas could be visible in pelvic venous plexus and iliac vessels (Fig. 4).

Figure 4. A 31-year-old patient with 7 years of infertility. Her proximal segment of the left oviduct and distal segment of the right oviduct were obstructed.A. Uterine cavity is visible.B. A small amount of upstream of contrast agent is seen in the myometrium.C. The right oviduct is visible (arrow). Upstream of contrast agent is increased in the myometrium and pelvic venous vessel.D. Myometrium and pelvic venous reflux is further increased. The right oviduct is not easy to distinguish.R-TUB: right side of the oviducts.

Concordance of results of chromolaparoscopy and 3D-HyCoSy

Three months after 3D-HyCoSy, 39 patients (78 oviducts) were examined by chromolaparoscopy. The sensitivity of 3D-HyCoSy was 84.8%, the specificity was 96.2%, the positive predictive value was 93.3%, and the negative predictive value was 86.2%. The Kappa coefficient test indicated that diagnoses based on the two methods were highly concordant (κ=0.765, P<0.001, Table 1).

Table 1. Comparison of results between transvaginal 3D-HyCosy and chromolaporoscopy (number of oviducts)

DISCUSSION

The timely and accurate evaluation of tubal patency is critical for the diagnosis and treatment of infertility. At present, chromolaparoscopy is the gold standard for evaluating tubal patency because it allows for direct diagnosis and concurrent treatment. However, this method is invasive and expensive.4In contrast, HyCoSy is noninvasive, safe, and accurate, and so has been widely used for screening tubal patentcy.5-8Current studies mainly focus on evaluation of tubal patency with 2D-HyCoSy, while few have compared the diagnostic utility of 3D-HyCoSy with such conventional methods as chromolaporoscopy. To this end, we used transvaginal 3D-HyCoSy with a contrast agent (SonoVue) to evaluate tubal patency and compared the result to those obtained by chromolaparoscopy in a subset of the same patient group.

With a contrast mode and contrast agent injected into the uterine cavity, 3D-HyCoSy uses volumetric ultrasound endovaginally to form a 3D image of uterine cavity and oviductal lumen. According to image characteristics of uterine cavity and tubal lumen displayed by the contrast agent, clinicians can evaluate intrauterine lesions and tubal patency. 3D-HyCoSy could display special details better so provides higher diagnostic accuracy than 2D-HyCoSy.2Either under physiological or pathological state, its space traveling lines show bends, folds, and distortion. 2D-HyCoSy can only display a single oviduct but usually cannot display the whole oviduct route in the same plane due to tortuosity of the tubes. Tubal follow-up examinations usually rely on examiners’ proficiency and inspection practices.9,103D-HyCoSy allows the transducer to be stabilized while acquiring images and contrast volume data, reducing information loss caused by instability of the transducer. Bilateral tubal contrast information can be completed in the same volume box while applying 3D-HyCoSy, therebyshortening the examination time and reducing the patient's pain. Simultaneous observation of the bilateral oviducts can reduce false negative occurrence when one side of the oviducts is patent and the other side is obstructed distally, the obstructed side may be mistaken as patent due to permeation of the contrast agent in the pelvis.

Before applying 3D-HyCoSy, a routine ultrasound examination needs to be done to detect uterine and ovarian disease, measure the size and location of the water sac in the uterus, and determine the spatial relationship between the uterus and the ovaries. The uterine cavity and ovaries should be displayed in the same image. The operator should also adjust best scanning angle and depths. If the distal sections of the tubes are too far away from each other, then it may be impossible to include both sides in the same image. In this case, each side should be displayed with volume imaging separately. After 3D-HyCoSy images are acquired, one should immediately complement a 2D complement in the contrast mode, to further observe the tubal route and contrast agent in the ovarian periphery and diffusion in the pelvic cavity. After removing the catheter to complete 2D uterine cavity observation and 3D imaging, one needs to further evaluate the uterine morphology to determine the presence or absence of congenital uterine malformations and intrauterine polyps. Injection of 5 ml saline before 3D-HyCoSy pre-scan positioning helps to observe intrauterine polyps and other lesions, display bilateral uterine horn and oviducts and visualize liquid near the tubal terminal spilling into the pelvis. By feeling the injection pressure, the operator can start scanning at the right time. Post-processing and analysis of 3D-HyCoSy image is crucial, so it is necessary to store the image and playback. By carefully cutting the image and multi-angling, one can distinguish the development of uterine cavity, oviducts from background noise and myometrium countercurrent. 3D-HyCoSy image analysis includes intrauterine imaging phase, oviduct imaging phase and pelvic dispersed phase. First, one needs to observe the abnormal uterine shape and finishing degrees, abnormal uterine morphology associated with congenital uterine malformations and unsmooth uterine cavity usually resulting from intrauterine polyps and intrauterine adhesions. When muscular countercurrent appears, it may affect the observation of the uterine cavity. In addition, it is necessary to observe the thickness, route and continuity of oviduct as well as the leakage of contrast agent through multi-angle and gain adjustment by rotating the image. It is also necessary to carefully distinguish the oviducts from perimetrial venous plexus while countercurrent appears. Oviducts connected with uterine horn, but the myometrium and venous plexus countercurrent can start from anywhere in the mesometrium. As it goes down the convergence, contrast agent is visible in the iliac vessels. Finally, one can observe the diffusion of contrast agent near the ovarian, uterine and intestinal clearances. Contrast agent is uneven when pelvic adhesions exist.

The newer ultrasound contrast agents and imaging technology progress have made 3D-HyCoSy images clearer and more intuitive. This study used a newer generation of ultrasound contrast agent sulfur hexafluoride microbubbles, which has been widely applied to the heart and the blood vessels angiography.11-13Here, we used it in the tubal cavity angiography. Reducing the concentration of contrast agents can also make a better image. With a low mechanical index contrast, the hyperechoic microbubbles can be easily distinguished from the surrounding tissues, and contrast imaging last for a longer time, which greatly improve image quality and increase contrast effect. Without intestinal gas interference through, this endovaginal approach provides closer observation of the structures. Volume vaginal probe and low mechanical index imaging techniques reduced the dependence on the skills of operator, and avoided missing and lost of diagnostic information for 2D tracking omissions. Stored volume image could be manipulated at any angle. Real time and intuitive images facilitated communication between doctors and patients.

In conclusion, transvaginal 3D-HyCoSy can clearly display the morphology, structure, and spatial path of the oviducts, and can identify tubal twisting and sites of tubal stenosis and obstruction. The procedure is simple and safe, and diagnostic efficacy is concordant with conventional sonographic methods. Therefore, this modality is an effective method for screening tubal patency.

ACKNOWLEDGMENT

We thank Min Zhou and Yun Hu from GE Corporation for their technical support.

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for publication May 16, 2014.

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△Supported by the Health Department of Guangdong Province (B2011259).