Abstract
While the uterus, cervix and ovaries can be well assessed by transvaginal ultrasound, normal fallopian tubes are not visible on ultrasound. Therefore, evaluation of the fallopian tubes needs special consideration. Tubal disease accounts for a significant proportion of female infertility and pelvic pain . The fallopian tubes may be damaged, most commonly due to pelvic inflammatory disease (PID), but endometriosis, previous pelvic surgery, fibroids, and pelvic tuberculosis may also be seen as frequent causes for tubal damage . Prior uterine surgeries like surgical or medical termination of pregnancy and myomectomy may predispose to subclinical inflammation or infection leading to tubal damage. Tubal patency may also be affected due to polyps, myomas or salpingitis isthmica nodosa, though the latter is not very commonly seen and not very confidently diagnosed on ultrasound.
Introduction
While the uterus, cervix and ovaries can be well assessed by transvaginal ultrasound, normal fallopian tubes are not visible on ultrasound. Therefore, evaluation of the fallopian tubes needs special consideration. Tubal disease accounts for a significant proportion of female infertility and pelvic pain [1]. The fallopian tubes may be damaged, most commonly due to pelvic inflammatory disease (PID), but endometriosis, previous pelvic surgery, fibroids, and pelvic tuberculosis may also be seen as frequent causes for tubal damage [2]. Prior uterine surgeries like surgical or medical termination of pregnancy and myomectomy may predispose to subclinical inflammation or infection leading to tubal damage. Tubal patency may also be affected due to polyps, myomas or salpingitis isthmica nodosa, though the latter is not very commonly seen and not very confidently diagnosed on ultrasound. These pathologies may lead to obstruction, stenosis, dilation, and impaired peristaltic function of the tubes [3]. Tubal function may also be affected by changes in the tubal mucosal lining, muscular wall or any pathology external to the tube. Proximal tubal involvement is more in the form of muscular spasm, stromal oedema, amorphous debris, mucosal agglutination and viscous secretions causing obstruction. Mid-tubal disease causes stenosis or occlusion, typically with bulbous termination due to scarring and fibrosis. Fimbrial end involvement may lead to hydrosalpinx.
Functional Anatomy of the Fallopian Tubes
Fallopian tubes are tubal structures extending from the lateral end of the uterus towards the ovaries and are about 10–12 cm in length. These can be divided into five parts (Figure 10.1): the intramural or interstitial part is the part of the tube in the muscular uterine wall and is 1 cm long; the isthmic part following the interstitial part is 2 cm; the following 5 cm is the ampullary part, which has a variable length; this is followed by the infundibulum – the wide part before the fimbria – and then the fimbria. The inner diameter of the tube is barely 1 mm. Fallopian tubes play an important role in the transport of sperm and egg, sperm capacitation, fertilization and embryo transport [4]. It is essential that the fallopian tubes are patent for the tubo-ovarian relationship to be normal. The fimbrial condition should be good and accommodative to envelop the ovary, and the cilia should be functional to guide the passage of ovum and embryo towards the uterus and guide the passage of sperm towards the ovum.
Assessment of the Tubes
Assessment of the tubes is done to check the patency and to rule out pathologies. Tubal patency cannot be assessed on a routine pelvic transvaginal ultrasound, although a fluid distended tube (hydrosalpinx) can be diagnosed reliably. It is essential to use fluid as a contrast to visualize the normal tubal lumen on ultrasound. Assessment of the tubal patency can be done under x-ray guidance (hysterosalpingogram; HSG), ultrasound guidance (saline infusion sonography; SIS) and hystero-contrast sono-salpingography (HyCoSy) or surgically by laparoscopic guidance. HSG, SIS and HyCoSy are less invasive and associated with less serious risks than surgical techniques like laparoscopy and the dye test (chromopertubation), although the latter is considered the gold standard for assessment of tubal patency and pathology.
HSG is widely used for tubal evaluation in subfertile women. This method is fairly accurate in detecting proximal tubal disease, is safe, inexpensive and may potentially be associated with increased pregnancy rates [5]. HSG provides optimal delineation of the fallopian tubes, tubal patency, lumen irregularity and peritubal disease. The radio-opaque solution (contrast) is injected in the minimal required dose. Under fluoroscopic guidance, filling of the uterine cavity and passage with the radio-opaque solution into the tubes and its spill from the fimbrial end is observed and documented in the form of x-rays (Figure 10.2). HSG also allows for a study of the endometrial cavity, diagnosing some Mullerian abnormalities and endometrial lesions (Figure 10.3).
Figure 10.3 Hysterosalpingogram showing normal endometrial cavity with free spill from the left fallopian tube and non-filling of the right tube, suggestive of right cornual block.
However, the main disadvantages include exposure to radiation, use of iodinated contrast, severe pain and high false-negative rates. The procedure is to be done in the radiology environment, where neither the gynaecologist nor the patient feels very comfortable, though that may not be an important issue. It gives a static image, and the tubo-ovarian relation that is vital for fertility cannot be fully evaluated. Further, tubal block seen on HSG will be confirmed by laparoscopy in only 38 per cent of women [6], with pooled estimates of sensitivity and specificity for HSG as a test for tubal obstruction of 0.65 (95 per cent CI 0.50–0.78) and 0.83 (95 per cent CI 0.77–0.88), respectively [7].
The ultrasound-guided tubal patency test avoids the risk of radiation as well as the risk of potential adverse reaction to iodinated contrast, but provides information similar to that obtained by HSG. The ultrasound-guided tubal patency test is commonly referred to as sonohysterosalpingography, but this is a group of investigations and the method of each varies a little depending on the contrast agent and the ultrasound technology used. The variations are:
1. SIS
2. SIS with pulsed wave Doppler
3. SIS with colour Doppler
4. saline and air infusion salpingography
5. SIS with 3D power Doppler
6. HyCoSy
7. hystero-foam salpingography (HyFoSy).
Saline Infusion Salpingography
Sonographic evaluation of tubes was initially described by various authors [8–10], who performed abdominal sonography following intracervical injection of fluid, but was reported first by Richman. For this procedure, 200 ml of saline was injected transvaginally. Fluid would fill the uterine cavity and pass through the tubes into the pelvic cavity. Retrouterine fluid documented on abdominal ultrasound was accepted as a criterion for patency. Tufekci reported use of isotonic saline with transvaginal ultrasound for assessment of tubal patency in 1992 [11]. Deichert was the first to report on transvaginal sonographic evaluation of tubal patency, following transcervical injection of echogenic ultrasonic contrast fluid [12].
Technique
Saline infusion salpingography is ideally done in the mid-proliferative phase (days 6–10 of a typical 28-day cycle), after menstruation stops but before ovulation occurs. Oral analgesic, ibuprofen 400 mg and/or paracetamol 500–1000 mg, may be given 1–2 hours before the procedure. Pre-procedural screening for infections like chlamydia and/or prophylactic oral antibiotics are recommended. Strict asepsis is essential. A detailed transvaginal ultrasound scan is done to assess the position of the pelvic organs and to rule out any pathologies, which would get in the way of visualization of the uterus and ovaries. Moreover, any free fluid in the pelvis is also checked for, as this may interfere with the observation for tubal patency.
The probe is removed and Cusco’s speculum is placed in the vagina to visualize the cervix. The cervix is cleaned with an antiseptic solution. If required, the cervix is fixed with tenaculum forceps and manipulated to align it with the uterus. A size 5–8 Fr balloon HSG or SIS catheter is used. It is attached to a 10–20 ml syringe prefilled with saline. The catheter is introduced through the cervix into the uterus. The balloon is placed just beyond the internal os and is distended with 1–2 ml of distilled water or normal saline. Alternatives to this catheter are paediatric feeding tubes or intrauterine insemination (IUI) catheters. A catheter with a balloon has the advantage of preventing any reflux of saline or contrast media through the cervical canal. Once the catheter is fixed, the speculum (and tenaculum if used) are removed and a transvaginal probe is introduced into the vagina for further assessment.
Saline is injected through the catheter slowly. Scanning is done to assess the uterine cavity that is distended by saline and also the passage of saline (fluid) seen through the tubes. When the uterine cavity is filled with saline, endometrial pathologies like polyps, synechiea and hyperplasia can be demonstrated and diagnosed (Figure 10.4). Spill of saline from the fimbrial end is seen as fluid flow surrounding the ovary and subsequently appears as a collection in the pelvis on B-mode scanning (Figure 10.5). The latter is seen more confidently when the uterus and ovary are seen in the transverse axis, on the same image.
Absence of spill may indicate blockage. At times, when there is unilateral blockage, it is difficult to judge the side of the blockage. In patients with bilateral block, distension of the uterine cavity causes severe pain. Once the procedure is completed, the catheter is removed after deflating the balloon. The patient is informed that she might get some pelvic cramping or spotting, but this is short term and expected.
The procedure is generally safe without any major complications. The risk of pelvic infection and associated peritonitis is approximately 1 per cent. Other risks include nausea or vomiting, vasovagal syncope and pain during or immediately after the procedure. The reported prevalence of the latter three risks combined is 8.8 per cent [13]. Failure to perform or complete the procedure was documented in 7 per cent in a meta-analysis of 24 studies and 2278 procedures [14]. The accuracy of SIS compared to laparoscopic chromopertubation varies from 81.82 per cent [15] to 100 per cent [16,17].
The shortcoming of the procedure is that even when patency of individual tubes can be confirmed, it does not give any information about the site of the blockage, the condition of the lumen or the tubo-ovarian relationship. Some variations in this technique were created to overcome those limitations.
SIS Using Pulse Doppler
If examination during conventional ultrasound reveals evidence suggesting tubal occlusion or if a small segment of the tube measuring less than 2 cm is not visualized, a pulse Doppler examination can be performed [18], although is not routinely done. A Doppler gate is placed where the block is expected. This is exactly the point beyond which the tube is not filled with saline or colour flow is not seen on injection of saline when examination is done with colour Doppler. The gate is reduced to the width of the tube. Brief injections of fluid/saline lasting for 5 s are done while Doppler signals are observed [19]. Patent tube is indicated by a short filling phase with rapid, steep increase in Doppler shift followed by slow, uniform fall in Doppler shift. Obstruction presents as short, steep Doppler shift with no subsequent noise signals (Figure 10.6).
Figure 10.6 Diagrammatic presentation of fluid flow in patent, partially obstructed and obstructed tube on pulse Doppler assessment for tubal patency [19].
SIS Using Colour Doppler
Under ultrasound guidance, the tip of the catheter is placed close to either cornu, one by one. First, the colour box is placed on the transverse section of the uterus. Colour signals in the uterine cavity confirm the passage of fluid in the uterus. The field of vision is immediately changed over to the ovary and adnexa, by spanning the probe from the transverse section of the uterus, laterally. While injecting saline in short jets, the colour box is placed to visualize the adnexa and ovary. Filling the box with colour signals immediately after colour signals are seen in the uterus indicates patency of the tube; absence of such signals indicates blockage [20] (Figure 10.7). The same procedure is repeated on the opposite side. A detailed evaluation for any pathology is important immediately prior to performing the procedure as hydrosalpinx may create turbulence in the fluid present in the tube and give a false impression of a patent tube.
In a study by Peters and Coulam of 129 infertile patients, Doppler SIS showed complete agreement with HSG in 81 per cent of cases. When compared with chromopertubation, Doppler SIS showed agreement in 86 per cent of cases, while HSG agreed with chromopertubation only in 75 per cent of cases [21]. In another small study by Kupesic et al., 91.5 per cent agreement was seen between colour Doppler SIS and chromopertubation [16]. Correlation of colour Doppler SIS and HSG with chromopertubation was 81 per cent versus 60 per cent, respectively, in another study [13].
SIS Using Saline with Air
When air is mixed with saline, bubbles are formed and this produces hyperechoic shadows which help better outline the tubal lumen. This can be done either by agitating air and saline or by injecting air after saline has already been pushed in to fill the uterine cavity and tubes (Figure 10.8). This technique was described by Jeanty et al. and showed a 79.4 per cent agreement with results of chromopertubation and a sensitivity of 85.7 per cent and specificity of 77.2 per cent for tubal patency [21].
SIS with 3D Power Doppler
Transvaginal three-dimensional saline infusion sonohysterosalpingography provides good visualization of the uterine cavity and myometrial walls in three orthogonal planes. However, it does not diagnose tubal occlusion or depict architecture of the fallopian tube as accurately as x-ray HSG. Although the distal fallopian tube and fimbria are seen with real-time imaging, the proximal tube is not satisfactorily imaged even with 3D power Doppler. This technique may be reserved as an initial screening test to evaluate the uterine cavity and to test tubal patency. Patients at high risk for tubal disease by history or with suspected tubal occlusion on 3D saline infusion HSG should be evaluated by either x-ray HSG or laparoscopy with chromopertubation [22].
Kiyokawa et al. reported that when 3D was added to saline salpingography, the positive predictive value, negative predictive value, sensitivity and specificity of predicting tubal patency were 100, 33.3, 84.4 and 100 per cent, respectively. Over and above this, this method also has the advantage of assessing the shape of the uterine cavity. The complete contour of the uterine cavity was depicted in 96 per cent of cases using 3D HyCoSy and 64 per cent by x-ray HSG [23].
Hystero-Contrast Salpingography
While intra-cavitary lesions are clearly delineated by anechoic media, very small hollow cavities, such as normal tubes, are not always easily visualized using SIS [24]. Demonstration of the lumen of tubes requires visualization of movement of fluid using a highly echogenic medium [25]. Hyperechogenic contrast medium enhances echo signals and allows detection of the flow, both by B-mode and Doppler ultrasound. Experimental and clinical data suggest that insonation of echo-enhancing contrast agents with high acoustic power produces disintegration of microbubbles, resulting in a phenomenon called stimulated acoustic emission (SAE). It is based on this principle that the positive ultrasound contrast media are developed [26]. A cheap and cost-effective option is the use of saline mixed with air, which produces a high-contrast fluid due to the presence of air bubbles, as discussed earlier. However, these bubbles exist only for a very short period and therefore tubal patency assessment may become practically difficult.
Commercially available contrast media consist of microbubbles that can exist for a longer time, including Echovist and Levovist (Schering AG, Berlin), which consist of a suspension of microbubbles made of special galactose microparticles. These are suspended either in galactose solution, as in Echovist, or in sterile water, as in Levovist. Just before use, these solutions are constituted by mixing and vigorously shaking the microparticles with the solvent and remain stable for 5–10 min. These solutions completely dissolve in the body within about 30 min. The use is unrestricted, except for patients with galactosaemia. Non-embryo toxic gel (ExEm-gel® Gynaecologiq BV, Delft, the Netherlands), containing hydroxyethylcellulose and glycerol, has also been used as an intrauterine medium for sonohysterography as an alternative to saline [27].
Gel instillation offers more stable filling of the uterine cavity. This gel and its compounds have been tested extensively and may be used safely. The foam contrast is reconstituted by mechanically mixing 10 ml of ExEm-gel and 10 ml of sterile water [28]. When the gel is pushed rigorously through small openings in syringes or tubes, turbulence causes local pressure drop, resulting in air dissolving in the solution, and yielding foam that is stable for several minutes. ExEm-gel (containing 88.25 per cent purified water), however, is rather viscous for passing into the fallopian tubes. Therefore, 10 ml of ExEm-gel is diluted with 10 ml of purified water (to give a mixture containing 94.12 per cent water) and mixed to create foam. The mixture at this ratio creates foam that is sufficiently stable to show echogenicity for at least 5 min and sufficiently fluid to pass through patent tubes. The viscosity of this foam (270 cP) is comparable to that of Echovist (400 cP) [29]. The foam is slowly injected into the endometrial cavity through the GIS catheter, or similar catheter, in repeated small (0.5–1 ml) boluses while observing for antegrade flow through the uterine cornua on the transverse plane using B-mode. Distal flow of contrast is followed through each tube until peritoneal spill is visualized (Figure 10.9). It is easier to visualize spill of the foam into the peritoneal cavity after locating the ovaries [28].
According to some studies it can maintain echogenicity for about 7 min, allowing it to be used as a contrast medium for HyFoSy [30]. The foam usually maintains its echogenicity long enough to allow acquisition of 3D volume images.
A positive contrast agent that is more easily available in most countries is Sonovue (Bracco, Italy). This contrast agent consists of sulphur hexafluoride microparticles and 5 ml of solvent in a prefilled syringe. After reconstitution it makes 5 ml of solution. For assessment of tubal status, 1 ml of Sonovue is diluted with 4 ml of normal saline and agitated to create a foam for injection through the cervix into the uterus. This contrast is safe for intravascular use also. It is used as an ultrasound contrast agent for vascular studies and for diagnosis of malignancy.
The scanning technique is the same as that for SIS. Using positive contrast, it is possible to delineate the whole tube along with the uterine cavity even on B-mode scanning (Figure 10.9).
There is ultrasound equipment with contrast mode (contrast-tuned imaging technology based on harmonics). The advantage is that it enhances the contrast and makes visualization of tubes even better (Figure 10.10). Using a contrast mode with positive contrast makes it easier to view the spill from the fimbrial end if the tube is patent. If the tube is not patent, the contrast column in the tube can identify the site of the blockage.
Technique
The procedure for HyCoSy is the same as for SIS. As delineation of the tube is better with HyCoSy, the total amount of contrast needed is as little as 2–3 ml per tube. For diagnosis of tubal patency, two or three observation phases per tube are needed, with an observation period of continuous flow of about 10 s. Visualization of long segments of tube beyond the intramural part of the tube usually indicates patency, though the whole tube must be observed and spill should be confirmed. Appearance or increase in the fluid in the pouch of Douglas may be an indirect sign of tubal patency, the same as for SIS.
HyCoSy is usually performed within the fertility unit. HyCoSy has several advantages over SIS in that it helps to provide clearer visualization of the uterine cavity, better assessment of tubal lumen and fimbriae, clearer visualization of spill and a more exact localization of the site of blockage. HyCoSy with contrast is more efficient than with saline solution in determining fallopian tube patency and is as efficient as HSG and can be used instead of HSG for screening infertile patients [28]. The test shows good concordance with lap-and-dye (chromopertubation) (80.4–92.5 per cent) and HSG (83.8–90.5 per cent) [31]. The main disadvantage of HyCoSy is that it is more operator-dependent compared to HSG and has a high false occlusion rate [32].
In a study comparing HyCoSy and chromopertubation, there was a high degree of correlation in assessing tubal patency, with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100, 55.6, 80 and 100 per cent, respectively [31]. HyCoSy is accurate in determining tubal patency and evaluating the uterine cavity and can supplant HSG as the first-line diagnostic test in an infertility work-up [33]. Compared to conventional HSG, HyCoSy provides a simultaneous ultrasound evaluation of the pelvis and a more cost-effective evaluation of tubal pathology and can be successfully used as a first-line non-invasive screening method [34]. In a diagnostic accuracy study of HyCoSy performed with air and saline (Hydro-HyCoSy) and with contrast media (SonoVue-HyCoSy) considering HSG and/or chromopertubation as reference tests, SonoVue-HyCoSy has been found to be more accurate than Hydro-HyCoSy for the assessment of fallopian tubes [31]. While the sensitivity, specificity, PPV and NPV of Hydro-HyCoSy were 91, 71, 55 and 95 per cent, respectively, they were 87, 84, 69, and 94 per cent respectively for SonoVue-HyCoSy. The diagnostic accuracy of Hydro-HyCoSy and of SonoVue-HyCoSy were 77 and 85 per cent, with a Cohen’s kappa of 0.52 and 0.66, respectively. In another small study comparing HyCoSy and chromopertubation, there was a high degree of correlation in assessing tubal patency, with sensitivity, specificity, PPV and NPV of 100, 55.6, 80 and 100 per cent, respectively [28].
Moreover, the amount of contrast agent required for adequate examination was also less with positive contrast. Mean volumes of contrast injections were 35.3 ml of saline, 14.4 ml of Infoson, and 13.8 ml of Iopamiron 370. Infoson-enhanced HyCoSy provided a significantly larger (p = 0.006) number of correct diagnoses (20/22 fallopian tubes) than did saline HyCoSy (12/24 fallopian tubes), and the same number as that achieved by HSG [33].
Yet another study has shown that HSG and HyCoSy demonstrated a high concordance with laparoscopy (83 and 80 per cent, respectively). The two methods had a high NPV for tubal disease (HSG, 94 per cent; HyCoSy, 88 per cent), and the PPVs were 47 and 75 per cent, respectively [35]. A study by Exacoustos et al. has also shown that HSG and HyCoSy had the same high concordance as laparoscopy, at 86.7 and 86.7 per cent, respectively [36]. The study concluded that HyCoSy proved to be superior to conventional HSG in evaluating adjacent myometrial structures, adnexa and degree of follicular maturation, was equal to HSG in visualizing the passage of the contrast medium into the peritoneum, but inferior to HSG in imaging the fallopian tubes owing to their tortuosity [36]. Conversely, Balen et al. found that both SIS and HyCoSy are insufficiently accurate and inferior to HSG [37]. They quoted a false-positive rate of 9 per cent and false-negative rate of 20 per cent for HyCoSy. This is because fallopian tubes are tortuous and usually not confined to a single plane. Moreover, distal parts of the tube may be obscured by bowel gas.
There are many factors that can give rise to a false occlusion result. First, the tubal lumen may be temporarily occluded by a mucous plug, blood clot, myometrial spasm or mucosal oedema [38]. The proximal segment, being the narrowest part of the fallopian tube, is especially prone to this, resulting in a diagnosis of a cornual block. Second, technical difficulties can arise for multiple reasons. Contrast leakage or cervical stenosis can occur, resulting in failure to achieve adequate pressure of hydrotubation [35]. Tubal convolution or distorted anatomy from pelvic adhesions can lead to difficulty in tracing the course of the tubes.
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