Hysterosalpingogram

Hysterosalpingography (HSG) is a radiographic diagnostic study of the uterus and fallopian tubes most commonly used in the evaluation of infertility. (See the images below.) Uterine abnormalities are thought to be a contributing factor in approximately 10% of infertile women and 50% of women with recurrent early pregnancy loss, while the prevalence of tubal abnormalities in infertility is approximately 20%.[1, 2] Thus, assessment of the uterine cavity and fallopian tubes is a standard practice in the baseline infertility workup.

Indications

HSG has long been recognized for its use in detecting tubal patency, polyps, submucosal leiomyomas, synechiae, müllerian anomalies, hydrosalpinges, salpingitis isthmica nodosum (SIN), and peritubal adhesions.[3]  It does not, however, provide significant information about the ovaries, other areas of the pelvis, or the microbiologic environment of the endometrium, the latter of which may contribute to poor reproductive outcome in approximately 25% of subfertile women.[4]

Contraindications

Known contrast allergy, pregnancy, and active pelvic infection are absolute contraindications to the procedure.

Procedure planning

The procedure should be performed in the late follicular phase of the menstrual cycle to ensure that the patient is not pregnant and to prevent false-positive intrauterine filling defects and proximal tubal occlusion due to endometrial thickening. Some facilities perform routine pregnancy tests prior to the procedure, but this practice results in an unfavorable cost–to-benefit ratio.

Elements of informed consent

Key points to be reviewed during informed consent include the risks of infection, contrast reaction, hemorrhage, uterine perforation, radiation exposure, the theoretical risk of harm to an undiagnosed pregnancy, and oil embolism after extravasation of an oil-based media. Significant contrast reactions are rare and more common in patients with a history of hypersensitivity to iodinated contrast agents, recurring in approximately 8-25% of cases.[5, 6] Other recognized risks include a history of asthma or ectopic allergic reaction. The age-old practice of inquiring about seafood allergies has no predictive value of contrast reaction.[7]

The radiation dose to the ovaries during HSG varies from 0.4t-5.5 mGy.[8] This compares to other procedures such as fluoroscopic tubal cannulation (8.5 mGy), barium enema (6.5 mGy), and pelvic CT (1-19 mGy).[9] One rad, or 10 mGy, at a rate of 1 rad/min for up to 10 minutes (100 mGy total) has been suggested as the threshold below which the added incidence of teratogenicity is exceedingly low.[8] Thus, conventional HSG is considered safe. Even so, equipment should be properly calibrated, repetitive procedures should be avoided, and the radiation exposure time during each procedure should be minimized.[8]

Diagnostic considerations

Even with proper technique, radiographic artifact is not an uncommon phenomenon. These filling defects include those caused by inspissated air, intrauterine mucous, broken fragments of endometrium, and extravasation of contrast. An inadvertent air bubble can be confused for a polyp or myoma but is distinguished by its tendency to migrate and settle in the nondependent portion of the cavity, especially as the patient moves.[10]

Significant extravasation of dye into the myometrial venous plexus and surrounding pelvic vasculature may be caused by excessive instillation pressure that usually occurs while attempting to overcome proximal tubal occlusion, or in the setting of recent uterine surgery.[10] Extravasation fills venous and lymphatic channels, appearing as multiple thin lines in a reticular pattern that usually dissipates once injection of dye stops (see the image below).[10] The procedure should be halted with the onset of extravasation.

The diagnostic accuracy of HSG has been widely investigated. Although hysteroscopy is very sensitive and specific for detecting uterine cavity pathology, no optimal standard of reference exits for assessing tubal patency. The criterion standard for tubal patency evaluation is generally considered to be laparoscopy with chromotubation. But this procedure has suboptimal sensitivity, specificity, and positive and negative predictive values.[11] Nevertheless, comparisons between HSG and laparoscopy with chromotubation are prevalent and have demonstrated discrepancies of up to 45%.[12]

Furthermore, a large Dutch meta-analysis reported HSG sensitivity and specificity of only 65% and 85%, respectively, for fallopian tube assessment.[13] Studies that have compared hysteroscopy to HSG have reported HSG sensitivity and specificity of approximately 80% in correctly identifying uterine cavity pathology with both false-positive and false-negative rates approximately 10-20%.[4, 14] In light of such figures, some authors have advocated that HSG be replaced by hysteroscopy as the first-line diagnostic procedure.[15]

Methods to determine tubal patency with ultrasound have been proposed for years. A medium of galactose microparticle granules (Echovist 200, Schering Co.) provides ultrasound contrast and is quickly metabolized. An analysis of 3 clinical trials showed a 68.3% agreement with HSG. Compared to HSG, ultrasound showed false occlusion in 12.8% of tubes and false patency in 3.9%. Compared to laparoscopic examination, ultrasound showed 10.3% false occlusion and 6.7% false patency rates.[16] An alternate ultrasound medium containing air-filled albumin microspheres has also been used.[17] Concomitant instillation of normal saline with air has been advocated for determination of tubal patency. In one study, this technique showed a 89.6% concordance with HSG.[18]

The role of antibiotic use in HSG is not standardized. In 1980, Stumpf et al reported an incidence of serious pelvic infection after HSG of 3.1%, most commonly occurring in women with a history of infertility or prior or current pelvic infection or adnexal mass.[19] The American College of Obstetricians and Gynecologists recommends empiric treatment for women with a history of pelvic infection or when hydrosalpinx is diagnosed at the time of the study. A common and effective regimen is doxycycline, 100 mg orally twice daily for 5 days.[20] Other situations in which treatment is common include when tubal blockage is suspected, unexpected distal occlusion is encountered, or significant vascular extravasation occurs.

A 2010 Cochrane review of antibiotic prophylaxis for transcervical procedures concluded that insufficient evidence existed to recommend for or against the routine use of antibiotics in such procedures.[21] Therefore, prophylaxis in HSG should be limited to patients deemed to be at higher risk of infection.

Unfortunately, many women have preconceptions that HSG is a painful test. Mild-to-moderate cramps are common but most often temporary. Unquestionably, patient discomfort is influenced by operator technique. Pain associated with HSG is generally related to cervical manipulation, uterine cavity distention with the instillation of the contrast media, and peritoneal irritation from dye that has spilled into the pelvis. Discomfort typically peaks at the time of dye injection until 5 minutes after the procedure and then begins to fall precipitously, so that 30 minutes after the procedure most patients report significant relief[22] .

A cross-sectional questionnaire study by Handelzalts et al suggested that HSG is associated with a higher degree of fear, anxiety, and pain than colposcopy, with women in the HSG group reporting significantly higher preprocedural anxiety and fear of pain and retrospectively reporting the procedure to be more painful than did the colposcopy group.[23]

Multiple trials have been conducted to assess the effect of analgesics on pain from HSG. A 2010 Cochrane meta-analysis reviewed investigations of opioid and nonopioid oral analgesics as well as paracervical block and local analgesics on reported pain during and after HSG. No overall benefit existed from any type of prophylactic analgesia for pain during or up to 30 minutes after HSG, but local analgesia (10 mL of 1% lidocaine injected into the uterine cavity before the contrast) may reduce delayed pain.[24]

Arnau et al conducted a randomized, double-blind, controlled study to investigate the efficacy of 5% lidocaine/prilocaine 25 mg/g cream applied to the uterine cervix for reducing pain during hysterosalpingography. One hundred successive patients scheduled to undergo hysterosalpingography were randomly assigned to receive either 3 ml of lidocaine-prilocaine cream or 3 ml of placebo, applied endocervically and exocervically, 10 minues before hysterosalpingography. Patients' intensity of pain was assessed at baseline (speculum application), after application of Pozzi tenaculum and cannula on the uterine cervix, during cervical traction, and after contrast medium injection, using a 10-cm visual analogue scale immediately after the procedure. The most painful step was also identified. The visual analogue scale was administered again at the 1-month follow-up visit. For both cohorts, the injection of contrast medium was the most painful step of hysterosalpingography. No differences were found between thetwogroupsduring this step. When comparing the pain scale after the application of Pozzi tenaculum and cannula and after cervical traction, significantly less pain was experienced by the group treated with lidocaine-prilocaine cream than by the group receiving placebo group. The invesgtigators concluded that endocervical and exocervical topical application of lidocaine-prilocaine cream 10 minutes before performing hysterosalpingography significantly reduced pain during cervical manipulation with tenaculum and cannula and during cervical traction. It did not reduce pain during injection of contrast, which was was the most painful step of the procedure.[25]

Usually completed in about 3-5 minutes, HSG is performed by instilling radio opaque contrast into the uterine cavity while using fluoroscopy with intermittent still images for documentation. Proper technique is important to enhance patient comfort and ensure the highest quality images. Having the patient empty her bladder prior to positioning may ease discomfort from the speculum, which should be warmed prior to insertion. Supporting the patient’s hips on a short stack of towels or an overturned bed pan often aids in visualization of the cervix. As with any pelvic examination, the operator should attempt to drape as much of the patient’s lower body as possible, have a female chaperone, and explain to the patient each step of the procedure.

Very few items are necessary to perform an HSG (see image below). Instillation devices include instruments that fit into the cervix such as a Cohen cannula or a 5-F catheter that has a balloon to prevent efflux of contrast from the cervix. An open-sided speculum is optimal since it is easier to remove with instruments in place.

The cervix is prepared with an antiseptic and grasped with a single-toothed tenaculum. Gentle, slow placement of the tenaculum, grasping only enough tissue for adequate stabilization of the cannula, is recommended. Distress experienced by the patient because of poor tenaculum placement is often a predictor of a negative patient experience. Cohen cannulas come with a narrow acorn tip for use in nulliparous patients or a wider acorn tip for multiparous patients. All air should be removed from the cannula by priming it in the vertical position. Holding the Cohen and applied tenaculum in one hand to occlude the cervix is preferable to attaching the cannula to the tenaculum since it usually causes less pain. A balloon catheter may be more suitable for patients with cervical stenosis since it has a smaller diameter than the tip of the Cohen cannula. Some patients experience discomfort during inflation of the balloon. Other methods such as using a balloon catheter are also frequently employed and avoid the useof the tenaculum.

For patients planning to undergo in-vitro fertilization, documenting how the catheter traverses the cervical canal may provide valuable information for the embryo transfer. The speculum should be removed both for patient comfort and to prevent nonvisualization of portions of the pelvis. Failure to remove the speculum is one of the most common errors made when performing an HSG. Gentle traction on the cervix is necessary so that the uterine body is perpendicular to the x-ray beam. Failure to properly position the uterus is another common mistake that may result in the inability to identify significant intrauterine filling defects or fundal contour abnormalities (see the image below). When using an intrauterine catheter, deflating the balloon at the end of the procedure and continuing to inject dye in order to visualize the uterine isthmus and cervix is very important.

To decrease uterine spasm, the media should be warmed to body temperature and injected slowly. A 1995 meta-analysis on the accuracy of HSG reported that proximal tubal occlusion can occur secondary to transient tubal spasm or obstructive endometrial debris in up to 20% and 40% of cases, respectively.[13] False-negative results can occur from excessively rapid or overinstillation of contrast, obscuring subtle filling defects. In fact, in one study, approximately 10-35% of women with a reportedly normal HSG were then found to have abnormal findings on hysteroscopy.[4] Historically, administration of glucagon and selective tubal catheterization have been performed in an attempt to combat proximal tubal occlusion. However, increased cost and technical complexity have caused these methods to become less popular.[11]

A scout radiograph is taken prior to the instillation of contrast. Then a series of at least 4 more images should be captured as the contrast spreads through the genital tract. The first image after the scout film documents initial cavity fill and is best for visualizing small filling defects.[3] The subsequent image should be obtained when the cavity is fully distended to assess uterine shape. The third and fourth images after the scout are obtained as the fallopian tubes are filling and after dye has spilled into the pelvis, respectively. Additional images may be required to better document any pathology that is seen.

Occasionally, the patient may need to be positioned obliquely or laterally to obtain optimal orientation of anatomy or to clarify pathology from artifact. As with all radiography procedures, the goal is to obtain an adequate study using as low as reasonably achievable (ALARA) radiation dose. Strategies include adjusting the dose for body mass index, shielding of other body areas, and using the smallest radiation field needed.

Both oil-based and water-based iodinated contrasts are used for HSG. The advantages and disadvantages of each have been debated for years. Most studies ultimately fail to show a difference in the diagnostic accuracy of uterine or tubal pathology with either of these media.

However, water-soluble dyes have been found to provide better detail of the uterine cavity and mucosal folds of the ampullary portion of the tube and are more quickly eliminated.[26] Oil-based dyes have been associated with less postprocedure vaginal bleeding, but in animal models oil-based dyes are reported to cause temporary granulomatous formation of the pelvic peritoneum.[26, 27]

Other studies have confirmed a higher incidence of lipogranulomas in women, as well as a higher rate of allergic reaction with oil-based media, prompting most practitioners to prefer the use of water-based media.[26, 28]  A meta-analysis showed that the most common complication after an HSG with oil-based contrast is intravasation, which was reported in 2.7% of procedures.[29]

Air polymer type A (ExEm Foam) is a water-soluble ultrasound contrast gel indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility. 

Approval of air polymer type A was based on 2 studies that compared 2D or 3D imaging to detect fallopian tube patency in women with infertility which was confirmed by laparoscopy with chromotubation as the reference standard. For 2D-sonohysterosalpingography imaging, the proportion of fallopian tubes correctly identified as occluded was 80% and the proportion of tubes that were correctly identified as patent was 92%. For 3D imaging, the proportion of tubes correctly identified as occluded was 98% and the proportion of tubes that were correctly identified as patent was 91%.[30]

Nonetheless, a Cochrane review from 2007 demonstrated a significantly higher post-HSG pregnancy rate (PR) when using oil-based contrast. In this meta-analysis, PR varied from 17-23% with water-soluble contrast to 24-38% with oil-based contrast, compared to 8-21% without the HSG.[31] These authors pointed to an improvement in endometrial receptivity after oil-based contrast exposure as a possible explanation for this. Another theory suggests a reduction in peritoneal macrophage function after oil-based media as a potential mechanism.[32, 33]

Complications from HSG are rare. The most common adverse event is a vasovagal reaction with bradycardia and hypotension, potentially resulting in syncope. This may occur anytime during the procedure such as with tenaculum placement, dye instillation, or shortly after completion. Most cases resolve with simple maneuvers including termination of the procedure and placement of the patient in a Trendelenburg position, if possible.

Extravasation of dye is also an indication to discontinue the procedure. Unabated extravasation may increase the risk of systemic reaction to the contrast, increase the risk of infection, and result in embolism with an oil contrast agent. Allergic reactions to contrast dye are much less common than with intravenous administration but have been reported. Most cases demonstrate urticaria. One case of angioedema with bronchospasm after extravasation requiring systemic administration of epinephrine and Benadryl was reported in a patient with asthma.[34]

The videos below further illustrate the procedure of hysterosalpingogram:

The goals of pharmacotherapy are to provide local analgesia and prevent infections.

Class Summary

Local anesthetics are used for local pain relief.

Lidocaine (Xylocaine)

Lidocaine is an amide local anesthetic used in 1% concentration. Administration of 10 mL of 1% lidocaine injected into the uterine cavity before the contrast may reduce delayed pain. The 1% preparation contains 10 mg of lidocaine for each 1 mL of solution; Lidocaine inhibits depolarization of type-C sensory neurons by blocking sodium channels.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. The American College of Obstetricians and Gynecologists recommends empiric treatment for women with a history of pelvic infection or when hydrosalpinx is diagnosed at the time of the study.

Doxycycline (Doryx, Adoxa, Ocudox, Vibramycin, Oraxyl)

Doxycycline is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. It is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.

Doxycycline inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly the 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. A common and effective regimen is 100 mg orally twice daily for 5 days.

Class Summary

Ultrasonograph with contrast imaging may be considered to detect fallopian tube patency. 

Air polymer type A (ExEm Foam)

Intrauterine foam is formed by mixing the clear (polymer type A [hydroxyethyl cellulose], glycerin, purified water) with air and sterile purified water. When mixed, an echogenic contrast agent is created, that when visualized with ultrasound, the foam appears echogenic or bright within the fallopian tubes and peritoneal cavity. It is indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility.