Saline infusion sonohysterography

INTRODUCTION — Saline infusion sonohysterography refers to a procedure in which fluid is instilled into the uterine cavity transcervically to provide enhanced endometrial visualization during transvaginal ultrasound examination [1,2]. The technique improves sonographic detection of endometrial pathology, such as polyps, hyperplasia, cancer, leiomyomas, and adhesions. In addition, it can help avoid invasive diagnostic procedures in some patients as well as optimize the preoperative triage process for those women who require therapeutic intervention. It is easily and rapidly performed at minimal cost, well-tolerated by patients, and is virtually devoid of complications. The American College of Obstetricians and Gynecologists (ACOG), in conjunction with the American College of Radiology and the American Institute of Ultrasound in Medicine, developed a technology assessment document for saline infusion sonohysterography [3,4].

INDICATIONS — There are a number of situations where fluid enhanced endovaginal scanning will aid evaluation of the uterine cavity. The American Institute for Ultrasound in Medicine's standard indications and contraindications to this procedure are shown in the table (table 1).

Unscheduled uterine bleeding — Unexpected uterine bleeding accounts for a large proportion of gynecologic patient visits. Endometrial biopsy and/or office hysteroscopy are often used as initial diagnostic procedures; in hospital dilation and curettage is no longer considered an appropriate initial diagnostic test in most women [5].

Transvaginal ultrasound is used increasingly as an initial triage for patients with abnormal uterine bleeding. Sonohysterography is a subset of transvaginal sonography that is used when it is difficult to visualize the endometrium or the endometrium is thickened.

Sonohysterography is particularly useful for finding focal endometrial abnormalities or confirming that a focal abnormality diagnosed by transabdominal or transvaginal ultrasound is present and better defining the nature of the abnormality [6,7]. As an example, one study performed both transvaginal ultrasonographic examination and sonohysterography on 106 patients with menometrorrhagia [8]. The sensitivity and specificity of saline infusion sonohysterography for detection of polyps were significantly higher than for transvaginal ultrasound alone (93 and 94 versus 75 and 76 percent for transvaginal sonography) and were comparable to hysteroscopy, a finding confirmed by others [9-12].

In addition, a prospective series of 214 consecutive pre- and postmenopausal women with abnormal uterine bleeding and a suspected uterine abnormality on transvaginal sonography found an initial approach of sonohysterography followed by hysteroscopy, if needed for diagnosis or therapy, was preferable to routinely proceeding to diagnostic hysteroscopy because the latter could be avoided in 84 percent of patients (sonohysterography was conclusive in 180 of 214 women) [13]. Although some women subsequently underwent operative hysteroscopy for treatment of uterine abnormalities, an initial approach using diagnostic non-office-based hysteroscopy under conditions allowing operative hysteroscopy if needed was also deemed unsatisfactory because preparation for the combined procedure requires general or regional anesthesia, despite the knowledge that a significant portion of women will have no anatomic abnormality and will not have a surgical intervention.

In addition, sonohysterography can help to reliably distinguish between:

●Premenopausal women with anovulatory bleeding, which is best treated hormonally, from those with an anatomic lesion, which may require tissue sampling for histologic diagnosis and/or resection for treatment [14]. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis".)

●Postmenopausal women with bleeding due to atrophy, the most common cause of bleeding in this age group, from those with anatomic lesions that might require tissue sampling to exclude carcinoma or for treatment. (See "Approach to the patient with postmenopausal uterine bleeding".)

●Patients with focal abnormalities best biopsied under direct hysteroscopic visualization from those with global abnormalities that can be sampled blindly [6].

Women with abnormal uterine bleeding in whom endometrial sampling is indicated should have saline instillation sonohysterography or office hysteroscopy prior to the sampling procedure. Blind sampling procedures are justified if an abnormality is symmetrically "pan uterine." When focal lesions (eg, polyps, fibroids, some hyperplasias, some carcinomas) are detected, then directed biopsies are preferable.

Infertility — Endometrial assessment is part of the routine evaluation of infertility and recurrent pregnancy loss (see "Overview of infertility" and "Recurrent pregnancy loss: Evaluation"). Saline infusion sonohysterography is useful for detecting potential anatomic causes of reduced fertility, such as submucous myomas, endometrial polyps, anomalies, and intrauterine adhesions and appears comparable to or better than hysterosalpingography (HSG) or hysteroscopy [1,2,15-18].

However, an outline of the fallopian tubes (as seen with HSG) is not observed with sonohysterography. Accretion of instilled fluid in the posterior cul-de-sac is a sign of patency of at least one tube.

Hysterosalpingo–contrast sonography (HyCoSy) — HyCoSy is a variation of sonohysterography that is mainly used to determine tubal patency in patients desiring pregnancy and confirm tubal occlusion after sterilization procedures [18,19]. Contraindications for HyCoSy are similar to those of traditional sonohysterography. For the procedure, sterile saline mixed with air, contrast, or foam is manually injected into the cervix, uterus, and fallopian tubes while observing with real-time ultrasound imaging [19-21]. Commercial devices that mix air and saline together to form the air-infused saline available; similar results can be achieved by filling a 30 mL syringe with half saline and half air and then rocking the syringe up and down while pushing the plunger to infuse air with saline. Use of a balloon catheter can reduce fluid backflow during the procedure.

Tamoxifen-induced changes — Tamoxifen, a potent antiestrogen, is being used extensively as adjunctive chemotherapy in women with estrogen receptor-positive breast cancer. Some patients taking tamoxifen, when viewed with endovaginal ultrasound, will display thickened central uterine echoes. These changes are sometimes polyps or abnormal endometrial tissue (proliferative, hyperplasia, or even cancer). However, sonohysterography has shown that these changes can often represent microcysts of the basalis of the endometrium or proximal myometrium that develop due to reactivation of focal adenomyosis [22]. Thus, sonohysterography can help to define suspected endometrial abnormalities noted on transvaginal ultrasound examination and avoid tissue sampling (image 1A-B and picture 1) [23-25].

Routine sonographic screening of the endometrium of asymptomatic women taking Tamoxifen has not been recommended by the American College of Obstetricians and Gynecologists (ACOG) [26]. This is a controversial area; some investigators have proposed that patients embarking on tamoxifen therapy should have pretreatment screening to determine if they have underlying endometrial abnormalities, such as polyps or endometrial hyperplasia, which place them at high risk of developing into or progressing to atypical hyperplasia. Such patients warrant ongoing periodic surveillance, which is best accomplished by transvaginal ultrasound and then sonohysterography if the endometrial echo is not adequately seen or not reliably thin [27]. Low risk patients could be followed according to the ACOG guidelines, which are briefly described above and in detail elsewhere.  

TECHNIQUE — The examination is typically scheduled early in the follicular phase of the cycle, after menstrual flow has ceased and before day 10, as the endometrium is very thin at this point in the cycle. Later in the cycle, focal irregularities in the contour of the endometrium may be mistaken for small polyps or focal areas of endometrial hyperplasia (image 2). One prospective blinded study reported a 27 percent false-positive rate in sonohysterography performed from day 16 to 28, but no false-positive when the procedure was performed prior to day 10 [28]. Sometimes the patient has such irregular bleeding that she cannot tell what is an actual menses. In such cases, it can be helpful to use an empiric course of a progestin, such as medroxyprogesterone acetate 10 mg daily for 10 days, to create a "medical curettage" and then time the ultrasound evaluation to the withdrawal bleed.

Anesthesia or analgesia is not required as the intrauterine insemination catheter is relatively painless while being inserted [29]. The procedure is well tolerated by the overwhelming majority of patients; a few experience minimal cramping.

A bimanual examination may be performed initially to determine the position and mobility of the uterus, although the initial transvaginal sonography can usually determine the degree of anteversion or retroversion, if present. The speculum is inserted and the cervix cleansed with a 10 percent iodine-based solution in patients who do not have an iodine allergy. A variety of commercially available sonohysterography catheters can be utilized. Most of these have similar efficacy but vary in small design elements [30]. Insertion can be with ring forceps, using a spear-like motion (for less flexible catheters), or with an internal stylet. To prevent run back of fluid, some employ an acorn-like device, and others have a balloon.

The catheter should be flushed with sterile saline or water prior to insertion to rid it of small amounts of air, which would cause an echogenic artifactual appearance. The catheter is inserted to the fundus by grasping the catheter with a ring forceps and gently feeding it through the cervical os. The speculum is then removed carefully to avoid dislodging the catheter. The catheter will still extend beyond the introitus when positioned in the uterus.

The vaginal probe is then reinserted and a syringe filled with sterile fluid rid of air bubbles is attached to the catheter. Fluid is instilled while the transducer is moved from side to side (cornua to cornua) in a long axis projection. The amount of instilled fluid will vary, depending upon the image produced on the ultrasound monitor.

After the uterus has been completely surveyed from cornua to cornua in a long-axis projection, the transducer is rotated 90 degrees into a coronal plane. More fluid is instilled while fanning down towards the endocervical canal and up towards the uterine fundus to recreate three-dimensional anatomy. Every portion of the uterine cavity should be imaged, because polyps, hyperplasia, or carcinomas may be focal. A reliable assessment requires that the endometrial echo be homogeneous, surrounded by an intact hypoechoic junctional zone, and that the operator constantly remember that the endometrial cavity is a three-dimensional structure. Failure to meticulously recreate three dimensional anatomy will result in error.

Three-dimensional ultrasound equipment will eliminate error that may occur if the operator does not pay meticulous attention to mentally recreating three dimensional anatomy. It usually requires a balloon catheter to prevent run back of fluid and results in increased patient cramping and discomfort. A prospective study showed no advantage of three-dimension sonohysterography over two-dimensional [31], although both types had significantly better sensitivity and specificity than ultrasound without fluid enhancement.

Some initial reports utilizing a hydroxyethyl cellulose gel containing anesthetic and antiseptic agents have proposed this as an alternative to saline or water. This may allow stable filling of the cavity without continuous injection [32].

FINDINGS — A normal sonohysterogram is shown for comparison with the abnormalities below (image 3).

Polyp — The typical sonohysterographic appearance of an endometrial polyp is a well-defined, homogeneous, polypoid lesion isoechoic to the endometrium with preservation of the endometrial-myometrial interface [33]. Atypical features include cystic components, multiple polyps, broad base, and hypoechogenicity or heterogeneity. Transvaginal sonograms before and after saline infusion in a patient with abnormal uterine bleeding due to an endometrial polyp are provided (image 4A-B). In a meta-analysis of 25 studies comparing saline infusion sonohysterography with 2D transvaginal sonography, saline infusion studies had significantly greater sensitivity for the detection of endometrial polyps (92 versus 55 percent) while the specificity was similar for the two modalities (93 versus 91 percent) [34].

The use of color flow or power Doppler for identifying the central feeder vessel pathognomonic of an endometrial polyp is an alternative to sonohysterography in the diagnosis of polyps (image 5). In one study, this techniques had a positive predictive value of 81.3 percent [35].

Leiomyoma — Submucosal fibroids are usually well-defined, broad-based, hypoechoic, solid masses with shadowing [33]. The overlying layer of endometrium is echogenic and distorts the endometrial-myometrial interface. Atypical features include pedunculation or a multilobulated surface. Sonohysterography's major benefit over transvaginal ultrasound alone is that it more accurately shows how much of the fibroid projects into the endometrial cavity (image 6A-B) [33,36]. In a meta-analysis of five studies, the pooled sensitivity and specificity of 2D saline infusion sonohysterography for the detection of submucosal leiomyomas were 94 percent (95% CI 89-97 percent) and 81 percent (95% CI 76-86 percent) [37].

Hyperplasia and cancer — Endometrial hyperplasia usually appears as diffuse echogenic endometrial thickening without focal abnormality, although focal lesions can occur (image 7A-B and picture 2) [33]. Endometrial cancer is typically a diffuse process, but early cases can be focal and can appear as a polypoid mass.

Adhesions — Adhesions usually appear as mobile, thin, echogenic bands that cut across the endometrial cavity [33]. Less commonly, they are thick, broad-based bands or completely obliterate the endometrial cavity (Asherman syndrome).

Adenomyosis — Some studies have observed communication between the endometrial cavity and adenomyotic lesions during saline infusion sonohysterography [38]. These were saline-filled defects extending from the endometrial cavity into the myometrium. Other experts claim that this entity is not adenomyotic, but rather represents a different process which has been named "endometrial-subendometrial myometrium unit disruption disease" and may have an influence on fertility and outcome of assisted reproductive techniques [39].

Endometrial assessment after non-resectoscopic endometrial ablation — Non-resectoscopic endometrial ablation has become a popular alternative to hysterectomy for treatment of heavy menstrual bleeding. When patients who have undergone this type of procedure subsequently have abnormal premenopausal bleeding or postmenopausal bleeding, routine methods of endometrial evaluation are often suboptimal, including sonohysterography [40].

TECHNICAL CONCERNS

Difficulty passing the catheter — Occasionally, it will be difficult to thread the flexible catheter into place because of cervical stenosis, uterine position, or abnormal uterine contour. Changing the toe of the speculum by moving the handle up or down may change the angle of the cervix with the fundus and will often allow successful insertion of the catheter. A catheter with a stylet or one made of less flexible material also can be useful. A cervical stabilizer rather than a standard tenaculum is another acceptable option. Medical or mechanical dilation may be necessary in some women.

Poor visualization — Saline infusion sonohysterography, unlike hysteroscopy, does not require distension of the uterine cavity. Even a small ribbon of sonolucent fluid will allow good visualization of endometrial contents on either side of the fluid. However, women with a patulous cervix may not retain even the small amount of fluid needed to visualize the endometrium. Sometimes there is excessive leakage of fluid out the fallopian tubes. Slow injection of fluid using minimal pressure can sometimes overcome these problems.

Infection — The risk of upper genital tract infection is similar to that with hysteroscopy or traditional hysterosalpingogram [41,42]. Obtaining appropriate cultures and prescribing prophylactic antibiotics depend upon the patient's risk factors and clinician preference. Risk factors for pelvic infection include women with multiple partners, having a partner with dysuria or urethral discharge, young age, and previous sexually transmitted disease or pelvic inflammatory disease. Routine use of prophylactic antibiotics is not warranted [43].

Dissemination of carcinoma — Concerns regarding the dissemination of malignant cells during saline infusion sonohysterography have been addressed in various studies [44]. In one study [45], 14 women with known endometrial cancer underwent sonohysterography in the operating room prior to their surgical hysterectomy and staging procedure. In cell washings, malignant cells could be identified in only 1/14 (7 percent) of cases.

In another similar study [46], 32 women with known carcinoma had sonohysterography in the operating room during their surgery. The fluid that spilled from the fallopian tubes was collected. Malignant cells were identified in only 2/32 (6 percent). (See "Overview of the evaluation of the endometrium for malignant or premalignant disease", section on 'Risk of tumor dissemination'.)

False-positive findings — False-positive findings (ie, suspected pathology not confirmed by hysteroscopy) have been attributed to blood clots, intrauterine debris, mucus plugs, shearing of normal endometrium, thickened endometrial folds, and misidentified endometrial fragments [47,48].

SIDE EFFECTS AND COMPLICATIONS — Procedure-related side effects and complications are mild and uncommon. A prospective study of 1153 women age 23 to 64 years undergoing saline infusion sonohysterography reported the following: failure to complete the procedure (7 percent), pelvic pain (3.8 percent), vagal symptoms (3.5 percent), nausea (1 percent), and postprocedure fever (0.8 percent) [49]. In patients who failed to complete the procedure, a second attempt on another day was always successful when these issues were addressed (eg, use of dilators for cervical stenosis, analgesia/local anesthesia for patients with significant discomfort).

Although a small proportion of women find sonohysterography painful, it is less painful than office hysteroscopy [50].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Female infertility".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Abnormal uterine bleeding (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Saline infusion sonohysterography is a procedure in which fluid is instilled into the uterine cavity transcervically to provide enhanced endometrial visualization during transvaginal ultrasound examination. (See 'Introduction' above.)

●Indications – Common indications include abnormal uterine bleeding, suspected uterine cavity abnormalities (including congenital anomalies), and infertility (table 1). Contraindications include pregnancy and active pelvic infection. (See 'Indications' above.)

●Technique – The examination is scheduled when the endometrium will be as thin as possible from the last day or two of staining until three to four days after the bleeding has ended. Anesthesia or analgesia is generally not required. Prior to insertion, the catheter is flushed with sterile saline or water prior to get rid of small amounts of air that could result in visual artifact. The vaginal probe is then inserted, a syringe filled with sterile fluid without air bubbles is attached to the catheter, and fluid is instilled while the transducer is moved from side to side (cornua to cornua) in a long axis projection. (See 'Technique' above.)

●Infection risk – The risk of upper genital tract infection is similar to that with a traditional hysterosalpingogram. Whether cultures are obtained and prophylactic antibiotics prescribed depends upon the patient's risk factors and clinician preference. (See 'Infection' above.)

●False-positive findings – False-positive findings have been attributed to blood clots, intrauterine debris, mucus plugs, shearing of normal endometrium, thickened endometrial folds, and misidentified endometrial fragments. (See 'False-positive findings' above.)

●Side effects – Procedure-related side effects and complications are mild and uncommon. (See 'Side effects and complications' above.)