Given the above information regarding the natural changes of the pelvis during a cycle, one can get much information during the baseline evaluation. Many infertility specialists recommend doing the baseline evaluation during the initial follicular time period, such as around cycle day 3 because it is the most informative regarding the ovarian reserve. However, if one understands the basic physiology of the menstrual cycle and its corresponding sonographic changes, a baseline sonogram can be meaningful at any time the patient comes into the office for the initial evaluation of infertility. This approach may be more convenient for the patient than separate visits. Yet, insurance billing currently does not allow for separate billing of evaluation and management visits and sonographic procedural visits on the same day with the same diagnosis code. So at this time, a sonogram done at the time of the first visit may be done and thought of as an extension of the physical exam; it can be very informative for counseling, but not billed separately unless there is a separate indication for the procedure. The cycle day 3 sonogram may provide more information regarding the ovarian reserve, which is important for counseling and guiding treatment.
The components of the baseline sonogram for infertility are very similar to the components of a pelvic sonogram done at any time. The important components are to identify, measure, and describe the uterus and ovaries and any pathologic findings. The uterus tends to be very sensitive to estrogen. So an individual who presents with amenorrhea, whose sonogram shows a smaller uterus with a thin endometrial echo and small ovarian volumes, is suggestive of premature ovarian failure or other hypoestrogenic state. The sonogram of the uterus may reveal an abnormal shape or separate endometrial echoes on a transverse view of the uterus, and the addition of 3D sonography may confirm a uterine anomaly, such as a bicornuate or septate uterus. More commonly, fibroids may be detected within the uterus or distorting the uterine cavity, which may impact fertility and miscarriage rates, and cause other pregnancy complications.
Sonography can identify the presence of polycystic ovaries and adnexal masses, such as endometriomas, dermoids, hydrosalpinges, and tubo-ovarian abscesses that may be associated with gynecologic infertility (Figure 37-4). Follow-up sonograms may be used to document the progression or regression of endometriomas, ovarian cysts, or postsurgical recovery or recovery after drainage of an abscess.24 Most cases of endometriosis consist of milder states that have mainly endometriotic implants that are small (approximately 5 mm or less) and are attached to parietal peritoneum or the serosal surfaces of bowel or other intraabdominal/pelvic organs or ligaments. These small lesions may not be detectable on sonography. Larger ones that are located separate from bowel can be delineated and followed during and after treatment.25 Endometriosis may invaginate into the ovary and cause the formation of endometriomas. Endometriomas can be seen with sonography and diagnosed sonographically with about 90% accuracy when the classic sonographic findings of low-level echoes throughout the ovarian cyst and smooth borders are present.26 The presence of an endometrioma automatically classifies the patient at stage 3 or higher on the American Society of Reproductive Medicine (ASRM) endometriosis classification system. This stage is associated with moderate endometriosis and is thought to have a significant impact on fertility.
Other conditions associated with infertility. A: Transvaginal sonogram demonstrating a complex cystic mass (arrow) superior to a mature follicle. This was found to represent an endometrioma. B: A simple hydrosalpinx of the left uterine tube (arrow). C: Transvaginal sonogram of a polycystic ovary showing multiple immature follicles along the periphery of this enlarged ovary. D, E: Transvaginal color Doppler sonogram of the right (D) and left (E) ovaries of a patient with polycystic ovaries. High-impedance flow is present in both ovaries.
If the TVS shows enlarged and rounded ovaries containing multiple immature, subcapsular follicles and increased amounts of stroma, then this pattern is suggestive of polycystic-appearing ovaries. Many sonologists use the Rotterdam criteria of more than 12 follicles in one or both ovaries that are less than 10 mm in size, or an ovarian volume greater than 10 cm3 to make the sonographic diagnosis of "polycystic-appearing ovaries." The polycystic ovary syndrome (PCOS) as described by the Rotterdam criteria consists of identifying 2 of 3 diagnostic criteria (anovulation or amenorrhea, evidence of hyperandrogenism by clinical or laboratory criteria, and sonographic findings consistent with polycystic-appearing ovaries) after ruling out other clinical scenarios that may have a similar appearance (thyroid disease, adrenal disorders, etc).27 In up to 30% of women with this disorder, the ovaries may not be abnormally enlarged.24,28 In these cases, it is also important to look at the endometrium. Patients with chronic anovulation, as in PCOS, are at increased risk of endometrial cancer. So if the endometrial echo is unusually thick, one needs to consider a further evaluation of the patient with an endometrial biopsy or hysteroscopy/dilation and curettage to obtain a sample for histology.
Dermoids, simple cysts, and paraovarian/paratubal cysts are very common in women of reproductive age. Occasionally, there is a more tubular cyst that may initially appear to be in the ovary. However, as one performs the TVS, changing position or changing pressure of the transvaginal probe or adding some abdominal pressure while TVS scanning, this tubular structure may appear separate from the ovary. One needs to consider whether a hydrosalpinx is present. Often the hydrosalpinx may have a tubular hypoechoic shape, incomplete septa, or "cogwheel" appearance that helps in making the diagnosis.29 Hydrosalpinges imply occluded or diseased tubes that may be the cause of the couple's infertility and may put them at increased risk for ectopic pregnancy if conception occurs on their own (with a partially open tube) or with assisted reproductive technology (ART).
The infertility sonographic evaluation not only includes an assessment of normal or pathologic findings within the pelvis, but also a close assessment of the ovaries and a count of the antral follicles in each ovary.
Ovarian Reserve Assessment
As women age their ability to conceive decreases; the idea of a test for ovarian reserve assessment is to identify women who are unlikely to respond to therapy prior to starting treatment. There is no test available to date that can quantify the number of oocytes that a woman has remaining in the ovaries. However, there are several laboratory tests and sonographic criteria that can help in counseling couples regarding their likelihood of success. The most common laboratory evaluations consist of a cycle day 3 FSH level with or without an estradiol level. A high FSH and/or estradiol level around cycle day 3 is a poor test result and represents a likely poor response to fertility therapy. A more dynamic laboratory evaluation is a clomiphene challenge test. This test evaluates the FSH on cycle days 3 and 10 and the patient takes two 50-mg tablets of clomiphene citrate on cycle days 5 to 9. Typically, the 2 FSH values are added together and the cutoff value of this sum is determined by each laboratory. The cutoff value is the value above which no pregnancies have occurred. Other laboratory criteria are also being used either separately or together to determine the ovarian reserve, and these consist of inhibin B and anti-müllerian hormone.
The sonographic criteria for ovarian reserve testing consists of an assessment of ovarian volume and/or the number of basal antral follicles.30 The ovarian volume may be obtained with either two-dimensional (2D) or 3D sonography. The ovarian volume is done in the early follicular time period (ie, around cycle day 3) to avoid the presence of an ovarian cyst, which would interfere with the results. A basal antral follicle count consists of the number of follicles in each ovary under the size of 10 mm. Some suggest that the presence of a follicle or cyst larger than 10 mm may impact this basal antral follicle count and make it less meaningful; others disagree. This antral follicle number does vary from cycle to cycle within women, but not significantly in most cases. The antral follicle count is done early in the menstrual cycle and can be predictive of therapeutic success. Typically, basal antral follicle counts under 3 to 5 bode poorly with treatment and those over 10 do well. However, the numbers in between tend to be less predictable. There appears to be a clear relationship between the decreased ovarian volume and antral follicle counts and advancing age and increasing cycle day 3 FSH levels. However, there are other factors that may affect the ovarian volume such as hormonal contraceptives, smoking, etc. CDS may also be helpful in predicting follicular response.
Applications of Color Doppler Sonography
TV-CDS can provide information regarding the flow within the ovary, uterus, and endometrium, as well as its use in assessment of the uterine cavity and tubal patency (Figure 37-5). Transvaginal CDS may be helpful to confirm the presence of small follicles and later of a dominant follicle.31,32 CDS and 3S power Doppler may be used to assess vascular patterns of growing or dominant follicles.13 Another study reported that CDS could be used in the early follicular time period (cycle day 2 or 3) to assess ovarian reserve or follicular response to ovulation stimulation. This group reported on the correlation of the mean ovarian stromal peak systolic blood flow velocity with follicular response and IVF aspirated egg count, but not pregnancy outcome.33 Lower velocities correlated with fewer follicles and, conversely, higher velocities with a higher number of follicles. Later in the cycle, transvaginal CDS can confirm the functionality of a corpus luteum by demonstrating characteristic low-impedance, high diastolic flow in vessels within its walls. In fact, corpora lutea that may not be apparent on gray scale may be detectable by their characteristic rim of vascularity, also referred to as the "ring of fire" (see Figure 37-1F).34
Assessment of tubal patency with transvaginal sonography. A: Transvaginal color Doppler sonogram showing flow of both tubes indicative of bilateral tubal patency. (Courtesy of R. Schief, MD.) B: Transvaginal sonogram showing no intraperitoneal "spill." The injected fluid and the balloon fill the lumen. A mature follicle is present within the right ovary.
Uterine blood flow can also be assessed with TV-CDS. It has been shown that higher impedance of uterine flow has a high association with infertility.35 Transvaginal CDS of some equipment can assess vascularity within the endometrium. The presence of flow within the endometrium, which represents the spiral vessels, is a good sign that the endometrium is primed for implantation.22 Three-dimensional endometrial volumes are reproducible from cycle to cycle, and the endometrial vascular parameters and patterns may provide information regarding endometrial receptivity.23
Another recently observed parameter that may have clinical significance is the depiction of "endometrial peristalsis" on TVS. This is particularly well seen if the examination is recorded on videotape and played back at fast forward. Endometrial peristalsis is directed toward the cervix during menses, but toward the fundus during the periovulatory period.36 Stronger directional endometrial peristalsis may be associated with a higher implantation rate.37
Infertility Assessment with Sonohysterography
Typically, the next evaluation for infertility has been the hysterosalpingogram (HSG), which is a radiologic test where iodinated contrast material is injected into the uterine cavity during fluoroscopy and x-rays are obtained (Figure 37-6). The HSG shows the contrast material within the uterine cavity and within the tubal canals and spilling into the peritoneal cavity when the result is normal. The HSG is done during cycle days 6 to 12, right after the menses is completed and prior to ovulation, to avoid early radiation exposure to an unsuspected pregnancy and to better evaluate the uterine cavity when the endometrial tissue is not too thick. TVS with saline infusion or sterile water infused into the uterine cavity can provide the same type of evaluation, without the radiation exposure. In addition, any filling defect detected during this procedure can typically be diagnosed with sonohysterography (SHG), unlike with HSG.
Sonohysterography (SHG) in infertility. A: Diagram of SHG using balloon-tipped catheter. The balloon is filled with saline and then retracted into the distal internal cervical os to prohibit reflux and obtain maximal distention. (Drawing by Paul Gross, MS.) B: Sonohysterography shows multiple polyps. C: Hysteroscopic view of multiple polyps seen in (B). D: Sonohysterography showing adhesion appearing as echogenic interface crossing the lumen. E: Hysteroscopic view of adhesion in patient in (D). (Courtesy of Esther Eisenberg, MD) F: Initial transvaginal sonogram of patient before SHG. The endometrium (between cursors) is slightly irregular in this patient who has a history of several miscarriages. G: After saline distention, there is mild irregularity of the endometrium in the fundus. H: Same patient as in (F) and (G), with more distention confirming slightly in the irregular fundal endometrium. I: Hysteroscopic images of patient in (F-H), showing "heaped up" endometrium fundal area. J: Sonohysterography showing a submucosal fibroid (between cursors). K: Hysteroscopic view of patient in (J) showing submucosal fibroid. L: Sonohysterography showing double lumina of bicornuate uterus. 3D US would be helpful in distinguishing a bicornuate from a septated uterus. Note the fundal cleft. M: Sonohysterography in an infertility patient showing a fundal polyp. N, O: Transvaginal color Doppler sonogram of patient in (M) showing vascular pedicle of the polyp in long (N) and short (O) axes.
Some of the surgically correctable causes of infertility include intrauterine adhesions (synechiae), submucosal fibroids, and polyps. Each of these is detectable using SHG. Adhesions differ, from echogenic to hypoechoic. On SHG they appear as interfaces that course between endometrial layers. Some have a free edge. Submucosal fibroids may extend into the lumen and displace the overlying endometrium. These can be removed by wire loop resection if they do not extend into the outer layers of myometrium. Polyps may create a hostile environment for implantation and should usually be removed.
We advocate the use of SHG followed by sonosalpingography (SSG) for the evaluation of most infertility patients. The SHG portion evaluates the uterine lumen, and the SSG assesses the tubes (further discussion of tubal patency is in the next section). A bulbed/balloon-ended catheter or catheter with an acorn is recommended to block fluid from exiting out the cervix. This type of reflux would be detrimental to obtaining maximal distention of the endometrial lumen and subsequent evaluation of the tube. SHG is important in the assessment of the uterine cavity for filling defects and for the evaluation of uterine anomalies. Sonohysterography provides anatomic information concerning the relation of the lumen to the surrounding myometrium. Bicornuate uteri can often be distinguished from septated ones by delineation of the fundus. If there is a fundal cleft, bicornuate is more likely than septated uterus. This feature is particularly well delineated using 3D sonography, since the 3D allows for depiction of the fundus in the coronal plane.
In studies where SHG, HSG, and hysteroscopy are compared, SHG is more accurate in identifying the presence, size, and location of uterine filling defects as well as diagnosing the defect (polyp, fibroid, adhesion, etc).38,39 More recently 3D sonohysterograms (3D-SHG) with contrast agents have been compared with x-ray HSG, and 3D-SHG also outperformed HSG in assessing the uterine cavity.40
Additionally, intrauterine filling defects found on HSG or on SHG can be identified with the help of TV-CDS. A round filling defect that appears to be of similar echogenicity as the endometrium is likely to be a polyp. And TV-CDS may show the presence of a single vessel going to the center of this endometrial protrusion, confirming a polyp. Occasionally, one may find multiple vessels pushed to the side in a finding like this, making the diagnosis more likely to be a fibroid. Typically, fibroids are more hypoechoic than endometrium and exhibit shadowing, but these findings are not highly specific and the TV-CDS aids in the appropriate diagnosis.
Transvaginal sonography has been used to detect intraperitoneal spillage of saline or contrast injected into the uterus and tubes. These techniques currently are performed at select centers, and with time will likely be more widely performed. Some have used a specific contrast material consisting of a suspension of galactose monosaccharide microparticles (Echovist, Schering, Berlin, Germany; not US Food and Drug Administration [FDA] approved in the United States) and CDS as a means to assess tubal patency. The advantage of this technique includes avoidance of radiation, the potential to conduct the procedure in the gynecologist's office, and high tolerance by the patient. One study showed that sonographic evaluation of the tube was less painful than standard hysterosalpingography.41 Patency of at least one tube can be inferred when there is spillage into the cul-de-sac, whereas tubal obstruction may result in the filling of the uterine lumen without spillage. Often cramping is more prevalent in the latter situation.
In the last few years there has been great interest in the evaluation of tubal patency by sonographic methods. The first reported studies assessed tubal patency with transabdominal sonographic methods.42,43 When they observed the collection of instilled fluid in the cul-de-sac, the investigators indirectly concluded that one of the fallopian tubes or both were patent. More recently, other investigators44 have compared transvaginal sonosalpingography (TVSS) with chromopertubation by laparoscopy in patients with unknown tubal function. In their study, TVSS and laparoscopy were completely consistent in 29 cases (76.3%) and partially consistent in 8 cases (21.05%). Transvaginal sonosalpingography accurately showed patency in 26 patients and bilateral nonpatency in 3 patients. Thus, they concluded that TVSS is a safe and accurate screening and diagnostic technique in the evaluation of tubal patency.
Other investigators have used pulsed-wave (PW) Doppler to improve the sensitivity to flow through the tube after injected fluid.45 They used transvaginal hysterosalpingocontrast sonography (THCS). They administered SH U 454 (Echovist) transcervically, then performed a THCS, and followed up with either chromopertubation with laparoscopy or hysterosalpingography. The diagnostic efficacies of gray-scale and PW Doppler were then compared with each other and against one of the conventional control procedures. Deichert et al45 concluded that PW Doppler in THCS is recommended as a supplement to gray-scale imaging in cases of suspected tubal occlusion and if there is intratubal flow demonstrable only over a short distance.
Color Doppler and power Doppler have been studied to assess tubal patency. Stern et al46 compared the results of color Doppler (CD) sonographic hysterosalpingography (US-HSG) and x-ray–HSG with chromopertubation at the time of laparoscopy. Saline was administered transcervically during TV-CDS in 238 women. Traditional x-ray–HSG was performed in 89 women, and laparoscopy and chromopertubation in 121 women. Forty-nine women had all 3 procedures performed. Correlation between CD US-HSG and x-ray findings with chromopertubation occurred in 81% versus 60% (P < .001) of all women studied. In the 49 women who had all 3 procedures, CD US-HSG results correlated with chromopertubation more often than x-ray–HSG (82% vs 57%; P < .05). Thus, color Doppler US-HSG appears to be an efficacious method of establishing fallopian tube patency in patients with infertility. Sladkevicius et al and Kiyokawa et al have evaluated the use of 3D sonography with contrast or power Doppler imaging to assess tubal patency and found advantages. Three-dimensional power Doppler imaging (3D-PDI) was compared with contrast SHG (using hysterosalpingo-contrast [HyCoSy]) for tubal patency. Color-coded 3D-PDI with surface rendering enabled the visualization of the entire length of the fallopian tube and documented free spill in most cases.40,47 Advantages of this approach include that it can be performed in an outpatient setting, and it has high patient acceptance and no radiation exposure.
Future infertility therapeutic approaches that may involve TVS include early tubal screening in the diagnosis of infertility, visualization and documentation of transcervical tuboplasties, and gamete or embryo tubal transfers following transvaginal ultrasound-guided ova retrievals.