Transvaginal Sonography in Gynecologic Infertility




KEY TERMS



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Key Terms




  1. Infertility: the inability to conceive after 1 year of unprotected intercourse.



  2. IVF (in vitro fertilization): a medical procedure involving ovulation induction, guided follicular aspiration, and in vitro (on glass) fertilization of eggs and subsequent transfer of embryo(s) into uterine lumen cavity.



  3. Ovarian hyperstimulation syndrome (OHSS): a group of symptoms which include signs and symptoms associated with ovarian enlargement, ascites, fluid shifts, and possible electrolytic imbalance precipitated by ovulation induction.





INTRODUCTION



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Infertility, the inability of a couple to achieve pregnancy with unprotected intercourse for 1 year, affects approximately 10% to 15% of couples in the United States and is increasing in incidence. The evaluation and treatment of infertility has undergone dramatic advances in the recent decade. Concurrently, transvaginal sonography (TVS) has a vital role in the evaluation and management of (sub-)/infertility as well as for a variety of gynecologic disorders.1,2 Transvaginal ultrasound has revolutionized how infertility specialists manage their patients over the last three decades.



Specifically, TVS has its greatest clinical applications in the baseline evaluations of the pelvic organ as well as follicular monitoring and guided follicular oocyte aspiration. Transabdominal sonography (TAS) and TVS are utilized for in guiding embryo transfers and in the initial evaluation of infertility. The initial evaluation of infertility consists of the assessment of pelvic organs, uterine cavity, and tubal patency. The baseline pelvic sonogram identifies any existing pathology, such as fibroids, congenital uterine anomalies, uterine adhesions, and adnexal masses of ovarian or tubal etiologies (ie, endometriomas, dermoids, other neoplasms, hydrosalpinges) that may impact fertility. Additionally, this baseline evaluation has become very helpful in determining the ovarian reserve for infertility counseling and for guiding the ovulation induction dosing. Sonography with the instillation of fluid into the uterus (saline hysterosonography) can determine the presence of uterine filling defects and can assess tubal patency. Follow-up of disorders that may be related to infertility, such as endometriosis, fibroids, and ovarian cysts, can be monitored with TVS. This chapter emphasizes the most frequently used applications and, in particular, stresses the role of transvaginal transducer/probes.




INSTRUMENTATION



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Transvaginal sonography is the method of choice for initial evaluation of the uterus and ovaries in most patients. TVS is typically performed with the bladder empty; in fact, a full bladder pushes the gynecologic structures away from view and may distort the anatomy. The transvaginal transducer/probe allows a detailed depiction of the uterus and ovaries because of the proximity of these structures to the vaginally placed transducer. In contrast to transabdominal scanning, transvaginal scanning displays images in nonconventional imaging planes. One limitation of transvaginal scanning is the focal length of the probe; the regions of interest are typically within this limitation of approximately 6 to 10 cm from the probe. In TVS, surrounding bowel loops usually are not interposed between the probe and the adnexa. If they are, gentle manual abdominal palpation or manipulation of the probe, or both, can be used to displace adjacent bowel. Additionally, this technique can be used as an extension of the pelvic exam and may be termed as an “ultrasound-guided pelvic examination.” This approach can help delineate whether adhesions are present between the uterus and the ovaries. The ovary should be mobile and free from the uterus. If it moves freely, it is referred to as “the sliding organ” sign. However, if the ovary is in contact with the uterus and abdominal palpation performed during the TVS does not move the ovary, then the ovary is likely adherent to the uterus. Sometimes this technique causes some mild discomfort for the patient if adhesions are present. Similarly, this technique may be useful to determine if a mass is separate from the ovary or uterus (ie, tubal pregnancy or pedunculated fibroid or bowel). This technique is referred to as the “sliding organ sign” for any structure that moves freely past the ovary or uterus.



Appendix 39-1 lists the equipment and documentation guidelines as well as the procedural parameters recommended by the American Institute of Ultrasound (AIUM) for performance of TVS in infertility patients. There are several types of transvaginal transducer/probes available, including curved linear array, phased array, and mechanical sector. The field of view of most of these probes is 100 degrees. The curved liner array probes afford a large sector field of view. Phased array probes may have resolution problems in the lateral aspects of the image due to side lobe artifacts. Color and Power Doppler capabilities have been added to most transvaginal scanners. The addition of color Doppler sonography (CDS) does not significantly increase the thermal intensities (TIs) used for imaging in most cases, but paying attention to TI and the mechanical index (MI) in early pregnancy is important. CDS reveals vascular patterns. CDS affords specific selection of the vessels and areas to be interrogated by pulsed Doppler techniques. Flow can be assessed by waveform analysis, which reveals relative impedance to flow, and by overall assessment of the color shown in the area of the uterus, which is related to the relative vessel density of a particular area. Vascular patterns have been more informative than wave form analysis in assessing pathology within the uterus and ovaries. Three-dimensional (3D) sonography is increasingly available on transvaginal ultrasound probes. 3D sonography is useful in the assessment of uterine malformations, fibroid mapping, Essure placement, and as an adjunct to sonohysterograms (SHG). SonoAVC (automated volumetric count) is a newer technique used to measure ovarian follicles using a color-coded inversion 3D ultrasound method during a single acquisition. Other applications are under investigation.




CLINICAL ASPECTS AND INDICATIONS



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As previously noted, infertility is defined as the inability to conceive after 1 year of unprotected intercourse, and it affects approximately 10% to 15% of couples in the United States. Approximately 80% of couples who are between 18 and 28 years of age will conceive during a 1-year period, and another 10% will conceive the following year, leaving 10% of couples in the United States (~2.4 million couples) with an infertility disorder. The breakdown of etiologies of infertility is 40% to 66% female factors; 33% to 40% male factors, and 15% unexplained. About 25% of couples have multiple factors. The most common gynecologic disorders related to infertility include occlusive tubal disease or endometriosis (30%-50%), ovulation disorders (40%), and uterine and cervical factors (10%).3 In 10% to 15% of cases the cause of infertility is unexplained.3,4



The initial evaluation of infertility includes an evaluation of each of these factors.5,6 After the medical histories of the couple are reviewed and the physical examination is done, the testing usually includes a semen analysis, some evidence of ovulation via an ovulation predictor kit (OPK) or mid-luteal progesterone level, an assessment of the uterine cavity and tubal patency (traditionally by hysterosalpingogram [HSG]), and hormonal evaluation (thyroid-stimulating hormone [TSH], prolactin, and sometimes gonadotropins). In the early 1990s, this initial evaluation also included diagnostic laparoscopy to evaluate the pelvis for endometriosis and pelvic adhesions. The prevalence of these disorders is high in infertility (30%-50%). However, with the improvement in sonographic technology and with more effective treatments (such as ovulation induction with gonadotropins and in vitro fertilization [IVF]), the diagnostic laparoscopy has dropped out of the initial infertility evaluation unless there is a medical indication (pelvic pain, adnexal mass, etc).



Sonography has taken a greater role in both the evaluation and treatment of infertility. The most common indications for sonography in infertility include:





  1. Baseline pelvic sonography




    1. Rule out adnexal and uterine pathology



    2. Assessment of ovarian reserve



  2. Saline-infused sonohysterography (SIS)




    1. Assessment of the uterus



    2. Assessment of the endometrium and uterine cavity



    3. Saline sonosalpingography (SSS): Assessment of tubal patency



  3. Serial monitoring of follicular development during ovulation induction treatment



  4. Assessment of endometrial development7



  5. Guided follicular oocyte aspiration



  6. Guided embryo transfer8



  7. Confirmation of intrauterine pregnancy (discussed further in Chapters 3 and 4)




3D sonography is helpful in diagnosing congenital uterine malformations and in evaluating the location of intrauterine masses during the baseline sonogram.9 For greatest accuracy with a noninvasive sonographic technique, 3D sonography is best performed in the luteal phase when the endometrium, which is more hyperechoic than the myometrium, can act as an endogenous contrast. Additionally, a saline or sterile water infusion SHG can be performed with 3D sonography to aid in the mapping of identified intrauterine abnormalities in the early follicular phase. Recently, a new technological advance with 3D sonography was introduced by General Electric (GE), called “SonoAVC” (sonographic automatic volume calculation). It is a method of using 3D sonography with inversion mode imaging and additional software, to automatically measure all follicles within the ovary within a few moments and color code the results for easy reference to the measurements. This technology is currently available, and a newer version called SonoAVC has just became available. This technology may reduce the time to measure follicles and may more accurately measure follicular volumes from day to day during stimulation, but it is too new to determine the impact on infertility centers, or whether this technology will really improve pregnancy outcomes.



CDS affords physiologic assessment of the ovaries and endometrium. Lack of the typical low-impedance, high diastolic flow within a corpus luteum, coupled with poor uterine or endometrial perfusion, may suggest luteal phase inadequacy.10 When endometrial abnormalities are noted on gray scale or on SHG, CDS may be able to identify a polyp or fibroid with its vascular pattern. CDS may also be helpful in the assessment of tubal patency because it is quite sensitive to the flow created when saline or contrast is injected through the tube.11



Spontaneous Cycles



To better comprehend the value of the baseline sonogram in infertility, an understanding of the physiology of natural, spontaneous cycles is essential. At the time of birth, the female neonate is estimated to have approximately 2 million primary oocytes within each ovary. When menarche begins, approximately 200,000 oocytes remain per ovary. During the child-bearing years, approximately 200 oocytes will be ovulated. This indicates that approximately 99.9% of primary oocytes become atretic or do not develop at all. Maturation of the oocyte and follicle is responsive primarily to circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and circulating levels of estradiol (E2). Small (<5-8 mm) follicles may grow within the ovary but remain small until there is gonadotropin signaling. With the cascade of events initiated by pulsatile release of FSH in the late secretory phase just before the onset of a period, a cohort of follicles develop. Typically, one follicle, sometimes two, becomes dominant by the midcycle, and the others regress. Estradiol is synthesized by the granulosa cells and provides important feedback to the pituitary impacting the production of FSH and LH. Elevated estradiol levels are thought to be part of the signaling process to trigger the LH surge. The surge of LH reinitiates meiosis of the oocyte, and ovulation typically occurs within 36 to 40 hours of this “surge” in circulating LH levels. After ovulation, the remaining follicle becomes a corpus luteum.



From the ultrasound perspective, the ovary tends to have a number of small follicles visible on TVS. The ovary develops a cohort of small (3-5 mm) follicles each month, and there are usually one or two follicles that develop beyond 10 mm in size, and are now gonadtrophic sensitive in the spontaneous cycle and continues to grow. As the follicle matures, it enlarges an average of 1.5 to 2 mm in diameter per day by two-dimensional ultrasound (2DUS) due to more fluid collecting in its center in association with an accumulation of granulosa cells lining the inside wall of the follicle. The oocyte itself, which is smaller than 0.1 mm, is surrounded by a cluster of granulosa cells. This complex is termed the cumulus oophorus. It measures approximately 1 mm and can be depicted occasionally inside mature follicles (Figures 39-1D and 39-2B). As the follicle reaches maturity, its inner dimensions range from 17 to 25 mm.12 Intrafollicular echoes may be observed within mature follicles, probably rising from clusters of granulosa cells that shear off the wall near the time of ovulation. After ovulation, the follicular wall becomes irregular as the follicle becomes “deflated.” The fresh corpus luteum usually appears as an echogenic structure usually smaller than the ovulatory follicle, but may vary. With the development of a corpus luteum, there is an immediate increase in vascularity within the ovarian cyst wall that can be observed on TV-CDS; some describe it as a “ring of fire.” Occasionally, the corpus luteum refills with serum and can look similar to a nonovulated follicle on grayscale, or fills with varying degrees of clotted blood, which can look unusual and may be quite large or painful.




Figure 39-1.


Normal folliculogenesis. A: Transvaginal sonogram (TVS) of the right ovary depicting a mature follicle (arrow) in a spontaneous cycle. B: Transvaginal sonogram of early corpus luteum (between +’s) containing low-level echoes, probably rising from hemorrhage within the corpus luteum. C: Transvaginal sonogram showing free intraperitoneal fluid (*) secondary to ovulation. D: Detailed TVS depiction of a mature follicle (between cursors). The cumulus oophorus is also seen in the posterior wall. E: Transvaginal color Doppler sonogram of the left ovary in the early follicular phase showing high-impedance flow within an intraovarian arteriole. F: Transvaginal color Doppler sonogram of a functioning corpus luteum showing low-impedance high-velocity flow.











Figure 39-2.


Follicular monitoring in induced cycles. A: Transvaginal sonogram of multiple follicles in various developmental stages in a patient undergoing ovulation induction with gonadotropins. B: Magnified transvaginal sonogram in a patient undergoing clomiphene citrate ovulation induction. Along the edge of the follicle, denoted by cursors, the cumulus can be identified (arrowhead).






On TV-CDS, folliculogenesis can be assessed by changes in impedance and velocity in intraovarian arterioles, and on 3D CDS and power Doppler with the percentage of volume showing a flow signal (VFS) and the perifollicular vascular network.13 With formation of a corpus luteum, impedance drops, a reflection of the vascular arcade that develops within the wall of the corpus luteum.



In addition to the readily identifiable sonographic changes in ovarian follicle size, morphology, and blood flow, the presence of intraperitoneal fluid can also be depicted on TVS (see Figure 39-1C) as well as endometrial morphology and thickness changes (Figure 39-3). It is not uncommon to have approximately 1 to 3 mL in the cul-de-sac before ovulation. After ovulation, there is typically between 4 and 5 mL within the cul-de-sac. This fluid is usually absorbed within a couple days. When the patient is scanned with a fully distended bladder, the fluid may be located outside the cul-de-sac, surrounding bowel loops in the lower abdomen, and upper pelvis. Although it is informative to learn about the sonographic changes of the natural or spontaneous cycle, it is not cost-effective to regularly monitor natural cycles on a daily or every other day basis to confirm ovulation or to time an intrauterine insemination treatment. TVS may be used more cost-effectively as an adjunct to OPKs with natural cycles, particularly when there is ambiguity in the OPK result.




Figure 39-3.


Endometrial changes. A: Transvaginal sonogram demonstrating isoechoic endometrium (arrowhead) in follicular phase. B: Multilayered endometrium (arrowhead) depicted on the long axis by transvaginal sonography. The multiple layers indicate a periovulatory endometrium. C: Transvaginal sonogram of echogenic secretory phase endometrium (between +’s). D: Diagram of the uterine arterial tree. The arcuate arterioles branch into radials, which course across the myometrium ending in the spiral arteries within the endometrium. E: Transvaginal color Doppler sonogram of arcuate artery flow at day 10. F: Same patient as in (E) showing the adnexal branch of the uterine artery. Note the area of flow within the myometrium.











ENDOMETRIAL ASSESSMENT



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Besides the factors involved in obtaining a mature ovum, the developmental state of the endometrium may also be a factor that influences the probability that conception will occur (see Figure 39-3).14 Because the endometrium can be delineated on scans performed for follicular monitoring, several investigators have evaluated this specialized epithelial membrane in an attempt to study whether or not there is an optimal thickness or texture.15-18 Clearly, there is an association of the texture of the endometrium as depicted sonographically and the circulating levels of estrogen and progesterone.14 In spontaneous and induced cycles, the sonographic appearance of the endometrium differs according to its specific phases of menstrual cycle. At the end of menses, the endometrium appears as a thin, broken echogenic interface. In the early proliferative phase, it thickens to 3 to 5 mm and then becomes trilaminar as it progressively increases in anterior–posterior width. This trilaminar pattern is thought to represent the relatively orderly organization of the glandular elements within the endometrium.



As ovulation approaches, the endometrium becomes more echogenic and thickens, probably related to development of secretions within the endometrial glands and the numerous interfaces that arise from distended and tortuous glands. A trilaminar appearance is typically described as the pattern in the late proliferative phase near ovulation with a typical maximal thickness ranging from 6 to 15 mm. This pattern is described as a hypoechoic area within the most central portion of the endometrium, probably within the compactum layer with a hyperechoic line at the periphery and centrally. This finding has been described as a means of confirming ovulation has occurred. With TVS, however, we have observed this finding both before and immediately after ovulation. During the secretory phase, the endometrium becomes uniformly hyperechoic and maintains a maximal thickness (between 6 and 12 mm). Stromal edema also causes the endometrium to become more echogenic during the luteal phase. In addition to the echogenic endometrium, a hypoechoic band beneath the endometrium may be identified, probably arising from the inner layer of the myometrium.



The fact that medications used for ovulation induction may alter the development of the endometrium has been shown by both sonographic and histologic studies.16 The relative importance of these changes to the success or failure of achieving pregnancy is only speculative, however.17,18 Other studies have indicated that the texture of the endometrium during the proliferative phase may be related to the success or failure of pregnancy. Specifically, the presence of a multilayered endometrium around ovulation to within 1 to 2 days of embryo transfer was associated with a high postovulatory conception; yet, an endometrium too thin (<6 or <4 mm) around ovulation is associated with lower pregnancy rates.19,20



CDS has shown that uterine blood flow can also predict pregnancy attainment.21 In one study, pregnancies did not occur in women with high-impedance (pulsatility index >3.0) uterine flow. Others have shown decreased pregnancy rates when intraendometrial spiral arterioles were not seen.22 3D ultrasonographic endometrial volumes and vascular patterns may be important in the future to assess endometrial receptivity.23




BASELINE SONOGRAPHY FOR INFERTILITY



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Given the aforementioned 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 early follicular time period, such as around cycle day 2 or 3, because it is the most likely time for the ovary to be quiescent (no large follicles or cysts) and thus, 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. A baseline ultrasound done in the presence of a dominant follicle or cyst may result in a slightly lower antral follicle count in this same ovary, and one needs to realize that the ovarian reserve is as good as or better than the antral follicle count during this time. This approach may be more convenient for the patient than separate visits. Although insurance billing currently allows for billing of both an evaluation and management visit and a sonographic procedural visit with modifier 59, reimbursement is lower than if these were done on separate days. A sonogram done at the time of the first visit may be thought of as an extension of the physical exam using the sliding organ test to determine if the ovary moves separately from the uterus and evaluating the ovarian reserve. 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 a little more information regarding the ovarian reserve, since there should not be a dominant follicle.



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 as well as 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. Alternatively, 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. 3D ultrasound may be helpful in showing where these fibroids are located within the uterus.



Sonography can identify the presence of polycystic ovaries (PCOs) and adnexal masses, such as endometriomas, dermoids, hydrosalpinges, and tubo-ovarian abscesses that may be associated with gynecologic infertility (Figure 39-4). Follow-up sonograms may be used to document the progression or regression of endometriomas, ovarian cysts, 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.




Figure 39-4.


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 TVS shows enlarged and rounded ovaries containing multiple immature, subcapsular follicles and increased amounts of stroma, then this pattern is called the “pearl necklace sign” and is suggestive of polycystic-appearing ovaries. The ESHRE/ASRM consensus guideline was the first time that ultrasound was included as one of the criteria for diagnosing PCO. “PCO-appearing ovaries” on ultrasound was defined as more than 12 follicles in one or both ovaries that are 2 to 9 mm in size without the presence of cyst larger than 10 mm or an ovarian volume greater than 10 cm3. Polycystic ovary syndrome (PCOS) as described by the Rotterdam criteria consists of identifying two of three diagnostic criteria: (1) anovulation or amenorrhea, (2) evidence of hyperandrogenism by clinical or laboratory criteria, and (3) 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 More recently, this ultrasound criteria was called into question because over 50% of young women met this PCO-appearing ovary criteria with the more advanced technological equipment.28 A taskforce was developed from the Androgen Excess and PCOS, and they evaluated the literature. The recommendations from this committee have changed, and they now recommend that the follicle number per ovary (FNPO) be counted. The criteria used to define PCOS is a follicle count per ovary of less than 25 in women 18 to 35 years old when using a transvaginal probe with less than 8 mHz.28 This number (>25) best distinguishes PCO from normal young ovaries. If a transvaginal ultrasound cannot be performed, then the ovarian volume (still 10 mL) is the next best metric.



In up to 30% of women with PCO, the ovaries may not be abnormally enlarged.24,29 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.30 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). 3D ultrasound with inversion may also help visualize the tube and related morphologic disorders.



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. Ideally, the idea of a test for ovarian reserve assessment is to identify women who will get pregnant with treatment from those who will not. However, the ovarian reserve tests are more likely to distinguish those who would respond to therapy from those who are unlikely to respond to ovulation induction 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. Nor is there an ovarian reserve test that predicts pregnancy. However, we typically use these ovarian reserve laboratory tests and sonographic results to assist in counseling couples regarding their likelihood of response to treatment with a good likelihood of having an IVF egg retrieval and not be canceled due to poor response. 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. In the past, we used a dynamic test, called the clomiphene citrate challenge test (CCCT). This has been replaced by the anti-Mullerian hormone (AMH) level, which is not cycle-specific and can be drawn at any time. Other laboratory criteria have essentially fallen by the wayside. Inhibins were used in research but not used clinically.



The sonographic criteria for ovarian reserve testing consists of an assessment of ovarian volume and/or the number of basal antral follicles.31 The ovarian volume may be obtained with either 2D or 3D sonography. The ovarian volume is done in the early follicular time period (ie, around cycle day 2 or 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 (making it a lower number) and make it less meaningful; there are divergent opinions on this issue. 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 three to five 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 39-5). Transvaginal CDS may be helpful to confirm the presence of small follicles and later of a dominant follicle.32,33 CDS and 3D 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.34 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 grayscale may be detectable by their characteristic rim of vascularity, also referred to as the “ring of fire” (see Figure 39-1F).35




Figure 39-5.


Assessment of tubal patency with transvaginal sonography. A: Transvaginal color Doppler sonogram showing flow of both tubes indicative of bilateral tubal patency. (Used with permission from 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.36 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 3D 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.37 Stronger directional endometrial peristalsis may be associated with a higher implantation rate.38



Infertility Assessment with Sonohysterography



Traditionally, the infertility evaluation includes the evaluation of the uterine cavity and tubes with an HSG, which is a radiologic test where iodinated contrast material is injected into the uterine cavity during fluoroscopy and x-rays are obtained (Figure 39-6). 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 and is best 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 SHG (or SIS for saline infusion sonohysterogram), unlike with HSG.




Figure 39-6.


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 used with permission from 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). (Used with permission from 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. Three-dimensional 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 or a nonelectrical morcelator (ie, Truclear or Myosure), 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 or SSS) 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. SHG 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. The 3D ultrasound is similar in diagnostic accuracy to MRI. 2DUS has a low accuracy rate in detecting congenital uterine anomalies.



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).39,40 More recently, 3D-SHG with contrast agents have been compared with x-ray HSG, and 3D-SHG also outperformed HSG in assessing the uterine cavity.41



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.



Tubal Patency Assessment



TVS 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 they 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.42 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.43,44 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 investigators45 have compared transvaginal sonosalpingography (TVSS, SSG, or SSS) 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%). TVSS 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.

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Jan 12, 2019 | Posted by in GYNECOLOGY | Comments Off on Transvaginal Sonography in Gynecologic Infertility

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