First-Trimester Ultrasound: A Comprehensive Guide

2. Ultrasound and Infertility

Sana N. Khan1 and Elizabeth E. Puscheck 

(1)

Department of Obstetrics and Gynecology, Wayne State University, 275 E Hancock Street, Detroit, MI 48201, USA

(2)

Department of Obstetrics and Gynecology, Hutzel Women’s Hospital, 3990 John R. Street, Box 158, Detroit, MI 48201, USA

Elizabeth E. Puscheck

Email: EPuschec@med.wayne.edu

Keywords

InfertilitySubfertilityUltrasoundEndovaginal or transvaginal sonographyAntral follicle count (AFC)Follicular monitoringUltrasound guided oocyte retrievalUltrasound guided embryo transferSaline infusion sonohysterogramSaline sonosalpingogram (SSS, a new term to describe an ultrasound tubal patency test)3D ultrasonographyCongenital uterine anomalies

Infertility is a growing problem in the USA and worldwide. In the developed world, approximately 12–40 % of the population reports infertility or subfertility, while one in every four couples in the developing world is affected by infertility [13]. In the USA, from 2006 to 2010, approximately 7.4 million women, aged 15–44, utilized some infertility service [4]. Typically, an infertility evaluation is performed after 1 year of unprotected intercourse, for women under the age of 35 and after 6 months, for women at or older than age 35. The traditional infertility evaluation included a history and physical exam, hysterosalpingogram (HSG), semen analysis, and laboratory evaluation (TSH, prolactin, early follicular FSH, LH, and estradiol level, and a mid-luteal progesterone level).

Over the last 30 years, ultrasound has transformed the practice of reproductive endocrinology and has become central to any infertility evaluation and treatment. In the late 1980s, the endovaginal or transvaginal sonography was developed, which utilized a higher frequency probe than transabdominal probes. This probe placed vaginally is in close proximity to pelvic organs, resulting in much improved resolution, based on the inverse relationship between the sound frequency of the probe with improved resolution and the shorter depth of penetration of sound waves. In other words, higher frequency probes (such as 6–9 MHz recommended for transvaginal probes) allow for better resolution of nearer objects (such as the uterus and ovaries), but have a shorter depth of penetration. In most cases, this is sufficient to evaluate the ovaries, often found in the posterior cul de sac [56]. Infrequently, the ovaries are located high and outside of the pelvis; in which case, a transabdominal probe (typically 2–5 MHz) may be necessary to locate the ovaries, or to assess the large fibroid uterus. Based on the above foundations, the transvaginal probe ultrasounds have become the preferred modality to examine pelvic structures, over all other imaging modalities. Ultrasound does have limitations: ultrasound cannot transmit sound waves through very dense fibroids, and the position of the uterus in certain planes may also limit visualization. Furthermore, ultrasound examination may be limited by body habitus, such as in obese patients in transabdominal sonography; however a transvaginal approach may have less limitation in visualization.

Ultrasound is used regularly in the evaluation, monitoring, and treatment of the infertile couple. In the female patient, ultrasound is used for the initial workup, which includes a baseline ultrasound to evaluate the uterus, ovaries and general pelvic anatomy and an HSG or a saline infusion sonohysterogram (SIS)/sonosalpingogram (SSS) assessment of the uterine cavity and tubes for patency. This evaluation is usually performed in the beginning of the menstrual cycle (cycle day 1–3), when the endometrium is expected to be thin and the ovaries should be relatively quiescent, according to the Rotterdam criteria [5].

Baseline Evaluation

A systematic approach to ultrasound of the pelvis begins with a complete sweep through the pelvis from one side to the other side, visualizing the cervix, uterus, ovaries, adnexae, and cul-de-sac, to ensure that no part of the exam has been omitted. The exam commences during the placement of the endovaginal probe in the vagina, and the bladder is initially evaluated. The bladder is optimally empty during pelvic examination, but if not, the bladder should be inspected for any abnormalities and then ask the patient to empty her bladder.

Uterus

Initial evaluation of the uterus begins with identifying the cervix at the end of the vagina and just below the bladder. The cervix should be examined for any pathology or defects (i.e., Nabothian cysts). In pregnant women, we recommend measuring the cervical length from the external os to the internal os (the junction of the endometrium) (Fig. 2.1). The cervical orientation can be helpful in directing the examiner to the rest of the uterus and help identify its location and position.

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Fig. 2.1

Cervix measurement

The baseline evaluation of the uterine body traditionally includes several features, comprising the overall size in standard dimensions of the uterus (length, height, width), position, the consistency of the endometrium, as well as any defects of the uterus or other pathology. The uterus is typically measured in the mid-sagittal plane for the longitudinal length and the height, measured in the anterior–posterior (AP) diameter (Fig. 2.2a). The length extends from the end of the cervix (external cervical os) to the top of the fundus. The transverse measurement of the uterus is also measured in the mid-corpus (see Fig. 2.2b). Additionally, the endovaginal ultrasound probe can be used as an extension of a pelvic examination to assess cornual tenderness, as well as a sliding organ sign, to show the movement of the ovaries in relation to the uterus, to establish fixed areas or adhesive disease [7]. Therefore, it is not only the images captured during the ultrasound, but much more information that can be gathered during the process of active sonography.

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Fig. 2.2

Uterus measurements. (a) Longitudinal (1) and anterior-posterior (2) measurements for length and height. (b) Transverse view, 1 = width. The endometrium is thickened, consistent with the luteal phase. The arrows indicate the presence of a C-section scar

The size of the uterus corresponds well to the overall estrogenation of the body, with lower and normal/elevated estrogen values correlating with smaller and larger uterine size, respectively. The assumption that smaller uteri may be associated with adverse pregnancy outcomes is erroneous; in fact, larger uteri were more highly associated with ectopic pregnancies in IVF/ICSI cycles [8]. The position of the uterus is also routinely recorded as a dynamic measurement. This information is important for procedures such as embryo transfer, which is subsequently discussed; furthermore, if the uterus is noted to remain motionless on serial exams, the concern is raised for adhesive disease or an entrapped uterus [9].

The uterine evaluation may reveal factors that contribute to infertility or result in early pregnancy loss. Common uterine abnormalities include polyps, fibroids, intrauterine adhesions, cesarean section scars, and congenital uterine anomalies. Submucosal fibroids (Fig. 2.3a) may affect early reproductive outcomes, by impairing blood flow to the endometrium/myometrium, resulting in failed implantation and pregnancy loss. Surgical correction of these defects has been found to improve pregnancy outcomes. In contrast, intramural fibroids (see Fig. 2.3b) may also increase pregnancy loss, but surgical correction does not reduce the loss rate [10]. Some fibroids may grow large enough to impact the tubal ostia, making the passage of gametes into and out of the fallopian tube more difficult [11].

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Fig. 2.3

Fibroids. (a) Intramural. (b) Subserosal

The endometrium is known to be a dynamic endocrine organ, which prepares itself and receives the developing embryo. Therefore, the endometrium is an important focus of the evaluation and treatment of the infertile patient. The overall thickness of the endometrium, when measured across the AP diameter, is correlated with the overall estrogenization of the pelvic organs. The endometrial lining is expected to be very thin during the initial part of the menstrual cycle, when estrogen levels are at a nadir, and is noted to increase around the time of ovulation and into the luteal phase, when the lining thickens in preparation of implantation (see Fig. 2.2b). Pathologies of the endometrium are known to affect reproductive outcomes, and are evaluated during the baseline examination. Intracavitary adhesions may be noted by an irregular or thin endometrium. Conversely, the presence of a thickened endometrial lining, on baseline ultrasound, may indicate a polyp or other defect is present within the endometrial cavity, which may need further evaluation to understand its impact on fertility. The thickness of the endometrium can be an indirect indicator of anovulation and possibly hyperplasia.

The ultrasound echo pattern of the endometrium is typically noted and followed during a treatment cycle. In the follicular phase, the endometrium grows in thickness and has a trilaminar appearance (Fig. 2.4). After ovulation, the endometrium becomes uniformly hyperechoic in this luteal phase portion of the menstrual cycle. These patterns have not correlated with pregnancy outcomes but this is often used as a part of the clinical assessment.

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Fig. 2.4

Proliferative endometrium with trilaminar appearance

The presence of endometrial glands and stroma located within the myometrium is termed, adenomyosis. Adenomyosis is known to be clinically associated with dysmenorrhea, abnormal uterine bleeding and pelvic pain [12]. Adenomyosis is traditionally diagnosed histologically; however, several ultrasonographic features are thought to indicate the presence of adenomyosis (Fig. 2.5). These include cystic areas in the myometrium as well as increased vascularity along the periphery of the uterine body [13]. These findings have been described as “venetian blinds” secondary to the shadowing produced by these defects on structures further from the ultrasound probe [14]. In addition, one can demonstrate asymmetry of the anterior and posterior aspects (in relation to the endometrium) of the myometrium. New information suggests that the presence of adenomyosis decreases reproductive outcomes after infertility treatment such as in vitro fertilization (IVF). Therefore, some sources are recommending sonographic screening for adenomyosis in the subfertile population [15].

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Fig. 2.5

Adenomyosis

Ultrasound is used to rule out any suspicion of congenital abnormality of the uterus. Congenital uterine anomalies require 3D ultrasound or MRI to make the diagnosis, since the coronal surface of the uterus must be evaluated along with the endometrial cavity to distinguish between an arcuate uterus, a septate or subseptate uterus (Fig. 2.6), and a bicornuate uterus [16]. The luteal phase is the best time to perform a 3D ultrasound to assess for a congenital uterine anomaly since the endometrium will be thickened and hyperechoic and thus will act as its own contrast material [16].

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Fig. 2.6

Congenital uterine anomaly: subseptate uterus with a pregnancy in one horn

Ovaries

As part of the baseline ultrasound evaluation, both ovaries are identified, measured in three dimensions, their position described (especially if located high out of the pelvis or posterior to the uterus) and the number of follicles (2–9 mm) in each ovary is counted (Fig. 2.7a, b). Any ovarian cysts or masses are described and further evaluation of these cysts/masses is performed with color or power Doppler.

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Fig. 2.7

Ovaries. (a) Longitudinal view in parallel with iliac vessels. 1 = length; 2 = height. (b) Transverse view with iliac vessel in transverse view (circle) with ovary width (3)

The iliac vessels are used as a guide to find the ovaries and to determine the measurements. The length of the ovary is parallel to the length of the iliac vessel and the height is perpendicular to these measurements (see Fig. 2.7). Next, an orthogonal view of the same organ is performed, resulting in a transverse view of the iliac vessel (circle) with the ovary above it. The width of the ovary is measured in this transverse view. The ovarian volume can be determined using a modified ellipsoid formula or a 3D volume. The ovarian size can be diminished by hormonal contraceptives, smoking, menopause (including premature menopause), radiation, among other disorders. A large ovarian volume (>10 cm3) is one of the measurements associated with a polycystic ovary appearance (Fig. 2.8) [6]. As expected, ovaries with cysts or masses will measure larger than normal.

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Fig. 2.8

A polycystic ovary (PCO). Several follicles are demonstrated in the organ. Periphery and the total volume of the ovary is increased above 10 cc

In the infertility population like all reproductive age women, ultrasound is most likely to identify benign ovarian pathology when an ovarian mass is present. Physiologic or simple cysts may be commonly visualized as follicular cysts, which are anechoic with no internal debris and usually round or potentially collapsed after ovulation (Fig. 2.9). These are thin-walled with posterior enhancement, and no internal color flow with Doppler ultrasound [17].

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Fig. 2.9

Simple ovarian cyst. No Doppler flow within the cyst

Other commonly visualized cysts include hemorrhagic corpus luteum cysts, endometriomas, and mature teratomas. Hemorrhagic corpus luteum cysts can have several appearances from an initial simple cyst when the blood is still liquid to more complex cystic masses, as the blood organizes into clots, which gives the appearance of a reticular pattern of internal echoes (a lacy appearance, generally due to fibrin strands) and/or, lastly, a combination appearance (cystic and solid), with solid-appearing area with concave margins, no internal flow on color Doppler ultrasound, and fluid (Fig. 2.10a). Usually the ovarian wall around the cyst has circumferential Doppler flow (see Fig. 2.10b) [17].

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Fig. 2.10

(a) Hemorrhagic corpus luteum with solid and cystic components. (b) Hemorrhagic corpus luteum cysts. Internal echoes can be seen (organized clots, with reticular pattern due to fibrin strands). No internal flow is seen on color Doppler US but circumferential flow is clearly demonstrated (“ring of fire”)

The typical endometriomas have internal homogeneous low-level echoes, sometimes described as a “ground glass” appearance, and have no internal color Doppler flow, wall nodules, or other neoplastic features. In such masses, the additional features of multilocularity and/or tiny echogenic wall foci may occur (Fig. 2.11a, b) [17]. Small endometriomas often do not need intervention and have not been found to affect reproductive outcomes [1820].

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Fig. 2.11

(a) Endometrioma. (b) Endometrioma with atypical findings. The image shows the low-level echoes consistent with an endometrioma. The atypical features include the irregular borders and the hyperechoic small nodules

“Dermoids” as they are commonly known are mature cystic teratomas of the ovary, consisting of sebaceous material, hair, and teeth. The ultrasound appearances of dermoids consist of focal or diffuse hyperechoic components, hyperechoic lines and dots, and area of acoustic shadowing, with no internal flow with color Doppler ultrasound (Fig. 2.12) [17]. Some have a nodule with shadowing called Rotkitansky’s nodule. Color and/or power Doppler should be used to assess adnexal masses. No Doppler flow should be going into the dermoid or Rotkitansky’s nodule. All abnormal findings need to be monitored with serial ultrasounds [17].

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Fig. 2.12

Dermoid or mature teratoma. Courtesy of Leeber Cohen, MD

Other presentations to note include that of premature ovarian insufficiency patient, in whom the ovaries will be much smaller, consistent with menopausal patients and few or no antral follicles will be visualized. This finding helps establish the diagnosis, in a patient presenting with unexplained amenorrhea, and may help with fertility counseling.

Adnexa

Another critical component of the baseline ultrasound is to evaluate for any adnexal pathology. The most commonly encountered tubal findings are hydrosalpinx (Fig. 2.13a) and paratubal cysts or cysts of Morgagni. Both of these findings can be confused with a dominant follicle, instead of a diseased tube, and it is important that the provider performing the ultrasound clearly assesses the location of the pathology (in, versus adjacent to, the ovary) and view the pathology in three dimensions, to ensure that most information is gathered from the study (see Fig. 2.13b).

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Fig. 2.13

Hydosalpinx. (a) Large hydrosalpinx. (b) Hydosalpinx en face can be confused with a blood vessel

Miscellaneous

A variety of other findings are noted on the baseline ultrasound of the patient presenting with infertility. These may include free fluid around the ovaries or in the posterior cul-de-sac, as well as abnormalities in the bowel or surrounding structures. All abnormalities should be noted in the report.

Saline Infusion Sonohysterogram

During the initial workup of the infertile patient, in addition to the baseline ultrasound, one needs to perform an evaluation of the uterine cavity and an assessment of tubal patency. This information is critical in the decision of need and type of treatment offered to the patient.

The uterine cavity is best evaluated as soon as possible after the menses is completed and before ovulation (cycle days 6–12). This evaluation has traditionally been a radiographic procedure, called a hysterosalpingogram (HSG) in which contrast dye is injected through a cannula into the uterine cavity under fluoroscopic guidance and x-rays are taken. Ultrasound can be used with saline infusion to perform a similar procedure, called a saline infusion sonohysterogram (SIS). This SIS procedure is reported in several studies to be superior to the HSG in evaluating the uterine cavity [21]. Although similar information is gathered from an HSG, there is no radiation exposure during an SIS. Being able to perform and interpret the ultrasound exam in real time is a benefit of the SIS, and, unlike an HSG, this test may also reveal the diagnosis resulting in the abnormal filling defect (i.e., polyp, fibroid, adhesions). An SIS procedure is best performed in the early follicular phase after the cessation of menses, and after a baseline ultrasound has been performed.

During an SIS procedure, a patient is placed in lithotomy position, vagina and cervix are prepped, and then, typically, a small balloon or acorn catheter is placed into the cervix or endometrial cavity. If a balloon is used, this balloon is then inflated to create a seal, preventing liquid from escaping the uterine cavity through the cervix. Sterile saline is then injected and the uterine cavity is thoroughly examined in multiple planes, to detect any filling defects (Fig. 2.14a, b), such as polyps (Fig. 2.15) or submucosal fibroid (Fig. 2.16) [22]. SIS used with color or power Doppler cannot only identify a filling defect (as noted by HSG), but also can identify the nature of the defect (i.e., polyp, fibroid, adhesion, etc.). Other pathology, which can be detected, includes endometrial adhesions, also known as Asherman syndrome (Fig. 2.17). In a population of subfertile women, SIS has been shown to be a highly sensitive tool and comparable to the gold standard tool, hysteroscopy in the detection of intrauterine abnormalities [23]. The evaluation of the uterine cavity has traditionally been performed utilizing 2D ultrasonography, with the operator examining and sweeping through the cavity in sagittal and coronal planes, to evaluate the entire uterine cavity. Evidence, however, is now mounting regarding the use and possible superiority of 3D ultrasound for the assessment of the uterine cavity, which is discussed later in the chapter.

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Fig. 2.14

Saline infusion sonohysterogram (SIS). (a) Sagittal view showing the longitudinal axis of the uterus with fluid, which appears black in the uterine cavity. No intrauterine filling defects. (b) Transverse view of the uterus with fluid in the uterine cavity at the mid-uterine level

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Fig. 2.15

(a) SIS of the uterus revealing a sessile polyp which measured at approximately 1 cm. (b) 3D SIS with polyp

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Fig. 2.16

SIS with submucosal fibroid

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Fig. 2.17

SIS with intrauterine adhesions (Asherman syndrome)

If a uterine anomaly is suspected, three-dimensional sonography (3D ultrasound) is often required to confirm the diagnosis. 3D ultrasound is also helpful in identifying the location of any intrauterine pathologies or the placement of an intrauterine device.

A more controversial topic is the use of ultrasound with agitated saline, in a saline sonosalpingogram (SSS) to study tubal patency. This new term differentiates the assessment of the cavity (SIS) from the tubes (SSS). SSS may require a different skill levels to perform this examination.

Either preceding the evaluation of the uterine cavity or after, the fallopian tubes can be assessed. This is completed by the injection of agitated saline into the uterine cavity. Saline can be agitated either manually or by commercially available product. A new FDA-approved device, Femvue, can be used to detect tubal patency, through the mechanized installation of saline with bubbles into the cavity and fallopian tubes. Utilizing a transverse view of the uterine fundus near the cornua, agitated saline can be visualized with air bubbles traversing the proximal fallopian tubes. More specifically, the cornual portion of the uterus can be identifiable as a “lemon-appearing” transverse view of the uterus. It is often apparent to see a pencil thin line going from the endometrium into the proximal tube; however, if this is not observed, then the passage of the echogenic bubbles can be visualized traversing the cornua.

After both sides are examined, a thorough inspection of the pelvis ensues, either to detect a hydrosalpinx or to detect free fluid around one or both ovaries, or in the cul-de-sac. Of note, if agitated saline is not clearly visualized extruding through the uterine cornua, but free fluid was noted, at least unilateral tubal patency has been confirmed. Once the uterine cavity and fallopian tubes are assessed, the balloon is deflated and procedure terminated [22].

Besides the initial infertility workup, ultrasound is an integral part of infertility treatments: follicular monitoring, oocyte aspiration, and embryo transfers.

Follicular Monitoring Ultrasounds

Ultrasound is essential for the follicular monitoring of the infertile patient through their treatments. Low level, oral fertility treatments often do not require regular ultrasound monitoring. Midcycle sonographic confirmation of a dominant follicle, however, may be employed. Any treatments using gonadotropin injections for ovulation induction, or any form of in vitro fertilization (IVF) requires monitoring on a daily or every other day basis.

During the midcycle period, normally, the ovary produces a dominant follicle within cycle days 10–20. The goal of the infertility specialist is to time the intrauterine insemination at the time of ovulation, time ovulation trigger shot when the follicles are mature, or time the oocyte retrieval, so that the oocytes can be aspirated, prior to ovulation. This critical timing process depends on serial ultrasounds and the monitoring of the growth of ovarian follicles in the mid and late follicular phase. Most programs utilize 2D ultrasound. Newer software has been developed, however, to allow 3D image capture of the ovary and automated calculation of follicular volume through ovarian mapping, called SonoAVC [2425] (Fig. 2.18). Follicular monitoring revolves around the tenet that once recruited, a stimulated ovarian follicle is expected to grow by approximately 2 mm per day, as detected by ultrasound, until ovulation; therefore the frequency, timing, and reliable sonographic measurements from serial ultrasounds is extremely important. Ultrasound, additionally, offers a key advantage over hormonal monitoring alone, as many clinical situations introduce variability in the hormonal milieu, including perimenopausal patients and PCOS patients with high LH levels, which may obscure ovulation predictor kits [26].

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Fig. 2.18

(a) 2D view of a stimulated ovary with multiple follicles. (b) SonoAVC. Each follicle volume is automatically calculated and color coded corresponding to a table with measurements

Ultrasound in Assisted Reproductive Technology (ART) Procedures

Oocyte Retrieval

The invasive procedures associated with IVF include oocyte retrieval and embryo transfer procedures; both of which are routinely performed under ultrasound guidance.

The oocyte retrieval procedure relies on the tenet that stimulated ovaries will be larger and heavier and sink into the posterior cul-de-sac, where they can be easily visualized and reached with the use of an endovaginal probe. Historically, many other routes were attempted to retrieve oocytes, including laparoscopic, transurethral, and transvesical; the endovaginal approach, however, was found to be superior [2729].

The endovaginal probe is fitted with a needle guide, which is projected onto the screen, so that the tract of the needle can be easily visualized and trajectory planned. The ultrasound probe can then be placed in the vagina near the ovary, needle inserted through the needle guide and into the ovary, where each follicle is serially aspirated (Fig. 2.19). This procedure obviously relies on the technical ultrasound expertise of the operator. Care must be taken since many vessels lie in the area near the ovaries, and these vessels may be confused with ovarian follicles, when seen on end [2630]. Some studies suggest that Doppler ultrasonography may hold the promise of increased safety during the procedure [31].

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Fig. 2.19

Ultrasound image of oocyte retrieval. (a) Stimulated ovarian follicles with needle guide track. (b) Needle appears hyperechoic and is easily seen entering the mature follicle

Finally, multiple studies have demonstrated that for patients in whom the ovaries are located abnormally high and out of the pelvis, these oocytes can be retrieved abdominally using the endovaginal probe for visualization [3233].

Embryo Transfer

Embryo transfer was originally performed without ultrasound guidance. Multiple studies, however, demonstrated improved outcomes when ultrasound was systematically used to ensure that embryos were being placed in the uterus and not in false tracts [3436]. Since that time, the use of ultrasound guidance for embryo transfer has become routine. It is likely that the difference in pregnancy rates was secondary to those cases in which cervical abnormalities or uterine malposition was present, which increased the risk of non-endometrial embryo placement [37]. Thus, the importance of a skilled transabdominal sonographer is established in cases of difficult anatomy, to ensure that embryos can be placed in the uterine cavity additionally with minimal pain, bleeding or discomfort, all of which have been associated with uterine activity and lower pregnancy rates (Fig. 2.20a, b) [38].

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Fig. 2.20

(a) Abdominal ultrasound-guided embryo transfer with white spot correlating the air bubble that often accompanies the embryo and fluid at time of transfer. (b) Transvaginal outer catheter at the inner os and measurements to the top of the uterus and anticipated placement. (c) 3D rendered view showing white spot (arrow) corresponding to an air bubble that was released at the time of the embryo transfer

In the near future, we anticipate that embryo transfer will be performed with real-time 3D ultrasound (see Fig. 2.20c) (4D ultrasound). Utilization of real-time 3D ultrasound may allow for more definite and accurate placement of the embryo transfer catheter, compared to 2D ultrasound, thus potentially improving embryo transfer technique [3940]. Of debatable significance is the three-dimensional volume estimation of the endometrial cavity as a marker of endometrial receptivity [4142].

Some studies suggest that 3D ultrasound can play a more important role in all elements of the evaluation and management of the infertility population [4344].

Miscellaneous

It must also be mentioned that the ultrasound forms a mainstay for the evaluation and monitoring of complications from fertility treatments, mainly ovarian hyperstimulation syndrome (OHSS). OHSS is a hormonally mediated vascular permeability disorder (related to VEGF and β-hCG), which is caused by controlled ovarian stimulation fertility treatments [45]. The clinical features of the disorder include potentially massive third spacing of fluid in the peritoneal, pleural, and even the pericardial cavities. Abdominal, pelvic, and even thoracic sonography are used to assess the amount of fluid in the peritoneal and pleural cavities, as well as to follow the size of the ovaries, which tend to be grossly enlarged despite oocyte retrieval (Fig. 2.21) [4546]. On occasion, drainage procedures are necessary, which are in general performed under ultrasound guidance as a paracentesis or culdocentesis [46].

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Fig. 2.21

Ovarian hyperstimulation syndrome. The abdominal cavity has a large amount of fluid with the uterus and ovaries floating within the ascites

Three-Dimensional Ultrasonography

There are many emerging applications of 3D ultrasound, including the evaluation of the uterine cavity, study of congenital uterine anomalies, follicular volume calculation programs and for optimal embryo transfer location. A recent study found that 3D SIS correlated better with hysteroscopy, which is known to be the gold standard [47]. 3D SIS performed better than traditional 2D ultrasound for the detection of intrauterine abnormalities; however, further, larger-scale research endeavors are needed to confirm these findings [47]. Additionally, the use of 3D ultrasound shows extreme utility for the diagnosis of congenital Müllerian anomalies. Recent research suggests that 3D ultrasound is very accurate at diagnosing abnormalities, which were correlated with endoscopic findings [4851]. Furthermore, the agreement between 3D ultrasound and MRI findings was very high, indicating that 3D ultrasound may replace MRI for certain studies (such as diagnosis of congenital uterine anomalies or intrauterine device [IUD] localization), decreasing the cost and risk of radioactive contrast exposure [52].

Pregnancy and Recurrent Pregnancy Loss

Pregnancy determination is typically done about 12 days after the embryo transfer. When there is a positive pregnancy test, most infertility specialists will perform a second hCG level about 2 days later. If there is an appropriate rise, an ultrasound is typically scheduled at about 5.5–6.5 weeks, to confirm an intrauterine pregnancy (Fig. 2.22a, b). According to the American Congress of Obstetrics and Gynecology (ACOG), the estimated due date (EDD) should be determined based on the embryo transfer. If a day 3 embryo transfer is performed, the EDD is 263 days later [53]. If a day 5 embryo transfer is performed, the EDD is 261 days later. This is the most accurate dating available. Ultrasound should not re-date these pregnancies. Other chapters discuss early pregnancy findings. Our patients tend to be very anxious, therefore a CPT code (V23.0) exists for “pregnancy with a history of infertility,” which allows for more than the usual ultrasounds, to allay anxiety. The literature from recurrent pregnancy loss shows that “tender loving care” can improve pregnancy outcomes and these early ultrasounds are certainly reassuring. There are new terms and criteria regarding pregnancy loss and the determination of nonviable pregnancies [5455]. Infertility patients have about a 40 % incidence of threatened abortion presenting with vaginal bleeding. So these patients may present to the physician’s office or the emergency room. It is critical that the pregnancy is not terminated inappropriately, since these patients have worked so hard to conceive. Doubilet et al. recommends waiting until the crown-rump length is 7 mm or more without fetal heart motion prior to declaring it nonviable. Our patients are eager to see the gestational sac, the yolk sac and most importantly the fetal heart motion in the uterus! When the fetal heartbeat is demonstrated, the likelihood of miscarriage is reduced significantly and, typically, the patient is referred back to the obstetrician for routine pregnancy care.

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Fig. 2.22

(a) Early pregnancy with yolk sac. (b) 3D rendering of early pregnancy

Recurrent pregnancy loss is also relegated to the REI for evaluation and treatment. Spontaneous miscarriage in the general population occurs in about 15–25 % of pregnancies and increases with age, approaching 50 % for women over 40 years old. Recurrent pregnancy loss is defined as two or more losses. Fewer than 5 % of women will have two consecutive pregnancy losses and less than 1 % of women will have three or more. The American Society of Reproductive Medicine (ASRM) produced a committee opinion, reviewing the evidence, and recommends the following workup: genetic evaluation of the parents and products of conception (karyotypic abnormalities are the most common cause, 60 %), anatomic evaluation of the uterus (SIS or HSG), endocrine evaluation for thyroid and prolactin abnormalities, anti-phospholipid evaluation (lupus anticoagulant, anticardiolipin antibody, anti-beta 2 glycoprotein 1), and psychological counseling [56]. One study referenced in this ASRM document reported significant improvement with tender loving care (TLC) in the form of: psychological support, weekly ultrasounds, and avoidance of heavy work, travel, and sexual activity, as compared with the controls, which led to a pregnancy rate at 85 % for the intervention group and 36 % for the control group [57]. ASRM cautions regarding the interpretation, since the groups were not randomized, but determined based on nearness of the subjects’ residence. In couples completing an RPL evaluation, approximately 50 % will have no identifiable etiology for their miscarriages which are, thus, unexplained. It is important to emphasize that those with an unexplained etiology for recurrent pregnancy loss still have a 50–60 % chance of a future successful pregnancy.

Teaching Points

·               Ultrasound is a critical part of the infertility evaluation and treatment.

·               Traditional 2D ultrasound is used for the baseline evaluation of the uterus to evaluate uterine dimensions (3D if a uterine anomaly is suspected), ovarian dimensions and volume, ovarian antral follicle count (AFC), and any pelvic pathology.

·               Saline infusion sonohysterography (SIS) is an important tool for the evaluation of the endometrial cavity and is comparable to hysteroscopy for the detection and diagnosis of intrauterine abnormalities when used with 3D ultrasound.

·               Saline sonosalpingography (SSS) can be used to assess tubal patency by ultrasound using an agitated saline approach.

·               Three-dimensional sonography is a required modality to diagnose congenital uterine anomalies or Intrauterine device placements (or misplacements). It is also used in infertility specifically for better assessment of the endometrial cavity and localization of intrauterine pathologies during SIS.

·               Either 2D or 3D ultrasound is used for the monitoring of controlled ovarian stimulation to assess follicular growth and endometrial thickness.

·               Transvaginal sonography is a critical component for Assisted Reproductive Technologies (i.e., oocyte retrieval and embryo transfer).

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