A BRIEF HISTORY OF MEDICAL ULTRASOUNDThe Early DaysBased on sonar and related technologies, research on the use of ultrasound in medicine began shortly after World War II in a variety of centers in Europe and Japan, including pioneering work by Ian Donald et al in Glasgow. From the mid-1960s onward, rapid technological advances in electronics and piezoelectric materials led to substantial advancement – from bistable to grayscale images and from still images to real-time moving images. The fusing of Doppler ultrasound and ultrasound imaging and the subsequent development of color Doppler imaging provided enhanced ability to investigate hemodynamics, tumors, blood supply to organs, and other physical processes. The adoption of the microchip in the 1970s triggered exponential increases in processing power, facilitating the development of faster and more powerful systems incorporating digital beam forming, signal processing advances, and new ways of developing and displaying data (Margaret et al 1999).Improved Images via Computer TechnologyOne of the most dramatic improvements in the ongoing development of ultrasound imaging has been the application of technology originally developed for use in computers. In the beginning, ultrasound technology was developed independently of computer technology. Existing scanners returned satisfactory images through electrical channels, but the images could not be refined because computers for ultrasound imaging did not exist. That all ended in the early 1980s with the development of the computerized beam former platform, which ushered in a whole new era in diagnostic ultrasound imaging. With the wedding of computer technology and diagnostic ultrasound, a computerized image formation process provided black-and-white images with superior resolution and clarity.Doppler ImagingContinuous wave Doppler instruments were available in the mid-1960s. However, it wasn’t until the introduction of pulsed-Doppler systems in the early 1970s that the technology had a major impact on ultrasound imaging, for the first time providing noninvasive localized measurements of blood velocity. The introduction of duplex pulsed- Doppler in the mid-1970s, an important milestone, enabled 2D gray scale imaging to be used in the placement of the ultrasound beam for Doppler signal acquisition. Doppler ultrasound analysis has been used in gynecology primarily to determine blood flow in ovarian tumors with neoplastic characteristics (Dickey 1997).Doppler ultrasound has the potential to study patterns of pelvic walls and hence identify functional changes. The availability of pulsed Doppler instruments has made it possible to sample signals at a chosen depth and thus to direct flow in any selected deep pelvic vessel. Transvaginal color Doppler is a system that uses pulsed Doppler that performs flow analysis at multiple points along each scan line of echo data. Flow information is then color coded and displayed on the entire corresponding anatomical image. The main advantage of this is a rapid and definitive determination of the position of the small vessel, accuracy of the measurements and precise indication of flow direction and velocity. After simultaneous visualization of morphological and blood flow information a pulsed Doppler gate is placed over the area of interest to provide flow velocity waveforms which may be analyzed in a conventional fashion (Kurjak and Kupesic 2000). POWER DOPPLERIn the case of power Doppler, no attempt is made to identify velocities. Instead, the total signal level across all frequencies at each depth is displayed. This gives a crude measure of how much energy or power there is in the local blood flow. It can be altered by changing either the local mean velocity or the total mass of moving blood in the

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locality. It has been described (wrongly!) as a perfusion map, although it can come close to this on occasions. There is no longer any angle dependency because velocities are not being measured. One advantage of power Doppler is its signal to noise ratio, which is normally better than that of its color flow counterpart. This improved signal-to-noise ratio will mean that small vessels can be imaged, which are otherwise invisible to ultrasound.Digital Beam formationThe development of a digital beam-former in the mid-1980s and the subsequent migration to a digital platform by ultrasound manufacturers substantially raised the level of performance industry-wide. This new technology allowed for more sensitive, consistent, and accurate acquisition of sonographic data, providing for higher-resolution images.Harmonic ImagingHarmonic imaging was first developed to increase blood flow detection sensitivity in color and power Doppler applications using echo enhancing contrast agents. Based on research results using Contrast Harmonic Imaging (CHI), researchers investigated the possibility that harmonic imaging would also improve B-mode imaging without contrast agents, particularly in difficult-to-image patients. The subsequent introduction of Tissue Harmonic Imaging (THI) has demonstrated that this technology can increase spatial and contrast resolution and more effectively suppress artifacts compared with conventional B-mode imaging not only in obese patients, but also in many other applications (Burns et al, 1997). Following the realization that ultrasound has some nonlinear properties. Returning echoes produced by the media are not only at the original fundamental generated by the transducer but at several different frequencies-multiples of the original one and secondary to vibrations of the contrast agent bubbles. Insonated tissues will also vibrate under the influence of the changing pressures induced by the incident ultrasound wave, and they will reflect echoes at different frequencies. Whereas this was once considered noise or artifact and was suppressed or was assumed to be too weak to be measured, the information has now been captured and turned into meaningful data. A low-frequency transducer may be used (affording better penetration) but the image resolution is improved since the returning frequency is twice as high. Harmonics are generated while the ultrasound wave travels through the tissues during the transmit phase of the pulse-echo cycle. The returning echoes, at higher frequency, travel only one way-back to the transducer, thereby reducing potential confusing information. Only echoes not at the "right" frequencies are canceled upon reception, thus reducing artifacts. Depending on the equipment vendor, this is called tissue harmonic imaging, native tissue harmonics, and so forth. The result is better signal-to-noise ratio with improved contrast and spatial resolutions. Since time (which equals depth, in ultrasound) is necessary for generation of the harmonics, they are helpful in larger, harder-to-image patients. Its advantages are less obvious in patients easier to scan, although some practitioners turn it on simply because of the better contrast. Improved imaging of the liver, gallbladder, pancreas, pelvis, kidneys, and retroperitoneal lymph nodes is on record (Shapiro et a. 1998).Contrast-enhanced ultrasound (CEUS)The introduction of US contrast agents has totally changed the depiction of specific vascular signs for a definite diagnosis by allowing a marked increase in signal from the vessels, especially with modern non-linear imaging techniques. Contrast-enhanced ultrasound (CEUS) allows an adequate depiction of vessels in relation to the pure intravascular characteristics of those agents, reinforced by the real-time assessment of the enhancement after contrast injection. The availability of this imaging technique for transvaginal applications has allowed physicians to use CEUS in

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gynecology, such as in ovarian or uterine lesions, for a better assessment of vascular patterns that could play a role in diagnosis management. Micro-bubbles represent an entirely new class of materials that are mainly used as intravascular contrast agents for US, though they can also be instilled into the urinary bladder to look for ureteric reflux and into the uterus to check tubal patency. Their effect depends on the compressibility of gases, which is markedly different from the near-incompressibility of tissue. Exploiting this difference has led to the development of several multi-pulse sequences that cancel tissue signals and emphasize those from the micro-bubbles, thus improving the contrast-to-tissue signal ratio. Overlay or side-by-side displays allow the agent image to be viewed along with the grey-scale image to facilitate locating the region of interest (Abramowicz 1997).Ultrasound images depend on echoes being produced by the insonated structures (acoustic backscatter). It is therefore easy to conceptualize that increasing the amount of echo-producing substance in the insonated area will create additional echoes and thus, if properly processed additional information. This may be important when dealing with tiny vessels beyond the resolution of gray-scale ultrasound, color imaging, or power Doppler. In oncology Ultrasound contrast media (UCM) may offer tremendous advantages. Neoangiogenesis (creation of new blood vessels) is common to all malignant tumors, and these new vessels are usually abnormal-irregular in size, branching, and distribution, with flow in bizarre directions. Ultrasound alone cannot detect these small vessels but with the addition of UCM, they may be visualized. This has already been demonstrated in breast cancer and undoubtedly will move into other areas like ovarian cancer screening. In obstetrics and gynecology, the use of UCM is limited, but placental perfusion and ovarian tumors are potential areas for this modality (Abramowicz 1997). Following an intravenous (IV) injection, the UCA reaches the organ of interest (such as the ovary) and time intensity curves can be created to evaluate the degree, speed (slope) and duration of pixel enhancement produced by the UCA (transit time studies). Generally, tumors demonstrate steeper rises and slower washouts secondary to angiogenesis. Furthermore, benign and malignant processes can be differentiated since in malignancy, absorption should be faster and the UCA should remain in tissues longer and should be excreted faster. Malignant tumors have a larger number of vessels and higher pixel density when examined with color Doppler. This has already been shown in breast, liver and prostate cancers and undoubtedly will be in the future in other fields such as ovarian cancer screening (Abramowicz 2005).3D ImagingThe first 3D scanner was produced in 1974, but it was not computerized and proved a disappointment. However, computerized modeling of ultrasound images began in the 1980s and the result of that research, combined with 3D scanning technology, ultimately led to the development of improved 3D imaging. This provided clinicians with a level of imaging detail substantially better than what had been previously available. And as data acquisition and display continue to improve, 3D imaging will be increasingly more clinically useful. In gynecology, 3-D offers indisputable advantages – planes not otherwise accessible are available, e.g. the coronal plane in uterine imaging. This may be particularly helpful to assess the uterine contour, both external and within the endometrial cavity, for instance for the diagnosis of congenital Müllerian anomalies or adnexal pathology (Merz 1999).Why 3 D US?Two-dimensional US is a flexible, cost-effective imaging tool that allows users to see and record a large variety of thin anatomic sections in real time. However, conventional US has several disadvantages that 3D US has the potential to rectify. One of its major

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disadvantages is operator dependency. The operator sweeps the US beam back and forth across an organ many times while mentally integrating multiple 2D images into a 3D impression of the underlying anatomy and disease. This process is universally acknowledged as time-consuming and inefficient, and there is considerable inter-observer variability. In contrast, 3D images can be reconstructed from data obtained with a single sweep of the US beam across the involved organ. Both the US information and the relative position of each tomographic section are accurately recorded. As a result, the exact relationship between anatomic structures is accurately recorded in the 3D image. Another disadvantage of conventional US is the limited viewing perspective it allows. Sometimes, the patient’s anatomy or position makes it impossible to orient the US transducer for optimal visualization of a clinically relevant relationship between two structures. Three-dimensional US allows unrestricted access to an infinite number of viewing planes. In addition, 2D US is ill suited for monitoring the effects of therapy over a long period of time. To minimize artifacts, 2D US images are usually acquired with nonstandard patient positioning during various phases of respiration. To accurately assess the long-term effects of treatment during follow-up, the ideal would be to replicate the US images that best demonstrated the abnormality. Although it is usually possible to approximate an earlier image, one can never be sure if the changes on a subsequent image are substantive or merely reflect slight differences in imaging technique. Three-dimensional US allow comparison of two full data sets over time, thereby improving accuracy of evaluation.Furthermore, with 2D US, a “flat” anatomic section is displayed on a video monitor or on film. With 3D US, different viewing algorithms allow the data to be displayed with a variety of techniques, including surface rendering, volume rendering, and multiplanar reformatting.Finally, quantitative volume estimates made at 2D US are often based on images that are approximately orthogonal to each other, which may lead to inaccurate and variable results. Three-dimensional US has been shown to provide a more accurate and repeatable method of evaluating anatomic structures and disease entities (Tong et al 1998).One of the main problems when using 2D US is reproducibility, both for volume and Doppler measurements. Three-dimensional ultrasound has been demonstrated to be a very reproducible technique (Raine et al 2003).

CLINICAL APPLICATIONS OF US IN GYNAECOLOGY:NORMAL ULTRASOUND APPEARANCESThe uterusThe position and relationship of the female pelvic organs vary considerably with posture and as a result of interactions with the surrounding viscera. The central location and large size of the uterus in the pelvis allow it to be used as a landmark for orientation. However, the position and flexion of the uterus itself can vary. In transvaginal sonography, with the image oriented so that the probe is positioned at the lowest point on the screen, an anteverted uterus projects from the anterior vaginal fornix towards the bladder and anterior abdominal wall. Conversely, a retroverted uterus projects from the posterior vaginal fornix and extends to the left of the screen away from the bladder. The position of the body of the uterus in relation to the cervix, which is anchored in the midline, can also vary and a uterus might be anteflexed (angled forward) or retroflexed (angled backward) in relation to the cervix. A uterus that is axial lies in the same axis as the vagina and cervix; the ultrasound beam in this case is no longer perpendicular to the endometrium and consequently image quality might be less satisfactory. The size and shape of the uterus vary greatly in relation to parity and age. The bulk of the uterus consists of myometrium, which is the smooth muscle substance of the uterus and is

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continuous with the cervix. As the organ is predominantly made of one tissue type, its appearance is homogenous with a fine echo-dense texture. The thickness of the uterine walls is variable with age, parity and the presence of pathology. The area of myometrium closest to the endometrium is known as the junctional zone, and this might be less echogenic and is not always visible. The outer layers of the myometrium can be punctuated by small cystic spaces, which represent the arcuate vessels in cross-section, the flow within these vessels is classically slow and, with age, they might sclerose and calcify giving a hyperechoic appearance (Fleischer et al 1990).Uterine blood flow during menstrual cycle:TV color Doppler sonography provides an opportunity to visualize quantify pelvic blood flow in relation to hormonal changes during the menstrual cycle. The follicles and the corpus luteum of the ovary and endometrium are the only areas in the normal adult where angiogenesis occurs. Uterine artery waveform analysis shows high to moderate flow velocity. The resistance index depends on the patient’s age, the menstrual phase of the menstrual cycle, and specific conditions such as pregnancy and uterine tumors. There is a small amount of end diastolic flow in the uterine artery during the proliferative phase. EDF disappears at the day of ovulation. Increased RI 3 days after LH surge has been observed (Kurjak et al 1991).

Fig 1 An anteverted uterus Figure 2 Normal uterus using 3D Contrast Imaging

Figure 3 Typical Pulsed wave Doppler waveform of the uterine artery during the luteal phase of the menstrual cycle.

Congenital Uterine Anomalies

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Although conventional 2D US has shown a good performance to discriminate among different types of uterine anomalies, it is highly dependent on the expertise of the examiner (Randolf et al 1986) , and it is limited by the impossibility to obtain the coronal plane of the uterus, in most cases. Several studies have demonstrated the advantages of 3D US. Jurkovic et al. (1995) compared 2D US, 3D US and hysterosalpingography (HSG) for diagnosing congenital uterine mal-formations. They used HSG as gold standard and found that 3D US was more accurate than 2D US for diagnosing arcuate uterus, and had a higher positive predictive value for diagnosing major anomalies, especially for differentiating subseptated and bicornuate uteri. Raga et al (1996) evaluated the diagnostic accuracy of 3D US for diagnosing congenital uterine anomalies, using laparoscopy and HSG as gold standard. They found that 3D US correctly classified 92% of all anomalies. Wu et al (1997) performed a similar study, but using laparoscopy and hysteroscopy as gold standard. They were able to detect septated uterus in 92% of the cases and 100% for bicornuate uteri. Three D US is more accurate than 2D US for diagnosing arcuate, subseptated, septated and bicornuate uteri, but not for didelphys. It is very useful to determine the dimensions of uterine septum, which may provide very useful information to surgeons during hysteroscopy.

Figure 4 Subseptate Uterus Figure 5 Complete Septate

Figure 6 Arcuate uterus. Figure 7 DES uterus.

The endometriumThe endometrium is a specialized form of mucous membrane that is responsive to circulating hormones and a variety of drugs. The appearance of the endometrium is therefore highly variable, depending on the timing of the menstrual cycle and the effect of any drugs. Measurement of the thickness of the endometrium conventionally includes both layers.

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Figure 8 The endometrium should be measures from the superior to the inferior endometrial / myometrial borders encompassing both levels of the endometrium.

This is because it is generally easier to visualize the junctional zone between endometrium and myometrium than it is to visualize the interface between the anterior and posterior layers of endometrium. In the absence of significant endometrial pathology, such as a polyp, the entire thickness of the endometrium appears uniform. The thickness and appearance vary with the timing of the cycle; a range of 5–14 mm is considered to be normal in women of reproductive age. In the proliferative phase of the menstrual cycle, the functional layer becomes responsive to the increasing levels of estrogen. This causes the proliferation, lengthening and increase in tortuosity of the endometrial glands. The thickness of the endometrium is in direct relation to follicular development and rising estrogen levels. As the proliferative phase progresses, the endometrium not only thickens but also becomes less echogenic; however, the myometrial–endometrial interface and the interface between the opposing two layers of endometrium becomes more echogenic and the classic three-stripe endometrial echo is observed. Toward the end of the proliferative phase, with continued exposure to high levels of circulating estrogens, the entire endometrial complex becomes increasingly echogenic as a result of glycogen accumulation and edema. After ovulation and the formation of the corpus luteum, increasing levels of progesterone cause a halt in endometrial proliferation. The endometrial glands, under the influence of progesterone, begin to secrete glycoproteins (Fleischer et al 1990). The secretory endometrium appears uniformly echogenic on ultrasound examination. If there is no pregnancy, the endometrium will not continue to grow, although it remains secretory. With the falling levels of estrogens and progesterone toward the end of the cycle, the functional layers begin to disintegrate and menstruation ensues. The endometrial appearance at this time is variable but it remains echogenic. In postmenopausal women who are not on hormone replacement therapy (HRT), the normal endometrium appears homogenous and echo-poor compared with the adjacent myometrium. An endometrial thickness of 4 mm or less is considered normal (Granberg et al 1996).

Endometrial Cavity and Sonohysterography:The endometrial cavity is best evaluated in conjunction with sonohysterography, also known as saline infused sonohysterography (SIS). This procedure involves the installation of normal saline into the uterine cavity, which in turn expands the cavity and acts as a negative contrast medium. Sonohysterography allows reliable differentiation between focal and diffuse endometrial and subendometrial lesions, with the most common being polyps and submucosal fibroids (Weinraub et al 1996). Three-dimensional imaging, volumes of the uterine cavity can be acquired and manipulated, enabling the best visualization of any mass within the cavity. Uterine synechiae/adhesions, polyps, submucosal fibroids and uterine anomalies can all be

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better evaluated with the use of saline enhanced sonohysterography and three-dimensional ultrasound (Sylvestre et al 2003). De Kroon et al (2004) compared 3D SIS versus 2D SIS in a series of 49 patients suspected of having intrauterine abnormalities. They concluded that, overall, 2D SIS and 3D SIS had similar performance, but 3D SIS added “relevant clinical” information in 7% of their patients.

Intrauterine synaechiae: Patients with endometrial adhesions may present with infertility or recurrent pregnancy loss. At initial transvaginal US evaluation, the diagnosis of adhesions is difficult because the endometrium often appears normal. However, occasionally adhesions may be seen at transvaginal US as irregularities or hypoechoic bands within the endometrium. At sonohysterography, adhesions typically appear as mobile, thin, echogenic bands that bridge a normally distensible endometrial cavity. Less typical appearances include thick, broad-based bridging bands and complete obliteration of the endometrial cavity . As the severity of adhesions progresses, the endometrial cavity may become difficult to distend during saline infusion . Adhesions can also be associated with endometrial scars, which have a variable appearance, ranging from small echogenic areas of focal endometrial thickening to areas of denuded endometrium (Cullinan et al 1995).3D ultrasound provides a more accurate depiction of adhesions and extent of cavity damage than HSG in patients with suspected Asherman’s syndrome, particularly when differentiating severe IUA from lower uterine segment outflow obstruction. Therefore, grading systems utilizing HSG to classify severity of disease should be revised to include 3D ultrasound findings (Cohen and Copperman 2000).

Figure 9 Thick endometrial adhesions. Figure 10 Uterine Adhesions 3D

PolypsPolyps are areas of endometrium that grow a little too much. As they grow, they usually fan out but remain attached to a small stalk. Polyps are usually about the size of a pencil eraser, although they can be smaller and rarely, polyps can grow to the size of an orange. Since most polyps are small, they quite often do not cause symptoms. However, when symptoms do occur, they usually include excessive bleeding during a period, bleeding in between periods, or even spotting after intercourse. Polyps cause these symptoms because they dangle from their stalks and irritate the surrounding tissue, which causes the tissue to rub off, exposing tiny blood vessels, which in turn bleed. Sonohysterograms are used to help in the diagnosis of uterine polyps. Polyps are almost always hyperechoic on ultrasound as compared to the myometrium, sometimes with cystic areas, and may have a feeder blood vessel. Because they are actually endometrial tissue, polyps can be hard to distinguish from the endometrium without performing SIS. The typical appearance of an endometrial polyp at sonohystero-graphy is a well defined, homogeneous, polypoid lesion that is isoechoic to the endometrial with preservation of the endometrialmyometrial interface ( Sylvestre et al 2003).

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Figure 11 An endometrial polyp (P) disrupting the midline eccho (thick arrow) and the endometrium (thin arrow) around the polyp

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Figure 12 Sonohysterogram of a patient with typical appearance of an endometrial polyp. Note the narrow base of attachment to the posterior endometrial surface (arrows).

Figure 13 Uterine polyp (3 D) Figure 14 Blood flow to Endometrial Polyp

Endometrial Hyperplasia Endometrial hyperplasia is caused by endometrial stimulation by unopposed estrogen. Endometrial hyperplasia is histologically defined as a proliferation of endometrial glands of irregular size and shape, with an increase in the gland-stroma ratio compared with the normal proliferative endometrium. Risk factors for developing endometrial hyperplasia are similar to those in carcinoma, including exposure to unopposed estrogen (either endogenous or exogenous), tamoxifen usage, nulliparity, obesity, hypertension, and diabetes. There is a range of histologic patterns of endometrial hyperplasia, ranging from hyperplasia without atypia, which has little or no malignant potential, to severe atypia in which 20% of cases progress to endometrial cancer. Endometrial hyperplasia accounts for approximately 4%–8% of cases of postmenopausal bleeding (Lev-Toaff et al 1995). At sonohysterography, endometrial hyperplasia typically appears as a diffuse thickening of the echogenic endometrial stripe without focal abnormality; however, focal endometrial hyperplasia can occasionally be seen. The latter form of hyperplasia is more difficult to differentiate from endometrial polyps at sonohysterography because the characteristics of the focal endometrial thickening occurring in both conditions overlap (Patricia et al 2002).

Figure 15 Cystic endometrial hyperplasia. The endometrium(e) is thick and hyperechoic in relation to the surrounding endometrium . It is irregular and cystic in appearance but a clear

hypoechoic line demarcates the myometrial boarder (arrow).10

Figure 16 Typical endometrial hyperplasia. Sonohysterogram reveals diffuse, irregular thickening of the endometrium (arrows).

Drugs and the endometriumOral contraceptive : The most common oral contraceptive pill currently in use is the combined pill containing estrogen and progesterone. The estrogen and progesterone are usually taken for the first 21 days of the cycle, followed by a pill-free interval of 7 days to allow shedding of the endometrium. The endometrial appearances are uniform through the cycle. After prolonged use of the contraceptive pill, the endometrium typically is thin, echogenic and regular in appearance. In the first few cycles of contraceptive pill use, however, a degree of stromal edema might be present. In such cases the endometrium appears thick and echogenic. Clomiphene citrate: Clomiphene citrate is widely used in the treatment of anovulatory infertility. It acts by upregulating the production of pituitary gonadotrophins and hence causes the maturation of ovarian follicles. The endometrium continues to progress through its normal cyclical changes with clomiphene use.

Figure 17 Atypical endometrial hyperplasia Sonohysterogram shows a focal hyperechoic polypoid mass resembling a broad-based endometrial polyp (arrows). The endometrial-

myometrial interface (arrowheads) is preserved.RU 486 – mifepristone :The antiprogestogenic action of this synthetic steroid causes shedding of the endometrium. The ultrasound appearances are of highly disorganized endometrium, as would be expected during menses. It is now widely used in the medical termination of pregnancy.Danazol : This synthetic derivative of ethisterone, with mild androgenic properties, is widely used in the treatment of endometriosis. It has minimal estrogenic and progestrogenic properties and causes the endometrium to become thin and atrophic with use.Cyproterone acetate: This is an antiandrogen with progestogenic properties. It is used in the treatment of hirsutism in women and is often prescribed in combination with the combined oral contraceptive pill (Dianette). The use of cyproterone and its preparations can cause the endometrium to become thick and echogenic.Tamoxifen: Tamoxifen is one of many steroid hormones with antiestrogenic properties. Its actions, however, are varied. It is used as an antiestrogen in the treatment and prevention of breast cancer. On the uterus, however, it has estrogenic properties,

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causing the proliferation of endometrium. These paradoxical effects are thought to result from the heterogeneity of the estrogen receptor – with response related to predominant subtype. The proliferation of the endometrium results in hyperplasia, metaplasia and can lead to carcinoma. Indeed, 50% of women taking tamoxifen will develop some type of endometrial pathology. Patients on longterm tamoxifen therapy have a six-fold increase in the risk of developing endometrial carcinoma, regardless of age. On ultrasound, the endometrium is usually thickened (> 10 mm), echogenic and might have an irregular outline, with endometrial cysts often being present. Large endometrial polyps are characteristic of tamoxifen therapy. These polyps can fill the entire uterine cavity and might be difficult to distinguish from the endometrium unless there is intracavity fluid present. The presence of abnormal uterine bleeding together with thickened endometrium in women on tamoxifen therapy should warrant further investigation. Outpatient endometrial biopsy is not sufficient because tamoxifen causes subendometrial hyperplasia of the endometrial glandular epithelium.Hormone replacement therapy (HRT): The use of cyclical estrogen and progesterone in women who are peri- and postmenopausal is common. The appearance of the endometrium is dependent on whether the woman is taking continuous combined estrogen with progesterone or cyclical estrogen and progesterone. With continuous combined therapy, the endometrium should be uniformly thin (< 4 mm) and similar in appearance to that of a postmenopausal woman who is not taking HRT. Cyclical HRT will cause changes in the endometrial appearance depending on when in a cycle the woman is examined. In such cases, ultrasound should be performed 7 days after the last progesterone tablet. At this time, the criteria for assessment of the endometrium are similar to all other premenopausal women. Increased endometrial thickness; (> 4 mm) in the presence of bleeding warrants further investigation with endometrial biopsy.

Figure 18 A large cystic hyperehoic endometrial polyp (arrow) secondary to tamoxifen therapy.

Ultrasonography in fibroid uterus:Uterine fibroids also known as leiomyomas, are benign tumors made of smooth muscle cells and fibrous tissue that grow within the wall of the uterus. They may grow as a single tumor or in clusters, and are not associated with malignancy. Fibroids are divided into three groups depending on their location. Submucosal fibroids grow just beneath the uterine lining, Intramural fibroids grow in between the muscle layers of the uterus, and Subserosal fibroids grow on the outside of the uterus. Among all leiomyomas, the submucosal type is most likely to cause clinical problems. Fibroids can be diagnosed as well-defined hypoechoc areas arising from within the myometrial layer, causing attenuation of the ultrasound beam and distal shadowing. The impact of fibroids on fertility is dependent on size and location. Large-intramural and-subserous fibroids can distort the uterus, resulting in difficulties in ovum pick-up because of abnormalities in the relationship between the ovary and the Fallopian tube. Intramural fibroids in the

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cornual region can affect tubal function. However, submucous fibroids are the most frequently missed pathology in women described as having unexplained infertility. Submucous fibroids distort the midline echo and are best diagnosed in the periovulatory phase (Lewit et al 1990).

Figure 19 A large submucous fibroid (F) distorting the uterine cavity (arrows). The fibroid is hypoechoic in relation to the surrounding myometrium

Figure 20 Typical fibroids with submucosal fibroid. The percentage of protrusion of the fibroid into the endometrial cavity should be classified as equal to or greater than 50%.

Figure 21 sonohystrogram with submucus fibroid The percentage of the protrusion into the endometrial cavity is less than 50%

The major advantage of sonohysterography over other imaging modalities is that it can accurately depict the percentage of the fibroid that projects into the endometrial cavity. This feature is important because only those fibroids in which at least 50% of the mass projects into the endometrial cavity may be removed hysteroscopically. At sonohysterography, submucosal fibroids are typically broad-based, hypoechoic, well-defined, solid masses with shadowing. Submucosal fibroids typically have an overlying layer of echogenic endometrium, which helps confirm their subendometrial location and helps distinguish them from endometrial polyps, which arise from the endometrial. In addition, as opposed to polyps, submucosal fibroids often distort the interface

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between the endometrium and myometrium and show acoustic attenuation (Dubinsky et al 1995).

Figure 22 Mural fibroids can have a submucosal component that deviates the endometrial cavity, but they are not considered submucosal fibroids unless the epicenter of the fibroid is

within the cavity.

Three-dimensional volume ultrasound is superior to two-dimensional views in identifying the degree of protrusion of a submucous fibroid into the cavity, as well as the amount of myometrium remaining outside of the submucous fibroid, all information which is needed before hysteroscopic resection of these lesions can be undertaken. One can also measure the volume of such a fibroid or polyp or even the volume of the entire endometrium, quickly and easily using a 3D volume set (Yaman et al 2002).Kurjac et al. (1993) noted that the diastolic flow in patients with fibroid uterus is usually present in the myometrial vessels and increased relative to the seen in the uterine arteries. Uterine artery flow velocity in the normal uterus has a mean RI of 0.84. In women with fibroids a slight decrease in the mean RI to 0.74 was observed. The mean RI of myometrial blood flow in these patients was 0.54.Fleischer et al. (2000) have reported the usefulness of 3D Power Doppler for assessing fibroid vascularization, before and after uterine embolization.

Figure 23 three D of a submucosal fibroid showing that the echogenicity of the endometrium acts as a contrast medium.

Contrast-enhanced sonography was performed just before UAE, immediately after left UAE, and after bilateral UAE. Pre-UAE images showed a completely perfused uterus with hyperenhanced areas corresponding to the leiomyomas. The next two acquisitions showed hypoperfused areas corresponding to the leiomyomas. The last acquisition, taken after complete bilateral uterine artery occlusion, Injection of SonoVue could provide a very precise description of the uterine vascularization more easily than with angiography and cheaper than MRI. After contrast injection, macro- and microcirculation of the myoma first appeared, followed by the normal myometrial enhancement and finally within the endometrium. Enhancement patterns vary markedly among the patients, from an absence of enhancement for the whole tumor, to a complete and rapid enhancement after injection. Wash-out was typically complete after 3

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minutes, giving a black hole corresponding to the whole lesion. This wash-out helps us to identify some tiny fibroids that are not visible on conventional sonography. Contrastenhanced Utrasound can also be proposed to detect the persistence of vessels within a treated myoma with higher confidence, as it was reported that this precedes the late recurrence confirmed by an increased size of the myomas . This will be a more sensitive method than color Doppler Ultrasound for an assessment of induced vascularity changes (Muniz et al 2002).

Figure 24: arterial enhancement within uterine fibroid (a) after SonoVue injection

demonstrating a quite globular and intense enhancement higher than from normal myometrium (b), followed by a marked wash out (c).

Adenomyosis

Figure 25 The echogenic nodules within the anterior myometrium (arrows) suggest adenomyosis

Figure 26 A large adenomyoma (a) seen at the fundus of the uterus casting an acoustic shadow (arrow). It is slightly distorting the cavity (broken arrow)

Adenomyosis is characterized histologically as benign invasion of the uterine musculature by the endometrium. The reported incidence of adenomyosis varies widely from one institution to another because adenomyosis is fundamentally a pathologic diagnosis. Adenomyosis is frequently accompanied by additional pelvic abnormalities such as uterine myomas, and it co-exists in 6–20% of patients with endometriosis. Adenomyosis is also associated with an increased incidence of endometrial hyperplasia

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and endometrial adenocarcinoma. It usually appears as diffuse disease, but may occur as a focal lesion (adenomyoma) similar in appearance to a myoma. Ultrasonographically, adenomyosis may appear as an anechoic area of thickened myometrium, consisting of blood-filled, irregular cystic spaces, or as an area of hyperechoic myometrium with several cysts (hypoechoic lacunae) ( Yaman et al 2002).

Figure 27 Adenomyosis - Note the mottled texture of the myometrium and hypoechoic areas within the hyperechoic area in the fundal region.

Table 1 Sonographic criteria for adenomyosis (Reinhold et al 1998)

Globular shaped uterus Myometrial cysts (2-6 mm in diameter) Mottled inhomogeneous myometrium Indistinct borders to a myometrial mass Indistinct endometrial stripe Hyperechoic myometrial nodules Asymmetric thickening of the anterior or posterior uterine wall Mimimal mass effect on the endometrium or serosa

Endometrial Cancer Endometrial cancer accounts for approximately 90 percent of uterine cancers. Adnocarcinoma, which originates in surface cells of the endometrium, accounts for most of the cases of endometrial cancer. Postmenopausal bleeding is the most common presenting symptom in women with endometrial carcinoma, but only 10% to 20% of women with postmenopausal bleeding will have cancer (Debra et al 2004). Adenocarcinoma is often detected at an early stage because it frequently produces vaginal bleeding between menstrual periods or after menopause. If discovered early, this slow-growing cancer is likely to be confined to the uterus. Endometrial cancer on ultrasound appears as diffuse thickening of the endometrium similar to hyperplasia, or as an inhomogeneous focal mass. Using a double-wall thickness of 5 mm or greater, the sensitivity for detecting endometrial cancer is 96% regardless of whether a woman is receiving hormone replacement therapy. A thin endometrium of 5 mm or less had a high negative predictive value, and this finding would support the diagnosis of atrophy (Bindman et al 1998). Laifer-Narin et.al(1999) found a lack of distentability of the uterine cavity during SIS as the most consistent finding in women with endometrial cancer. In addition, transvaginal power Doppler blood flow mapping can be useful to differentiate benign from malignant endometrial pathology in women presenting with postmenopausal bleeding and thickened endometrium at baseline sonography ( Alcazar et al 2003). Even at sonohysterography, endometrial cancer can be difficult to distinguish from endometrial hyperplasia and polyps. This diagnosis should be suspected when the single layer of the endometrium is thicker than 8 mm, irregular, broad based, or poorly

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marginated or when the endometrial-myometrial interface is disrupted. Endometrial thickness measurements often overlap in benign and malignant conditions. However, it has been shown that a single layer endometrial thickness less than 2.5 mm is rarely associated with malignancy (Goldstein et al 1997). At sonohysterography, early cases can appear as a polypoid mass. An intact subendometrium is suggestive of localized disease, whereas extension of heterogeneity and increased echogenicity in the myometrium is seen with advanced invasive endometrial carcinoma (Karlasson et al 1995).Gruboeck et al (1996) reported that the assessment of endometrial volume in women with postmenopausal bleeding was more accurate than endometrial thickness measurement for detecting endometrial pathology. Bonilla-Musoles et al (1997) reported that 3D US improved the diagnostic accuracy of ultrasound to determine myometrial and cervical invasion in endometrial carcinoma.

Figure 28 Typical endometrial cancer. Sonohysterogram demonstrates diffuse, irregular, inhomogeneous thickening of the anterior endometrium(between arrowheads).

Figure 29 Atypical endometrial cancer. an irregular, polypoid lesion (white arrows) arising from

the posterior endometrial surface. The polypoid nature of the mass is atypical for endometrial cancer.

Ultrasonography and cervical carcinoma:Cancer of the cervix is frequent and is accompanied by local extension or lymph node extension, which guides treatment planning, i.e., the choice between initial treatment by surgery or by radiochemotherapy. An intense enhancement is reported for these lesions before specific treatment, with an improvement in the definition of limits but with some limitations in the positive diagnosis as reported by Testa et al (2005). . Local assessment of angiogenesis will be of value to follow local changes under chemotherapy or radiotherapy and to better schedule surgery. This method could be used in place of MRI to assess treatment efficacy and in conjunction with positron emission tomography (PET) for treatment planning. Chou et al (1997) compared tumor volumes estimation using two- and three- dimensional US to volumes estimated by histology (IB and II A cancer only). The staging approach using three D Ultrasound is new, and the relatively good results

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yielded by using sub-optimal equipment in the hands of a non gynecologist indicate a potential future for the technique (Bega et al 2000) . Three D power Doppler ultrasound provides a useful tool to investigate intra-tumor vascularization and volume of cervical cancer. Alterations of 3D USG derived vascular indices were found in patients with cervical cancer and some vascular indices proved to be associated with tumor size (Teta et al 2004).

Figure 30 Typical strong and homogeneous enhancement from cervical cancer (a) after

SonoVue injection (b)

Update in ultrasonography of the adnexae The ovaries

The ovaries are usually located in the ovarian fossa, inferior to the pelvic vessels on the lateral pelvic wall. However, they are mobile structures and can be found in the pouch of Douglas or above the uterine fundus; they can be located by following the broad ligament laterally. They appear as ellipsoid structures, which are slightly hypoechoic in comparison with the myometrium. Ovarian follicles are simple, anechoic cysts with clear and well-defined walls. They grow at an average rate of 2 mm/day until they reach 20–25 mm in diameter, just before ovulation. Strictly speaking, the diagnosis of an ovarian follicle can only be made on a follow-up scan that demonstrates normal follicular growth or signs of ovulation. However, in practical terms every simple ovarian cyst measuring less than 25 mm in size in a premenopausal woman can be classified as a follicle. Doppler examination of the follicles reveals only limited vascularity. Corpora lutea can be solid, cystic or hemorrhagic. Solid corpora lutea are sometimes difficult to differentiate from the surrounding ovarian tissue and can be identified only by their high vascularity. Cystic corpora lutea can contain either anechoic fluid or low level echoes. In comparison to follicles, their walls are thicker and often irregular. A hemorrhagic corpus luteum is recognized by the typical honeycomb appearance of its contents. The characteristic blood flow of a corpus luteum is halo-like and of high velocity and low resistance (Fleischer et al 1990).Ovarian blood flow during the menstrual cycle:Doppler blood studies of the ovarian blood flow during menstrual cycle are based on semi-quantative analysis of Doppler flow waves recorded over the ovarian artery at their entery into the ovary and color flow mapping of intraovarian vessels. Blood flow from the follicle can be seen when it reaches 10-12 mm in diameter. The RI is approximately 0.54 until ovulation approach. A decline begins 2 days before ovulation and reaches a nadir at ovulation. Immediately after follicular rupture, there is another dramatic increase in the velocity of blood of blood flow to the early corpus luteum. The RI remains at that level for 4-5 days and then gradually climbs to 0.5 which is still lower than that seen during the proliferative phase (Collin et al 1991).

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Figure 31 Small vessels around the mature follicle can also be visualized by power Doppler sonography

.Figure 32 intraovarian blood flow during the proliferative phase of the normal menstrual cycle.

Figure 33 Corpus luteum blood flow during the early secretory phase. The rich vascular supply shown here by color Doppler sonography is typical.

Figure 34 Pulsed wave Doppler waveform analysis typical for corpus luteum neovascularization

The role of ultrasound in detecting early ovarian carcinomaUltrasound has demonstrated utility in detecting ovarian cancer in asymptomatic

women, but its value for the detection of early stage disease is uncertain. Among ‘high-risk’ women (women with a family history of ovarian cancer or a personal history of breast cancer) the sensitivity for detection of Stage I disease was 25% ( 95% CI 3-65%) while the sensitivity for low-risk women was 67 % (95% CI 22-96) . This less-than-ideal sensitivity is not unexpected, because in many Stage I ovarian cancers, the ovaries are neither enlarged nor morphologically abnormal. In addition, the use of color or Power Doppler imaging has not been shown to add significantly to the diagnosis of early-stage disease. The low annual prevalence of ovarian cancer within the general population, the large number of women who must therefore be screened to identify a single ovarian cancer, and the poor sensitivity of the test for Stage I disease make routine use of ultrasound for detection of ovarian cancer impractical (Narod et al 2000).

Specificity of Grayscale Ultrasound

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One of the major limitations of ultrasound screening is the large number of false positive examinations. Coincident operative intervention has varied between 3 and 100 operations for each case of malignant disease identified. The grayscale scoring systems of Sassone et al (1991) and its modification by Lerner et al (1994) report specificities of 83% and 77%, respectively. These scoring systems require grading for echogenicity, wall thickness, solid elements, and degrees of septation.

Table 2 (a&b) Ovarian tumor B-mode sonography and color Doppler scoring system:a) (Sassone et al 1991).ClassificationMass Fluid score Internal borders ScoreUnilocular Clear 0 Smooth 0

Internal echo 1 Irregular 2Multilocular Clear 1 Smooth 1

Internal echo 1 Irregular 2Cystic- solid Clear 1 Smooth 1

Internal echo 2 Irregular 2Papillary projection Suspicious 1 definite 2Solid Homogeneous 1 Echogenic 2Peritoneal fluid Absent 0 Present 1Laterality Unilateral 0 Bilateral 1Ultrasound score ≤ 2 = benign, 3-4 = Questionable ; > 4 = Suspicious for malignancy.b)Parameters Color Doppler: score

Vessels seen by color Doppler No vessels seen 0Regular separate vessels 1Randomly dispersed vessels 2

RI by pulsed Doppler No Doppler Signals 0≥ 0.4 1< 0.4 2

NB if suspected corpus luteum blood flow, repeat scan during next cycle in the proliferative phase.Color Doppler score ≤ 2 = benign, 3-4 Questionable for malignancy

Figure 35A simple cyst. Power Doppler reveals flow around the periphery of the cyst. These cysts will usually resolve spontaneously within six to eight weeks

Ferrazzi et al (1997) found, in a prospective series of 330 patients, that the Sassone score and Lerner score were less specific, with values of 65% and 59%, respectively.

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The suboptimal specificity of these and other grayscale scoring systems can result in many unnecessary operations when an asymptomatic population is screened for ovarian cancer. The major limitation of transvaginal architectural screening is that ovarian cancers can arise from normal-sized ovaries, of apparently normal structure, observed using advanced diagnostic imaging technology (Fishman and Cohen (1995).

Figure 36 Typical appearance of peritoneal adhesions followed myomectomy .

Color and Power Doppler ImagingBourne et al (1994) evaluated ‘high-risk’ women with a family history of ovarian cancer, and suggested that color Doppler analysis had value as a secondary test to decrease unnecessary operative interventions. An initial report by Kurjak et al (1991) found that a color Doppler resistive index (RI) of < 0.4 had a sensitivity and specificity of 100% and 99%, respectively, in predicting ovarian cancer. Tekay and Jouipilla

(1995)f ound that vessels with low impedance, RI < 0.4, could be identified in 43% of benign premenopausal tumors. The National Institute of Health (NIH) in 1995, reported that color Doppler may improve the specificity of ultrasound for predicting ovarian cancer, although its use should be considered investigational. The limitations of spectral Doppler impedance measurements in accurately predicting ovarian cancer were reviewed by Tailor et al (1997). They found that time-averaged velocity measurements (TAMV) were more accurate than impedance measurements (RI , PI). However, they recommended that Doppler be used as part of a combined score that included the patient’s age and papillary projection score. Schelling et al. (2000), using multiple logistic regressions, found that the presence of central solid elements with vascular flow was the most important criterion in distinguishing benign from malignant masses. In a prospective study of 257 women, they reported a 92% sensitivity and 94% specificity.

Power Doppler EnergyTailor et al (1998) explored the use of Power Doppler energy in the investigation of adnexal masses, and identified vascular flow within 100% of malignant and borderline tumors, and 80% of benign tumors. They found that the pulsatility indices and diagnostic accuracy in predicting ovarian malignancy were similar. Sensitivities were 93% and 87%, and specificities were 60% and 63%, for color Doppler and Power Doppler, respectively. The authors did not find that the use of Power Doppler was more advantageous than that of color Doppler. Guerriero et al (1998) used Power Doppler as a secondary test performed after assigning a grayscale impression based on probable histology. The Power Doppler assessment was based simply on the presence or absence of central vascularity within solid elements or excrescences. Specificity improved from 83% to 92% with the addition of Power Doppler as a secondary test. Significantly, the authors observed that requiring an impedance Doppler RI value of < 0.4 resulted in a marked drop-off in sensitivity, from 100% to 58%.

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Figure 37 A hemorrhagic corpus luteum cyst. Power Doppler reveals flow around the periphery of the cyst

Figure 38 A resolving hemorrhagic corpus luteum cyst. Color Doppler imaging reveals no evidence of flow within the central areas of the cyst..

Figure 39 A 6 x 5 cm endometriotic cysts in a premenopausal woman. Typically on transvaginal ultrasound, these cysts are filled with uniform low-level echoes.

Figure 40 Typical appearance of a densely echogenic cystic teratoma, measuring. Color Doppler reveals no evidence of flow within the densely echogenic region of the mass.

3-D Ultrasound3-D volume acquisition and 3-D Power Doppler may help in the early identification of abnormal vascularity and architectural changes within the ovary. Excrescences not seen by 2-D technology may be observed. While 3-D Power Doppler provides a new tool for measuring the quality of ovarian vascularity, its clinical value for the early detection of

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ovarian carcinoma has yet to be determined. The efficiency of 3-D Power Doppler imaging in identifying Stage I ovarian cancer has yet to be determined (Cohen et al 2001).

Figure 41 This complex predominantly cystic mass with a small area of internal papillae, 3D-

Power Doppler imaging revealed no evidence of vascularity within the cyst wall or the excrescence.

Figure 42 a vascular projection in a cyst Figure 43 surface rendering of a papillary in a cyst

UPDATE IN ULTRASONOGRAPHY IN INFERTILITY Ultrasound is probably the single most important test when making a diagnosis, as to

the cause of infertility in a particular woman. A well-performed and derailed ultrasound examination of the female pelvic organs will give more information than any other single test. It must be emphasized that ultrasound examinations should be performed with the use of transvaginal probes. The use of abdominal ultrasound probes is outdated, It is inaccurate and uncomfortable to patients; it lacks detail and is indicated only when a large mass in the pelvis makes it difficult to visualize the uterus, ovaries and adnexal regions adequately. The ultrasound examination should be performed in a systematic manner. The examination is target orientated and a firm sequence should be adhered to at every examination. The simplest order of examination would be the uterus, adnexal region, ovaries and pouch of Douglas. The 'sliding organs sign' described by Timor-Tritsch et al. (1988) should become routine practice at all gynecological ultrasound examinations. Finally, uterine and tubal pathology can be missed, or physiological changes in the ovary may be wrongly diagnosed as pathological, if the ultrasound examination is performed at an inappropriate time of the menstrual cycle.Uterine factorsUterine size and position and the endometrial cavity are studied in detail. The endometrial cavity and contours are inspected for irregularities and echo patterns and the myometrial—endometrial interphase examined in the longitudinal and transverse planes. The midline endometrial echo, where the anterior and posterior uterine walls are apposed to each other, are studied from the internal os to the fundus and any discontinuity and distortion of this echo should be noted. Longitudinal and oblique scans are performed to study the region of the tubal ostia (Grunfield et al 1991).

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Figure 44 Longitudinal scan of the uterus. Note the uninterrupted midline echo, indicative of a normal uterine cavity.

Ovarian factorsThe unstimulated ovary, in premenopausal women, usually contains a small number

of ooyte. These are randomly dispersed and if the ultrasound examination is performed between day 6 and day 14 of the menstrual cycle a leading follicle can be identified. A normal ovary usually measures 2.5 cm X 2.2 cm X 2.0 cm and ovaries with diameters in excess of 3.5 cm should be considered as abnormal. The mean volume of a normal ovary is 5.4 ml (Poison et al 1988).

Ovarian cysts are best diagnosed in the preovularory phase. This is to avoid confusion with corpus luteum cysts, which are characteristically irregular, containing solid and semi-solid areas in many cases corpus luteum cysts will mimic pathological cysts of the ovaries. Cysts that are sharp and smooth in their outline and unilocular are usually physiological and do not warrant surgery (Granberg et al 1991).

Figure 45 A multiloculated ovarian mass by 3D Power Doppler flow, revealed no evidence of central flow.

Figure 46 A biloculated cystic mass in a perimenopausal woman on Tamoxifen.

Multicystic masses are not uncommon in preand perimenopausal women on Tamoxifen.

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Cysts that contain low-level echoes, which may be unilocular or multilocular, are usually indicative of intra-ovarian endometriosis. Dermoid cysts can give a similar appearance to endometriosis on ultrasound examination and the differential diagnosis can often be difficult to make. Dermoid cysts usually contain hyperechogenic areas and some of these may cause distal shadowing (Granberg et al 1991).

The presence of ovarian endometriosis may have a significant bearing on the ovarian response to stimulation drugs and may become obvious only during controlled ovarian hyperstimulation, carried out for IVF therapy or intrauterine insemination (Diugi et al 1989).If only one ultrasound examination is to be performed, then this should be performed in the periovulatory phase, in order to optimize the chances of diagnosing ovarian abnormalities accurately. Ideally, if the diagnosis of an ovarian cyst is made, a repeat ultrasound scan should be performed approximately 8 or 12 weeks later, between day 6 and day 10 of the menstrual cycle. In many cases physiological cysts will subside spontaneously and do not require further surgery. The benefit to the patient is that unnecessary surgery can be avoided and in cases where pathological cysts are diagnosed these cysts can be treated laparo-scopically at the time of the diagnostic laparoscopy(Diugi et al 1989).

In cases of polycystic ovaries, the ovaries may contain ten or more cystic structures distributed peripherally around a central core of stroma . Such ovaries have been termed polycystic and are usually associated with menstrual irregularity, raised luteinizing hormone (LH) levels, hirsutism, anovulation and an increased incidence of miscarriage (Adams et al 1986).

Eshel et al (1988) have shown that the presence of polycystic ovaries is more likely to be associated with infertility if the woman has a raised body mass index.Three D ultrasound has been used to measure ovarian and stromal volumes, providing

information that is not available from two-dimensional (2D) ultrasound. In a study by Kyei-Mensah et al, (1996) the difference in ovarian size was accounted for by the differences in stromal volumes, there being no differences in follicular volume between

normal ovaries and PCO. However, 3D ultrasound is governed by the same principles as 2D ultrasound and hence its resolution is reduced in obese women. Expertise and experience is therefore important, as numerous volume measurements of sufficient quality may be necessary to permit meaningful analysis.

Figure 47 Polycystic ovaries. Three-dimensional sonography facilitates objective assessment of the ovarian stroma, through measurement of its mean grey signal intensity, its vascularity and its volume, which may be calculated by subtracting total follicular volume from total ovarian volume (a). Ovarian blood flow is increased and associated with significantly higher three-

dimensional indices of vascularity than ovaries with a normal appearance (b).

MONITORING OF TREATMENT CYCLESSerial monitoring of follicular development is useful in both natural and stimulated ovarian cycles. In natural cycles, several small follicles may be seen in the early

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follicular phase. However, the dominant follicle is selected between day 5 and day 7 and other follicles will gradually decrease as this follicle develops (Packi et al 1990). Follicular rupture occurs between 18 mm and 28 mm during natural cycles, with an average growth rate of 1.2 mm to 2.0 mm per day. It is essential that serial monitoring is carried out to determine normal growth of the Graafian follicle and to determine follicular rupture (Renaud et al 1980).

Figure 48 A typical flow velocity diagram at the stroma shows higher velocity in a 35-year-old polycystic ovary syndrome patient.

A baseline scan should be performed early in the menstrual cycle to avoid misinterpreting pre-existing cystic structures with developing follicles. A luteal cyst is commonly seen and may decrease in size during the follicular phase. In order to monitor follicular development and rupture, the first scan should be performed between day 10 and day 12 of the cycle and then, depending on the size of the leading follicle, serial scans can be performed every 2 or 3 days (Narayain et al 1994).

Fig.49 ovary shows random distributed follicles Figure 50 Simple ovarian cyst.

Ovulation induction and Intrauterine inseminationOvulation induction treatment may be carried out with clomiphene in combination with gonadotropins, or with gonadotropins on their own. An initial scan performed on day 2 or 3 of the cycle prior to commencing ovularion induction is again advisable; a second scan performed on day 8 or day 9 of the cycle will help to establish the number of ovarian follicles. Ultrasound scans should then be performed on alternate days and the injection of human chorionic gonadotropih (hCG) given to induce ovulation when the mean follicular diameter of the leading follicle is between 18 and 20 mm (Narayain et al 1994).In vitro fertilizationIt is important that ultrasound examination is performed between day 10 and day 15 in a cycle preceding IVF, for the following reasons:(1) The examination is used to check that the uterine cavity is normal. The presence ofsubmucous fibroids ' will decrease the chances of conception with IVF.

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(2) The presence of hydrosalpinges should be noted because this may also decrease the chances of implantation with IVF. It is now almost routine practice in IVF centers that hydrosalpinges are removed or sealed at the cornual end in order to avoid toxic effects of hydrosalpinx fluid on embryos and implantation.(3) The presence of ovarian cysts, especially endometriosis can affect follicular development and may warrant treatment prior to IVF. In many cases, if the cyst is below 3 cm in size, aspiration of the cyst, if performed prior to stimulation, will aid the ovarian response.(4) When ovaries are enlarged to greater than 3.5 cm, the risk of hyperstimulation syndrome is increased, and if the enlargement is due to endometriosis then the ovarian response may be compromised. However, if the ovaries are smaller than the normal size, i.e. less than 2 cm in maximum diameter, this may be indicative of decreased ovarian reserve. In these cases higher than usual doses of gonadotropins may be required in order to provoke an adequate ovarian response.5) The examination is used to check-the distribution of the follicles in the ovary. Follicles should normally be randomly dispersed, with the dominant follicle being observed in one or other ovary. If the follicles are distributed around the periphery, this may indicate an increased risk of ovarian hyperstimulation syndrome. In these cases ovarian stimulation with gonadotropin should be started at a lower than normal dose and can be increased after 6 or 7 days of therapy, if necessary.Monitoring of IVF cycles is essential in order to avoid the hyperstimulation syndrome and to assess the ovarian response during the treatment cycle. Most centers use ultrasound alone, to monitor the ovarian response and to time the hCG injection, prior to oocyte recovery. The first scan should be performed prior to stimulation for the reasons given above and the next scan should be performed approximately 6-8 days after stimulation has commenced. Subsequent ultrasound scans can be performed on a daily or alternate day basis, depending on the ovarian response. The injection of hCG is usually given when at least 2 or 3 leading follicles are above 18 mm in size (Narayain et al 1994).Frozen embryo replacementIn most centers frozen embryos are replaced during a natural cycle. In anovulatory women, clomiphene citrate or gonadotropins or a combination of both can be used in order to stimulate ovulation. Monitoring is performed as for a natural cycle, ovulation induction or intrauterine insemination, and embryos are usually replaced 2 or 3 days after ovulation. If urine or blood monitoring is not performed to monitor the LH surge, then ultrasound scans must be performed on a daily basis once the lead follicle reaches a mean follicular diameter of 16 mm.Ovarian ReservePellicer et al (1998) used three-dimensional sonography as an adjunct to conventional markers of ovarian reserve when they examined ovarian volume and the number of 'selectable follicles' measuring 2–5 mm in a small group of low responders on day three of the menstrual cycle. Both the number of selectable follicles and the total number of antral follicles were significantly decreased in the 'low responder' group who also demonstrated significantly higher serum FSH levels despite having values within the normal range. There is no doubt that antral follicle counts, when used in categorical classifications, are an important predictor of 'ovarian reserve' and may be measured with a high level of agreement both between and within observers (Scheffer et al 2002). Kupesic et al (2003) showed the number of oocytes retrieved and subsequent conception rate to be greater in patients with a greater ovarian volume and a greater ovarian stromal vascularity but not independently of a higher number of antral follicles.

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Figure 51 Ovarian volume calculation

Figure 52 three D sonography in controlled ovarian stimulation measures follicular diameter (a) and rendering allows demonstration of the cumulus oophorus in mature follicle (b).

Ultrasound for predicting endometrial receptivity in ARTs Uterine Biophysical profile (UPP)The term "uterine receptivity" refers to a state when endometrium allows a blastocyst to attach, penetrate and induce changes in the stroma, which results in the so-called process of implantation. It appears that a favorable endometrial milieu is necessary for successful implantation and, although various endocrine parameters correlated with endometrial receptivity and implantation are well-documented (Schild et al 1999). Several sonographic parameters have been used to assess uterine receptivity, including endometrial thickness, endometrial pattern and endometrial subendometrial and uterine blood flows and assessment of endometrial and subendometrial vascularization (Chien et al 2004). Three-dimensional power-Doppler angiography (3D-PDA) allows quantitative assessment of vessel density and blood flow within the endometrium and sub-endometrial region. Schild et al (2000) evaluated 96 patients undergoing IVF program by 3D-PDA. They found that all 3D-PDA indices were significantly lower in conception than non-conception cycles. However, a great overlapping existed.

Tubal patency and Fallopian assessmentUnder normal circumstances, the fallopian tubes are not visible with ultrasound imaging unless there is fluid within the pouch of Douglas. However, when the tubes are damaged by infection they can become enlarged and form fluid-filled hydrosalpinges. These are generally readily visible during scanning because the fluid within the tubal lumen provides a negative echo contrast. The presence of hydrosalpinges is an important prognostic feature. Where they are bilateral, it is believed that their presence could interfere with embryo implantation following IVF. The fluid contained within the tubal lumen appears to be embryotoxic. An assessment of fallopian tube patency has a key role in the investigation of subfertility. Blocked fallopian tubes are a common cause of female subfertility. Conditions such as pelvic infection and endometriosis are relatively common and can be of an insidious nature. They can cause significant tubal damage without much in the way of symptoms to indicate this. In addition, any surgical procedure performed within the pelvis involves the risk of scarring and adhesions,

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which can impact on tubal function. Determining tubal patency will help guide the clinician in the right choice of fertility treatment. Where the tubes are patent then the patient is more amenable to simpler fertility treatments, such as ovulation induction or intrauterine insemination, whereas in the situation of non-patent tubes, the patient will most likely require more sophisticated treatment, such as IVF (Arronet et al 1996).

Table 3 Uterine Scoring System for Reproduction (USSR)Parameter Determination score

Endometrial thickness (mm) <7 07-9 2

10-14 3> 14 1

Endometrial Layering No layering 0Hazy 5- line appearance 1

Distinct 5 lines appearance 3Myometrial contractions (seen as

endometrial motion)< 3 0

≥ 3 3

Myometrial echogenicity Course inhomogeneous 1Relative homogeneous 2

Uterine artery Doppler flow evaluation (PI)

2.99-3.0 02.49 1<2 2

Endometrial blood flow in zone 3 Absent 0Present but sparse 2

Present multifocally 5Gray-scale myometrial blood flow Absent 0

Present 2A USSR "perfect score" of 20 has been associated with conception 100% of the time. (The number of patients in which we predicted successful conception cycles based upon the UBP and USSR perfect score was 5. This group included 2 spontaneous cycles (non-IVF, non-IUI), 2 IUI and 1 IVF.) Scores of 17 - 19 (10 patients) have been associated with conception 80% of the time. Scores of 14 - 16 (10 patients) have a 60% chance, while scores of 13 or less (25 patients) have resulted in no pregnancies (Applebaum 2004). 

Hysterosalpingo-contrast sonography (HyCoSy) involves the instillation of a positive contrast agent, such as Echovist® (Schering AG, Germany), into the uterine cavity during scanning. Flow of the contrast medium through the tubes and into the peritoneal cavity can be readily seen. Using either pulsed or color Doppler, improved sensitivity for contrast flow can be obtained. HyCoSy can provide similar information about tubal patency as the more traditional modes of investigation. When combined with saline contrast hysterosonography, the uterine cavity can equally be assessed. Three-dimensional CPA has also proved useful in assessing tubal morphology and patency. With conventional 2D HyCoSy it is often difficult to view the entire tubal length in a single scanning plane. By using power Doppler, which is sensitive to a slow flow of contrast medium, and by capturing the volume, it is possible to reconstruct a 3D image of the fallopian tube. The combination of contrast media and three-dimensional sonography has also been used to assess tubal patency. Kiyokawa et al (2000) found three-dimensional saline sono-hystero-salpingography was able to demonstrate the entire contour of the uterine cavity in 96% of cases compared to only 64% cases with conventional X-ray hysterosalpingography (p < 0.005) and was associated with a positive predictive value and specificity of predicting tubal patency of 100% in 25 unselected infertile patients. Sladkevicius et al (2000) found three-dimensional power

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Doppler imaging demonstrated free spill almost twice as often as conventional imaging (114 versus 58 tubes respectively) when used during hysterosalpingo-contrast sonography. Jarvela et al (2002) reported less promising results with the same technique when they reassessed tubal patency in 15 women who had normal X-ray HSG examinations within the previous year. An important distinction was their use of saline rather than a positive contrast agent but it maybe that the technique has a distinct learning curve and numbers were small.

Figure 53 Three-dimensional color power Doppler HyCoSy demonstrating free peritoneal spill of contrast dye. following surface rendering.

Figure 54 The ‘beads-on-a-string’ sign (arrows) considered as additional evidence of the presence of hydrosalpinx.

Figure 55 The typical colour Doppler energy findings of hydrosalpinx.

Ectopic pregnancy:The introduction of beta hCG testing and transvaginal ultrasound has changed our approach to the patient suspected of an ectopic pregnancy. Important advantage of the most currently used trans-vaginal transducers is the ability to perform simultaneous color and spectral Doppler studies, allowing easy identification of the ectopic peritrophoblastic flow. Therefore, color Doppler may be applied whenever a finding is suggestive of ectopic pregnancy.

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Figure 56 Ectopic pregnancy in lt tube Figure 57 Rt interstitial ectopic pregnancy

Further progress in diagnostic procedures is made with introduction of 3D ultrasound. Transvaginal 3D ultrasound enables the clinician to perceive the true spatial relations and thus easily distinguish the origin of an adnexal mass, while 3D power Doppler allows detailed analysis of the vascularization. Transvaginal color and pulsed Doppler imaging may be used for detection of the patients with less prominent tubal perfusion, suitable for the expectant management of ectopic pregnancy. It is expected that increased sensitivity of the serum beta hCG immunoassay and the quality of transvaginal B-mode, color Doppler ultrasound and more recently 3D with color and power Doppler facilities will allow even earlier detection and conservative management of ectopic pregnancies. Diagnostic advances are becoming very important since fertility outcomes and number of women attempting to conceive after ectopic pregnancy will further increase (Kupesic 2005).

Figure 58 Transvaginal color Doppler imaging of ectopic pregnancy. Note color Doppler signals indicative of invasive trophoblast (left). Pulsed Doppler waveform analysis (right)

demonstrates low resistance index (RI = 0.43).

Figure 59 Gestational sac measuring 12 mm is visualized in the left adnexal region. Color Doppler depicts a small area of angiogenesis characterized by a high resistance index (RI =

0.73). This finding is indicative of tubal abortion.

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Ultrasound and Pelvic floor assessment:Ultrasound imaging of the pelvic floor developed as an adjunct to physical examination taking advantage of the large availability of the US equipments, of the possibility to repeat the imaging both at rest and during provocation manoeuvres. Modern ultrasound probes provide a large view angle encompassing both the anterior and the posterior compartments of the pelvic floor. The possibility to image not only the pelvic organs but also muscle and fascial components of the pelvis offer a possible advantage over standard X-ray imaging and place US in competition with MRI. Three D pelvic floor ultrasound has been used for the evaluation of the urethra and its structures, for imaging of the more inferior aspects of the levator ani complex (pubococcygeus and puborectalis), for the visualization of paravaginal supports, as well as for prolapse and implant imaging. One of the major advantage of 3D US is the possibility to acquire information on a patient “volume”, to store it and to have it available for further analysis and review along any plane.

Figure 60 The axial plane on MRI and US (freehand 3D). While these images were obtained in different patients, all significant structures can be identified by both methods.

Figure 61 The effect of a Valsalva manoeuvre on the levator hiatus (left, at rest; right, on Valsalva) in a young nulliparous woman without significant pelvic organ descent. The dimensions of the levator hiatus are measured in the sagittal (1) and coronal (2) planes.

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Figure 62 The levator hiatus at rest (left) and on Valsalva (right) in a young woman with significant pelvic organ descent. On Valsalva the levator is situated partly outside the

acquisition volume.

Ultrasonography has become an established procedure in the diagnostic evaluation of female incontinence and functional disorders of the pelvic floor and has replaced X-ray procedures to a large extent. Introital ultrasound provide panoramic views of the true pelvis. Sonography demonstrates the dynamics of the temporal change in the positions of the urethra and bladder under standardized Valsalva pressure. Three dimensional ultrasound offers several advantages over two dimensional. Within a scanned volume every plane including sagittal, tranversal and coronal views can be depicted, a reconstruction of the organs can be done and volumes can be accurately measured.

3D ultrasound enables the physicians to very well understand the anatomical relationships of the urethrovesical junction. That could be used to better characterize changes to the pelvic floor, understand the ethiology of incontinence and optimalize therapeutic decisions

Rectovaginal septal defects are readily identified on translabial 3D USG as a herniation of rectal wall and its contents into the vagina. Approximately one third of clinical rectoceles do not show a sonographic defect, and the presence of a defect is associated with age, not parity (Diez et al 2005). While 3D pelvic floor imaging is a field that is still in its infancy, it is already clear that the method has opened up entirely new opportunities for the observation of functional anatomy.

The issue of levator trauma, one of the most significant developments in clinical obstetrics in the last decade, will take pelvic floor ultrasound from a niche application into the mainstream. The crucial issue, as always, is teaching and the provision of up-to-date resources. It may still be another decade or two before this new imaging method truly becomes part of the gynaecological mainstream (Dietz 2007).Table 4 Proposed indications for pelvic floor ultrasound: Recurrent Urinary tract infection Urgency, frequency, nocturia and/or urge urinary incontinence Stress urinary incontinence Insensible urinary loss Bladder related pain Persistent dysuria Symptoms of voiding dysfunction Symptoms of prolapse, i.e. , the sensation of a lump or a dragging sensation Symptoms of obstructed defecation such as straining at stool. Chronic constipation,

vaginal or perineal digitations and the sensation of incomplete bowel empting Faecal incontinence Pelvic or vaginal pain after anti – incontinence or prolapse surgery Vaginal discharge or bleeding anti – incontinence or prolapse surgery

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Figure 63: Standard acquisition screen of 3D pelvic floor ultrasound. The midsagittal plane is shown in (A), the coronal plane in (B), the axial plane in (C) and a rendered axial plane

(i.e., a semitransparent representation of all pixels in the box seen in A–C) in (D).

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INTERVENTIONAL ULTRASOUND

Intrauterine device (IUD):

Sonography is used to confirm the proper insertion, to localize its position in cases of lost strings and to evaluate the cause of pain and bleeding in patients using this type of contraceptions (Allem et al 1992) .

Ultrasonography and embryo-transfer:

Ultrasound-guided embryo transfer has been around since 1985 and has become almost universal in the past three years. The advantages of ultrasound-guided embryo transfers include the facilitation of embryo transfer as well as the physician’s ability to visualize catheter and embryo placement.

Three-dimensional ultrasound enables the physician’s to visualize the uterine cavity as a whole. Three-dimensional sonography can improve visualization of the uterus in patients with normal anatomy and especially in those with uterine anomalies such as bicornuate uterus. Along with the 3D ultrasound the maximal implantation potential (MIP) point is defined.

The uterine cavity resembles an inverted triangle and the fallopian tubes open into the cavity, one in each of the upper regions of the triangle. The MIP is the intersection of these two imaginary lines, one originating in each fallopian tube, within the inverted triangle. In natural pregnancies, implantations usually occurs in the anterior or posterior segment of the uterus close to its trajectory line, where the endometrium is the thickest and has the greatest blood flow. In patients undergoing IVF, the fallopian tubes are bypassed, placing the embryos directly into the uterus. By using the MIP point, placement of the embryos occurs where nature intended.

Because of individual anatomic differences, the MIP point can be individually tailored. Further advances in 3D ultrasonography as well as the introduction of 4D sonography

have enabled us to visualize the transfer catheter in real time as it moves towards its target, the MIP point cavity, after which the MIP point was identified. The physicians sterilized the perineum in the usual fashion using culture media and inserted a speculum into the vagina. Once the MIP was identified by the 3D/4D US machine, the physician inserted the transfer catheter that he or she deemed appropriate (Gergely et al 2005).

Tubal catheterization:

Tubal catheterization performed under fluoroscopic visualization must be very carefully monitored so not exceed the acceptable limit. Ultrasonographic monitoring is inferior in resolution to that of fluoroscopy but, because of the elimination of radiation, this technique is gaining popularity (Brosens et al 1987). The use of ultrasound contrast media and Doppler imaging have improved the accuracy of this modality in the diagnosis of tubal disease during fertility work up (Deichert et al 1989). In addition to diagnosis of tubal disease, trans-cervical tubal catheterization has been employed in the

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treatment of tubal occlusion. This procedure, called transcervical ballon tuboplasty, has been performed with both fluoroscopy and ultrasonography (Confino et al 1988).

Figure 64 IUD in place Figure 65 IUD's in the coronal plane in the cervix

Ultrasound puncture of adnexal cysts:

It is generally proposed only in entirely cyst masses. A puncture is acceptable when the diagnosis of a functional cyst is very likely, in patient with previous ovarian hyperstimulation or in patient whose previous surgical history suggests that severe pelvic adhesions may explain the masses. Ultrasonographic puncture is contra-indicated in masses with thick septae or with more complex appearances. Color flow mapping and color Doppler has been used by (Bonilla - Musoles et al. 1993) to select patients before US guided puncture.

Interstitial brachytherapy:

Brachytherapy plays an important role in the treatment of gynecological malignancies. Recurrent , metastatic or residual tumor can be treated by interstitial brachytherapy using irradiating implants or after load needles. They can be brought into position by abdominal, rectal or transvaginal ultrasound guidance. Correct positioning is critical for therapeutic distribution of the isodoses. Hoetzinger et al (1990) have used rectosonographic guidance for transvaginal positioning of afterloading needles.

Focused ultrasound:

Magnetic resonance imaging–guided focused ultrasound is a promising new noninvasive treatment option for women with symptomatic uterine fibroids. Treated patients were noted to have shorter menstrual cycles (from a mean of 6.1 days before treatment to a mean of 4.9 days after treatment) and longer mean intervals between changing protective pads or tampons (from 1.7 hours at peak flow before treatment to 2.25 hours after treatment). Magnetic resonance imaging– guided focused ultrasound treatment was also effective in patients with pressure symptoms: 49% had complete relief of their symptoms, and another 49% had symptomatic improvement.

Complications and adverse effects resulting from MRgFUS treatment are uncommon. The discomfort patients experience after treatment is usually mild and requires only over-the-counter pain relievers. However, it is important to be aware of potential complications such as skin burns, nerve damage, and deep venous thrombosis (Gianfelice et al 2003). Although MRgFUS has not yet been approved for women who

36

want to preserve their fertility, a recent article described a successful pregnancy after MRgFUS treatment of focal adenomyosis ( Rabinovici et al 2006).

Laparoscopy-assisted intrapelvic sonography:

laparoscopy-assisted intrapelvic sonography with a high-frequency, real-time miniature transducer might be a valuable diagnostic modality for the assessment of tubal texure in tubal disorders, possibly in infertility practice (Senoh et al 1999).

Figure 66 Fimbrial end of Fallopian tube. C catheter.

Myometrial biopsy The basis of possible new modalities of diagnosis of adenomyosis uteri, myoma and lciomyosarcoma for example, might be myometrial biopsy guided by ultrasonography using an automatic cutting needle device. Morphological and immunohistochemical examination of myometrial samples may enable more specific ways of treatment. Parametrial biopsy and biopsy of recurrent or metastatic pelvic tumours For obtaining samples for histological evaluation from an infiltrated parametrium or a suspected recurrent or metastatic pelvic tumour, vaginosonographically guided puncture, comparable to follicular puncture (Querleu 1998).

US Guided ovarian biopsy

Small turnout s might be considered for vaginosonographically guided ovarian biopsy. However, it can be difficult to define the target area within the sonomorphological complexity of many ovarian tumors and high rates of false-negative results must be expected. Also, the risk of needle tract seeding in case of a malignant tumour is unknown (Querleu 1998).

Fetal reduction

Vaginosonographically guided intrachorionic injection of antitrophoblastic substances has been performed since 1987 using methotrexate , potassium chloride, hyperosmolar glucose solution and other substances (Querleu 1998).

Transcervical metro plasty

Transcervical metroplasty is at this time the procedure of choice for the treatment of septate uteri with reproductive failure. Ultrasound scanning enhances the safety of the procedure, as it allows precise checking of the thickness of myometrium left intact.

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Progress in ultrasound imaging has led us to investigate the possibility of performing metroplasty without hysteroscopic vision (Querleu 1998).

Treatment Of Tubal Ectopig Pregnanctfs (SALPINGOCENTESIS): The diagnosis of a tubal ectopic pregnancy is made when a patient presents with a positive 3 human chorionic gonadotrophin (beta-hCG) and on TVS has an empty uterus as well as the typical adnexal ‘ring’ or ‘bagel sign’. Viable tubal ectopic pregnancies may be present in up to one-third of all ectopic gestations. Cases of tubal ectopic pregnancies to be considered for transvaginally guided puncture must meet several criteria: the ectopic gestational sac must contain a viable fetus with a menstrual age of less than 8.5 weeks’ gestation, and the tubal diameter should not exceed 2.5—3 cm. The reported complication rates of salpingocentesis at this time are about ‘5%. However, it is hard to compare the success rate between different groups since there is no agreed basis for comparison. In the literature, different kinds of ectopic pregnancy, non-viable and viable with different gestational ages and different sizes, have been treated by injection. Careful evaluation of these reports reveals that, due to lack of understanding of the natural course of the disease after the injection, some of the reported cases do not match the strict definition of a failed treatment. The most important signs and symptoms of the post-puncture convalescent period include the following. A relatively slow decrease of serum ,beta-hCG levels. The slope of the decay curve for serum 3-hCG levels after salpingocentesis depends upon which substance (potassium chloride or methotrexate) was injected during the procedure. When potassium chloride is injected during salpingocentesis it takes 3 0—80 days for the beta-hCG to become negative. On the other hand, when methotrexate is injected, the 3-hCG levels fall more abruptly, taking only 10—35 days to reach non-pregnant levels . Lower abdominal cram ping or pain. Between 3 and 7 days after puncture the patient may experience lower abdominal pain or cramping . The possible cause of this pain is either uterine contractions as the decidual cast is being expelled from the uterus or tubal abortion with varying degrees of intra-abdominal bleeding. If the patient’s vital signs and the amount of free fluid (blood in the pelvis) is not significant, the patient may be followed up conservatively. Transvaginal sonographic and color Doppler findings. These include increasing distension of the haematosalpinx, increasing color vascu larity and increasing venous spaces (Querleu 1998).

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