(TO TABLE OF CONTENTS)ULTRASOUND IN INFERTILITY WEB BOOK
by Michael Applebaum, MD, JD, FCLM
The following is a revised version of a book chapter that appeared in the text: Doppler Ultrasound in Obstetrics and Gynecology, edited by Drs. Kathy Reed and Josh Copel. It was written primarily for physicians. It is not an easy, casual read for the lay person. However, it can be a worthwhile read.
I have chosen to include the sections on ultrasound scan technique for the health care professionals reading this. If you are an infertility patient, you may find this section and some of the other more technical sections valuable. This information may help you become a more critical consumer of health services.
The numbers in parentheses refer to the references which appear at the end. There are no individual hyperlinks to the references.
TIP! -- If you hyperlink to another section of the book to benefit from the hypertext features, click the "BACK" button of your browser to return to your previous location.
REMEMBER! -- This book is not a substitute for medical advice from your physician. Always consult directly with your physician regarding any and all issues/questions you may have about your treatment.
Introduction
Examination Technique
The Ovaries
The Uterus
The Endometrium
Ovulation Induction and IVF
Conclusion
References
For one practicing diagnostic ultrasound, examination of the female pelvis presents a unique challenge. Virtually no other area within the human body undergoes transformations as frequently as the reproductive tract of a woman during her fertile years. Its organs are not static and change on a daily basis. Familiarity with the diverse presentations of the various structures during different times of the menstrual cycle is important. This allows the experienced sonologist or sonographer to picture, in the "mind's eye", the expected normal appearance prior to performing an ultrasound study. Knowing what to anticipate anatomically, together with the clinical history, makes detection of abnormalities more likely.
Chance favors the prepared mind.
Sonographic examination of the female pelvic organs is most commonly performed using two different approaches. The first and older, is transabdominal, the second and more recent, is transvaginal. (1,2,3) A third method, transperineal, is also employed, though less frequently. (4,5,6) A thorough ultrasound examination of the pelvis should include both complete transabdominal and transvaginal studies, unless either limited information is needed (e.g., follicle size) or extenuating circumstances dictate otherwise (e.g., patient refusal). The techniques are complementary, not mutually exclusive.
The person performing the ultrasound examination can vary certain parameters to optimize the quality of the study. These include: bladder distention, manual manipulation of the anatomy and patient positioning.
BLADDER FILLING -- Transabdominal ultrasound of the female pelvis should be performed with the bladder optimally distended. The operative phrase is "optimally distended". If too full, the patient may experience excessive discomfort, which might result in guarding. Also, the overdistended bladder may push the target structures so far from the transducer that image quality suffers. Optimal distention of the bladder can be achieved by having the patient void incrementally. If too empty, near-field artifacting and overlying bowel gas may degrade image quality. Optimal distention of the bladder can be achieved either by waiting for the bladder to fill more completely or having the patient ingest additional fluid and then waiting.
Unequivocally, there are occasions in which the empty bladder transabdominal examination may yield better results than either the transvaginal or filled bladder approaches. This is particularly true when relatively large, especially fundal, fibroids are present.
Transvaginal (or endovaginal) ultrasound is generally performed with the bladder empty. The operative phrase is "generally performed". If too full, the patient may experience excessive discomfort. Also, the distended bladder may push the target structures so far from the transducer that image quality suffers. Optimal distention of the bladder may be achieved by having the patient void, perhaps incrementally.
Unequivocally, there are occasions in which the transvaginal examination may yield better results with a filled or filling bladder than with an empty bladder. If a structure of interest is either not apparent or is suboptimally seen, patience and bladder filling may result in better visualization.
MANIPULATION -- Manual manipulation of the anatomy using the transducer and/or the non-examining free hand can significantly improve the quality of the study. All manipulations are performed to move target structures into more favorable scanning circumstances (e.g., location). When employing a two-handed technique, one hand is placed generally between the pubis and umbilicus to shift the pelvic and abdominal structures while the other is maneuvering the transducer.
PROBE PRESSURE -- When using any technique, more or less pressure may be placed on the probe. This maneuver improves image quality in a manner similar to manually manipulating the anatomy and, possibly, by compressing the tissue between the transducer and the target structure.
POSITIONING -- Proper patient positioning can also improve examination quality. When performing endovaginal ultrasounds, elevating the patient's hips or placing the patient at the end of the examining table facilitates greater downward excursion of the probe handle. Occasionally, placing the patient's leg on the examiner's shoulder allows for increased lateral range of motion of the transducer. Further, some findings are more apparent when the examination is performed with the patient placed in a position similar to the one employed during a proctoscopy or colonoscopy. To see images demonstrating this technique, click here. With a 14.4 modem, this may take about 1.5 minutes to load.
To assist in characterizing findings, having the patient move or roll from side-to-side may demonstrate motion in structures which would otherwise appear static (e.g., swirling within endometriomas. Endovaginally, palpation with the probe may produce similar results.). Moving the patient can also place target structures in more accessible locations.
In conclusion, after positioning the patient properly, the technique of the ultrasound study can be remembered by the following mnemonic: KID CAN, where:
K = Know what you expect to see based upon the patient's clinical history and presentation prior to the exam
I = Incremental bladder voiding, to achieve...
D = optimal bladder Distention
C = Compression, with the non-scanning hand and/or the transducer
A = Angulation of the transducer to place target objects an optimal distance from the transducer and use favorable superficial structures as acoustic "windows"
N = be Nice to the patient. A relaxed patient is much easier to examine than a tense patient.
THE MOST VALUABLE IMAGING SKILLS WE POSSESS ARE OBSERVATION, CREATIVITY AND TECHNIQUE.
The ovaries are generally situated on either side of the uterus, although locations superior or posterior to the uterus are not uncommon. In addition to the techniques described above, if one has difficulty finding the ovaries, a search along the internal iliac artery may prove useful. The ovary is often located anterior to the vascular bifurcation into anterior and posterior branches. (7,8) Successful visualization of the ovaries varies among investigators and also depends upon patient age. (9, 10)
During the REPRODUCTIVE years of a normal female, the ovaries undergo changes characterized by the cyclical development and resolution of functional cysts. In fact, the identification of an ovary is made by demonstrating follicle cysts surrounded by ovarian parenchyma. (8) The normal dimensions of a pre-menopausal ovary are 2.2 to 5.5 cm in length, 1.5 to 2.0 cm in width and 1.5 to 3.0 cm deep (anteroposterior dimension). (11) Others have obtained different measurements. (12, 13, 14)
The blood supply to the ovaries is derived from two sources. Arising from the abdominal aorta, just caudal to the origins of the renal arteries, the ovarian arteries enter the pelvis through the infundibulopelvic ligament. They reach the ovaries through the hilus via the mesovarium. From each artery originate primary and secondary branches. These branches spiral, perhaps allowing for extension as follicles grow. The ovaries are also supplied by the ovarian branches of the uterine arteries. The ovarian divisions of the uterine arteries anastomose with the ipsilateral ovarian arteries. (15).
The gray-scale findings of the ovaries during the normal menstrual cycle are predominantly related to the development and resolution of follicular cysts. From Day 1 of a normal menstrual cycle until the mid-cycle, progressive enlargement of the follicle cysts occurs. The inner dimension of a mature follicle measures between 17 and 25 mm. (16) The average diameter of a pre-ovulatory follicle is 20 mm. (17, 18) Others have obtained different measurements. (19, 20) Around the mid-cycle, the dominant follicle cyst ruptures, releasing the egg and fluid it contains. (21, 22) The ruptured follicle forms the corpus luteum cyst. (13) This structure will either undergo resolution if no pregnancy occurs or will remain in the event of a normal pregnancy. (23)
It should be remembered that the corpus luteum is the great sonographic mimic within the female pelvis. Its appearance can simulate other entities including an endometrioma, an abscess, a neoplasm or an ectopic pregnancy. (24)
Multiple ovulation is an event which occurs in approximately 5 per cent of unstimulated cycles. (19) Of interest, in our experience, a substantial proportion of spontaneous multiple ovulators have a family history (self, mother, grandmother, aunt, cousin) of multiple births.
Concomitant with the gray-scale changes, both color and duplex Doppler changes can be demonstrated.
The ovarian arterial supply exhibits different flow characteristics during the different phases of a normal menstrual cycle. (25, 26, 27) These phases are: the early follicular phase (days 5-7), the late follicular phase (days 11-13), the early luteal phase (days 15-17) and the late luteal phase (days 26-28). In general, the index values for these arteries are relatively high during the early follicular phase. They progressively decrease to the lower values seen in the early luteal phase. During the late luteal phase a rise in values is seen. (25, 26, 27) The variations are believed to be hormone related and reflect changes in vascular compliance. Increased compliance leads to the increased blood flow seen during the late follicular and early luteal phases. Other patterns have been described. (26)
Kurjak et al. determined that ovarian artery blood flow is detectable when the dominant follicle reaches a size of 12-15 mm. (28) The Resistance Index (RI) is 0.54 +/- 0.04 and declines the day before ovulation. The nadir of 0.44 +/- 0.04 is reached 4-5 days later and rises to 0.50 +/- 0.04 before menstruation.
Differences in flow characteristics between the dominant and non-dominant ovaries have been demonstrated. (25, 27) These differences are significant and appear to develop relatively early during the menstrual cycle. (25, 26, 27) End-diastolic flow may not be seen until later than Day 7. In the ovary containing the dominant follicle, continuous diastolic flow may be seen from one cardiac cycle to the next by the early luteal phase. In contrast, both diastolic flow and cyclical changes may be absent in the ovary without the corpus luteum. (25, 27) Multiple ovulators may not demonstrate interovarian differences in flow velocity waveforms and index values when each ovary contains a corpus luteum.
Color Doppler ultrasound can demonstrate the neovascularity within the wall of the corpus luteum. (21) Demonstrable color flow surrounding the developing dominant follicle becomes more apparent as the mid-cycle approaches and continues around the corpus luteum until the late luteal phase. In the event of a pregnancy, both the low resistance flow AND the color flow to the corpus luteum may remain until approximately the eleventh week of amenorrhea. (29) To see an image demonstrating normal blood flow surrounding a corpus luteum, click here. With a 14.4 modem, this may take about 1.0 minutes to load.
Luteal phase abnormalities may be diagnosed by duplex and color Doppler. The functional status of a corpus luteum may be assessed by detecting its characteristic low impedance flow and the appearance of the color flow surrounding it. (23, 30, vide infra Ovulation Induction and IVF) To see images comparing normal vs. abnormal blood flow surrounding a corpus luteum, click here. With a 14.4 modem, this may take about 1.25 minutes to load.
Is the flow to the corpus luteum different between patients who are pregnant and those who are not? Yes, according to the work of Zalud & Kurjak. (29) Comparing Resistance Index values, these investigators found significant flow differences between the two groups. The RI for pregnant patients (0.53 +/- 0.09) was higher than those who were not pregnant (0.42 +/- 0.12).
Is the flow to the corpus luteum different between patients who are pregnant with ectopics from those who have intrauterine pregnancies (IUPs)? According to these same investigators, the answer is, yes. (29) Patients with ectopic pregnancies were found to have lower RIs (0.48 +/- 0.07) than those with IUPs (0.53 +/- 0.09), but not lower than non-pregnant patients (0.42 +/- 0.12).
Many women on stimulation protocols are concerned about ovarian cancer. Ovarian cancers may manifest their presence as cysts. (10, 44, 51, 52, 53) In fact, 80% of ovarian neoplasms occur in women older than 50 years of age and of these as much as 85% - 90% are of a cystic epithelial type. (40, 54, 55) Also, some patients clinically diagnosed as "post-menopausal" are, in reality, peri-menopausal and continue to "cycle", though irregularly. This latter differential diagnostic possibility can generally be confirmed clinically, biochemically or by follow-up ultrasound examination.
For characterizing a discovered mass, gray-scale and Doppler (both duplex and color) ultrasound, may be of significant utility in distinguishing benign from malignant processes. (45, 48, 49, 56, 57, 58)
Gray-scale sonography has been used with varying success to characterize adnexal disease. (45, 59, 60, 61, 62) Findings such as septations, papillary projections and mural nodules are more likely to be associated with malignant changes than are clear cystic masses. (46, 56, 59, 63) Also, size may be important. (31, 34, 40, 42, 50, 59, 64, 65, 66, 67). Rulin and Preston found that masses less than 5.0 cm were unlikely to be malignant. (42) In their series, only one case of a cystic ovarian mass in 32 (3%) was malignant. In a study by Goldstein et al, the results of sonographically detected simple cysts (defined as cysts without internal septations or solid components) of the adnexa, yielded a 0% incidence of malignancy in patients with cysts less than 5.0 cm in maximum diameter. (40) Hall and McCarthy included septated cysts in their definition of "simple cyst." They found an 8% malignancy rate in their series of cysts ranging from 1.5 to 10.0 cm. The malignancy was within a 3.5 cm non-septated cyst. (67)
Some investigators have concluded that both color and duplex Doppler are valuable tools for the diagnosis of ovarian and other malignancies. (44, 51, 53, 68, 69, 70, 71, 72) These conclusions are based upon the unique differences between normal and tumoral vascularity (neovascularity) and the apparent ability of Doppler sonography to distinguish between them. (68, 73)
Tumor vessels are disorganized. The standard hierarchical organization of normal vessels, in which flow progresses from arteries of decreasing size through capillaries to veins of increasing size, is absent. Instead, tumoral flow may be short-circuited through shunts. (30, 70) Also, tumor vessels may possess altered architecture. (74, 75)
Abnormal flow patterns can be demonstrated in vessels surrounding malignant masses. (70, 76, 77) Finding these areas of neovascularity may not be possible on gray-scale examination only. Because color Doppler may make these vessels visible, it allows the examiner to survey the anatomy of the target structure for vascular areas of interest. (78)
There is substantial data to suggest that the flow characteristics of some malignant diseases of the ovary are different from benign processes. (29, 44, 53, 79, 80) In general, a low resistance pattern is unusual in the ovary of a post-menopausal patient, as are low index values, and may be associated with malignancy. (52) False positives do occur. (44) The absence of neovascularity and the presence of a normal index value has been shown to exclude malignancy, while the presence of neovascularity had a high association with malignant change. (51, 81)
When performing a Doppler ultrasound for adnexal masses, it should be performed between days 3-10 of the menstrual cycle in menstruating patients; between days 3-10 in post-menopausal patients on hormone replacement therapy; at anytime in post- menopausal patients not on replacement. (78)
The uterus is located in the lesser pelvis between the urinary bladder and the rectum. Although generally a midline structure, lateral deviations of the uterus are not uncommon. The broad ligaments extend from the uterus laterally to the pelvic side walls. They contain the fallopian tubes and vessels. The uterosacral ligaments serve to keep the uterus in an anterior position. They arise from the upper cervix posteriorly and extend to the fascia over the second and third sacral vertebrae. The round ligaments arise anterior to and below the fallopian tubes and cross the inguinal canal to end in the upper portion of the labia majora. (82)
The normal adult uterus measures approximately 7.0 - 9.0 cm long, 4.5 - 6.0 cm wide and 2.5 - 3.5 cm deep (anteroposterior dimension). (82) Its corpus-to-cervix ratio is 2:1. (82, 83) To see an image demonstrating a normal appearing uterus, click here. With a 14.4 modem, this may take about 1.0 minutes to load.
The blood supply to the uterus is via the uterine artery, a branch of the internal iliac artery. This vessel enters the uterus at the cervico-corporal junction and ascends along the lateral aspect of the uterine body to the cornua. At the uterine cornua an adnexal branch originates which supplies the ipsilateral ovary and anastomoses with the ipsilateral ovarian artery. (84)
From the uterine artery arise perforating branches which extend through the serosa. The uterine arteries anastomose through the anterior and posterior arcuate vessels. These vessels are located in the outer one-third of the myometrium, between the exterior longitudinal muscle fibers and the inner oblique muscle fibers. (85)
The blood supply to the endometrium is derived from branches of the uterine arteries. Radiating from the arcuate arteries are the radial arteries. These vessels extend through the myometrium to just outside the endometrium where they form terminal branches of two types: straight and coiled. The straight branches, also called basal arteries, supply the basalis layer of the endometrium. The coiled branches, also called spiral arteries, traverse the endometrium and supply the functionalis layer. The spiral arteries, like the endometrium and unlike the basal arteries, are remarkably responsive to the hormonal changes of the menstrual cycle. (86)
During the REPRODUCTIVE years of a normal female, the uterus undergoes sonographically detectable changes characterized by cyclical alterations in the appearance of the endometrium. In fact, it is possible to infer the approximate day of a normal woman's menstrual cycle by the ultrasound appearance of her endometrium. (87)
From Day 1 of the menstrual cycle until the mid-cycle, progressive thickening and layering of the normal endometrium occur. Past the mid-cycle, brightening and progressive thinning of the endometrium occur. (88) These sonographic endometrial patterns appear to be related to the changes in the glandular and vascular elements of the endometrium during the menstrual cycle. (89, 90, 91)
Fleischer et al determined that the endometrium is thickest during the secretory phase (3.6 +/- 1.4 mm), less thick during the proliferative phase (2.9 +/- 1.0 mm) and thinnest during menstruation. (90, 91) The values obtained are for half-thickness as measured from the endometrial canal to the endometrial-myometrial interface. Full thickness measurements ranged from 4 to 12 mm, with an average thickness of 7.5 mm. The endometrium will either slough if no pregnancy occurs or will undergo various changes in the event of a pregnancy.
Concomitant with the gray-scale changes, both color and duplex Doppler changes can be demonstrated.
The general pattern of uterine blood flow throughout the menstrual cycle is that perfusion increases in response to rising plasma estrogen and progesterone and decreases with the periovulatory fall in estrogen. (29, 92, 93, 94) The lowest Pulsatility Index (PI) values are seen around Days 8 and 21, while the highest values are seen around Days 1, 14 and 17. (92, 94) Significant changes in diastolic blood flow at the different times of the cycle may not be noted. (26, 95) In general, the index values for the uterine artery ipsilateral to the ovary containing the dominant follicle are lower than the contralateral artery. (87)
Other patterns of uterine artery blood flow have been described. (87) When the uterine arteries were interrogated at the level of the uterine cornua, the PI reached its peak by Day 11 and remained relatively constant until Day 16. The lowest values were generally seen around Days 1 and 21. At this anatomic level, end-diastolic flow was commonly absent during the early follicular phase but was demonstrable by the luteal phase.
The cyclical changes reflected by the flow velocity waveforms and index values appear to be mediated by the reproductive hormones. (96) Patients with inactive ovaries on transdermal estradiol and vaginal progesterone therapy were studied using transvaginal ultrasound technique. These patients received their medications on a 28 day regimen. The baseline evaluation (pre-treatment) demonstrated a narrow systolic spectral flow pattern with a mean PI of 5.2 +/- 0.4. Evaluations performed on Days 13-14, showed a spectral tracing that was broader with an uninterrupted diastolic component. The mean PI was 1.5 +/- 0.2. On Days 26-27, no significant differences were noted (mean PI = 1.7 +/- 0.3).
The blood flow to the endometrium undergoes changes which are described below (vide infra, Ovulation Induction and IVF)
In the event of a pregnancy, low resistance flow to the uterus remains. In my experience, the finding of blood flow within the endometrium, on gray-scale examination, has been reliably associated with the gravid state. (97) I have seen this in both IVF and non-IVF patients. False positives or false negatives have rarely occurred. This flow has been visible as early as Day 27 after the last normal menstrual cycle, prior to visualization of the gestational sac and with a beta hCG of 156. (97) The distribution of this finding may not be generalized. This is similar to the pathologic specimens in which endometrial changes induced by the sex hormones demonstrate non-uniform, regional differences. (86) In one case, very localized changes were demonstrated. It was in this area that the gestational sac eventually appeared. Histologically, at the time of implantation (the seventh day following ovulation), hypertrophic and proliferative changes of the spiral arterioles occur within the endometrium. (86) As the blastocyst implants over these spiral vessels, those beneath the lower pole of the implanting blastocyst hypertrophy further with the capillaries in the surrounding stroma dilating widely and their walls thinning. It is possible that these are the changes that were reflected on ultrasound examination. (86) The finding of endometrial blood flow is not specific for intrauterine gestations, as it can be seen in the presence of ectopic pregnancies. (97, 98) Perhaps this represents a sonographic appearance of the Arias-Stella reaction. (99)
All IVF treatment regimens are designed to maximize the likelihood of a successful implantation (and, hopefully, a take-home baby). To this end, IVF protocols attempt medical hyperstimulation of the ovaries to produce multiple follicles of sufficient size for an egg harvesting procedure. (122) The aspirated eggs are exposed to sperm for fertilization. Fertilized eggs are subsequently transferred to the uterus via catheter, in the hope that one or more will implant. Other strategies, such as ZIFT (zygote intrafallopian transfer), GIFT (gamete intrafallopian transfer) and transfer of thawed embryos are also employed. (123)
Infertility is the end result of numerous causes. These include (this list is not exhaustive):
Many of these conditions are diagnosable by ultrasound.
Rather than describe each of the myriad causes of infertility, the reader is referred to the available texts on this subject. Instead, some of the more common causes, their associated ultrasound findings and the potential value of Doppler imaging will be presented.
FIBROIDS -- Uterine leiomyomas may be associated with infertility. (124, 125) Although fibroids are generally seen on gray-scale examination, their borders are not always well demarcated. In this situation, color flow Doppler imaging may be of benefit. Frequently, vascular structures can be seen surrounding the myoma, making localization and measurement more accurate. This can be of significance in patients undergoing medical treatment to decrease fibroid size and blood flow prior to surgical removal or attempted IVF. (126, 127) Monitoring is thereby made easier. Patients receiving gonadotropin-releasing hormone (GnRH) agonists demonstrate impedance to vascular flow while on treatment. This suggests that any decrease in fibroid size may be related to hypo-estrogenic mediated reduction in blood flow. (128) I have investigated pre-and post- treatment flow velocities to fibroids, but have yet to define predictors of response to medical therapy with GnRH agonists. Of interest, careful examination using gray-scale can also reveal flow differences between fibroids and the surrounding myometrium. Also, color Doppler can help make an otherwise isoechoic myoma apparent by demonstrating either its blood supply or the vessels it displaces.
ENDOMETRIOSIS -- Endometriosis is also associated with infertility. The mechanism by which this occurs is either mechanical or uncertain. Gray-scale scanning may detect the classical homogeneously echogenic intraovarian endometrioma. Occasionally, small endometriomas may appear as subtle, mottled areas within the ovary. Again, color Doppler may demonstrate flow around and not within these apparently solid structures, thereby highlighting and confirming their presence and suggesting the diagnosis. Extraovarian endometriosis is usually difficult to visualize.
TUBAL ABNORMALITIES -- The application of ultrasound to the diagnosis of tubal abnormalities has been broadened through the use of Doppler. By using contrast medium and duplex Doppler, disorders, especially obstructions, can be evaluated with greater accuracy than by gray-scale alone. (129) To diagnose patency, the addition of color flow Doppler may not provide any advantage over duplex Doppler. (130) Fallopian tube masses can be diagnosed and characterized by color and duplex Doppler techniques. (131)
VASCULAR -- The possibility that decreased uterine blood flow may be associated with infertility was investigated by Goswamy et al. (132) In their study, the uterine arteries of patients who had been unsuccessful in 3 attempts at IVF were interrogated using Doppler ultrasound. Almost half demonstrated a poor mid-secretory uterine response. Of these, patients demonstrating improved uterine perfusion on oral hormone therapy had a pregnancy rate comparable to or better than that obtained in the first three attempts by other patients. Although the numbers of patients in each group studied were too small for statistical analyses, the trend suggested that improving uterine perfusion may improve the outcome of IVF therapy. Two years later, results from a greater number of patients were reported. (133) This confirmed the results of the earlier work. The data indicated that 20% of all women undergoing IVF therapy would have poor uterine perfusion. This latter work utilized the concept of a Perfusion Index to analyze the flow velocity waveform. This index is derived from the ratio of the area under the curve of the systolic component of the flow velocity waveform (*S) over the area beneath the diastolic component (*D) (Perfusion Index = *S/*D). This analysis allows for a different approach to the evaluation of the waveform.
In preparation for implantation, the endometrium undergoes transformations influenced by the ovarian hormones produced during the early secretory phase. These modifications include: an increased rate of blood flow, an increase in the number of cells in the stroma and epithelium, an increase in uterine oxygen consumption, an increase in oxygen diffusion into the uterine lumen and a generalized edema. (13) The spiral arteries, like the endometrium (and unlike the basal arteries), are remarkably responsive to the hormonal changes of the menstrual cycle and undergo transformations, as well. (86) These include: endothelial proliferation, wall thickening and coiling. These vessels play an important role in implantation. The chances for a normal implantation may be reduced if the spiral arterioles are inadequately developed. (100)
In my experience, changes in endometrial vascularity appear present on color Doppler examination which may reflect the histologic changes described by the pathologists. (134, 135) Vascular penetration towards the endometrial canal differs among patients. Some investigators appear unable to demonstrate this. (136) Perhaps this is due to equipment or technique differences.
If one divides the endometrial and periendometrial areas into the following four zones :
Zone 1 -- a 2 mm thick area surrounding the hyperechoic outer layer of the endometrium
Zone 2 -- the hyperechoic outer layer of the endometrium
Zone 3 -- the hypoechoic inner layer of the endometrium
Zone 4 -- the endometrial cavity
it is possible to see variations in the depth of vascular penetration before, during and after the mid-cycle. In patients with uterine artery PIs of less than 3.0, my preliminary results have not revealed any successful pregnancies in IVF patients unless there is vascularity demonstrated either within Zone 3 or within Zones 3 and 4 prior to transfer. Successful pregnancies with demonstrable blood flow in Zone 4, suggesting the presence of an intracavitary mass, have been noted. I have also been looking at both the thicknesses and the relative thicknesses of these Zones, the spectral tracings obtained from the different Zones, the ratio of the index values and the ratio of the values obtained from the endometrial vessels and the uterine and ovarian vessels, but have yet to reach a conclusion. Most patients without diagnosed infertility (presumed normal) usually demonstrate flow into Zone 3 by the mid-cycle. (134) I have not yet determined if patients without both diagnosed infertility and mid-cycle flow past Zone 2 are more likely to be infertile. Such a prospective study may prove interesting. (Figures 5, 6, 7, 8, 9)
These color Doppler findings in unsuccessful cycles may relate to the histologic findings described by Sterzik et al. (137) In their study of 58 IVF patients, a majority demonstrated an immature endometrium at the time of embryo transfer. The abnormalities included a variety of patterns, all indicating a lack of secretory transformation, suggesting unpreparedness for implantation.
The complete evaluation of the IVF patient may require attention to the gray-scale appearance of the endometrium as well. Glissant et al noted that the thickness of the endometrium was significantly greater in cycles resulting in a pregnancy than those which did not, although it was not possible to predict the probability of a pregnancy based upon endometrial thickness. (138) In contrast, Welker et al were unable to relate endometrial thickness to outcome, but were able to relate endometrial pattern to outcome. In their experience, the five-line appearance was the most likely to be associated with implantation. (139) Smith et al felt that both endometrial thickness and pattern were important. (140) Other investigators have also looked at the relationship between endometrial thickness or texture and outcome. (141, 142, 143, 144)
In a retrospective study of non-IVF medically stimulated cycles, Kepic et al determined that endometrial thickness and pattern, follicle size and estradiol levels correlated not only with the likelihood of pregnancy, but also with subsequent outcome (i.e., miscarriage v. non-miscarriage). (145, 146)
During ovarian stimulation, the waveform and index value differences normally noted between the two ovaries may be absent. Bilaterally, the ovarian arterial blood supply may demonstrate pulsatility waveforms typical of low impedance. (27)
During the stimulation process, ultrasound has its greatest contribution in monitoring follicular development and guiding the oocyte harvesting procedure. (147, 148)
Different stimulation protocols may produce mature follicles at different size thresholds. (149) Also, the gross sonographic morphology of the follicles may be different depending on the medication used. For example, ovaries stimulated with human menopausal gonadotropins tend to have more polygonal cysts and "stacked coin" appearances, while clomiphene citrate induced follicles are generally more spherical. Depending on the stimulation protocol, aspiration may be performed following the administration of hCG. The hCG acts as a surrogate LH surge. (122) The timing of the hCG administration may be determined by the size of the follicles. (150, 151) Gray-scale evaluation of ovarian follicles can help distinguish physiologic from insufficient or abnormal cycles. Transvaginal color Doppler can be employed to assess the physiologic development of the follicles through depiction of flow parameters. (85, 152, 153)
Egg aspiration, performed transvaginally under ultrasound guidance, is considered the state of the art. Prior to this method, various laparoscopic techniques were employed. (154, 155) Obviously, the ultrasound guided procedure is far less invasive. (156)
The application of duplex and color Doppler ultrasound to the aspiration phase of the IVF process is not widespread. This is to be expected because:
1) there is good success in monitoring follicle growth and obtaining eggs using gray-scale technique only, and
2) the inherent annoyance in monitoring an aspiration under color Doppler (due to motion artifacting) would be undesirable.
Ovarian Hyperstimulation Syndrome (OHS) is one of the possible complications of IVF treatment. Various investigators have attempted to predict its occurrence. (157, 158) Generally, the presence of multiple small or intermediate size follicles prior to stimulation is associated with the development of OHS, while the presence of several large follicles is associated with no OHS development. Color Doppler imaging is most useful for the diagnosis of ovarian torsion, a complication of OHS. In this case, lack of blood flow may be demonstrated. It is important to remember, that the ovary possesses a dual blood supply, one of which may be compromised to a greater degree than the other. Duplex Doppler findings include a lack of diastolic flow with a "spike" configuration of the systolic peak or a loss of phasic venous flow. (159)
Some IVF programs use ultrasound to guide the transfer catheter to an optimal location by the uterine fundus. (156) This is accomplished using gray-scale technique. Others use ultrasound to guide GIFT procedures, claiming superiority over hysteroscopically guided tubal cannulation. (160)
Doppler ultrasound has been used as a means to predict a negative outcome for a given IVF cycle. Pre-transfer, if failure could be predicted, the embryos could be frozen until a more favorable cycle occurs. This could prevent embryo wastage and subsequent patient disappointment. Post-transfer, earlier prediction of failure could help some patients cope better with the setback.
Sterzik et al examined the ovarian and uterine arteries on the day of follicle aspiration. The conclusion they derived was that in patients who became pregnant after embryo transfer, the RI of the uterine arteries was significantly lower than those who did not get pregnant. (137)
Steer et al demonstrated that patients with a low uterine artery PI on the day of embryo transfer were more likely to conceive than those with a high PI. In this series, no one with a PI > 3.0 conceived. (161)
In my experience, inadequate vascular penetration of endometrial blood flow (not within Zone 3) prior to transfer has been associated with an unfavorable outcome (vide supra).
Taylor et al showed that the absence of luteal flow could be used to predict an abortion. (30) In general, the normal corpus luteum demonstrates relatively bright flow almost completely around its periphery. In both the IVF and non-IVF settings, I have seen pregnant patients whose corpus luteum demonstrated subjectively decreased color flow -- either in intensity or surface area. This has accompanied both low progesterone levels and subsequent embryonal demise. Whether earlier detection and initiation of treatment would salvage such a pregnancy remains to be seen.
Baber et al, showed that patients with a successful transfer cycle, demonstrated RI values for the blood flow to the corpus luteum that were significantly different from those who were unsuccessful.
These investigators concluded, that no patients who became pregnant had an RI greater than 0.5. Spectral tracings, without color visualization of the vessels, were obtained. (162)
Battaglia et al, demonstrated a progressive decrease in the PI of the uterine arteries during the second half of the menstrual cycle in successful IVF pregnancies. (163)
Of course, one of the consequences of IVF is an increased incidence of ectopic pregnancy. According to Taylor et al, transabdominal duplex Doppler evaluation appears superior to gray-scale technique in diagnosing extrauterine gestations. (30) For Doppler, the positive predictive value (PPD) was 85% and the negative predictive value (NPD) was 81%. For gray-scale the PPD was 47% and the NPD was 60% Color flow Doppler ultrasound evaluation of ectopic pregnancies has been performed. (164, 165) Transvaginally, ectopics may appear as very colorful areas of low impedance flow with an RI below 0.40, although others have obtained different values. (166) (Figures 12, 13) It has been suggested that the behavior of ectopic pregnancies may be predicted based upon the duplex and color Doppler findings. (30, 167, 168) This may assist in making management decisions and choosing the correct treatment. (166, 167)
Ultrasound imaging of the female pelvis has contributed greatly to the understanding, identification, diagnosis, treatment and management of numerous conditions. The introduction of endovaginal scanning represented a quantum leap in our ability to image the anatomy. The advent of Doppler imaging, both duplex and color, has enabled us to extend our evaluation much further. We now possess the means to perform a sonographic physiologic assessment of the structures we visualize. How we apply this technology is currently limited only by our imaginations.
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