Special contribution FERTILITY AND STERILITY Copyright

Cl

1991 The American Fertility Society

Vol. 55, No.4, April 1991

Printed on acid-free paper in U.S .A.

Ultrasound imaging-2000: assessment of utero-ovarian blood flow with transvaginal color Doppler sonography; potential clinical applications in infertility*

Arthur C. Fleischer, M.D.t Departments of Radiology and Radiological Sciences, and Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee

The recent incorporation of color Doppler processing in transvaginal transducer/probes extends the scope of sonographic imaging from an anatomic to a physiological basis. The ability to assess uteroovarian blood flow will have several applications in the assessment of women with fertility problems. Specifically, changes in ovarian and uterine perfusion during spontaneous or induced folliculogenesis can be assessed and thereby optimized so that embryo replacement is performed when most conductive to implantation. Other possible applications of transvaginal color Doppler sonography include definitive diagnosis of ovarian torsion, assessment of perfusion to either normotopic or ectopic early (5 to 9 weeks) pregnancies by their choriodecidual flow, and detection and differentiation of sonographically complex benign ovarian masses from malignant ones. INSTRUMENTATION AND SCANNING TECHNIQUES

Color Doppler imaging involves detection of changes in phase and frequency in the incident and returned ultrasonic beam. This change in frequency and phase is primarily related to the flow of blood

Received November 1, 1990; revised and accepted December 5,1990. • The Herbert C. Thomas, M.D., Ortho Lecture, Presented at the 46th Annual Meeting of The American Fertility Society, Washington, D.C., October 13 to 18, 1990. t Reprint requests: Arthur C. Fleischer, M.D., Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2675. 684

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cells within blood vessels. With color flow Doppler sonography, flow toward the transducer is encoded in shades of red, flow away in blue, and highest frequencies in white shades. The frequency waveforms seen in a frequency spectrum can be analyzed according to their frequencies in systole and diastole. The resistive and pulsatility indices are used to quantitate blood flow because they are unitless and angle-independent. The resistive index is defined as the systolic peak minus diastolic peak divided by the systolic peak and ranges from 1.0 to 0, with 1.0 representing the highest resistance for forward flow. The pulsatility index, on the other hand, takes into account more of the frequencies in the waveform and is defined as the systolic peak minus diastolic peak divided by the mean. To calculate a pulsatility index, the frequency peaks are traced manually, and the on-board computer calculates the mean frequencies and the pulsatility index. If the vessel itself is seen and its size and angle of interrogation can be calculated, a volume flow can be determined. This is usually difficult because these two parameters are not evident in the smaller pelvic vessels. However, with further refinement in transducer reception, it may be possible to detect vessel size and course more accurately, thereby allowing calculation of a volume flow. In the future, it may also be possible to derive a "vascularity index" by the estimation of the number of pixel elements excited with color in the digitized memory of the scanner. Also, by automatic differentiation of typically phasic arterial from homogenously lower frequency turbulent venous flow, it may be possible to assign red colors to oxygenated and blue to deoxygenated blood. Fertility and Sterility

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c Figure 1 Uterine blood flow. (A), Triplex image showing arterial waveform arising from main uterine artery. This image was taken during follicular phase; (B), Triplex image of main uterine artery showing increased diastolic flow (arrowhead) during secretory phase; (C), Triplex image showing venous flow from main uterine vein; (D), Transvaginal color Doppler image showing arcuate and radial vessels; and (E), Dilated and tortuous uterine vein adjacent to uterine cervix.

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Figure 2 Ovarian flow. (A), Arterial flow to ovary containing two immature follicles. Pulsatility index= 1.89; (B), Triplex image of ovary containing mature follicle demonstrating arterial flow; (C), Same as A showing venous flow; (D), Triplex image of right ovary containing two immature follicles. There is absent and reversed diastolic flow; and (E), Same patient as D in the luteal phase showing increased diastolic flow arising from artery within the wall of the CL.

The interobserver and intraobserver error for calculation of the pulsatility index in the uterine and ovarian arteries has been studied in a few limited series. 1•2 The coefficient of variation for measurement of the ovarian and uterine arteries 686

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ranges from 4% to 39%. Thus, the calculation of a pulsatility index is a relatively reliable but imperfect measurement. Variables include the angle at which the vessels are studied and the gain settings used. Fertility and Sterility

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c Figure 3 Induced ovulation. (A), Triplex image showing respiratory variation in venous return arising from ovary containing three immature follicles; (B), Same patient after ovulation induction with Pergonal (Serono Laboratories, Inc., Norwell, MA) showing several mature follicles. Venous flow is demonstrated; and (C), Triplex image of hyperstimulated ovary showing increased diastolic flow.

The intensities used for transvaginal color Doppler sonography are below the suggested limit of 94 mw/cm2 (spatial peak temporal average) by the Food and Drug Administration (Washington, D.C.). Because the use of color Doppler alone is associated with less intensities than when combined with pulsed Doppler, it is recommended that the use of pulsed Doppler be limited only after an optimal field of view is established by color Doppler. The image derived by transvaginal color Doppler sonography is termed "triplex" because it involves a simultaneous color Doppler image with a waveform derived from pulsed Doppler interrogations. The simultaneity of the imaging process allows placement of the sample volume of the pulsed Doppler over specific vessels.

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Currently, the cost of a transvaginal color Doppler sonography scanner is approximately $250,000. However, with electronic refinement and economic competition, it is anticipated that the cost of such a scanner for gynecological purposes would be approximately $150,000. Although this cost would preclude office use, it is anticipated that transvaginal color Doppler sonography will be used at most major infertility clinics in the next few years. NORMAL UTERO-OVARIAN CIRCULATION

Because of the proximity of the transvaginal probe to the uterus and ovaries, both major (i.e., main uterine, ovarian) and the smaller vessels (i.e., ar-

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pregnancy showing arterial flow within choriodecidua. Resistive index = 0.64; (B), Same as A showing venous flow; (C), Transvaginal color Doppler sonography of a twin 6-week pregnancy demonstrating vessels within choriodecidua even in an area of retrochorionic hemorrhage (arrowhead); and (D), Pregnancy within one horn of a bicornuate uterus. No flow is seen within decidua of nongravid horn, whereas choriodecidual flow is seen surrounding the living fetus.

cuate, radial) within the uterine and ovarian parenchyma can be depicted and flow characteristics analyzed. 3 The main uterine artery and vein are best depicted at the cervico-corporeal junction. The main uterine artery and vein course along the lateral aspect of the uterine corpus, giving off an adnexal branch to the ovary near the cornu. Within the uterus, the arcuate vessels can be seen along the outer one third of the myometrium (Fig. 1). Occasionally, the radial branches from the uterine arteries and veins can be depicted coursing toward the endometrium. The ovary has a dual blood supply: one derived from the adnexal branch of the uterine artery and one as a branch directly from the abdominal aorta. Transvaginal color Doppler sonography is helpful

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in depicting both of these blood supplies (Fig. 2). Two studies, one with duplex Doppler and the other with transvaginal color Doppler sonography, have examined changes in the pulsatility index in uterine and ovarian vessels during induced and spontaneous cycles. In general, the uterine pulsatility index decreased during the secretory phase because of increased diastolic flow within the corpus luteum (CL).4 Higher pulsatility indices are typical in the late secretory and menstrual phases, with intermediate values during the follicular phase. These changes seem to depend on the formation of a mature dominant follicle and its conversion to a functional (endocrine) CL. Whether these changes in pulsatility indices are statistically significant and, therefore, of clinical value remains to be studied in

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Figure 5 Ectopic pregnancy. (A), 7-week EP with exuberant flow within the choriodecidua imbedded within the tubal wall; (B), Cervical EP showing arterial flow within choriodecidua at the beginning of methotrexate therapy; (C), Same as B showing venous return; (D), Same patient as in Band C after four doses of methotrexate showing reduced arterial velocities; and (E), Same as D showing reduced venous flow.

larger populations of normal patients. However, in our experience with five patieuts who were studied in the proliferative, midcycle, and secretory phases

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of the cycle, a trend toward decreased pulsatility indices (average drop with formation of the CL was 0.7) in the uterine and ovarian arteries was found.

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Figure 6 Ovarian masses. (A), Endometrioma appearing as a complex mass. The high pulsatility index indicated that it was benign; (B), Slightly enlarged ovary in patient 9 weeks pregnant demonstrating no arterial flow to ovary confirming the diagnosis of ovarian torsion. This ovary was successfully detorsed; (C), Hemorrhagic ovarian cyst with moderate diastolic flow; and (D), Solid mass with marked diastolic flow and a low pulsatility index (0.9) from ovarian malignancy.

Changes in pulsatility index were more evident within single individual cycles rather than taken as a group.

OVULATION INDUCTION

Duplex Doppler sonography (using transvaginal sonography and duplex Doppler without color identification of vessels) has demonstrated in one study a clear correlation with follicular development and pulsatility index. 5 The stimulated ovary containing mature follicles tends to have higher arterial velocities as well as venous return (Fig. 3). The pulsatility index is also dependent on the number of mature follicles present. In another study performed with duplex Doppler sonography, improved conception rates with increased uterine perfusion were documented. 6 690

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Transvaginal color Doppler sonography affords assessment of the hyperstimulated ovary for the presence or absence of arterial and venous flow. It is possible that, with hyperstimulation, transvaginal color Doppler sonography can detect reduced venous flow relative to arterial flow that contributes to a back-up of venous blood within the ovary. Evaluation of uterine perfusion with transvaginal color Doppler sonography may have implications to the probability of conception. Those uteri with sustained diastolic flow in the early and midsecretory phase seem to have a higher chance for conception. 6 In addition, those that demonstrate sustained diastolic flow arising from a well-formed and functioning CL may promote successful implantation. 4•7•8 EARLY PREGNANCY

The chance of being pregnant after embryo transfer (ET) has been studied with transvaginal color Fertility and Sterility

Doppler sonography.8 In a limited series of in vitro fertilization and ET, a pulsatility index > 3 was found to be associated with little chance for conception. In fact, the authors suggest that if the pulsatility index is >3 on the day of ET, the embryo should be cryopreserved for transfer in a subsequent cycle. Transvaginal color Doppler sonography may have a role in assessing the development of adequate choriodecidual vascularity. In early pregnancies, choriodecidual arterial and venous signals can be seen within the spiral arteries and endometrial veins (Fig. 4). In abortions or nonviable pregnancies, there is initially reduced or absent diastolic flow followed occasionally by increased diastolic flow secondary to disrupted choriodecidual flow. However, the accuracy of this determination awaits confirmation. Transvaginal color Doppler sonography may be helpful in identifying early ectopic pregnancies (EPs) that may not demonstrate a definite adnexal or tubal ring with conventional transvaginal sonography (Fig. 5). However, for transvaginal color Doppler sonography to detect flow within a chorionic ring, a minimum threshold velocity must be present, which may be below velocities that are detectable with currently available scanners. OTHER APPLICATIONS

Preliminary work suggests a difference in the diastolic blood flow in benign versus malignant ovarian masses (Fig. 6).9-11 With malignant masses, there is typically a paucity of muscular lining of the tumor vessels. This finding, combined with increased arteriovenous shunting within the tumor, increases diastolic flow and results in low pulsatility indices. In our series of approximately 30 ovarian masses, five malignancies could be differentiated from their benign counterparts with overlap in one endometrioma that incited a vascular peritoneal response. 11 Other applications of transvaginal color Doppler sonography may include detection of parauterine vessels that should be avoided during needle aspirations. Similarly, dilated uterine and ovarian veins may be seen in some patients with pelvic congestion. The enhanced ability of transvaginal color Doppler sonography to detect flow may be used to evaluate contrast infused within the uterine lumen and tube to determine tubal patency, thereby supplementing or replacing the need for a hysterosalpingogram or replacing the need for a hysterosalpingogram in some cases. 12

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In summary, transvaginal color Doppler sonography promises to have a major role in sonographic imaging in the 21st century. The added information concerning vascular physiology of the uterus and ovaries may help in management decisions as well as in therapeutic trials involving induced ovulation. Acknowledgments. The author acknowledge the contribution of Donna M. Kepple, R.D.M.S., Vanderbilt University Medical Center, in obtaining the images displayed in this article, and the assistance of the Toshiba America Medical Systems, Inc. (Tustin, California) in providing the transducer prototype is also appre· ciated. Publication of the color plates was underwritten by To· shiba America Medical Systems, Inc.

REFERENCES 1. Farquhar CM, Rae R, Thomas DC, Wadsworth MS, Beard RW: Doppler ultrasound in the nonpregnant pelvis. J Ultrasound Med 8:451, 1989 2. Steer CV, Campbell S, Pampiglione JS, Kingsland CR, Mason BA, Collins WP: Transvaginal colour flow imaging of the uterine arteries during the ovarian and menstrual cycles. Hum Reprod 5:391, 1990 3. Scholtes MCW, Wladimiroff JW, van Rijen HJM, Hop WCJ: Uterine and ovarian flow velocity waveforms in the normal menstrual cycle: a transvaginal Doppler study. Fertil Steril 52:981, 1989 4. Zalud I, Kurjak A: The assessment of luteal blood flow in pregnant and non-pregnant women by transvaginal color Doppler. J Perinat Med 18:215, 1990 5. Deutinger J, Reinthaller A, Bernaschek G: Transvaginal pulsed Doppler measurement of blood flow velocity in the ovarian arteries during cycle stimulation and after follicle puncture. Fertil Steril51:466, 1989 6. Goswamy RK, Williams G, Steptoe PC: Decreased uterine perfusion--a cause of infertility. Hum Reprod 3:955, 1988 7. Baber RJ, McSweeney MB, Gill RW, Porter RN, Picker RH, Warren PS, Kossoff G, Saunders DM: Transvaginal pulsed Doppler ultrasound assessment of blood flow to the corpus luteum in IVF patients following embryo transfer. Br J Obstet Gynaecol 95:1226, 1988 8. Tan SL, Steer C, Mills C, Rizk B, Mason BA, Campbell S: Vaginal colour Doppler assessment on the day of embryo transfer (ET) accurately predicts patients in an in-vitro fertilisation (IVF) programme with suboptimal uterine perfusion who fail to become pregnant. (Abstr. 0-070) Presented at the 46th Annual Meeting of The American Fertility Society, Washington, D.C., October 13 to 18, 1990. Published by The American Fertility Society, in the Program Supplement, 1990, p 530 9. Bourne T, Campbell S, Whitehead M, Collins W: Transvaginal colour flow imaging: a possible new screening technique for ovarian cancer. Br Med J 299:1367, 1989 10. Kurjak A, Jurkovic D, Alfirevic Z, Zalud I: Transvaginal color Doppler imaging. JCU 3:52, 1990 11. Fleischer A, Rao B, Kepple D: Transvaginal color Doppler sonography of ovarian masses. J Ultrasound Med. (In press). 12. Coulam C: Personal communication, 1990

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Ultrasound imaging--2000: assessment of utero-ovarian blood flow with transvaginal color Doppler sonography; potential clinical applications in infertility.

Special contribution FERTILITY AND STERILITY Copyright Cl 1991 The American Fertility Society Vol. 55, No.4, April 1991 Printed on acid-free paper...
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