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24
M. Murtinger et al.
SonoAVC (GE Medical Systems, Kretztechnik, Zipf, Austria) are user-friendly systems, which can accurately determine follicle number and size.
Currently, 3D ultrasound is widely used for monitoring the course of pregnancy. It allows imaging the developing fetus. With the quality 3D images that this type of ultrasound produces, physicians can clearly assess the health condition of the infant or any anomalies, such as cleft pal­ate, spina bifi da, anencephaly, and cardiac defects. It provides quantifi able nuchal scan mea­surements to facilitate the calculation of the risk of chromosomal defects such as Down syndrome [ 41 ]. In addition, it facilitates gender determina- tion [ 42 ]. 3D ultrasound is not only applied in fetal and gynecologic imaging, but also in other medical procedures such as surgeries or biopsies [ 43 , 44 ]. Moreover, 3D US is being adopted by other medical fi elds such as cardiology and neu­rology [ 45 – 47 ]. Furthermore, it is used in several other fi elds and its application is at the forefront of current medical technology.

Conclusions

Three-dimensional US opens up new clinical
applications and facilitates many of the proce-
dures originally performed with 2D US. The
advantages of this relatively new, noninvasive
technique have been reported in many special-
ties. Only a few limitations must be kept in
mind, such as the more complex interface that
requires a steeper learning curve. However,
the advantages it provides not only in the fi eld
of ART is striking, and instruments as well as
supporting software programs are becoming
more and more user friendly. Operation of the
systems has become facilitated and the pro-
cessing time has been signifi cantly shortened.
The progress in software regarding imaging
and image remodeling as well as the variety of
imaging modes facilitates optimal diagnosis
and therapy. Three-dimensional sonography
has been adopted by several medical fi elds
such as prenatal care, and it is becoming
increasingly acceptable as a diagnostic tool.
There is no doubt that this innovative method
will also be fully established in ART.

References

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2. Hershkovitz R, Sheiner E, Mazor M. Ultrasound in obstetrics: a review of safety. Eur J Obstet Gynecol Reprod Biol. 2002;101:15–8. Review.
3. Brinkley JF, Muramatsu SK, McCallum WD, Popp RL. In vitro evaluation of an ultrasonic three­dimensional imaging and volume system. Ultrason Imaging. 1982;4:126–39.
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18. Ruano R. Recent advances in sonographic imaging of fetal thoracic structures. Expert Rev Med Devices. 2005;2:217–22. Review.
19. Jouannic JM, Rosenblatt J, Demaria F, Jacobs R, Aubry MC, Benifl a JL. Contribution of three­dimensional volume contrast imaging to the sono­graphic assessment of the fetal uterus. Ultrasound Obstet Gynecol. 2005;26:567–70.
20. Benacerraf BR. Inversion mode display of 3D sonog­raphy: applications in obstetric and gynecologic imag­ing. AJR Am J Roentgenol. 2006;187:965–71. Review.
21. Weber G, Merz E, Bahlmann F, Macchiella D. Ultrasound assessment of ovarian tumors–compari­son between transvaginal 3D technique and conven­tional 2-dimensional vaginal ultrasonography. Ultraschall Med. 1997;18:26–30.
22. Campbell S. The potential diagnostic capabilities of three-dimensional surface rendering. Ultrasound Obstet Gynecol. 1999;14:148.
23. Turan S, Turan O, Baschat AA. Three- and four­dimensional fetal echocardiography. Fetal Diagn Ther. 2009;25:361–72. Review.
24. Adriaanse BM, Tromp CH, Simpson JM, Van Mieghem T, Kist WJ, Kuik DJ, Oepkes D, Van Vugt JM, Haak MC. Interobserver agreement in detailed prenatal diagnosis of congenital heart disease by telemedicine using four-dimensional ultrasound with spatiotemporal image correlation. Ultrasound Obstet Gynecol. 2012;39:203–9.
25. Hongmei W, Ying Z, Ailu C, Wei S. Novel application of four-dimensional sonography with B-fl ow imaging and spatiotemporal image correlation in the assess­ment of fetal congenital heart defects. Echocardio­graphy. 2012;29:614–9.
26. Yeo L, Romero R, Jodicke C, Oggè G, Lee W, Kusanovic JP, Vaisbuch E, Hassan S. Four-chamber view and ‘swing technique’ (FAST) echo: a novel and simple algorithm to visualize standard fetal echocar­diographic planes. Ultrasound Obstet Gynecol. 2011; 37:423–31.
27. Merz E, Miric-Tesanic D, Welter C. Value of the elec­tronic scalpel (cut mode) in the evaluation of the fetal face. Ultrasound Obstet Gynecol. 2000;16:564–8.
28. Powers J, Kremkau F. Medical ultrasound systems. Interface Focus. 2011;1:477–89.
29. Udupa JK. Three-dimensional visualization and analysis methodologies: a current perspective. Radio­graphics. 1999;19:783–806. Review.
30. Nelson TR, Pretorius DH, Lev-Toaff A, Bega G, Budorick NE, Hollenbach KA, Needleman L. Feasibility of performing a virtual patient examination using three­dimensional ultrasonographic data acquired at remote locations. J Ultrasound Med. 2001;20:941–52.
31. Merz E, Abramowicz JS. 3D/4D ultrasound in prena­tal diagnosis: is it time for routine use? Clin Obstet Gynecol. 2012;55:336–51. Review.
32. Rizzo G, Pietrolucci M, Aiello E, Mammarella S, Bosi C, Arduini D. The role of three-dimensional ultra­sound in the diagnosis of fetal congenital anomalies: a review. Minerva Ginecol. 2011;63:401–10. Review.
33. Bulletti C, DE Ziegler D, Levi Setti P, Cicinelli E, Polli V, Stefanetti M. Myomas, pregnancy outcome, and in vitro fertilization. Ann N Y Acad Sci. 2004; 1034:84–92.
34. Raga F, Bonilla-Musoles F, Blanes J, Osborne NG. Congenital Müllerian anomalies: diagnostic accuracy of three-dimensional ultrasound. Fertil Steril. 1996; 65:523–8.
35. Wu MH, Hsu CC, Huang KE. Detection of congenital müllerian duct anomalies using three-dimensional ultrasound. J Clin Ultrasound. 1997;25:487–92.
36. Ghi T, Casadio P, Kuleva M, Perrone AM, Savelli L, Giunchi S, et al. Accuracy of three-dimensional ultrasound in diagnosis and classifi cation of congeni­tal uterine anomalies. Fertil Steril. 2009;92:808–13.
37. Rosendahl M, Ernst E, Rasmussen PE, Andersen CY. True ovarian volume is underestimated by two­dimensional transvaginal ultrasound measurement. Fertil Steril. 2010;93:995–8.
38. Vanderzwalmen P, Zech NH, Ectors F, Stecher A, Lejeune B, Vanderzwalmen S, Wirleitner B. Blastocyst transfer after aseptic vitrifi cation of zygotes: an approach to overcome an impaired uterine environ­ment. Reprod Biomed Online. 2012;25:591–9.
39. Sladkevicius P, Ojha K, Campbell S, Nargund G. Three-dimensional power Doppler imaging in the assessment of Fallopian tube patency. Ultrasound Obstet Gynecol. 2000;16:644–7.
40. Deb S, Campbell BK, Clewes JS, Raine-Fenning NJ. Quantitative analysis of antral follicle number and size: a comparison of two-dimensional and automated three-dimensional ultrasound techniques. Ultrasound Obstet Gynecol. 2010;35:354–60.
41. Shaw SW, Hsieh TT, Hsu JJ, Lee CL, Cheng PJ. Measurement of nuchal volume in the fi rst trimester down screening using three-dimensional ultrasound. Prenat Diagn. 2009;29:69–73.
42. Youssef A, Arcangeli T, Radico D, Contro E, Guasina F, Bellussi F, Maroni E, Morselli-Labate AM, Farina A, Pilu G, Pelusi G, Ghi T. Accuracy of fetal gender determination in the fi rst trimester using three- dimensional ultrasound. Ultrasound Obstet Gynecol. 2011;37:557–61.
43. Jang M, Kim SM, Lyou CY, Choi BS, Choi SI, Kim JH. Differentiating benign from malignant thy­roid nodules: comparison of 2- and 3- dimensional sonography. J Ultrasound Med. 2012;31:197–204.
44. Smeenge M, de la Rosette JJ, Wijkstra H. Current status of transrectal ultrasound techniques in prostate cancer. Curr Opin Urol. 2012;22:297–302. Review.
45. Downey DB, Fenster A. Vascular imaging with a three-dimensional power Doppler system. AJR Am J Roentgenol. 1995;165:665–8.
46. Houck RC, Cooke JE, Gill EA. Live 3D echocardiogra­phy: a replacement for traditional 2D echocardiography? AJR Am J Roentgenol. 2006;187:1092–106. Review.
47. Pooh RK, Kurjak A. 3D and 4D sonography and mag­netic resonance in the assessment of normal and abnormal CNS development: alternative or comple­mentary. J Perinat Med. 2011;39:3–13.
Two-Dimensional and Three- Dimensional Doppler in Reproductive Medicine
Ernest Hung Yu Ng
3

Introduction

In vitro fertilisation (IVF) is an effective treatment for various causes of infertility and typically involves multiple follicular development, oocyte retrieval and embryo transfer after fertilisation. Multiple embryos are still being replaced in order to compensate for their low implantation poten­tial, which have remained steady at 20–30 % for a long time. Development of multiple follicles in response to gonadotrophin stimulation is consid­ered as the key factor leading to successful out­come. Successful implantation is dependent on interaction between a good quality embryo and a receptive endometrium.
Ultrasound is essential during the IVF treat­ment for monitoring the ovarian response to gonadotrophin and guiding the transvaginal aspiration of oocytes and transfer of embryos to the uterine cavity. Angiogenesis plays a critical role in various female reproductive processes such as development of a dominant follicle, for­mation of a corpus luteum, growth of endome­trium and implantation [ covers the use of two dimensional (2D) and three dimensional (3D), in particular the role of endometrial and subendometrial blood fl ow determined in predicting the IVF success
E. H. Y. Ng , MD, FRCOG (UK) Department of Obstetrics and Gynaecology , The University of Hong Kong, Queen Mary Hospital , Pokfulam , Hong Kong , Hong Kong e-mail: nghye@hku.hk
1 , 2 ]. This chapter
and the role of ovarian stromal blood fl ow determined in predicting ovarian response to gonadotrophin stimulation.

Endometrial Blood Flow

Ultrasound examination of the endometrium serves a non-invasive evaluation of the endome­trium during IVF treatment [ 3 ]. Parameters such as endometrial thickness, endometrial pattern, endometrial volume and Doppler study of uterine arteries and the endometrium are most commonly used to evaluate the endometrial receptivity. Endometrial thickness and pattern have low posi­tive predictive value and specifi city for the IVF outcome [ 4 , 5 ], whereas endometrial volume measured by 3D ultrasound is not predictive of pregnancy [ 6 – 9 ].
Assessment of endometrial blood fl ow gives a physiological dimension to the anatomical ultra­sound parameters. A good blood fl ow towards the endometrium is usually considered as an essential requirement for successful implantation. Jinno et al. [ 10 ] measured endometrial tissue blood fl ow in infertile patients by the intrauterine laser Doppler technique between days 4 and 6 of the luteal phase of a spontaneous cycle preceding IVF. The IVF pregnancy rate was signifi cantly higher in women with endometrial tissue blood fl ow of at least 29 mL/min/100 g of tissue than in women with lower values (42 % vs. 15 %, respectively, P < 0.05).
Endometrial blood fl ow comes from the radial artery, which divides after passing through the
L.A. Stadtmauer, I. Tur-Kaspa (eds.), Ultrasound Imaging in Reproductive Medicine, DOI 10.1007/978-1-4614-9182-8_3, © Springer Science+Business Media New York 2014
27
28
E.H.Y. Ng
myometrial-endometrial junction to form the basal arteries that supply the basal portion of the endometrium and the spiral arteries that continue up towards the endometrium. Endometrial blood fl ow can be determined by colour and power Doppler ultrasound. Power Doppler imaging is more sensitive than colour Doppler imaging at detecting low-velocity fl ow and hence improves the visualisation of small vessels [ 11 ]. In combi- nation with 3D ultrasound, power Doppler can objectively examine both endometrial and suben­dometrial blood fl ow.
a

Blood Flow of Uterine Vessels

Doppler study of uterine vessels refl ecting down­stream impedance to fl ow is assumed to refl ect the endometrial blood fl ow. It is usually expressed as the pulsatility index (PI) and the resistance index (RI) (Fig. 3.1 ). PI is calculated as the peak sys- tolic velocity (PSV) minus end-diastolic velocity divided by the mean, whereas RI is the ratio of PSV minus end-diastolic velocity divided by PSV.
Flow velocity waveforms are obtained from the ascending main branch of the uterine artery
Fig. 3.1 Right ( a ) and left ( b ) uterine blood fl ow measured by 2D Doppler ultrasound
b
3 Two-Dimensional and Three-Dimensional Doppler in Reproductive Medicine
29
on the right and left side of the cervix in a longitudinal plane before it enters the uterus. The ‘gate’ of the Doppler is positioned when the vessel with good colour signals is identifi ed on the screen. The PI and RI of the uterine arteries were calculated electronically when three simi­lar, consecutive waveforms of good quality were obtained.
Good uterine blood fl ow as shown by low PI or RI is correlated with successful IVF out­comes [ 12 , 13 ]. Steer et al. [ 12 ] classifi ed PI measured on the day of ET as low, medium and high in the ranges of 0–1.99, 2.00–2.99 and ≥3.00, respectively, and reported a 35 % implan­tation failure when PI was >3.0. Using a PI upper limit of 3.0 [ 12 ] or 3.3 [ 13 ], the uterine Doppler fl ow indices have a high negative pre­dictive value and sensitivity (in the ranges of 88–100 % and 96–100 %, respectively) and a relatively higher range of positive predictive value and specifi city (44–56 % and 13–35 %, respectively) when compared with endometrial thickness and pattern [ 5 ].
Uterine artery Doppler study may not refl ect the actual blood fl ow to the endometrium as the major compartment of the uterus is the myome­trium and there is collateral circulation between uterine and ovarian vessels. I have shown 2D Doppler study of uterine vessels is a poor refl ec­tion of subendometrial blood fl ow by 3D power Doppler in both stimulated and natural cycles as
endometrial and subendometrial 3D Doppler fl ow indices were similar among patients with aver­aged uterine PI <2.0, 2.0–2.99 and ≥3.0. [ 14 ].

Endometrial and Subendometrial Blood Flow by 2D Doppler

Endometrial and subendometrial blood fl ow examined by colour (Table 3.1 ) and power Doppler (Table 3.2 ) was correlated with implan- tation or pregnancy rates during IVF treatment. 2D Doppler fl ow indices of spiral arteries such as PI and PSV are not predictive of pregnancy [ 8 , 19 , 22 ], although Battaglia et al. [ 16 ] and Kupesic et al. [ 23 ] found signifi cantly lower spi- ral artery PI in pregnant cycles than nonpregnant cycles.
Yang et al. [ 18 ] used a computer software to measure the area and intensity of colour signals present in the endometrium in a longitudinal axis, i.e. intraendometrial power Doppler area (EDPA). Signifi cantly higher EDPA was found in pregnant cycles than nonpregnant cycles (8.8 mm 2 vs.
5.8 mm 2 respectively). Patients with EDPA <5 mm 2 had signifi cantly lower pregnancy rate (23.5 % vs. 47.5 %; P = 0.021) and implantation rate (8.1 % vs. 20.2 %; P = 0.003) than those with ≥5 mm 2 . Contart et al. [ 20 ] graded endome- trial blood fl ow by the visualisation of power Doppler in the quadrants in the fundal region of
Table 3.1 Summary of studies of endometrial blood fl ow by 2D colour Doppler
Study Popovic-Todorovic
15 ]
et al. [
Battaglia et al. [
Chien et al. [
USS ultrasound, PI pulsatility index, PSV peak systolic velocity, OR oocyte retrieval, ET embryo transfer
IVF cycles USS parameters USS day
96 cycles using a long protocol
16 ] 60 cycles Uterine and spiral PI OR Uterine and spiral PI lower in
17 ] 623 cycles using
ultrashort and ultralong protocols
Spiral PI and PSV hCG No difference in subendometrial PI
Presence of endometrial and subendometrial fl ow
Presence of endometrial blood fl ow
Uterine and spiral PI and RI
Presence of endometrial and subendometrial (<10 mm) blood fl ow
ET Signifi cantly lower implantation and
Results
and PSV between pregnant and nonpregnant cycles
Absent subendometrial fl ow associated with no pregnancy
pregnant than nonpregnant cycles Absent subendometrial fl ow
associated with no pregnancy
pregnancy rates in patients without endometrial/subendometrial fl ow
Presence of subendometrial fl ow 5.9 times to become pregnant than those with absent fl ow
30
Table 3.2 Summary of studies of endometrial blood fl ow by 2D power Doppler
Study Yang et al. [
Yuval et al. [
Contart et al. [
Schild et al. [
Maugey-Laulon
21 ]
et al. [
USS ultrasound, PI pulsatility index, PSV peak systolic velocity, OR oocyte retrieval, ET embryo transfer
IVF cycles USS parameter USS day
18 ] 95 cycles using long
and short protocols Endometrium
≥10 mm
19 ] 156 cycles using
a long protocol
20 ] 185 cycles using
a long protocol
8 ] 135 cycles using
a long protocol; fi rst cycle only
144 cycles using a long protocol
Intraendometrial power Doppler area (EDPA)
2
; ≥5 mm 2
<5 mm
PI and RI OR and ET No difference in any USS
Fundal region along transverse plan; grades I, II, III and IV according to visualisation of power Doppler in the quadrants
PI and PSV of vessels in endometrium and subendometrial area (<5 mm)
Presence of endometrial and subendometrial blood fl ow
Results
OR Higher EDPA in pregnant
cycles Lower implantation and
pregnancy rates when EDPA
2
<5 mm
parameters between pregnant and nonpregnant cycles
hCG Implantation and pregnancy
rates similar in all grades of endometrial vascularity
OR No difference in spiral artery
PI and PSV between pregnant and nonpregnant cycles
Non-detectable spiral blood fl ow was not associated with a lower implantation rate
ET Absent endometrial and
subendometrial fl ow associated with a lower pregnancy rate
E.H.Y. Ng
the transverse plane but could not demonstrate any predictive value of such grading system.
Presence of endometrial and subendometrial blood fl ow can be identifi ed easily in 2D Doppler ultrasound. Absent endometrial and subendome­trial blood fl ow has been shown to be associated with no pregnancy [ 16 , 22 ] or a signifi cantly lower pregnancy rate [ 17 , 21 ].

Endometrial and Subendometrial Blood Flow by 3D Doppler

3D power Doppler ultrasound with the aid of the VOCAL® (Virtual Organ Computer-Aided Analysis) imaging program for the 3D power Doppler histogram can be used to measure the endometrial volume and indices of blood fl ow within the endometrium (Fig. 3.2 ). Vascularisation index (VI), which measures the ratio of the num­ber of colour voxels to the number of all the voxels, is thought to represent the presence of blood vessels (vascularity) in the endometrium,
and this was expressed as a percentage (%) of the endometrial volume. Flow index (FI), the mean power Doppler signal intensity inside the endome­trium, is thought to express the average intensity of fl ow. Vascularisation fl ow index (VFI) is a com­bination of vascularity and fl ow intensity [ 24 ].
The subendometrium can be examined through the application of ‘shell imaging’ which allows the user to generate a variable contour that parallels the originally defi ned surface contour. The VI, FI and VFI of the subendometrial region are obtained accordingly (Fig. 3.3 ). The intra- observer reliability and interobserver reliability of endometrial and subendometrial blood fl ow by 3D power Doppler have been confi rmed to be high with all measurements obtaining an intra­class correlation of above 0.9 [ 25 , 26 ].
Studies addressing the role of endometrial and subendometrial blood fl ow measured by 3D Doppler in IVF treatment are summarised in Table 3.3 . Schild et al. [ 27 ] measured the subendometrial blood fl ow after pituitary downregulation but prior to ovarian stimulation
3 Two-Dimensional and Three-Dimensional Doppler in Reproductive Medicine
a
31
b
Fig. 3.2 Endometrial volume ( a ) and blood fl ow ( b ) measured by 3D Doppler ultrasound
32
E.H.Y. Ng
a
b
Fig. 3.3 Subendometrial volume ( a ) and blood fl ow ( b ) measured by 3D Doppler ultrasound
3 Two-Dimensional and Three-Dimensional Doppler in Reproductive Medicine
33
(continued)
Results
pregnant than nonpregnant cycles
Subendometrial FI is the strongest predictive
factor for IVF in logistic regression analysis
(endometrium <5 mm, no ovarian
cyst of >2.5 cm, serum oestradiol
<60 pg/mL)
Serum FSH < 10 IU/L
No fi broid, ovarian cysts and ovarian
endometriosis
Inclusion criteria hCG Subendometrial VFI higher in pregnant cycles
Age <38 years
Normal uterine cavity
Serum FSH <15 IU/L
between pregnant and nonpregnant cycles
Polycystic ovary syndrome
≥2 good quality embryos
No difference in endometrial and
subendometrial VI between pregnant and
OR
Endometrium <6 mm
Gynaecological surgery
nonpregnant cycles on both days
Endometriosis
Single ovary
Previous operation on uterus or
cycles
Inclusion criteria OR Endometrial VI and VFI lower in pregnant
salpingectomy
subendometrial 3D Doppler fl ow indices
between pregnant and nonpregnant cycles
Normal uterine cavity
Table 3.3 Summary of studies of endometrial and subendometrial blood fl ow by 3D power Doppler ultrasound
IVF cycles Inclusion/exclusion criteria USS day
27 ] 75 cycles using a long protocol Inclusion criteria Before stimulation Subendometrial VI, FI and VFI lower in
Study
Schild et al. [
ET 2 days after TUGOR Downregulation confi rmed
Blastocyst transfer 5 days after
TUGOR
23 ] 89 cycles using a long protocol Inclusion criteria ET (hCG +7) Higher subendometrial FI in pregnant cycles
Kupesic et al. [
ovarian stimulation and ET not given)
28 ] 54 cycles; fi rst cycle only (details of
Wu et al. [
ET 2 days after TUGOR Uterine fi broids
29 ] 42 cycles using a long protocol Exclusion criteria OR No difference in subendometrial VI, FI and VFI
Dorn et al. [
30 ] 35 cycles using a long protocol Exclusion criteria After stimulation and
Järvelä et al. [
cycle only
31 ] 451 cycles using a long protocol; fi rst
Ng et al. [
ET 2 days after TUGOR Normal uterine cavity on scanning
Frozen-thawed embryo transfer
cycles
32 ] 193 cycles Inclusion criteria LH + 1 No difference in endometrial and
Ng et al. [
34
Results
in pregnant cycles
E.H.Y. Ng
subendometrial 3D Doppler fl ow indices on the
2 days and changes in these indices between
pregnant and nonpregnant cycles
First cycle
Normal uterine cavity
Serum FSH <10 IU/L
Regular cycles
IVF cycles Inclusion/exclusion criteria USS day
33 ] 80 cycles using a long protocol Inclusion criteria hCG Higher endometrial VI, FI and VFI
Table 3.3 (continued)
Study
Mercè et al. [
Non-smokers
Normal uterine cavity
ET 2 days after OR First cycle
34 ] 293 cycles using a long protocol Inclusion criteria OR and ET No difference in endometrial and
Ng et al. [
USS ultrasound, VI vascularisation index, FI fl ow index, VFI vascularisation fl ow index, OR oocyte retrieval, ET embryo transfer