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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5772_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •Color Doppler Sonography in Gynecology and Obstetrics
- •Preface
- •Contributors
- •Contents
- •Physical and Technical Principles
- •Principles of Ultrasound Instrumentation
- •Analysis of B-Mode Information and Artifacts
- •Duplex and Color Doppler Sonography
- •Physical Principles of Motion Detection
- •Technical Principles and Equipment Settings
- •1 Physical and Technical Principles of Color Doppler Sonography
- •Historical Development
- •B-Mode Sonography
- •Physical Principles of Echo Production
- •Analysis of Doppler Information and Artifacts
- •New Technical Processes and Approaches
- •New Developments in Transducer Technology
- •New Techniques of Signal Acquisition and Processing
- •2 Safety Aspects of Doppler and Color Doppler Sonography
- •Mechanisms of Tissue Effects
- •Heating
- •Cavitation
- •Risk Assessment of Various Ultrasound Techniques
- •Duplex Sonography
- •Color Doppler
- •Power Doppler
- •Color Velocity Imaging (CVI)
- •Transvaginal Scanning
- •Ultrasound Contrast Agents
- •Exposure of Gas-Containing Tissues
- •Measures to Limit Risk
- •Recommendations
- •General Recommendations
- •Pulsed Doppler
- •Appendix: Statements on the Biological Safety of Diagnostic Ultrasound Fields
- •EFSUMB Statement on the Clinical Safety of Diagnostic Ultrasound
- •WFUMB Statement on Thermal Effects in Clinical Applications
- •3 Uterine Blood Flow in Fertile and Infertile Women
- •Uterine Blood Supply
- •Changes in Uterine Blood Flow during the Menstrual Cycle
- •Blood Flow Parameters in the Uterine Arteries
- •Uterine Blood Flow in InfertileWomen
- •Uterine Blood Flow and Fertilization Rate
- •Uterine Blood Flow in the Normal Cycle and during Ovarian Stimulation with Confirmed Ovulation
- •Endometrial Imaging
- •Conclusions
- •4 Uterine Causes of Infertility
- •Ultrasound Detection of Uterine Abnormalities
- •Congenital Anomalies
- •Endometrial Polyps
- •Submucous Leiomyomas
- •Adenomyosis
- •Endometritis
- •Asherman Syndrome
- •Ultrasound Detection of Endometrial Causes of Infertility
- •Effect of Endometrial Thickness and Morphology on Fertility
- •Effect of Age on Endometrial Function
- •Endometrial Peristalsis
- •Cervical Factor
- •Decline of Fertility in the Perimenopausal Period
- •Uterine Receptivity
- •Oocyte Quality
- •Ovarian Function
- •Effects of Estradiol and Progesterone on Vascular Resistance
- •Sympathetic Innervation of the Uterus
- •Estrogen Effect
- •Progesterone Effect
- •Effect of Age on Ovarian and Uterine Perfusion
- •Authors’ Study
- •Interpretation of the Results
- •Functional Evaluation of the Endometrium
- •Authors’ Studies
- •Patients and Methods
- •Examination Procedures
- •Results
- •Discussion of the Role of Doppler Examinations
- •Summary
- •Applications of Doppler Sonography in Reproductive Medicine
- •Assessment of Tubal Patency
- •Patients and Method
- •Examination Technique
- •Results
- •Discussion of the Value of the Test Procedures
- •Summary
- •8 Abnormalities of Corpus luteum Function
- •Morphology and Biochemistry of the Corpus luteum
- •Conventional Methods in the Diagnosis and Treatment of Luteal Phase Defect
- •Possible Causes of Luteal Phase Defect
- •Diagnosis of Luteal Phase Defect
- •Treatment of Luteal Phase Defect
- •Ultrasound and Doppler Sonography in the Detection of Luteal Phase Defect
- •LUF Syndrome
- •Blood Flow in the Corpus luteum during Early Pregnancy
- •Fallopian Tube Catheterization
- •Aspiration of Ovarian Cysts
- •Drainage of Cul-de-Sac Abscesses
- •Selective Reduction of Multiple Pregnancies
- •Techniques of Ultrasound Tubal Imaging
- •Hysterosonosalpingography
- •9 Interventional Ultrasound in Reproductive Medicine
- •Follicular Aspiration in Assisted Reproduction
- •Transabdominal Follicular Aspiration
- •Transurethral Follicular Aspiration
- •Transvaginal Follicular Aspiration
- •Embryo Transfer
- •Obstetric Ultrasound
- •Overview
- •Monitoring Folliculogenesis
- •Development of the Corpus luteum
- •Changes in Endometrial Blood Flow
- •Luteal Blood Flow in Normal and Abnormal Pregnancies
- •Trophoblastic Invasion and Development of the Placenta
- •Implantation
- •Development of the Intervillous Circulation
- •Classic Theory
- •Objections and Alternative Theories
- •Color Doppler Studies
- •Vascularization of the Yolk Sac and Vitelline Duct
- •Changes in Uterine Perfusion after Placentation
- •Uterine Arteries and Spiral Arteries
- •Embryonic and Fetal Circulation
- •Fetal Vessels
- •Summary
- •12 Color Doppler Sonography in Ectopic Pregnancy
- •Importance of Transvaginal Sonography and Serum hCG
- •Transvaginal Color Doppler Sonography
- •Diagnostic Efficiency
- •Author’s Studies
- •Assessment of the Method
- •Summary
- •Conditions of Intrauterine Life
- •Physical Principles
- •Anatomical and Physiological Principles
- •Adaptive Processes during Pregnancy
- •Technique of Transvaginal Pulsed Doppler Flowmetry
- •Authors’ Studies
- •Uterine Perfusion in a Normal Pregnancy
- •Uterine Perfusion in an Abnormal Pregnancy
- •Discussion
- •Uterine Perfusion in a Normal Pregnancy
- •Uterine Perfusion in an Abnormal Pregnancy
- •Uterine Perfusion on Medication or after Uterine Manipulation
- •Summary
- •Doppler Flowmetry of Maternal Vessels as a Screening Test?
- •Applications of Color Doppler Sonography during Pregnancy
- •Technique of Transvaginal Doppler Sonography
- •Normal Development of Uterine Artery Doppler Spectra
- •Normal Values in Early Pregnancy
- •Early Doppler Examination of Uteroplacental Blood Flow in Abnormal Pregnancy
- •Patients
- •Results
- •Discussion
- •Summary
- •Establishing Normal Curves
- •Methodology
- •Defining the Normal Population
- •Plotting Quantile Curves
- •Results
- •Discussion
- •16 Venous Doppler Sonography
- •Historical Development
- •Physiology
- •Umbilical Vein
- •Ductus venosus
- •Inferior Vena Cava
- •Hepatic Veins
- •Clinical Applications
- •Intrauterine Growth Retardation Due to Chronic Placental Insufficiency
- •Growth Discordance in Multiple Pregnancy
- •Hydrops fetalis
- •Conclusion
- •Other Diseases
- •Specific Obstetric Problems
- •Importance of Nuchal Cord
- •Color Doppler Study on the Diagnosis of Nuchal Cord
- •Examination Technique
- •Results
- •Importance of Nuchal Cord Diagnosis in the Biophysical (ABCD) Profile
- •Role of Doppler Sonography in NC
- •Summary
- •18 Chronic Placental Insufficiency
- •Definitions
- •Definition and Incidence of Chronic Placental Insufficiency
- •Intrauterine Growth Retardation
- •Diagnosis of Chronic Placental Insufficiency
- •Diagnostic Systems
- •Indications for Doppler Sonography
- •Clinical Management of Chronic Placental Insufficiency Suspected from Doppler Findings
- •Antenatal Fetal Heart Rate Monitoring
- •Pathological Changes in Organ Systems
- •Biophysical Profile
- •Summary
- •Identifying Cases with IUGR
- •Obstetric Management
- •Surveillance of Compromised Fetuses
- •Absent End-Diastolic Flow (AEDF) and Reverse Flow
- •Absent End-Diastolic Flow in the Umbilical Artery and/or Fetal Aorta
- •Reverse Flow in the Umbilical Artery and/or Fetal Aorta
- •Clinical Results of AEDF or Reverse Flow in the Umbilical Artery and/or Fetal Aorta
- •Significance of Severely Abnormal Doppler Findings
- •Summary
- •20 Fetal Doppler Findings in Late Pregnancy
- •Physiological Findings in Late Pregnancy
- •Aorta: Quantitative Analysis
- •Aorta: Qualitative Analysis
- •Cerebral Arteries
- •Renal Arteries
- •Femoral Arteries
- •Changes in Findings at Term and in Postterm Pregnancies
- •Term Effect
- •Circulatory Balance
- •Summary
- •Pathophysiology and Technical Problems
- •Changes in Uterine ArteryWaveforms during Labor
- •Our Results
- •Discussion of Uterine Doppler Changes during Labor
- •IntrapartumWaveform Changes in Umbilical and Intrafetal Vessels
- •Umbilical Cord Doppler during Labor
- •Effect of Intrapartum FHR Decelerations on Quantitative Parameters of Umbilical Blood Flow
- •Direct Effect of Intrapartum Fetal Hypoxia or Hypoxemia on Blood Flow Patterns in the Umbilical Arteries and Vein
- •Summary
- •22 Color Doppler Ultrasound in Fetal Echocardiography
- •Congenital Heart Disease—Incidence and Risk Factors
- •General Introductory Remarks on Color Doppler Sonography of the Fetal Heart
- •Special Features of Fetal Echocardiography
- •Ultrasound Examination of the Fetal Heart
- •Normal Findings
- •Management of Suspected Congenital Heart Disease
- •23 Use of Color Doppler in Echocardiography
- •Importance of Color Doppler Echocardiography in Prenatal Diagnosis
- •Examination of the Normal Heart
- •Equipment Settings
- •Examination Technique
- •Cardiac Valve Regurgitation
- •Functional Physiological Tricuspid Regurgitation
- •Pathological Tricuspid Regurgitation
- •Tricuspid and Mitral Valve Regurgitation
- •Semiquantification of AV Valve Regurgitation
- •Anomalies of Visceroatrial Blood Flow
- •Anomalies of Atrioventricular Blood Flow
- •Anomalies of Ventriculoarterial Blood Flow
- •Anomalies of Blood Flow through the Cardiac Septa
- •Color Doppler Sonography in Fetal Arrhythmias
- •Summary
- •Structure of the Human Placenta
- •Weight and Dimensions
- •Early Development of the Human Placenta
- •Structure of the Villous Tree
- •Microstructure of the Terminal Villus
- •Maturation of the Placenta
- •Vascular Architecture of the Villous Tree
- •Regulation of Villous Blood Flow
- •Concept of the Placentone
- •Morphology and Physiological Transformation of the Maternal Basal-Plate Vessels
- •Placental Insufficiency
- •Definition and Etiology of Placental Insufficiency
- •Placental Compensatory Mechanisms
- •Classification of Placental Insufficiency by its Progression
- •Morphological Counterparts of Latent or Overt Placental Insufficiency
- •Clinical Aspects of Placental Insufficiency
- •Pathophysiological Aspects of Placental Insufficiency
- •Pathomorphological Aspects of Placental Insufficiency
- •Validation of Doppler Findings by Placental Histology
- •Resistance Index of the Umbilical Arteries
- •End-Diastolic Blood Flow Velocities in the Umbilical Arteries
- •Clinical and Diagnostic Value of Doppler Sonography of the Umbilical Arteries
- •Gynecological Ultrasound
- •Classification of Uterine Anomalies
- •Diagnosis and Complications of Septate Uterus
- •Ultrasound in the Diagnosis and Treatment of Septate Uterus—Authors’ Results
- •Patients and Methods
- •Results
- •New Thoughts on Old Problems
- •Changes in the Normal Endometrium during the Menstrual Cycle
- •Changes in Endometrial Blood Flow during the Menstrual Cycle
- •Submucous Leiomyomas
- •Endometrial Polyps
- •Endometrial Hyperplasia
- •Adenomyosis
- •Endometritis
- •Incomplete Abortion
- •Decidua
- •Examination Technique, Anatomy, and Physiology
- •Leiomyomas (Fibroids)
- •Vascularization of Leiomyomas
- •Management of Uterine Leiomyomas and the Importance of Color Doppler Sonography
- •Medical Treatment with GnRH Agonists
- •Surgical Treatment
- •Vascular Diseases in the Lesser Pelvis (Varicose Veins or Arteriovenous Malformations)
- •Incidence of Endometrial Carcinoma
- •Diagnostic Investigation of Suspicious Endometrial Findings
- •Color Doppler Sonography
- •Examination of the Uterine Artery
- •Experience at the Department of Obstetrics and Gynecology, Homburg University Hospital, Saar
- •Patients and Methods
- •Visualization and Morphology of the Vessels
- •Resistance Indices of Endometrial Vessels
- •Effect of Menopausal Status and Hormone Use
- •Effect of Histopathological Parameters, with Reference to Prognostic Factors
- •Subendometrial and Myometrial Vessels
- •Summary
- •30 Malignant Uterine Tumors
- •Endometrial Carcinoma
- •Incidence
- •Risk Factors
- •Target Group for Screening
- •Screening: Dream or Reality?
- •Authors’ Experience
- •Review of the Literature
- •Uterine Sarcoma
- •Authors’ Experience
- •Cervical Carcinoma
- •Conclusion
- •Treatment of Cervical Carcinoma
- •Assessing Treatment Response with Pulsed Color Doppler Sonography
- •Authors’ Studies
- •Discussion
- •Summary
- •Appearance of Normal Ovaries by B-Mode and Color Doppler Ultrasound
- •Specific Adnexal Masses
- •Cystic and Cystic-Solid Ovarian Masses
- •Solid Ovarian Masses
- •Conclusions
- •33 Malignant Adnexal Tumors
- •Color Doppler Sonography of Adnexal Malignancies
- •Review of the Literature
- •Neoangiogenesis
- •Detecting Blood Vessels and Defining their Location
- •Vascular Patterns
- •Pulsed Doppler Waveforms
- •Vascular Impedance
- •Blood Flow Velocities
- •Stages of Malignant Tumors
- •False-Positive Results
- •Conclusions
- •Contribution of Transvaginal Color Doppler Sonography
- •Three-Dimensional Imaging
- •Three-Dimensional Imaging of Vascular Patterns
- •Display Modes for Three-Dimensional Vascular Images
- •Ultrasound Technology in Tumor Diagnosis
- •Problems in the Interpretation of 3D Power Doppler Data
- •Current Methods for Evaluating Vascular Geometry and Function
- •Technique for Evaluating Vascular Geometry
- •Example of 3D Power-Mode Imaging of Benign and Malignant Gynecological Tumors
- •Advances in Tumor Therapy
- •Summary
- •Future Outlook
- •35 Ovarian Cancer Screening
- •Incidence and Five-Year Survival Rates of Ovarian Cancer
- •Requirements of a Screening Program
- •Definition
- •Screening Methods
- •Screening Parameters
- •Possible Screening Tests
- •Bimanual Pelvic Examination
- •Cul-de-sacWashings and Radiological Studies
- •Tumor Marker
- •Ultrasound
- •Who Should be Screened?
- •Age Distribution
- •Family History
- •Conclusion
- •Other Risk Factors
- •Historical Development
- •Blood Flow Detection
- •Number of Tumor Vessels
- •Resistance Index
- •Absolute Velocities
- •Doppler Waveform
- •Comparison of “Mirror Image Areas”
- •Conceptual Misunderstandings in the Interpretation of Doppler Measurements
- •Evolution of Breast Cancer Diagnosis
- •Continuous-Wave Doppler
- •Pulsed Doppler Techniques
- •Color Doppler
- •Equipment Settings
- •Examination Technique
- •Blood Flow Analysis
- •Study Results
- •Discussion
- •Conclusions
- •Flow Resistance in Malignant Breast Tumors
- •Authors’ Studies
- •Patients and Methods
- •Results and Discussion
- •Summary
- •Menopausal Status and Benign–Malignant Tumor Discrimination
- •Authors’ Studies
- •Patients and Methods
- •Results
- •Discussion
- •Summary
- •Applications of Color Doppler Sonography in Breast Cancer
- •Authors’ Studies
- •Methods
- •Results
- •Discussion
- •Conclusion
- •Index

Color Doppler Sonography for the Optimization of Assisted Reproduction
of the endometrium after hormonal stimulation with hMG/
35
%
30
25
20
15
10
5
0
Successful
Implantation
Failed
Grade A
Grade B
Grade C
Grade D
hCG and the findings were compared with biopsies taken from
spontaneous cycles.
In cycles stimulated with gonadotropins, 9 of 16 biopsies
that had been taken on the day of the planned embryo transfer
showed normal dating, while the other 7 were deficient. Compared with nonstimulated cycles, the stimulated endometria
showed a greater number of ciliary cells with longer and more
prominent cilia.
Degenerative developmental changes usually did not affect
the whole endometrium but were confined to a localized area.
Secretion was rarely impaired. Both apocrine and droplet
secretion could be demonstrated even in areas that appeared
morphologically “deficient.“
Fig. 6.14 Distribution of endometrial echo patterns (grades A–D
after Smith et al. 1984
16
%
6
14
12
10
8
6
4
2
0
Normal
dating
Fig. 6.15 Endometrial echo patterns (grades A–D after Smith et al.
38
) following hormonal stimulation related to the histological
198 4
38
) in stimulated cycles, shown separately for
Grade A
Grade B
Grade C
Grade D
Deficient
secretion
Abortive
secretion
Deficient
proliferation
Atrophy
evaluation of endometrial biopsy specimens taken on the day
scheduled for embryo transfer.
Doppler Sonography
Figures 6.16 –6.18 show the values measured in spontaneous
cycles and the subsequent cycles stimulated with
gonadotropins. The median resistance values in the spontaneous cycles were lower and the blood flow velocities higher
than in the previous nonstimulated cycles. The differences
were small, however, and only some were statistically significant.
Resistance index. The median resistance index (RI) of the
uterine artery in the stimulated cycle was less than in the spontaneous cycle (Fig. 6.
significant (p = 0.14). A comparison of the different cycle
phases and the stimulated cycles using regression analysis
showed a correlation coefficient of 0.21 for the proliferative
phase. The correlation coefficient was 0.28 in the periovulatory
phase and 0.35 in the secretory phase.
Pulsatility index. The pulsatility index (PI) of the uterine artery
was significantly lower than in the periovulatory phase
(p ⬍ 0.001) and secretory phase (p ⬍ 0.01) of the corresponding spontaneous cycles (Fig. 6.
phase correlated weakly with the corresponding values
measured in the stimulated cycle (correlation coeffi-
16), but the difference was not statistically
17). The PI in the proliferative
62
greatest endometrial thicknesses (19 and 14mm) were
measured in the two cases that showed deficient proliferation.
In a comparison group of 53 patients who were biopsied on
the scheduled day of embryo transfer after failure of oocyte
fertilization, the endometrium was histologically healthy in
57% of the cases. Comparing the sonographically classified endometrial patterns with the histological diagnoses (Fig. 6.
15),
we find that in cases with normal histology the distribution of
sonographic findings most closely matched the conditions
seen in the periovulatory phase of the spontaneous cycle.
However, because all sonographic grades occur in association
with nearly all the histological diagnoses, we must conclude
that the echogenicity of the endometrium is not a reliable predictor of the histological diagnosis.
Findings after stimulation. In a subgroup of patients, light microscopy was supplemented by scanning electron microscopy
0.9
RI
0.8
0.7
0.6
0.5
7–10
12–16 21–24
Day of cycle
0.89
0.83
0.78
Stimulated
Fig. 6.16 Resistance index (RI) of the uterine artery in spontaneous
and stimulated cycles (median values plus upper and lower quartiles).

Authors’ Studies
cient = 0.15). The correlation coefficient was 0.39 at midcycle
3.5
PI
and 0.34 in the secretory phase.
3.0
2.5
2.0
1.5
1.0
0.5
7–10
12–16 21–24 Stimulated
Day of cycle
2.94
2.57
2.06
Fig. 6.17 Pulsatility index (PI) of the uterine artery in spontaneous
and stimulated cycles (median values plus upper and lower quartiles).
0.6
(m/s)
0.5
max
V
0.4
0.3
0.2
0.1
0.0
7–10
12–16 21–24
Day of cycle
Fig. 6.18 Peak systolic velocity (V
) of the uterine artery in spon-
max
0.61
0.45
0.39
Stimulated
taneous and stimulated cycles (median values plus upper and lower
quartiles).
0.5
0.4
0.3
Implantation rate
0.2
0.1
Blood flow velocities. The peak systolic flow velocities and the
mean intensity-weighted uterine flow velocities were both
higher in the stimulated cycles than in the previous untreated
cycles.
The peak blood flow velocity (Fig.6.
18) after hormonal
stimulation was significantly higher than the values measured
in the periovulatory and secretory phases (p ⬍ 0.05, Wilcoxon
test). The correlation between spontaneous and stimulated cycles was higher in the proliferative phase (correlation coefficient = 0.54) and secretory phase (correlation coefficient = 0.55) than at midcycle (correlation coefficient = 0.30).
Similar patterns were observed for the intensity-weighted
mean blood flow velocity. This velocity, too, was higher than
the values measured in spontaneous cycles, but the difference
was statistically significant only in the periovulatory phase
(p ⬍ 0.01, Wilcoxon test). It slightly exceeded the 0.05 significance level during the secretory phase (p = 0.07, Wilcoxon test).
The correlation coefficient between stimulated and spontaneous cycles was 0.53 in the proliferative phase, 0.47 in the
secretory phase, and 0.17 in the periovulatory phase.
Correlation of Doppler Measurements with
Implantation
Semiquantitative studies of uterine blood flow were performed in all patients on the day of follicular aspiration. When
the measured values are related to clinical course, we find that
cases with successful implantation show significantly lower
resistance values than cases in which pregnancy was not
achieved. The Wilcoxon test indicated a 0.045 probability of
error for the resistance index and 0.03 for the pulsatility index.
Table 6.
values, 25th and 75th percentiles (upper and lower quartiles),
and the extreme values for the resistance index and pulsatility
index for patients with successful and failed implantations.
Both groups showed the same age distribution (successful implantation: 32.8⫾ 3.8 years; failed implantation: 31.1 ⫾ 3.2
years, NS), hormone parameters (successful implantation:
estradiol 1190⫾ 76 pg/ml, progesterone 0.92 ⫾ 0.07 ng/ml;
failed implantation: estradiol 1262⫾ 65 pg/ml, progesterone
0.89 ⫾ 0.06 ng/ml, NS), and number of transferred embryos
(successful implantation: 2.4 ⫾ 0.6; failed implantation:
2.5 ⫾ 0.04, NS).
index (Fig. 6.
satility index of 3.5 or above a resistance index of 0.95. A pulsatility index over 3.5 or a resistance index over 0.95 signified a
nonreceptive endometrium with a specificity of 100% and a
sensitivity of 14%. The positive predictive value for these cutoff
limits is 100 %.
2 shows the mean values, standard deviations, median
The implantation rate declines with increasing pulsatility
19). No pregnancies were achieved above a pul-
Infertility Evaluation and Assisted Reproduction
0
1.5 5.5 6.5
0
2.0 2.5 3.0 3.5 4.0 4.5 5.0 6.0
Pulsatility index
Fig. 6.19 Implantation rate as a function of pulsatility index (PI).
63

Color Doppler Sonography for the Optimization of Assisted Reproduction
Table 6.2 Resistance index (RI) and pulsatility index (PI) of uterine vessels in
RI Successful implantation
successful and failed implantations. The
difference between the two groups is
statistically significant (p ⬍ 0.05, Wilcoxon
test)
Mean value ⫾ SD 0.81 ⫾ 0.06 0.84 ⫾ 0.08
Median 0.78 0.83
Lower quartile 0.76 0.78
Upper quartile 0.88 0.90
Minimum 0.67 0.73
Maximum 0.93 1.00
PI Successful implantation
Mean value ⫾ SD 2.25 ⫾ 0.61 2.82 ⫾ 1.16
Median 2.23 2.59
Lower quartile 1.91 2.09
Upper quartile 2.61 3.05
Minimum 0.88 1.30
Maximum 3.41 7.05
6
Discussion of the Role of Doppler Examinations
The ovary and uterus are the only organs in which significant
neoangiogenesis takes place under physiological conditions in
adults. The flow velocity waveforms of the uterine arteries reflect the architecture of the terminal vascular branches. They
also relate to the functional status of the downstream arterioles, as vasoconstriction can produce characteristic changes in
the Doppler waveforms
27
.
Failed implantation
(n =27)
(n = 90)
Failed implantation
(n =27)
(n = 90)
although their case numbers were insufficient for statistical
analysis. Goswamy and Steptoe
15
found that uterine vascular
resistance in 16 subjects declined over the course of the menstrual cycle. Steer et al.
40
performed transvaginal color Doppler examinations in 23 patients and concluded that a complex
relationship exists between hormonal and histological parameters. The uterine artery pulsatility index in this study was
lowest during the secretory phase and rose briefly at the time
of the midcycle estrogen surge. By contrast, when Battaglia et
2
al.
examined 19 patients stimulated with clomiphene/hCG or
hMG/hCH, they found that the pulsatility index fell during the
64
Effect of Sex Hormones on Uterine Blood Flow
Neuroanatomical studies show that uterine blood flow is controlled by a complex substrate that is sensitive to sex
steroids
31, 32, 50
. Besides the classic neurotransmitters norepinephrine and acetylcholine, researchers have identified a number of neuropeptides that act on the vessel wall of uterine arteries (Fig. 6.
20)
20, 30, 49
. With Doppler ultrasound, it is possible
to study uterine and ovarian blood flow under the influence of
endogenous and exogenously administered sex hormones
This type of study can advance our understanding of how
vascular processes are involved in the pathophysiology of reproductive biology
3, 4, 5
. It also provides a simple, noninvasive
tool for measuring the effect of pharmacological treatment regimens on uterine and ovarian hemodynamics.
Blood Flow Changes during the Menstrual Cycle
There is considerable debate in the literature over whether
uterine and ovarian blood flow follow a cyclical pattern. The
data published to date suggest that uterine and ovarian perfusion increase at the middle of the cycle
Feichtinger et al.
12
performed repeated transvaginal ultrasound measurements of uterine and ovarian blood flow in
spontaneous cycles and concluded that the resistance index is
higher at the beginning and end of the cycle than at midcycle,
12.15,16,23, 24, 40
SP
α NA
9
.
VIP
NPY
+
–
–
+
NPY
ACh
VIP
NPY
CGRP
–
+
–
+
–
+
+
Fig. 6.20 Effect of various neurotransmitters on the vessel wall tonus
of the uterine artery. (Modified from reference 50.)
ACh Acetylcholine
.
αNA Norepinephrine
VIP Vasoactive intestinal polypeptide
NPY Neuropeptide Y
SP Substance P
CGRP Calcitonin gene-related polypeptide

Authors’ Studies
proliferative phase and rose during the luteal phase. Mean-
while, Scholtes etal.
37
found in the transvaginalexamination of
16 women with regular cycles that the uterine artery pulsatility index was involved only marginally in the cyclic variations
observed in ovarian blood flow patterns. Long et al.
25
could find
no significant differences in the pulsatility index of uterine
artery waveforms before and after ovulation.
In our own study population, we observed a slight but
statistically significant rise of resistance indices in the periovulatory period. Quantitative measurements showed a largely
constant median peak systolic velocity of approximately
40 cm/s, regardless of the phase of the cycle
19
.
In interpreting the data, it should be considered that
uterine blood flow in spontaneous cycles is apparently subject
to a circadian rhythm. When Zaidi et al.
53
measured uterine
artery blood flow during the proliferative phase, they found a
significantly higher pulsatility index in the morning and a significantly lower blood flow velocity than in the evening.
Blood Flow in Stimulated Cycles
So far there have been no reports of hemodynamic measurements performed in spontaneous and stimulated ovarian cycles in the same population. Battaglia et al.
parative Doppler examinations of uterine blood flow in 10
spontaneously ovulating controls and in 19 patients receiving
clomiphene/hCG or hMG/hCG stimulation in an IVF program.
Except for two cases in the stimulated group that had strongly
elevated RI values and showed a premature fall of estradiol
levels, the proliferative phase was characterized by a fall of the
pulsatility index in both the treated and untreated groups. The
index values were higher in the stimulated patients than in the
control group. Between days 7 and 13 of the cycle, the PI in the
treated group fell from 5.2 ⫾ 0.8 to 3.4 ⫾ 0.8 while the PI in the
control group declined from 4.4 ⫾ 0.6 to 2.3 ⫾ 0.3.
In our own population, we found that the resistance values
after gonadotropin stimulation were lower and the blood flow
velocities higher than in the previous, nonstimulated cycles.
The pulsatility index proved to be a more statistically rewarding parameter than the resistance index. The difference between the two indices is related to methodology: given the
quantities that enter into the pulsatility index, waveforms with
absent or greatly decreased diastolic flow can be differentiated
better with this parameter than with the resistance index
The increased blood flow velocities and decreased pulsatility
index after gonadotropin treatment can be explained by the
significantly higher estradiol levels in the treated cycles
higher pulsatility index that Battaglia et al.
stimulated cycles may result from the study design. They obtained their measurements in two contrasting groups rather
than in a uniform population, so there may have been significant, uncontrolled differences between the control group and
treated group. Moreover, they employed two different stimulation regimens, one with clomiphene/hCG and one with hMG/
hCG. Our own results indicate a lower vascular resistancein the
uterine artery after hormonal stimulation than in spontaneous
cycles.
Tekay et al.
46
found no change in uterine or ovarian blood
flow in nine patients with ovarian hyperstimulation syndrome
compared with 21 stimulated control patients. After the symp-
2
performed com-
9
2
described in
26
. The
toms subsided, however, the uterine artery pulsatility index
was significantly lower in the five patients who had become
pregnant than in the pregnant controls.
Oyesnaya et al.
33
found a positive correlation between oocyte yield and the vascular index of the follicles in an IVF-ET
population. This index was defined as the ratio of follicles with
a demonstrable pulsatile pattern to the total number of follicles. The timing of hCG administration could be optimized
with the aid of these measurements. Another study showed
that blood flow measurements in the stroma of suppressed
ovaries can be used to evaluate ovarian responsiveness to
stimulation
10
.
Uterine Blood Flow and Implantation
An even more important clinical issue is the correlation between Doppler parameters and implantation. Goswamy et al.
found a significantly lower pregnancy rate in a selected clinical
population with four or more unsuccessful IVF attempts than
in patients with fewer attempts. Doppler ultrasound studies of
uterine blood flow showed decreased uterine perfusion in 48%
of the patients who had previous unsuccessful IVF attempts.
Drawing on a previous study in 16 subjects
classified the flow velocity waveforms by qualitative criteria
based on the presence and pattern of diastolic flow. A complete
or partial absence of diastolic flow was classified as decreased
uterine perfusion, while continuous diastolic flow was
classified as normal uterine perfusion. Goswamy and Steptoe
found improvement of uterine perfusion in 31 of 38 patients
who had been pretreated with estradiol valerate, and 15 of
these patients subsequently conceived with in-vitro fertilization. The authors performed transabdominal scans with a fullbladder technique, noting that excessive bladder filling could
alter the uterine waveforms and lead to an erroneous classifi-
15
cation
.
Our own group of authors scanned the uterine artery of IVF
patients by the transvaginal route.They found that the vascular
resistance was lower in patients with successful implantation
than in patients who failed to conceive
18
sampled on the day of follicular aspiration were significantly
lower in the successful patients than in those who did not con-
43
ceive
finding (Table 6.
color Doppler examinations of the endometrium, finding that
.
. The results of more recent studies have confirmed this
3). Zaidi et al.
52
achieved similar results in
nonvisualization of subendometrial and intraendometrial vessels indicated poor endometrial receptivity. Salle et al.
grated uterine blood flow and sonomorphological criteria into
a score for predicting uterine receptivity.
The data indicate that the implantation rate and pulsatility
index are inversely correlated with each other. In all studies
published to date, no pregnancies occurred above a critical cutoff level of approximately 3 to 3.5. Although values below this
cutoff have little prognostic value owing to the broad overlap
between the pregnant and nonpregnant populations, the results indicate that severely decreased uterine perfusion can be
an important cause of infertility.
15
, the authors
. Uterine waveforms
36
16
Infertility Evaluation and Assisted Reproduction
inte-
65

Color Doppler Sonography for the Optimization of Assisted Reproduction
Table 6.3 Association between implantation and uterine vascular resistance. Review of published studies
Authors n Pregnancy
rate (%)
Pregnant Not preg-
Strohmer et al.
(1991)
Steer et al.
41
(1992)
Spernol et al.
39
(1993)
Favre et al.
11
(1993)
Cacciatore et al.
6
(1996)
Zaidi et al.
54
(1996)
Tekay et al.
48
(1996)
Our data 124 22 0.81 ⫾ 0.06 0.84 ⫾ 0.08 ⬍ 0.05 2.25 ⫾ 0.61 2.82 ⫾ 1.16 ⬍ 0.05 RI ⬎ 0.95 or
6
* = Frozen embryo transfer.
NI = not indicated.
NS = not significant.
105 12 NI – 2.32 ⫾ 0.84 2.84 ⫾ 1.29 ⬍ 0.05 NI
82 34 NI – 2.08 ⫾ 0.43 2.62 ⫾ 0.85 ⬍ 0.05 PI ⬎ 3
117 17 NI – 1.86 ⫾ 0.48 2.11 ⫾ 0.55 ⬍ 0.05 PI ⬎ 3.09
185 21 NI – 2.80 ⫾ 0.48 2.90 ⫾ 0.55 NS PI ⬎ 3.55
200 35 0.85 ⫾ 0.04 0.87 ⫾ 0.04 ⬍ 0.05 2.45 ⫾ 0.54 2.66 ⫾ 0.39 ⬍ 0.05 RI ⬎ 0.95 or
139 25 NI – 2.52 ⫾ 0.50 2.64 ⫾ 0.80 NS NI
32* 13 NI – 3.33
25 36 2.47
RI p PI p No implanta-
Pregnant Not preg-
nant
(2.04 –3.91)
(1.52– 3.77)
nant
3.02
(2.13– 6.72)
2.38
(1.79– 4.87)
NS
NS PI ⬎ 4
tion when:
PI ⬎ 3.3
PI ⬎ 3.5
66
Conclusions for the Clinical Management of
Assisted Reproduction
Study results indicate that Doppler measurements of uterine
blood flow can be incorporated into the clinical management
of assisted reproduction. Very high resistance values in the
uterine artery Doppler waveforms reflect poor endometrial receptivity and imply a poor outcome of assisted reproductive
procedures. In our own study, uterine vascular resistance
above the 90th percentile signified a nonreceptive endometrium with 100% specificity and a positive predictive
value of 100%. Doppler measurements of uterine blood flow
can be integrated into the transvaginal ultrasound examina-
Summary
Hormonal influences. Color Doppler sonography provides a
simple, noninvasive means of investigating uterine and ovarian blood flow under the influence of endogenous and exogenous sex hormones. Our own studies in 68 spontaneous cycles and 161 cycles treated with gonadotropins show that
uterine vascular resistance rises slightly in response to endogenous progestins, while the systolic blood flow velocities (V
remain constant at approximately 40 cm/s.
Significantly lower uterine vascular resistance and significantly higher blood flow velocities were measured following
hormonal stimulation with gonadotropins.
max
tion of the lesser pelvis with only a slight increase in scanning
time and no additional patient discomfort. Low vascular resistance values indicate normal endometrial receptivity.
Higher-order multiple pregnancies can be avoided by using
stimulation sparingly and by limiting the number of transferred embryos, although when uterine artery vascular resistance is increased the capabilities of assisted reproduction
should be fully utilized owing to the markedly decreased implantation rate in these cases. When uterine vascular resistance is greatly increased, it should be concluded that the
endometrium is nonreceptive. These patients should not be
subjected to the physical and emotional ordeal of in-vitro
fertilization without appropriate prior hormonal treatment.
Endometrial receptivity. Doppler measurements of uterine
blood flow can be used in the assessment of endometrial receptivity. High uterine vascular resistance implies a markedly
reduced chance of fertilization. Our own measurements and
the data published by other groups of authors indicate that
decreased uterine perfusion can be a significant obstacle to im-
)
plantation in infertile patients. Very high vascular resistance in
the uterine arteries reflects poor endometrial receptivity and
suggests that assisted reproductive techniques will be unsuccessful. Although the sensitivity of uterine artery impedance measurements is only 14% owing to the numerous
factors that affect receptivity, resistance values above the 90th

References
percentile predict a nonreceptive endometrium with 100%
specificity and a positive predictive value of 100 %. This disorder cannot be detected by the use of classic noninvasive and
invasive diagnostic tests. With a severe decrease in uterine perfusion, the likelihood of implantation is so low that assisted reproduction therapies should be discontinued without appropriate preliminary treatment.
Comments. The data indicate that Doppler ultrasound studies
of uterine blood flow should be incorporated into the clinical
management of assisted reproduction. The Doppler measurements can be added to the transvaginal ultrasound evaluation
of the lesser pelvis with no additional patient discomfort and
can significantly advance the differential diagnosis and treatment of infertility.
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68

Pulsed Doppler and Color Duplex Sonography in the
7
Assessment of Tubal Patency
B. Hüneke, A. Kleinkauf-Houcken, C. Lindner, and W. Braendle
Applications of Doppler Sonography in Reproductive Medicine
Since Fitzgerald and Drumm introduced the Doppler principle
into obstetric and gynecological diagnosis in 1977
cations of this ultrasound technique havespread from obstetric
medicine to the fields of gynecology and reproductive medi-
3, 7,15
cine
and especially of the internal genital organs are investigated by
continuous-wave (CW) Doppler, pulsed-wave (PW) Doppler,
and color-flow mapping (CFM). These techniques can be used,
for example, to study the dependence of blood flow changes on
the ovarian cycle or the hemodynamic effects of pregnancy or
neoplasia.
Tubal patency. To date, only a few reports have been published
on the assessment of tubal patency with spectral Doppler ultrasound
. The hemodynamics of the vessels of the lesser pelvis
3a
. Fallopian tube disease is one of the most frequent
6
, the appli-
causes of infertility, accounting for approximately25 % of cases.
The detection of tubal patency, then, is an important element
in the evaluation of infertility. Conventional methods of testing
such as pertubation, radiographic hysterosalpingography, and
laparoscopic chromopertubation have drawbacks that include
lack of precision, radiation exposure, and invasiveness. One alternative is the sonographic assessment of tubal patency
first such experience at our center was gained with the trans-
vaginal scanning of the passage of saline solution through the
oviducts. When a suitable ultrasound contrast medium became available (Echovist, Schering), we were able to improve
the quality of B-mode
done to determine whether the use of pulsed Doppler and
transvaginal color duplex scanning could furnish additional information in the noninvasive evaluation of tubal
visualization
9
10
. Subsequent studies were
patency
9a
. The
Infertility Evaluation and Assisted Reproduction
.
Assessment of Tubal Patency
Patients and Method
Clinical population. Since the advent of ultrasound tubal imag-
ing, 210 women have been examined with B-mode and Doppler ultrasound at our infertility clinic. The average patient age
was 33 years. Two-thirds of the patients had primary infertility, and one-third had secondary infertility (Table 7.
20% of the patients had been previously evaluated for a tubal
factor, but nearly all of the women had received prior infertility
treatment.
Timing of the examination. The examination was performed in
an initial series before a planned laparoscopy in patients with
stimulated cycles. The patients were eventually assigned to a
gamete intrafallopian transfer (GIFT) program or an in-vitro
fertilization (IVF) program based on tubal imaging results and
laparoscopic findings. Written informed consent was obtained. The ultrasound assessment of tubal patency was performed in the late follicular phase, as this offers the best conditions for passing an intrauterine catheter atraumatically
through the canal of the estrogen-primed cervix.
Preparations for the examination. Prior to the outpatient procedure, acute genital infection was excluded by the determination of erythrocyte sedimentation rate (ESR), hemoglobin, and
white blood cell count and by gynecological examination with
1). Only
Table 7.1 Patients enrolled in the study
Characteristics of the patients examined
Number (n)210
Age (years) 32.5 (25–41)
History of infertility (years) 3.4 (2–10)
Primary infertility (%) 65
Secondary infertility (%) 35
Duration of study (months) 60
a speculum and bimanual palpation. The ultrasound study was
performed in a gynecological chair with no premedication or
general anesthesia. After careful aseptic preparation of the
vagina, a pediatric Foley catheter 2.7 mm in diameter (see
Chapter 8) was passed through the cervical canal into the
uterine cavity using sterile technique,and the cathetercuff was
inflated with 2 ml of saline solution. In a few cases (e.g.,
patients with a previously operated cervix), it was necessary to
grasp the cervix with a tenaculum or dilate the cervical canal.
Next the endovaginal probe was introduced.
69

Pulsed Doppler and Color Duplex Sonography in the Assessment of Tubal Patency
Ultrasound equipment. The following ultrasound systems
were used in the examinations:
➤
Mechanical rotary scanner with a forwardscan direction and
240⬚ wide-angle view, a B-mode frequency of 5 and 7.5 MHz,
a pulsed Doppler frequency of 4.5 MHz, and a pulse repetition frequency (PRF) of 3.9–15.6 kHz (Kretztechnik Combison 320–5 and 410, Zipf, Austria). The active Doppler beam
could be freely steered over the entire B-mode area (240⬚),
Doppler
beam
Sample
volume
Intrauterine
catheter
Vaginal
probe
7
Fig. 7.1 Instrumentation used for tubal imaging with Doppler ultra-
sound. The catheter for contrast instillation is inside the uterus, and
the endovaginal probe is in the posterior fornix. The Doppler sample
volume has been positioned over the intramural and near-proximal
tubal segment.
and the Doppler sample volume (1–15 mm) could be positioned at any depth over the 17 cm range of the scanner
(Fig. 7.
1).
➤
Electronic curved linear array with a forward-directed 150⬚
beam, a B-mode frequency of 5–9 MHz, a pulsed Doppler
frequency of 5MHz, color duplex Doppler, and a penetration
depth of 8–10cm (Ultramark 9 HDI ESP, ATL, Bothell, WA,
USA).
Contrast medium. The contrast medium consisted of a freshly
prepared suspension of galactose microparticles (Echovist R,
Schering, Berlin). Microbubbles adsorbed to the surface of the
particles provide enhance d reflection of the ultrasound waves
and increased sonodensity.
Examination Technique
The uterine fundus is imaged in a B-mode reference plane in
which the echogenic catheter tip and inflated cuff can be identified, and then a small contrast bolus is injected (Fig. 7.
B-mode analysis. Contrast enhancement can be seen in the
uterine cavity,across the uterotubal junction, in the intramural
part of the tube, and even in distal tubal segments in some
cases. The flow of contrast medium can be tracked in the realtime image. The contrast agent is administered in small, pulsatile injections for optimum B-mode visualization of the flow
dynamics.
2).
70
a
Fig. 7.2 Appearance of the inflated catheter cuff within the uterus.
a Longitudinal scan.
b Transverse scan.
c Initial contrast appearance in the uterine fundus. The sample
volume is positioned over the proximal part of the right fallopian tube.
c
b

Doppler mode. Following the initial B-mode analysis, the
Doppler sample volume is positioned over the intramural and
proximal tubal segment, using the maximum available sample
length (15 mm). The machine is switched to Doppler mode,
and the contrast medium is again administered in short pulsatile injections.
Based on the visual and acoustic analysis of the Doppler
frequency shift of the fluid bolus passing through the fallopian
tubes, the tubes are classified as patent, partially obstructed, or
completely obstructed (Fig. 7.
3).
Patent tube. If the tube is patent, the pulsatile contrast injection flows into the intramural and adjacent proximal tubal segment, where the Doppler sample volume has been placed. The
inflow phase is brief and characterized by a sharp rise in the
Doppler frequency shift. Unobstructed distal outflow is characterized by a slow and steady decline in the Doppler shift over
time (Fig. 7.
3a).
Partial obstruction. With a partially obstructed tube, the Doppler spectrum shows a sharp initial peak caused by intratubal
turbulence. This is followed by a brief stoppage of contrast
flow, with absence of a Doppler shift, caused by increased peripheral resistance (Fig. 7.
3b). If the contrast volume is able to
surmount this resistance, the Doppler trace shows an additional phase of lower-frequency shifts as a sign of decreased
outflow against a resistance. This phase is always of lower
amplitude and shorter duration than in a patent tube.
Assessment of Tubal Patency
a
kHz
b
c
Fig. 7.3 Doppler shift of contrast medium injected into the uterine
fundus (schematic diagram).
a Patent tube.
b Partial obstruction.
c Complete obstruction.
Patent
Partially obstructed
Completely obstructed
Time
Infertility Evaluation and Assisted Reproduction
Complete obstruction. If the tube is completely obstructed, the
contrast medium enters the sample volume in the intramural
part of the tube, where it produces short, intense Doppler
shifts of low amplitude. There are no additional signals following these initial peaks, signifying an absence of outflow distal
to the sample volume (Fig. 7.
3c).
Color flow. When the flow of the contrast medium is additionally analyzed by color-flow imaging, the already intense signals from the Echovist solution may produce conspicuous
noise and superimposed artifacts in the patent tube unless the
sensitivity of the system for flow velocities is set extremely
low. Color-flow analysis (flow direction, turbulence) is indicated only if the B-mode and spectral findings are equivocal or
if an obstruction is suspected. Color flow is often the only technique that can detect the spillage of contrast medium from the
fimbriated end of the tub e.
Documentation. When Doppler scanning is added to the qualitative B-mode analysis, it becomes possible to make a rough
quantitative evaluation of flow through the fallopian tubes.
The entire examination is recorded on videotape, and selected
images are documented with hard copies.
Figures 7.
4–7.8 show typical frequency spectra that il-
lustrate the categories of findings along with original colorflow images. After the Doppler study is completed, a final Bmode assessment is made to check for fluid collections in the
tubes or cul-de-sac.
Fig. 7.4 Original image with the Doppler sample volume placed over
the proximal part of the left tube. The lower part of the image shows a
uniform decline in Doppler shift associatedwith an unobstructed tubal
passage.
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