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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

Changes in Uterine and Ovarian Perfusion with the Onset of Menopause
patic estrogen metabolism resulting in lower plasma estradiol
levels.
Progesterone Effect
So far, the effect of progesterone on the pulsatility index (PI) in
humans has not been definitively evaluated. Progesterone acts
as a vasoconstrictor in lower mammalian species
23, 35
. This has
raised concern that a sequential or continuous progesterone
regimen administered for endometrial protection
23
may cause
a partial or complete reversal of the vasodilatoraction of estrogen.
Effect of Age on Ovarian and Uterine Perfusion
Authors’ Study
Kurjak and Kupesic analyzed the relationship between age
(“ovarian aging”) and uterine and ovarian perfusion
5
hundred and ninety women were studied: 91 fertile women
with normal menstrual cycles, 65 postmenopausal women,
and 34 postmenopausal women receiving hormone replacement therapy.
Timing of examinations. Doppler signals from the ovarian
artery were characterized by low flow velocity and high resistance. The women in the control group were examined between days 5 and 10 of their cycle and every day thereafter
until clinical ovulation occurred. The values after ovulation
were measured at least twice during the luteal phase. The
ovary that contained the follicle or corpus luteum was
classified as “dominant.” In the postmenopausal group of
women, the examinations were performed at randomized intervals.
26
. One
Hillard et al.23used transvaginal color and pulsed Doppler to
measure the PI in the uterine arteries during and after estrogenonly and combined estrogen–progesterone therapy. In all patients,
the addition of norethindrone acetate (0.7 mg/day) or medroxyprogesterone acetate (10mg/day) partially antagonized the response to transdermal estradiol. The PI was approximately 34 %
lower than the pretreatment value during the combined estrogen–
progesterone phase of treatment, but it was 13% higher compared
with the estradiol-only phase. It is unclear whether the effects of
progesterone on uterine arterial PI are related to a decrease in pro-
tection against arterial disease on estrogen replacement therapy
when progesterone is added.
a marked decrease in vascular resistance (RI = 0.86 ⫾ 0.04)
(Fig. 5.
1). Doppler measurements repeated in the luteal phase
demonstrated a further rise of end-diastolic flow velocity,
which was most apparent on day 21 of the cycle. This finding
was reflected in a significant decline of the RI to 0.83 ⫾
0.04. The nondominant ovarian artery did not show the cyclic
variations described for the dominant side.
Postmenopausal women. In postmenopausal women who had
had their last menstrual period 1–5 years earlier, Doppler
measurements of the ovarian artery showed no significant
changes compared with the nondominant side in the healthy,
fertile controls. When the values in the postmenopausal group
were compared with ovarian vascular resistance in the early
follicular and luteal phase of women with normal cycles, significant differences were observed (p ⬍ 0.01, p ⬍ 0.001). The
ovarian artery in the postmenopausal group showed a marked
interruption of diastolic flow signals in 55% of the women. Absence of diastolic flow in the ovarian artery was detected in
52
Vessels examined. The uterine artery was scanned lateral to
the cervix at the level of the corpus–cervix junction. The average value for both uterine arteries was taken. Radial artery
waveforms were recorded within the myometrium, and the
spiral arteries were sampled at the level of the myometrial–endometrial junction. During each examination, the resistance
index (RI) was automatically computed from the Doppler
waveform using the formula: (Systole–diastole): systole. The
ovarian artery was scanned lateral to the ovary. If a clear signal
was not obtained, the sample volume was moved across the
ligament until an arterial signal was identified.
Ovarian Artery
Women with normal cycles. Longitudinal studies in which the
ovarian artery was examined in women with normal cycles
demonstrated narrow systolic waveforms with an RI of 0.92 ⫾
0.08 (mean ⫾ SD) in the early postmenstrual phase. In the periovulatory phase (days 12–14 of the cycle), the Doppler traces
recorded from the ovarian artery on the dominant side showed
marked broadening with continuous diastolic flow, indicating
1.0
0.96
6–10 years
1.0
0.96
0.92
>16 years
11– 16 years
>5 years
1–5 years
Patients
on HRT
1.0
RI
0.9
0.8
0.7
Fig. 5.1 Ovarian artery blood flow in premenopausal and postmenopausal women (with and without HRT). ND =nondominant ovarian artery; FP = follicular phase; LP = luteal phase, years = years after
menopause; HRT = hormone replacement therapy.
0.96
0.86
0.83
NDFPLP
Premenopausal
patients
0.96
1–5 years
Postmenopausal
patients

most women who had been menopausal for 6–10 years
(84.2%), while interrupted diastolic flow and an RI of 1.0 were
consistently found in women who had been menopausal for
more than 11 years.
Patients on hormone replacement therapy (HRT). We found no
significant differences when we compared the ovarian artery
RI of patients who had been on HRT for less than fiveyears with
patients who had received the therapy for more than five years.
We also found no difference in ovarian artery resistance between patients receiving HRT and untreated patients. Wewere
unable to record Doppler flow signals from the ovarian
parenchyma of our postmenopausal subjects, regardless of
whether or not they were receiving HRT.
Uterine Artery
Effect of Age on Ovarian and Uterine Perfusion
RI
1.0
0.94
0.92
0.90
0.9
0.8
0.7
0.88
0.84
FP
LP
Premenopausal
patients
0.89
1–5 years
6–10 years
11– 16 years
Postmenopausal
patients
0.85
0.83
>16 years
>5 years
1–5 years
Patients
on HRT
Women with normal cycles. The RI values of the right and left
uterine arteries correlated strongly in every evaluation, and so
we were able to use both values for statistical analysis. The
mean RI of the uterine artery during the proliferative phase
was 0.88 ⫾ 0.04. Doppler measurements of the uterine artery
during the luteal phase showed a decreased RI value (0.84 ⫾
0.004) (Fig. 5.
2).
Postmenopausal women. A significant correlation was found
between the baseline RI and time after menopause in the postmenopausal group of patients. The highest impedance values
were found in the women who had been menopausal for the
longest time. Absence of uterine artery diastolic flow was seen
in 15% of the womenwho had been in menopause for 1–5 years
(Fig. 5.
3). A marked interruption of uterine artery diastolic flow
was found in 31.6% of the women who had been menopausal
for 6–10 years and in 54.5 % of the women who had been
menopausal for 11–15 years. Finally, 79.2 % of the women who
had been menopausal for more than 16 years showed an absence of diastolic flow, which signifies high vascular impedance.
Patients on HRT. The uterine artery RI was significantly lower
in patients who were receiving HRT. Increased diastolic flow
and hence a lower RI were particularly evident in patients who
had been taking hormones for more than six years.
Radial Arteries
The change in the flow velocity patterns of the radial arteries in
premenopausal and postmenopausal women (with or without
HRT) was similar to the flow patterns observed in the uterine
arteries. The mean RI of the radial arteries decreased from 0.74
in the proliferative phase to 0.68 in the luteal phase (Fig. 5.
The RI values showed a tendency to increase after menopause.
Patients who were receiving HRT showed a broadening of the
systolic waveform and continuous flow signals during diastole,
attributable to decreased resistance in the radial arteries.
4).
Fig. 5.2 Uterine artery blood flow in premenopausal and postmenopausal women (with and without HRT). FP = follicular phase;
LP = luteal phase; years = years after menopause; HRT =hormone replacement therapy.
Fig. 5.3 Absence of diastolic flow and reverse flow in the uterine
artery of a postmenopausal patient.
1.0
RI
0.92
0.9
0.8
0.7
0.6
0.5
0.74
0.68
FP
LP
Premenopausal
patients
Postmenopausal
0.86
0.80
1–5 years
6–10 years
patients
0.89
11– 16 years
0.72
0.70
>16 years
>5 years
1–5 years
Patients
on HRT
Infertility Evaluation and Assisted Reproduction
Spiral Arteries
A significant difference in spiral artery resistance was found
between the proliferative phase (RI = 0.64) and the luteal phase
Fig. 5.4 Radial artery blood flow in premenopausal and postmenopausal women (with and without HRT). FP = follicular phase;
LP = luteal phase; years = years after menopause; HRT =hormone replacement therapy.
53

Changes in Uterine and Ovarian Perfusion with the Onset of Menopause
Fig. 5.5 Hyperechoic endometrial layers demonstrated by transvaginal sonography. Analysis of the Doppler waveformof the spiral arteries
(right) shows decreased resistance in the midluteal phase of the menstrual cycle (RI = 0.51).
(RI = 0.50) in the control group of healthy fertile women
(Fig. 5.
5
5). Clear Doppler signals could be recorded from the spi-
ral arteries in only 30% of the women who had been
menopausal for 1–5 years (Table 5.
1). This postmenopausal
group also showed significantly higher impedance in the spiral
arteries than the control group. In women who had been
menopausal for more than six years, we were unable to record
flow signals from the periphery of the endometrium. The spiral
artery detection rates were higher (p ⬍ 0.001) in women who
were receiving HRT (Table 5.
2). The flow velocity waveforms of
the spiral arteries in these women showed a decreased RI
(p ⬍ 0.01) compared with postmenopausal women not receiving HRT.
Interpretation of the Results
The results of our Doppler study agree with other clinical studies that have documented a sudden change in ovarian function
after 40 years of age
Ovarian blood flow during the menstrual cycle. The use of color
Doppler has simplified the analysis of sequential changes in intraovarian blood flow. The highest resistance is observed on
the first day of the menstrual cycle, the lowest on the day of the
LH peak. With transvaginal color Doppler, it is also possible to
observe perfused areas at the periphery of the follicle. The RI is
0.54 shortly before ovulation, starts to decline two days before
ovulation, and reaches its low point of 0.44 at the time of ovulation. The mature corpus luteum normally has a diameter of
1–3 cm and shows low impedance values (mean RI 0.43). On
just the 23rd day after menstruation, the corpus luteum begins
to undergo regressive changes. Decreased blood flow velocities
and an increased RI (mean value 0.49) are the typical signals of
these changes
Ovarian blood flow after menopause. Absent diastolic flow in
the ovarian artery was a common finding in the early postmenopausal period and was consistently present in women
who had been in menopause for more than 11 years. We could
detect no intraovarian blood flow in the group of postmenopausal women. This may be due to a progressive increase
in fibroblasts and connective tissue accompanied by a decline
in circulating estrogen levels. For this reason, any signals that
are detected with color Doppler ultrasound in the postmenopausal ovary should be considered highly suspicious for
abnormal neovascularization and should prompt a detailed investigation with pulsed Doppler.
7,11, 29, 30, 31,38, 44, 46
1,5, 8, 25, 28,48
.
.
54
Table 5.1 Detection rates of the uterine, spiral, and radial arteries in postmenopausal patients
Number of patients Duration of menopause
(years)
15 1–5 100 100 30
14 6–10 100 89.5 0
17 11–15 100 76.2 0
19 ⬎ 15 100 33.3 0
Total 65 100 76.2 7.14
With permission from Kurjak and Kupesic27.
Table 5.2 Detection rates of the uterine, spiral, and radial arteries in postmenopausal patients receiving HRT
Number of patients Duration of menopause
(years)
21 1–5 100 100 35.7
17 ⬎ 5 100 94.1 17.6
Total 38 100 97.7 28.8
With permission from Kurjak and Kupesic27.
Detection rate of uterine
artery (%)
Detection rate of uterine
artery (%)
Detection rate of radial
artery (%)
Detection rate of radial
artery (%)
Detection rate of spiral
artery (%)
Detection rate of spiral
artery (%)

References
Uterine blood flow after menopause. We found continuous diastolic flow in the uterine arteries of all healthy, fertile control
subjects. The uterine arteries of postmenopausal women
showed increasing vascular impedance that was manifested by
a narrow systolic waveform and a high RI. Bonilla Musoles et
2
al.
found increased vascular resistance in the uterine arteries
after the onset of menopause.
It should be noted, however, that the change in vascular impedance and absence of diastolic flow in the ovarian arteries
are the most conspicuous signs. The fact that the uterine artery
RI does not change significantly during the initial postmenopausal years supports the thesis that the aging process
affects the uterus less than was previously supposed
27
.
Hormone replacement therapy. The profound decline of vascular resistance in our patients who were receiving HRT was
manifested by changes in the Doppler signal patterns of the
radial arteries and uterine artery. Other, earlier Doppler stud-
9, 23, 49
ies
documented a marked decline of uterine artery resistance following treatment with physiological amounts of
transdermally administered E
. This implies that it is relatively
2
easy to manipulate the uterine system with controlled hormone regimens. The authors discovered a rapid and profound
response of uterine blood flow to hormone replacement therapy. The cardiovascular benefits are apparent and are seen
even in women who do not start hormone replacement therapy until late in menopause.
At the same time, there are other variables that can influence uterine perfusion after menopause. A possible persistence of residual ovarian activity and the use of vasoactive
drugs can decrease the values of uterine vascular resistance.
Even dietetic and psychosocial factors can affect the local
uterine blood flow in postmenopausal women.
Conclusions. These data confirm and support the observation
that oocytes donated by young women, together with appropriate hormonal support of the endometrium, can help to overcome the problems of deficient uterine receptivity and high
abortion rates that occur in postmenopausal women
3
.
There is no doubt that transvaginal color and pulsed Doppler ultrasound provide a noninvasive method that will help us
to understand the possible effects of aging on female fertility.
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2α
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by
1α
56

Color Doppler Sonography for the Optimization of
6
The inability to conceive is a problem that affects some 10–15%
of all couples. The causes of infertility are multifactorial in
many cases. In addition to primary ovarian, hypothalamicpituitary, extragenital endocrine, psychogenic, immunological,
genetic, tubal, uterine, cervical, and vaginal causes of infertil-
Assisted Reproduction
D. Grab and K. Sterzik
Functional Evaluation of the Endometrium
For all therapeutic approaches that are applied in assisted reproduction (Table 6.
functional status of the endometriumis a major determinant of
successful implantation. The outcome of any procedure in reproductive medicine depends critically upon whether the embryo encounters an endometrium that is receptive to implantation. Theoretical considerations led Paulson et al.
clude that a lack of endometrial receptivity in hormone-induced cycles is responsible for two-thirds of all treatment
failures.
Histological studies. Histological studies have shown that
different stimulation protocols lead to different distributions
of endometrial abnormalities, with clomiphene showing a particularly high association with significant endometrial dysfunction ranging to complete atrophy
findings, Dallenbach et al.
tology should be an essential study in the investigation and
treatment of infertility. The disadvantage of histological examination is its invasiveness.
Sonomorphological studies. The value of sonomorphological
studies of the endometrium in monitoring the cycles of infertile patients is discussed controversial. While it is true that
Table 6.1 Methods in reproductive medicine
Method Abbreviation
1), it must be considered that the
34
to con-
8, 42, 51
8
state that endometrial biopsy his-
. Based on these
ity, there are growing numbers of cases that result from a male
infertility factor or have an unexplained cause (“idiopathic infertility”). In 30 % of cases, the causes of infertility relate to both
partners
modern high-frequency endovaginal probes can accurately define the sonoanatomy of the endometrium
has been unable to establish whether ultrasound can supply a
clinically useful prognosis with regard to endometrial receptivity
are not consistently reflected in either the thickness or echo
pattern of the endometrium.
Pulsed Doppler ultrasound. Hemodynamic measurements of
uterine and ovarian blood flow with Doppler ultrasound represent a new approach in the diagnosis of infertility. These
measurements are based upon studies by Taylor et al.
authors recorded waveforms from the uterine and ovarian arteries by transabdominal pulsed Doppler scanning and distin-
guished them from other blood vessels in the lesser pelvis by
their location and distinctive flow patterns.
endovaginal transducers. Feichtinger et al.
tain nonsuperimposed scans of the uterine and ovarian blood
vessels by the transvaginal route and investigated uterine and
ovarian blood flow under physiological and pathological conditions.
Color Doppler sonography. The use of color Doppler sonography can provide an anatomically precise view of the vascular
supply in the lesser pelvis
sels can be rapidly identified and evaluated with this technique
(Figs. 6.
22
.
7
, research to date
21, 44
. Our own studies indicate that histological findings
45
. These
Another advance was the development of Doppler-capable
3, 13
. Uterine and ovarian blood ves-
1 and 6.2).
Goswamy et al.
16
presumed that a relationship existed be-
12
were able to ob-
Infertility Evaluation and Assisted Reproduction
Intrauterine insemination IUI
In-vitro fertilization and embryo transfer IVF-ET
Gamete intrafallopian transfer GIFT
Pronucleus stage transfer PROST
Zygote intrafallopian transfer ZIFT
Intratubal embryo transfer TET
Intracytoplasmic sperm injection ICSI
Partial zona dissection PZD
Subzonal insemination SUZI
the basis of their Doppler investigations of uterine blood flow.
Shortly thereafter, we were able to confirm this observation in
our own patients
determine whether Doppler measurements of uterine blood
flow could be useful in predicting the outcome of implanta-
17
tion
.
18, 4 3
. We later studied a larger population to
57

Color Doppler Sonography for the Optimization of Assisted Reproduction
Fig. 6.1 Color Doppler image of the as-
cending main branch of the uterine artery.
Parasagittal scan at the level of the uterine
cervix.
Fig. 6.2 Color Doppler image of ovarian
blood flow in a spontaneous cycle.
Fig. 6.1 Fig. 6.2
Authors’ Studies
Patients and Methods
Patients. Our study population consisted of 124 patients with a
tubal or male infertility factor who were undergoing in-vitro
fertilization (IVF) after a standard hormone stimulation proto-
6
col with human menopausal gonadotropin (hMG) and human
chorionic gonadotropin (hCG)
sonographic examinations were performed in a total of 68
spontaneous cycles and 161 treated cycles.
Methods of assisted reproduction and controls. Ultrasoundguided transvaginal follicular aspiration was performed in 105
patients. The harvested oocytes were inseminated with
washed spermatozoa from the male partner within 12hours
after collection. Embryo transfer was performed at the 4-cell or
8-cell stage.
Nineteen patients underwent pelviscopic follicular aspira-
tion with subsequent gamete intrafallopian transfer (GIFT).
In both the IVF-ET and GIFT groups, the endometrium was
endosonographically evaluated and uterine blood flow was
measured just prior to follicular aspiration.
Sonographic and Doppler sonographic examinations were
performed in 36 patients during the proliferative phase of a
spontaneous cycle, at midcycle, in the secretory phase of the
cycle, and between days 8 and 10 of the next hormone-stimulated cycle.
42
. Sonographic and Doppler
Examination Procedures
Endometrial Sonography
Ultrasound examinations of the endometrium were performed
with a 5 MHz endovaginal probe. The uterus was scanned in
sagittal section, depending on the position of the anterior fornix (anteflexed uterus) or posterior fornix (retroflexed uterus).
Endometrial thickness was determined as twice the thickness of the endometrial layer, disregarding the periendometrial vascular zone
The endometrium was also classified by its echo pattern
using the grading system proposed by Smith et al.
6.
4–6.7).
The endosonographic findings were related to the phase of
the cycle (spontaneous cycles), the result of the histological examination, and the clinical course (implantation rate).
7
(Fig. 6.3).
38
(Figs.
Histology
A uterine fundus biopsy was performed in 70 patients during
the secretory phase of the spontaneous cycle (n = 17) or stimulated cycle (n = 53). The biopsy material was immediately fixed
in formalin and embedded in paraffin. Sections were prepared
58
Comparison group. Consistent with the definition of our study
population, no biopsies were performed in the stimulated cycles. For comparison, we formed a group of 53 women with
normal cycles in whom oocyte fertilization did not occur after
hormonal stimulation with gonadotropins during the study
period. These patients underwent an endometrial biopsy on
the day of the planned embryo transfer.
Results. Pregnancy was confirmed sonographically in 34 of 124
patients (27%) following successful fertilization of the oocytes
and embryo transfer (n= 105) or GIFT (n = 19) (29 singleton
pregnancies, 3 twin pregnancies, and 2 triplet pregnancies). A
total of six abortions and one tubal pregnancy were recorded.
Twenty-seven pregnancies culminated in a live birth (22%).
Fig. 6.3 Transvaginal scan of the anteflexed uterus from the anterior
fornix. The boundaries of the endometrium are marked with cursors.

Authors’ Studies
Fig. 6.4 The endometrium is echo-free except for a prominent cen-
tral echo (grade D pattern of Smith et al. 1984
Fig. 6.6 Endometrial echogenicity is comparable to that of the myometrium. A hypoechoic zone (periendometrial vascular zone) can be
identified between the myometrium and endometrium (grade B pat-
tern of Smith et al. 1984
38
).
38
).
Fig. 6.5 Increasing echogenicity of the endometrium. The endometrium is always less echogenic than the surrounding myometrium, however (grade C pattern of Smith et al. 1984
Fig. 6.7 The endometrium is more echogenic than the myometrium
(grade A pattern of Smith et al. 1984
38
).
38
).
Infertility Evaluation and Assisted Reproduction
and stained with hematoxylin–eosin or van Gieson stain, and
the specimens were evaluated according to the criteria of
Noyes et al.
28
All histological examinations were performed at
the Prof. Dallenbach Institute in Mannheim.
Scanning electron microscopic examinations were addi-
tionally performed in a subgroup of patients (Figs. 6.
8–6.10 ).
Doppler Sonography
Equipment. The Doppler studies of uterine blood flow were
performed with an endovaginal probe using duplex technique.
The probe was a mechanical 5 MHz transducer (B-mode) combined with an integrated 4.5 MHz Doppler transducer (Combison 320–5 with 300 Doppler module, Kretztechnik, Zipf,
Austria). The color Doppler scanner was equipped with a
5 MHz endovaginal probe (Toshiba 270 A, Neuss, Germany).
Parameters. The probe was positioned in the vaginal fornix,
and the uterine artery was scanned in parasagittal section at
the level of the cervix. The Doppler beam was then directed
toward the uterine vascular bundle at an angle that produced a
maximum frequency shift. The waveforms were subjected to
semiquantitative analysis using the resistance index
satility index
14
. These values reflect the degree of vascularity
35
and pul-
and functional state of the distal arteriolar and capillary bed.
High indices signify a low degree of vascularity with a correspondingly high vascular resistance, while low indices reflect a
low vascular resistance and high degree of vascularity in the
distal bed.
Semiquantitative measurements. Semiquantitative measurements were performed on the day of follicular aspiration in all
124 patients and in the previous spontaneous cycle of 39
patients. Twenty-three other patients were examined in the
spontaneous cycle but not in the subsequent, stimulated cycle.
Thus the semiquantitative parameters determined for spon-
taneous cycles are based on a population of 62 patients.
Quantitative measurements. Quantitative measurements are
possible only if the angle of the Doppler beam is known. This
requires a precise longitudinal image of the vessel to be examined. Color Doppler can provide an extended view of the ascending main branch of the uterine artery (Fig. 6.
11). A total of
272 quantitative measurements of systolic and mean uterine
blood flow velocities were performed in 32 untreated cycles
and in 33hormone-stimulated cycles.
59

Color Doppler Sonography for the Optimization of Assisted Reproduction
Fig. 6.8 Normal histological endometrial structure in the secretory
phase of the cycle.
a Light micrograph (⫻240).
6
Fig. 6.9 Deficient secretion.
a Light micrograph (⫻100).
b Scanning electron micrograph (⫻1250).
b Scanning electron micrograph (⫻1250).
60
Fig. 6.10 Abortive secretion.
a Light micrograph (⫻100).
b Scanning electron micrograph (⫻1250).

Authors’ Studies
12
Fig. 6.11 Color Doppler image of the uterine artery in parasagittal
section. The sample volume has been placed over the vessel lumen at
an insonation angle of 52⬚. At left the Doppler spectrum is recorded
from that area.
Evaluation. Both the semiquantitative and quantitative
measurements were performed bilaterally. For statistical
analysis, the mean value of the measurements taken on the
right and left sides was used for each parameter.
The hemodynamic parameters were correlated with the
sonomorphological, hormonal, histological, and clinical parameters (implantation rate). The dependence of hemodynamic parameters on the phase of the cycle and on hormonal
stimulation was also evaluated.
10
8
6
4
Endometrial thickness (cm)
2
0
7–10
12–16 21–24
Day of cycle
9.8
9.1
8.3
Stimulated
Fig. 6.12 Endometrial thickness measured endosonographically in
spontaneous cycles and after hormonal stimulation. Mean values ⫾
standard deviation.
100
%
80
60
40
20
Grade A
Grade B
Grade C
Grade D
Infertility Evaluation and Assisted Reproduction
Results
Endometrial Sonography
Endometrial thickness. Figure 6.12 shows the sonographically
determined endometrial thickness in spontaneous cycles and
after hormonal stimulation (mean values ⫾ standard deviation). Analysis of variance indicates a highly significant increase of endometrial thickness over the course of the cycle
(p ⬍ 0.001). Intergroup testing (t-test) shows a highly significant difference in endometrial thickness between the midproliferative phase and midcycle (p ⬍ 0.001). The values
measured at midcycle and in the mid-secretory phase do not
differ significantly (p = 0.2). The endometrial thickness in these
phases corresponds to the values measured in the stimulated
cycles (p = 0.5).
Echo pattern. A characteristic change of echo pattern was observed in the spontaneous cycles (Fig. 6.
pattern
38
was noted most frequently during the proliferative
phase, grades A and B were more prevalent at midcycle. The
echo pattern in the secretory phase was almost exclusively
grade A. The echo pattern in the stimulated cycles most closely
resembled the pattern observed in the proliferative phase.
Implantation rate. Neither the endometrial thickness nor the
echo pattern showed a definite correlation with implantation
13). While a grade C
0
7–10
Fig. 6.13 Endometrial echo patterns (grades A–D after Smith et al.
38
) in spontaneous cycles and after hormonal stimulation.
198 4
12–16 21–24
Day of cycle
Stimulated
rate. No significant difference was found in endometrial thickness following successful or unsuccessful implantation
(9.5 mm versus 9.1 mm; p = 0.71). Figure 6.
14 shows the dis-
tribution of echo patterns by successful or failed implantation.
Clinical pregnancies occurred in association with all four endometrial grades as defined by Smith et al.
38
.
Histology
Sonographic findings and histological diagnosis. Most en-
dometria in the secretory phase were assigned to grade A as
defined by Smith et al.
sis. Two endometria that were grade B by sonographic criteria
were either healthy or showed deficient transformation by histological evaluation. Also, the sonographic endometrial thickness did not consistently match the histological thickness: the
widths measured sonographically weresometimes larger with
nonreceptive histology than in the receptive cases, and the
38
, regardless of the histological diagno-
61
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