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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.
References
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and periarterial sympathetic
2α
Infertility Evaluation and Assisted Reproduction
55
Changes in Uterine and Ovarian Perfusion with the Onset of Menopause
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38 Sauer MV, Paulson RJ, Lobo RA: Pregnancy after 50: application of
5
oocyte donation to women after natural menopause. Lancet 341 (1993) 321–323
39 Serafini P, Tran C, Tan T, Norbryhn G, Batzofin J: Oocyte aging is the
main factor responsible for the decline in fertility with chronological advancement. Evidence from the IVF surrogacy and egg donation pro­grammes. 48th Annual meeting of the American Fertility Society. New Orleans 1992, Abstract 0–011, 5
40 Steinleitner A, Stancyzk FZ, Levin JN, d’Ablaing G, Vijod MA, Shabha-
gian VL: Decreased in vitro production of 6-keto-prostaglandin F uterine arteries from postmenopausal women. Amer. J. Obstet. Gyne­col. 161 (1989) 1677–1681
41 Stevenson JC, McDonald DWR, Waren RC, Booker MW, Whitehead MI:
Increased concentration of circulating calcitonin gene related peptide during normal human pregnancy. Br. Med. J. 29 (1986) 1329–1330
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hormone level is a better predictor of in vitro fertilization performance than age. Fertil. Steril. 55(4) (1991) 784–791
44 Van Noord-Zaadstra BY, Looman CWN, Alsbach H, Rabbena JDF, Te
Velde ER, Karbaat J: Delaying child bearing: effect of age on fecundity and outcome of pregnancy. Br. Med. J. 302 (1991) 1361–1365
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pregnancy. N Engl. J. Med. 319 (1988) 189–194
46 Wiro MS, Schewchuk AB: Pregnancy outcome in 242 conceptions after
arteficial insemination with donor sperm and effects of maternal age on the prognosis for successful pregnancy. Amer. J. Obstet. Gynecol. 148 (1984) 518–524
47 Yuthasastrakosol P, Palmer WM, Howland BE: Luteinizing hormone,
oestrogen and progesterone levels in peripheral serum of anoestrous and cyclic ewes as determined by radioimmunoassay. J. Reprod. Fertil. 43 (1975) 57–62
48 Zalud I, Kurjak A: The assessment of luteal blood flow in pregnant and
non-pregnant women by transvaginal color Doppler. J. Perinat. Med. 18 (1990) 215–221
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