Advances in ultrasound assessment in the establishment and development of pregnancy

Advances in ultrasound assessment in the

establishment and development of pregnancy

Current data demonstrate that angiogenesis in the ovaries and uterus is an

essential component of both follicular and luteal phases of menstrual cycle,

tightly correlating with the levels of bioactive substances such as hormones,

growth factors and interleukins. Ultrasound is used principally to demonstrate

follicular growth, a receptive triple layer endometrium and to exclude

pathologies such as fibroids and ovarian tumours. However, the development of

new technologies such as CDI, CPA, 3D-US, 3D-CPA is now set to expand the role

of ultrasound in the assessment of the processes in the ovaries, uterus and early

pregnancy. There is growing evidence that studies of peri-follicular vascularity

will predict the development of a healthy oocyte and subsequently an embryo.

Endometnal blood flow studies with conventional CDI and the newer

techniques of CPA and 3D-CPA will be important in predicting endometrial

receptivity. Ovarian stromal vascularity appears to correlate with vascular

endothelial growth factor (VEGF) levels and high vascularity is associated with

PCO and a risk of ovarian hyperstimulation syndrome. 3D-CPA may improve our

ability to assess ovarian and endometrial vascularization and blood circulation,

to diagnose tubal patency. Increasingly, 3D ultrasound is being applied to

diagnose the pathology of early singleton and multiple pregnancies.

The female reproductive system is unique in that this is the only site in the

uninjured adult body where angiogenesis (i.e. the formation of new blood

vessels) occurs in a repetitive cyclic fashion. It is taking place in the ovary

during folhcular development and corpus luteum formation, and in the

endometrium during proliferative phase of menstrual cycle. Soon after

formation of the follicular antrum, the follicle acquires a vascular sheath

in the theca layer. The establishment of the vascular sheath, particularly

the expansion of the inner capillary plexus of the theca interna, co-incides

with a period of rapid growth and differentiation of the follicle1. The

granulosa and theca cells of ovarian follicles are sources of angiogenic

activity, which appear to be under the control of gonadotropins. At about

the time of folhcular rupture, vessels of the theca begin to sprout and

penetrate the membrana granulosa; then, they anastomose to form a

dense network, ultimately bringing each lutein cell into close approximation

to the vascular system. It has been shown that the rates of

follicular and luteal blood flow are among the highest in the body (5-10

and 10-30 ml/min/g, respectively) as compared to normal renal flow of

approximately 4—8 ml/min/g2'3. Endometrial growth and development in

response to systemic concentrations of ovarian steroids are well known.

The rate of blood flow to uterine tissues also varies throughout the menstrual

cycle and during the pregnancy4.

Details of angiogenic events in the ovary and endometrium have been

pivotal in understanding folliculogenesis and implantation. Therefore, by

coupling various ultrasound technologies to high frequency transvaginal

probes it is possible to perform detailed studies of ovarian and endometrial

vascularity which is important for the establishment and development of

pregnancy.

Recently, the introduction of colour Doppler imaging (CDI), colour

power angiography (CPA) and three-dimensional ultrasound (3D-US) has

increased the range of diagnostic information on angiogenesis within the

ovary and endometrium, and morphological conditions in the uterus and

Fallopian tubes.

Doppler ultrasound makes use of the Doppler effect where the changes

of frequency (frequency shift) caused when an ultrasound beam interacts

with moving erythrocytes in blood vessels can be measured and displayed.

This Doppler shift can be displayed either as a colour map of the blood

vessels within the organ being studied or as a flow velocity waveform

(spectral Doppler) which allows the measurements of absolute velocity

(cm/s) and resistance to flow (pulsatility index). New modalities such as

colour power angiography use the amplitude of the Doppler signals which

represents the density of erythrocytes within the vessels being studied. This

provides a more sensitive display of vasculature within an organ.

Three-dimensional ultrasonography (3D-US) has been used to assess the

uterine anatomy and to detect congenital anomalies of uterus. 3D-US differs

from conventional 2D scanning m that a volume of echoes is captured

instead of the usual 2D 'slices'. This volume can be obtained by equipment

which can capture the volume from a free-hand sweep (positional information

being provided by an electromagnetic sensor) or by means of an

automatic capture of the volume by the transducer itself which moves in

two planes. This latter device is quicker and more accurate and will obtain

a volume within 5-20 s. When the volume has been obtained, it can be

analysed in several different ways.

Re-slicing

This means that volume can be analysed with traditional 2D slices but

now all planes can be obtained, even the plane at right angles to the surface

of the probe which cannot be obtained by conventional imaging. An example

of the value of this was demonstrated by Jurkovic et als, who showed that

this technique could display the coronal plane of the uterus making it useful

in detecting major congenital anomalies and intra-uterine defects.

Volume measurements

More accurate measurements of the volume especially of irregular

structures can be obtained by using multiplanar reformatted sections

method and built-in software. This has been shown to improve the

measurements of ovarian, follicular6'7, uterine and endometrial volumes7'8.

Improved volume measurements provide better staging of endometrial

cancer9. However, the usefulness of those improved volume measurements

have yet to be demonstrated in reproductive medicine.

Surface rendering

By means of shading and thresholding, surface rendered views can provide

impressive 3D images of structures, especially if there is a solid/fluid

interface. Impressive images can be obtained of the early embryo, but

unique images can also be obtained of ovarian cysts, especially those with

vegetations and submucous fibroids, particularly if hydrosonography is

used. One of the most innovative applications of the surface rendering in

gynaecology is its use to demonstrate tubal patency by obtaining threedimensional

views of flow along the Fallopian tube by 3D-CPA10.

Colour power angiography

CPA is monochromatic and does not provide directional information, but

its sensitivity to low flow makes this more useful to study tissue perfusion11.

Quantitative analysis of the blood flow in the predefined volume is available

by implementing the colour histogram mode, the results of which are

expressed as various indices. The indices are calculated by the built-in or

separate computer using specially developed software.

Vascularization index (VI)

This describes the vessel density in the selected volume (colour

voxels/fcolour voxels + grey scale voxels]).

Flow index (Fl)

This describes the intensity of blood flow in these vessels (weighted

colour voxels/colour voxels).

Vascularization-flow index (VFI)

Vascularization-flow index reflects to some extent perfusion of the selected

volume (weighted colour voxels/[colour voxels + grey scale voxels]).

Assessment of uterine receptivity

At present, ultrasonographic parameters of endometrial receptivity have a

strong negative value in setting some minimum criteria, although their value

as prognostic indicators for implantation following embryo transfer has yet

to be proven. Good uterine perfusion, as shown by good diastolic flow and

low resistance to flow indices, was correlated with conception following

assisted reproduction treatment. Several authors demonstrated statistically

significant difference in the measurements of uterine artery pulsatUity index

(PI) between those women who became pregnant and those who did not

after IVF treatment. Steer et aJ}2 suggested that measurement of mean

uterine PI on the day of embryo transfer to assess endometrial receptivity is

a good method of assessing uterine receptivity in women undergoing FVFET

treatment. A mean PI of greater than 3.0 before embryo transfer could

predict up to 35% of failures to become pregnant. Similar results have been

obtained by other authors in studies investigating uterine PI and

implantation rates whether on the day of folhcular aspiration13 or on the

day of human chorionic gonadotrophin (hCG) injection14'15. However, some

authors were not able to demonstrate any predictive value of uterine artery

PI in terms of uterine receptivity in IVF patients16"19. The uterine artery

blood flow impedance on the day of embryo transfer was unrelated to the

risk of the conceptus ending in spontaneous abortion or ectopic

pregnancy20. This finding implies that poor uterine blood flow does not

increase the risk of adverse pregnancy outcome, if pregnancy was achieved.

Velocities and resistance indices were not correlated with endometrial

thickness. However, combination of triple layered endometrium (thickness

more than 8 mm) and of low vascular impedance in the uterine arteries (PI

less than 3.0) have been suggested as reliable ultrasound markers for

endometrial receptivity21. The uterine scoring system which included

multiple ultrasonographic and colour Doppler parameters on day 22 of the

menstrual cycle prior IVF treatment cycle appeared to be a useful predictor

of implantation22.

Assessment of subendometrial blood flow has been of interest recently.

Using conventional CDI, the degree of penetration of vessels into the endometrium

correlated with the success of implantation. Absent subendometrial

vascularity correlated with failure of implantation21'23. Yang

and coworkers24 used power Doppler imaging in assessment of endometrial

vascularization by measuring the coloured area in the endometrium. Those

women with an intra-endometrial coloured area <5 mm2 achieved a

significantly lower implantation rates (8.1% versus 20.2%, P = 0.003

than those with area >5 mm2. Therefore, the number of transferred

embryos should be determined on the basis of the quantity of intra-endometrial

vascularity as well as the endometrial thickness, so as to improve

the reproductive outcome for those with poorly vasculanzed endometrium,

and to reduce the potential risk of multiple pregnancies for those

containing adequate intra-endometrial vascularity24. Three-dimensional

CPA quantitative assessment of blood circulation gives a deeper insight

into evaluation of endometrial receptivity. On the day of pituitary

suppression, Schild et aP5 found significant differences in subendometrial

blood flow and vessel density between women who became pregnant and

those who failed to become pregnant in an in vitro fertilisation

programme. Surprisingly, they found lower 3D indices of volume flow in

conception cycles compared with non-conceptional cycles, suggesting that

a lesser degree of intra-uterine vascularization and perfusion at the beginning

of ovarian stimulation indicated a more favourable endometrial

milieu. Possibly, this reflected a better functional pituitary suppression

following GnRH agonist administration which increases the chances of

successful implantation.

Various regimens of medications such as low dose aspirin, heparin and

NO (nitric oxide) have been found to improve endometrial receptivity due

to their promoting effects on uterine perfusion. Low-dose aspirin treatment

in patients undergoing in vitro fertilisation cycles significantly

improved ovarian responsiveness, uterine and ovarian blood flow velocity,

subsequent implantation and pregnancy rates in FVF patients as shown in

a large randomized, double-blind study26. In studies of women who had

increased uterine artery PI in a previous IVF cycle, administration of NO

donor27 or cGMP promoter (sildenafil)28 have been shown to improve

uterine and endometrial blood flow which may lead to improvement of an

in vitro fertilisation outcome. Further studies are needed to understand

and evaluate the endometrial vascular pattern both in spontaneous and

stimulated ovarian cycles using conventional CDI and also the 3D-CPA

technique, as well as safety of the agents used to promote better endometrial

vascularization.

Fallopian tubes are important part in the chain of pregnancy establishment.

Normally they have to be patent, which means hollow through

the entire tubal length. Hysterosalpingo-contrast sonography (HyCoSy)

using a positive contrast has been widely used to provide a rapid

ultrasound-based test of tubal patency29. This method can be incorporated

into the set-up of the initial investigation for infertility patients. However,

a number of difficulties in tubal visualisation are encountered. Due to

tubal tortuosity, the entire tube can rarely be seen in a single scanning

plane and the echo-contrast medium is usually observed in small sections.

In theory, by manipulating the probe, the contrast agent can be followed

to the fimbrial end of the tube where free spill may be observed; but, in

reality, this is infrequently achieved because the contrast agent has the

same echogenicity as the surrounding bowel. Three-dimensional ultrasound

helps to overcome these problems, because it enables the capture of

a volume which should include the full length of the tube. Power Doppler

which is sensitive to slow flow makes it possible to detect the flow of

contrast medium along the tube up to the fimbrial end where free spill is

identified10. It allows the storage and retrospective analysis of the information

acquired. More studies are required to estimate the cost-effectiveness

of this procedure and to establish whether it can replace conventional

diagnostic hysteroscopy and laparoscopy in the diagnosis of tubal patency.

The reported low specificity in the various studies, ranging between

15—44%, obviously indicates that uterme receptivity is one among several

different factors contributing to implantation. Studies using donor oocytes

have generally demonstrated equivalent implantation and pregnancy rates

among reproductive young and older recipients, suggestmg that oocyte and

embryo quality are paramount in successful implantation30"32. However,

good embryos can derive only from eggs in normally developmg follicles.

Studies of ovarian stromal blood flow

Adequate ovarian blood circulation is an important precondition for

normal ovarian function. Blood flow patterns are different in the

polycystic ovaries as demonstrated by Doppler ultrasound assessment

than those in the normal ovaries33'34. Zaidi et al3S have shown that

ovarian stromal blood flow velocity is significantly higher (P <0.001) in

women with polycystic ovaries (PCO) compared to women with normal

ovaries. The reason for this increased stromal flow is unknown, but it

may be related to high levels of angiogenic cytokines in the theca cell

layer. It has been shown that women with PCO have a higher ovarian

stromal PSV and serum concentration of VEGF than those with normal

ovaries36. It is well known that women with PCO are more susceptible

to ovarian hyperstimulation syndrome (OHSS) and increased stromal

flow may predict an increased susceptibility to this condition. VEGF is

used to assess ovarian response during infertility treatment and a

significant rise in serum VEGF concentration after hCG administration

appears to be one of the most important predictors of OHSS37.

Stromal flow velocities have also been used to study ovarian responsiveness

in IVF treatment. Engmann et al38 studied 81 women with normal

baseline serum FSH levels and normal ovaries; the ovarian stromal blood

flow velocities measured after pituitary suppression appeared to be an

independent predictor of ovarian response. In this study, patients with

peak systolic velocity (PSV) greater than 10 cra/s has a better ovarian

response and had a higher clinical pregnancy rate than those with PSV

<10 cm/s. However, some of the studies16'17 have failed to demonstrate

any significant difference in the intra-ovarian PI between those women

who became pregnant and those who did not following an in vitro

fertilisation treatment. This may be because PI is a less sensitive

indicator of angiogenesis than PSV.

Using three-dimensional power Doppler imaging, prominent changes

of the vascularization and blood circulation in the dominant ovary

during normal menstrual cycle were found. In midluteal phase, the

vascularization index, flow index and vascularization-flow index in the

dominant ovary were, respectively, 6.6-, 1.3- and 9.2-folds higher than

in the non-dominant ovary39. This way of assessment of ovarian vascularization

in normal menstrual cycles and pathological conditions may

be more sensitive and more accurate in diagnosing the changes than

colour and pulsed Doppler measurements.

Evaluation of follicular function

Campbell et at*0 first reported that indices of blood flow in the wall of the

leading follicle could be monitored by transvaginal ultrasonography with

colour Doppler imaging and spectral Doppler over the peri-ovulatory

period. They showed that peak systolic velocity (PSV) around the follicle

was a better indicator of angiogenesis than resistance (pulsatility index, PI).

There was a significant rise in PSV from the time of the LH surge indicating

a marked increase in blood flow during peri-ovulatory period40. There may

be relationship between low follicular blood velocity and luteinised

unruptured follicle (LUF) in spontaneous cycles41.

Follicular vascularity in the stimulated ovary during in vitro fertilisation

and embryo transfer (IVF-ET) treatment has also been studied. Analysis

of these data showed that there was a significant relationship between the

follicular PSV immediately before ultrasound-guided follicular aspiration,

oocyte recovery and subsequent production of good quality preimplantation

embryos. There was a 70% chance of producing a grade I

or II embryo if the follicular PSV was greater than 10 cm/s but only 18%

if no blood flow was detected42. The results of the study also showed that

there was no direct relationship between follicular volume or flow

resistance as indicated by the PI before the administration of human

chorionic gonadotrophin (hCG). There was, however, a significant

positive correlation between the detection of a follicular flow velocity

waveform within a given follicle and the recovery of an oocyte. The

factorial increase m PSV after hCG administration was significantly

higher in follicles that subsequently produced good quality embryos43.

Chui and coworkers17 developed the grading system of assessing the

percentage of follicular circumference in which flow was identified from a

single cross-sectional slide. Poor follicular blood flow was significantly

associated with poor outcome, and successful pregnancies occurred more

frequently in those women with good blood flow17-44'45. A strong

relationship between follicular vascularity and the cumulus activity in vitro

was found46. Similar findings were observed in the stimulated intra-utenne

insemination cycles when the grade of vascularized dominant follicles

(larger than 16 mm in diameter) was recorded. As in IVF cycles, there was

significant association between pregnancy rates and live birth rates and

good blood flow47. The findings are consistent with the suggestion that

changes in follicular vascularity may initiate biochemical events, which are

essential within the follicular environment. There have been reports

showing an association between oxygen concentration in follicular fluid48'49,

or the oxygen consumption or adenosine tnphosphate (ATP) content of an

oocyte50-51, and the production of a good pre-implantation embryo. Moreover,

the dissolved oxygen content of the follicle has been shown to be

related to colour Doppler qualitative patterns and vascular endothelial

growth factor and subsequently associated with developmental competence

of the corresponding oocyte52.

The current findings of an association between follicular PSV and subsequent

clinical pregnancy are consistent with the assumption that

follicular blood flow may be associated with events essential for successful

establishment of pregnancy. The knowledge gained from studies on

follicular vascularity may be useful for designing future studies to

understand physiological and biochemical events during folliculogenesis

and to improve success rates of infertility treatment.

Assessment of early pregnancy

Key chronological landmarks in early human development seen on transvaginal

sonography are still the same despite the developing ultrasound

technique. The normal gestational sac can be first seen in the endometnum

on transvaginal sonography 5 weeks after the last menstrual period (3

weeks after conception). It reaches the size of about 10 mm in diameter.

Yolk sac becomes identifiable a few days later. The embryo adjacent to

yolk sac and fetal heart pulsations (about 125 bpm) are first seen at 6

weeks. From then until 14 weeks, the growth of the embryo is measured

from its crown-rump length (CRL). At 6 weeks of gestation, embryonic

CRL is about 3 mm. At 8 weeks of gestation, embryo CRL is about 16

mm, heart rate 175 bpm and fetal body movements can now be observed.

Recently, 3D ultrasound scanning in the first trimester was applied to

visualize the surface of anatomical structures of the embryo and early fetus.

The results of the investigations suggested that 3D ultrasonography is

becoming an important modality in future embryological and early fetal

research and detection of embryonic and fetal developmental disorders53"56.

3D power Doppler imaging has the potential to study process of placentation

and fetal cardiovascular development.

Over the last few years, intervillous blood circulation has been widely

studied during the first trimester of pregnancy57"59. Findings were in

concordance with histomorphological evidence that spiral arteries begin

to open directly into the intervillous space during the second month of

gestation57'60. The number of areas with the established intervillous

circulation increases gradually with embryonic and placental growth.

These findings indicate that establishment of the intervillous circulation is

a continuous process rather than an abrupt event at the end of the first

trimester. 3D power Doppler seems to be useful in visualizing intervillous

blood circulation in the developing placenta56.

Colour Doppler measurements failed to show the difference in uteroplacental

circulation between patients with threatening miscarriage with a

living embryo and those with normal pregnancy61'62. It was speculated that

vascular injury is possibly so minimal that it cannot be detected by currect

Doppler tecgniques. However, it appeared useful to select the patients who

should undergo conservative or surgical management of first trimester

miscarriages63 which were already imminent. Perhaps application of 3D

power Doppler imaging in the studies of early pregnancy miscarriages will

help to obtain more clinically useful results56.

Perinatal morbidity and mortality of twin gestations is higher among

monochorionic in comparison with dichononic twins64. Therefore, early

diagnosis of multiple pregnancy is very important because it allows

mothers and obstetricians to anticipate various multiple pregnancy related

problems. Data in which both zygosity and chorionicity were determined

support the observation that chorionicity rather than zygosity determines

outcome65. Using high resolution, first trimester transvaginal sonography

chorion and amnion types have been assessed in a number of large

prospective studies64'66. If only one embryo is found in each gestational

sac, the number of amnion and chorion sacs is equal. If two or more

embryos are seen within any chorionic sac, the number of amnion sacs

can be determined usually at about 8 weeks of pregnancy, because the

earlier amniotic sac contains a small amount of fluid and membranes are

too thin for visualisation. Mono-amniotic twins will be surrounded by a

single amnion. Pregnancies are classified as dichorionic if there is a single

placental mass and there is extension of placental tissue into the base of

the inter-twin membrane, the 'lambda' sign. Pregnancies are classified as

monochorionic if there is a single placental mass in the absence of the

lambda sign67-68. Three-dimensional ultrasound scanning was described

as a useful method to study inter-relationships and contacts of twin and

triplet embryos and fetuses55'69. By rotating and translating the planes

inside the acquired volume containing the whole gestational sac, two yolk

sacs and two embryos could be clearly visualized and precise diagnosis of

chorionicity and amnionicity can be achieved.

The significantly adverse outcome of monochorionic twins is attributed

mainly to the presence of communicating placental vascular anastomoses.

Up to 35% of monochorionic twin gestations are complicated by twin-totwin

transfusion syndrome70, which can be essentially disregarded after

ultrasonographic diagnosis of a dichorionic gestation65-71.

Conjoined twins is the most frequently reported first trimester structural

anomaly unique to twins72. The commonest type of conjoined twins is

thoracopagus, where the twins are joined at the thorax; 3D transvaginal

sonography has been used to depict thoraco-omphalopagus73. Although it

was not essential, 3D scanning aided diagnosis by using multiplanar

imaging as well as spatial surface animation. As a rule, due to the unclear

prognosis associated with conjoined twins, whenever a mono-amniotic

twin gestation is diagnosed, the possibility of conjoined twins should be

considered.

There are few data available on detection of fetal structural anomalies by

high resolution transvaginal scans in early pregnancy in unselected populations.

Detection rates reported in the literature are reaching up to 65%74'75.

Sonographic recognition of congenital anomalies depends on knowledge of

normal fetal development, ultrasound equipment used, and natural histories

of the particular disorders. Scans during the first stage of pregnancy will

miss some fetal anomalies because they appear later in pregnancy or might

be undetectable at this stage. This is a scope of whole separate review. One

thing is worth mentioning: 3D ultrasound appears useful in diagnosing fetal

anomalies during the first trimester of pregnancy76.

References

Richards JS. Maturation of ovarian follicles actions and interactions of pituitary and ovarian

hormones on follicular cell differentiation. Physiol Rev 1980; 60: 51-89

Abdul-Karim RW, Bruce N. Blood flow to the ovary and corpus luteum at different stages of

gestation in the rabbit. Ferttl Steril 1973; 24: 44-7

Wiltbank MC, Ballagher KP, Dysko RC et al. Regulation of blood flow to the rabbit corpus

luteum: effects of estradiol and human chononic gonadotrophin. Endocrinology 1989; 124:

605-11

Reynolds LP. Utero-ovanan interactions during early pregnancy role of conceptus-induced

vasodilaaon. / Arum Sa 1986; 62 (Suppl 2); 47-61

Jurkovic D, Geipel A, Grubeck K et al. Three-dimensional ultrasound for the assessment of

uterine anatomy and detection of congenital anomalies: a comparison with hysterosalpingography

and two-dimensional sonography. Ultrasound Obstet Gynecol 1995; 5: 233-7

Kyei-Mensah A, Zaidi J, Pittroff R et al. Transvaginal three-dimensional ultrasound: accuracy

of follicular measurements. Ferttl Stertl 1996; 65: 371-6

Kyei-Mensah A, Maconochie N, Zaidi J et al. Transvaginal three-dimensional ultrasound

reproduabihty of ovarian and endometnal volume measurements. Fertd Stertl 1996; 66: 718—22

8 Lee A, Sator M, Kratochwil A et al. Endometnal volume change during spontaneous menstrual

cycles: volumetry by transvaginal three-dimensional ultrasound. Fertil Stertl 1997; 68 831-5

9 Gruboeck K, Jurkovic D, Lawton F et al. The diagnostic value of endometnal thickness and

volume measurements by three-dimensional ultrasound in patients with postmenopausal

bleeding. Ultrasound Obstet Gyneco\ 1996; 8: 272-6

10 Sladkevicius P. Three-dimensional power Doppler imaging of the Fallopian tube. Ultrasound

Obstet Gynecol 1999, 13: 287

11 Pairletner H, Sterner H, Hasenoehrl G, Staudach A. Three-dimensional power Doppler

sonography: imaging and quantifying blood flow and vasculanzaoon. Ultrasound Obstet

Gynecol 1999; 14: 139^3

12 Steer CV, Campbell S, Tan SL et al. The use of transvaginal color flow imaging after m wtro fertilization

to identify optimum uterine conditions before embryo transfer Fertil Stenl 1992, 57: 372-6

13 Sterzik K, Grab D, Sasse V et al. Doppler sonographic findings and their correlation with

implantation in an in vitro fertilization program. Ferhl Stertl 1989; 52: 825-8

14 Strohmer H, Herczeg C, Plockinger B et al. Prognostic appraisal of success and failure in an in

vitro fertilisation program by transvaginal Doppler ultrasound at time of ovulation induction.

Ultrasound Obstet Gynecol 1991; 1: 272-4

15 Zaidi J, Pittroff R, Shaker A et al. Assessment of uterine artery blood flow on the day of human

chononic gonadotrophin administration by transvaginal colour Doppler ultrasound in an in vitro

fertilization program. Fertil Stenl 1996, 65- 377-81

16 Tekay A, Mamkainen H, Jouppila P Blood flow changes in uterine and ovarian vasculature, and

predictive value of transvaginal pulsed colour Doppler ultrasonography in an in-vttro fertilisation

programme Hum Reprod 1995, 10 688-93

17 Chui DKC, Pugh ND, Walker SM et al. Follicular vasculanty - the predictive value of

transvaginal power Doppler ultrasonography in an ln-vitro fertilization programme, a

preliminary study. Hum Reprod 1997; 12: 191-6

18 Aytoz A, Ubaldi F, Tournaye H et al. The predictive value of uterine artery blood flow

measurements for uterine receptivity in an intracytoplasmic sperm injection program Fertil Stertl

1997; 68 935-7

19 Bloechle M, Schreiner T, Kuchler I et al. Colour Doppler of ascendent uterine artery perfusion in

an in-vttro fertilizauon-embryo transfer programme after pituitary desensiuzation and ovarian

stimulation with human follicle stimulating hormone. Hum Reprod 1997; 12: 1772-7

20 Isaaksson R, Tiinnen A, Cacaatore B. Uterine artery impedance to blood flow on the day of embryo

transfer does not predict obstetric outcome. Ultrasound Obstet Gynecol 2000; 15: 527-30

21 Zaidi J, Campbell S, Pitroff R, Tan SL. Endometnal thickness, morphology, vascular penetration

and velocimetry in predicting implantation in an xn vitro fertilisation programme. Ultrasound

Obstet Gynecol 1995, 6 191-8

22 Salic A, Bied-Damon V, Benchaib M et al. Preliminary report of an ultrasonography and colour

Doppler utenne score to predict utenne receptivity in an tn-vttro fertilization programme Hum

Reprod 1998; 13: 1669-73

23 Applebaum M. The 'steel' or 'teflon' endometnum - ultrasound visualization of endometnal

vasculanty in IVF patients and outcome. Ultrasound Obstet Gynecol 1993; 3 (Suppl 2): 10

24 Yang J-H, Wu M-Y, Chen C-D et al. Association of endometnal blood flow as determined by a

modified colour Doppler technique with subsequent outcome of in-intro fertilization Hum

Reprod 1999, 14: 1606-10

25 Schild RL, Holthaus S, d'Alquen J et al Quantitative assessment of subendometnal blood flow

by three-dimensional-ultrasound is an important predictive factor of implantation in an in-vttro

fertilization programme. Hum Reprod 2000; 15: 89-94

26 Rubinstein M, Marazzi A, Polak de Fned E. Low-dose aspinn treatment improves ovanan

responsiveness, utenne and ovanan blood flow velocity, implantation, and pregnancy rates in

patients undergoing in vitro fertilization: a prospective, randomized, double-blind placebocontrolled

assay. Fertil Stenl 1999; 71: 825-9

27 Cacciatore B, Tiitinen A. Transdermal nitroglycenn administration improves uterine blood flow

in infertile women / Assist Reprod Genet 1997; 14 (Suppl): 20

28 Sher G, Fisch J Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve

uterine artery blood flow and endometnal development in patients undergoing IVF. Hum

Reprod 2000; 15: 806-9

29 Campbell S, Bourne TH, Tan SL, Collins WP. HyCoSy and its future role within the

investigation of infertility in Europe. Ultrasound Obstet Gyntcol 1994; 4: 245-53

30 Bonni A, Bianchi L, Violini F et al. Oocyte donation program: pregnancy and implantation

rates in women of different ages sharing oocytes from single donon Fertil Stertl 1996; 65: 94-7

31 Abdalla HI, Wren ME, Thomas A, Korea L Age of the uterus does not affect pregnancy or

implantation rates; a study of egg donation in women of different ages sharing oocytes from

the same donor. Hum Reprod 1997; 12: 827-9

32 Paulson RJ, Hatch IE, Lobo RA, Sauer MV. Cumulative conception and live birth rates after

oocyte donation: implications regarding endometnal receptivity. Hum Reprod 1997; 12: 835-9

33 Battaglia C, Artini PG, D'Ambrogio G et al. The role of color Doppler imaging in the diagnosis

of polycystK ovary syndrome. Am] Obstet Gynecol 1995; 172: 108-13

34 Battagha C, Artini PG, Salvaton M et al. Ultrasonographic patterns of polycystic ovanes: color

Doppler and hormonal correlations. Ultrasound Obstet Gynecol 1998; 11: 332-6

35 Zaidi J, Campbell S, Pitroff R et al. Ovarian stromal blood flow in women with polycystic

ovaries - a possible new marker for diagnosis? Hum Reprod 1995; 10: 1992-6

36 Agrawal R, Sladkevicius P, Engmann L et al. Serum vascular endothehal growth factor

concentrations and ovarian stromal blood flow are increased m women with polycystic ovanes.

Human Reprod 1998; 13: 651-5

37 Agrawal R, Tan SL, Wild S, Sladkevicius P et al. Serum vascular endothehal growth factor

concentrations in an in vitro fertilization cycles predict the risk of ovarian hyperstimulation

syndrome. Fertil Steril 1999; 71: 287-93

38 Engmann L, Sladkevicius P, Agrawal R et al. The value of ovarian stromal blood flow velocity

measurement after pituitary suppression in the prediction of ovarian responsiveness and

outcome of in vitro fertilization treatment. Fertil Steril 1999; 71 22-9

39 Sladkevicius P, Ojha K, Campbell S, Nargund G. Changes in ovarian vasculanzaoon during die

menstrua] cycle as assessed by 3-dimensional Power Doppler imaging (3D-PDI). Ultrasound

Obstet Gynecol 2000; 16 (Suppl 1): 51

40 Campbell S, Bourne TH, Waterstone J et al. Transvaginal color blood flow imaging of the

pcnovulatory follicle. Fertil Steril 1993; 60: 433-8

41 Zaidi J, Jurkovic D, Campbell S et al. Lutemised unruptured follicle morphology, endocrine

function and blood flow changes during menstrual cycle. Hum Reprod 1995; 10: 44-9

42 Nargund G, Bourne TH, Doyle PE et al. Assoaanon between ultrasound indices of folhcular blood

flow, oocyte recovery and pre-implantanon embryo quality Hum Reprod 1996; 11: 109—13

43 Nargund G, Doyle PE, Bourne TH et al. Ultrasound derived indices of follicular blood flow before

hCG administration and the prediction of oocyte recovery and pre-implantanon embryo quality.

Hum Reprod 1996; 11: 2512-7

44 Bhal PS, Pugh ND, Chui DK et al. The use of transvaginal power Doppler ultrasonography to

evaluate die relationship between penfollicular vasculanty and outcome in tn-vttro fertilization

treatment cycles. Hum Reprod 1999; 14: 939-45

45 Coulam CB, Goodman C, Rinehart JS Colour Doppler indices of follicular blood flow as

predictors of pregnancy after m-vitro fertilization and embryo transfer. Hum Reprod 1999; 14:

1979-82

46 Gregory L, Wells C, Thomas L et al. Peri-folhcular vasculanty and m-vitro activity of human

cumulus cells, markers of implantation from IVF-ET Fertil Steril 1998; 70 (Suppl): S14

47 Bhal PS, Pugh ND, Chui DK et al. The evaluation of ovanan vascular perfuson and its relationship

widi outcome in IUI treatment cycles using power Doppler imaging. / Reprod Fertil 1997; 19

(Suppl.): 24

48 Gosden RG, Byatt-Smith JG. Oxygen concentration gradient across the ovanan follicular

epithelium model, predictions and implications. Hum Reprod 1986; 1: 65-8

49 Fisher B, Kunzel W, Kleinstein J et al. Oxygen tension in follicular fluid falls with follicle

maturation. Eur J Obstet Gynecol Reprod Biol 1992, 43: 39-43

50 Magnusson C, Hillensjo T, Hamberger L et al. Oxygen consumption by human oocytes and

blastocysts grown in vitro. Hum Reprod 1986; 1: 183—4

51 Van Blerkom J, Davis PW, Lee J ATP content of human oocytes and developmental potential

and outcome after in vttro fertilisation and embryo transfer Hum Reprod 1995; 10: 415-24

702 British Medical Bulletin 2000,56 (No 3)

Advances in ultrasound assessment in the establishment and development of pregnancy

52 Van Blerkom J, Antczak M, Schrader R. The developmental potential of the human oocyte is

related to the dissolved oxygen content of follicular fluid: association with vascular endothelial

growth factor levels and penfollicular blood flow characteristics. Hum Reprod 1997; 12: 1047-55

53 Hata T, Aoki S, Manabe A et al. Three-dimensional ultrasonography in the first trimester of

human pregnancy Hum Reprod 1997; 12: 1800-4

54 Hata T, Manabe A, Aoki S et al. Three-dimensional intrautenne sonography in the early firsttnmester

of human pregnancy preliminary study. Hum Reprod 1998; 13: 740-3

55 Hata T, Aoki S, Miyazaki K et al. Three-dimensional ultrasonographic visualization of multiple

pregnancy. Gynecol Obstet Invest 1998; 46: 26-30

56 Kurjak A, Kupesic S, Banovic I et al. The study of morphology and circulation of early embryo

by three-dimensional ultrasound and power Doppler. / Pennat Med 1999; 27: 145-57

57 Valentin L, Sladkevicius P, Launni R et al. Uteroplacental and luteal circulation m normal firsttrimester

pregnancies Doppler ultrasonographic and morphologic study. Am J Obstet Gynecol

1996; 174: 768-75

58 Kurjak A, Kupesic S. Doppler assessment of the intervillous blood flow in normal and

abnormal early pregnancy. Obstet Gynecol 1997; 89: 252-8

59 Kurjak A, Kupesic S. Hafner T et al. Conflicting data on intervillous circulation in early

pregnancy. / Perinat Med 1997; 25: 225-32

60 Carter AM. When is the maternal placental circulation established in man? Placenta 1997; 18: 83

61 Kurjak A, Zudenigo I, Predamc M et al. Assessment of the fetomatemal circulation in

threatened abortion by transvaginal color Doppler. Fetal Diagn Ther 1994; 21: 521-6

62 Alcazar JL, Ruiz-Perez M. Uteroplacental circulation in patients with first trimester threatened

abortion. Fertil Steril 2000; 73: 130-5

63 Schwarzler P, Holden D, Nielsen S et al. The conservative management of first trimester

miscarriages and the use of colour Doppler sonography for patient selection. Hum Reprod

1999; 14: 1341-5

64 Sepulveda W. Chononicity determination in twin pregnancies: double trouble? Ultrasound

Obstet Gynecol 1997; 10: 79-81

65 Bajona R, Kingdom J. The case for routine determination of chononicity and zygosity in

multiple pregnancy. Prenat Diagn 1997; 17: 1207-25

66 Monteagudo A, Timor-Tntsch IE, Sharma S. Early and simple determination of chononic and

amniotJC type m multifetal gestations in the first 14 weeks by high frequency transvaginal

ultrasonography. Am J Obstet Gynecol 1994; 170: 824-9

67 Sepulveda W, Sebire NJ, Hughes K et al. The lambda sign at 10 to 14 weeks of gestation as a

predictor of chononicity in twin pregnancies. Ultrasound Obstet Gynecol 1996, 7: 421—3

68 Sebire NJ, Smjders RJ, Hughes K et al. The hidden mortality of monochononic twin

pregnancies. Br J Obstet Gynaecol 1997; 104 1203-7

69 Babinszki A, Mukherjee T, Kerenyi T et al Diagnosing amnionicity at 6 weeks of pregnancy with

transvaginal three-dimensional ultrasonography: case report Fertil Steril 1999; 71: 1161-4

70 Ville Y. Monochononic twin pregnancies: 'les liaisons dangereuses'. Ultrasound Obstet

Gynecol 1997; 10- 82-5

71 Brunner JP, Rosemond RL. Twin-to-twin transfusion syndrome: a subset of the twin

oligohydramnios-polyhydrammos syndrome. Am] Obstet Gynecol 1993; 169: 925-30

72 Hill LM. The sonographic detection of early first trimester conjoined twins. Prenat Diagn

1997; 17: 961-3

73 Maymon R, Halpenn R, Wemtraub Z et al Three-dimensional transvaginal sonography of

conjoined twins at 10 weeks: a case report. Ultrasound Obstet Gynecol 1998: 11: 294-7

74 Economides DL, Braithwaite JM. First trimester ultrasonographic diagnosis of fetal

abnormalities in a low-nsk population. Br J Obstet Gynaecol 1998; 105: 53-7

75 Whitlow BJ, Chatzipapas DC, Lazanakis ML et al. The value of sonography in early pregnancy

for the detection of fetal abnormalities in an unselected population. Br] Obstet Gynaecol 1999;

106: 929-36

76 Merz E Three-dimensional ultrasound - a requirement for prenatal diagnosis? Opinion.

Ultrasound Obstet Gynecol 1998; 12: 225-6

http://researchkorner.blogspot.com/2014/03/advances-in-ultrasound-assessment-in.html