(TO TABLE OF CONTENTS)THE UTERINE BIOPHYSICAL PROFILE ("UBP")
by Michael Applebaum, MD, JD, FCLM
The following is a revised version of a book chapter that appeared in the text: Endosonography in Obstetrics and Gynecology, edited by Dr. Gautam Allahbadia. It was written primarily for physicians. It is not an easy, casual read for the lay person. However, it can be a valuable read.
The numbers in parentheses refer to the references which appear at the end. There are no individual hyperlinks to the references. A full list of references from the original version is presented.
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INTRODUCTION
GENERAL PELVIC ULTRASOUND EXAMINATION
TECHNIQUE
ULTRASOUND
TECHNIQUE UNIQUE TO THE UTERINE BIOPHYSICAL PROFILE
THE UTERUS
THE ENDOMETRIUM
ENDOMETRIAL BLOOD FLOW
THE UTERINE BIOPHYSICAL PROFILE
CONCLUSION
REFERENCES
Infertility is a devastating disease. Its victims are affected at a very basic level -- the ability to reproduce, to leave a legacy. This can be divisive to the couple involved, their relatives and friends. The sphere of influence this disease has can be immense.
Attendant to the medical consequences of infertility are the psychological sequelae. Afflicted patients and their families can suffer loss of esteem, disappointment and depression.
Several years ago, I undertook the project of attempting to predict the outcomes of conception cycles during both IVF and medically stimulated non-IVF attempts. The possible advantages to the patient in providing such a service are medical, psychological, economic and emotional. Ideally, such information would be provided prior to embryo/gamete transfer. I thought that if it were possible to optimize the time of embryo transfer based upon sonographic signs of endometrial preparedness, unsuccessful cycle rates could be decreased. Further, if the likelihood of an unsuccessful cycle existed, the patient could be informed prior to the time of aspiration or transfer that the embryos would be returned during a frozen cycle and thus, not be disappointed either by the failure of the current cycle and/or the wastage of embryos. Although in my experience there is no Holy Grail for predicting successful conception during any given menstrual cycle, there do appear to be some sonographic findings which may be useful in foretelling the outcome. I have compiled these findings into an examination I call the Uterine Biophysical Profile ("UBP"). The findings are weighted according to the Uterine Scoring System for Reproduction ("USSR"). Both of these will be described below.
GENERAL PELVIC ULTRASOUND EXAMINATION TECHNIQUE
ULTRASOUND TECHNIQUE UNIQUE TO THE UTERINE BIOPHYSICAL PROFILE
To perform the UBP special care should be taken. The following guidelines are recommended:
1. To determine the presence of a 5-line appearance, information from both the transabdominal and transvaginal studies may be useful. For example, although a 5-line appearance may be noted transabdominally, it may not always be possible to see it endovaginally due to uterine position (and vice versa). In this case, a 5-line appearance is considered to be present and endometrial vascular penetration may be estimated when performing the endovaginal study.
2. Perform the Doppler study slowly. The flow of blood in the endometrium is of low velocity. It may take time for the ultrasound machine to register the presence of blood flow and create the image. If one sweeps through the endometrium too quickly, flow may not be seen. Additionally, endometrial blood flow has a mercurial personality -- it may appear as if it comes and goes. It may also appear in some areas and not others. Do not observe hastily.
3. Endeavor to make the endometrium as specular a reflector as possible. Use the techniques of manual manipulation of the anatomy and probe pressure to achieve this.
4. Scan endovaginally both coronally and sagittally. There may be a difference in how well the blood flow is imaged.
5. When measuring the endometrium in the A-P dimension, try to obtain the value when no contraction affecting it is present. Contractions may alter this value. Also, when possible, obtain the measurement in a standard plane such as when both the endometrial and cervical canals appear continuous.
Sonographically, the endometrium is one of the most dynamic structures in the body. During the reproductive years of a normal female, the uterus undergoes ultrasonographically detectable alterations characterized by cyclical changes in the echo pattern of the endometrium. In fact, it is possible to infer the approximate day of a normal woman's menstrual cycle by the sonographic appearance of the endometrium. (18)
From the first day of the menstrual cycle until the mid-cycle, the normal endometrium progressively thickens and develops sonographically detectable strata. This appearance can be described as layered, trilaminar or 5-line (my term of preference). Past the mid-cycle, the normal endometrium brightens and progressively thins. (22) These sonographic endometrial patterns appear to be related to the changes in the glandular and vascular elements of the endometrium during the menstrual cycle. (23, 24, 25)
Fleischer et al determined that the endometrium is thickest during the secretory phase (3.6 +/- 1.4 mm), less thick during the proliferative phase (2.9 +/- 1.0 mm) and thinnest during menstruation. (24, 25) These values are for the half-thickness as measured from the endometrial canal to the endometrial-myometrial junction. Full thickness measurements ranged from 4 to 12 mm, with an average thickness of 7.5 mm.
The endometrium will either slough if no pregnancy occurs or will undergo various changes in the event of a pregnancy.
The blood supply to the endometrium is derived from branches of the uterine arteries. Emanating from the arcuate arteries (vide supra) are the radial arteries. These vessels run through the myometrium to just outside the endometrium where they form terminal branches of two types: straight and coiled. The straight branches, also known as the basal arteries, supply the basalis layer of the endometrium. The coiled branches, also known as the spiral arteries, traverse the endometrium and supply the functionalis layer. The spiral arteries, like the endometrium and unlike the basal arteries, are responsive to the hormonal changes of the menstrual cycle. (26)
In preparation for implantation, the endometrium undergoes transformations influenced by the ovarian hormones produced during the early secretory phase. These modifications include: an increase in the rate of blood flow, an increase in the number of cells populating the stroma and epithelium, an increase in uterine oxygen consumption, an increase in oxygen diffusion into the uterine lumen and a generalized edema. (27)
The spiral arteries respond to the hormonal changes of the menstrual cycle and undergo transformations, as well. (26) These responses include: proliferation of the endothelium, thickening of the wall and coiling. These vessels play an important role in implantation. The chances for a normal implantation may be reduced if the spiral arterioles are inadequately developed. (28)
In my experience, changes in the endometrial vascularity appear present on color Doppler examination which may reflect the histologic changes described by the pathologists. (29, 30) Some investigators appear unable to demonstrate this. (31) Perhaps this is due to equipment and/or technique differences.
If one divides the endometrial and periendometrial areas into the following four Zones:
Zone 1 -- a 2 mm thick area surrounding the hyperechoic outer layer of the endometrium
Zone 2 -- the hyperechoic outer layer of the endometrium
Zone 3 -- the hypoechoic inner layer of the endometrium
Zone 4 -- the endometrial cavity
it is possible to see variations in the depth of vascular penetration before, during and after the mid-cycle. Based upon my observations, most patients without diagnosed infertility (presumed normal) usually demonstrate flow into Zone 3 by the mid-cycle. (29)
Doppler ultrasound has been used as a means to predict a negative outcome for a given IVF cycle. Pre-transfer, if failure could be predicted, the embryos could be frozen until a more favorable cycle occurs. This could prevent embryo wastage and subsequent patient disappointment.
Sterzik et al examined the ovarian and uterine arteries on the day of follicle aspiration. The conclusion at which they arrived was that in patients who became pregnant after embryo transfer, the RI of the uterine arteries was significantly lower than those who did not get pregnant. (32)
Steer et al demonstrated that patients with a low uterine artery PI on the day of embryo transfer were more likely to conceive than those with a high PI. In this series, no one with a PI > 3.0 conceived. (33)
Battaglia et al, demonstrated a progressive decrease in the PI of the uterine arteries during the second half of the menstrual cycle in successful IVF pregnancies. (34)
In my experience, using color Doppler technique, inadequate vascular penetration of endometrial blood flow (not within Zone 3) prior to transfer has been associated with an unfavorable outcome.
Vascular penetration towards the endometrial canal differs among patients. In patients with uterine artery PIs of less than 3.0, thus far, my results have not revealed any successful pregnancies in IVF patients unless there is vascularity demonstrated either within Zone 3 or within Zones 3 and 4 prior to transfer. Successful pregnancies with demonstrable blood flow in Zone 4, suggesting the presence of an intracavitary mass, have been noted. Subsequent investigations have confirmed the validity of this finding in patients undergoing non-IVF stimulation cycles.
These color Doppler findings in unsuccessful cycles may relate to the histologic findings described by Sterzik et al. (32) In their study of 58 IVF patients, a majority demonstrated an immature endometrium at the time of embryo transfer. The abnormalities included a variety of patterns, all indicating a lack of secretory transformation, suggesting unpreparedness for implantation.
THE UTERINE BIOPHYSICAL PROFILE
In my experience, certain sonographic qualities of the uterus are noted during the normal mid-cycle. These include:
1. Endometrial thickness in greatest AP dimension of 7 mm or greater (full-thickness measurement)
2. A layered ("5 line") appearance to the endometrium
3. Blood flow within Zone 3 using color Doppler technique
4. Myometrial contractions causing a wave like motion of the endometrium
5. Uterine artery blood flow, as measured by PI, less than 3.0
6. Homogeneous myometrial echogenicity
7. Myometrial blood flow seen on gray-scale examination (internal to the arcuate vessels)
The Uterine Scoring System for Reproduction ("USSR") comprises evaluation of the following parameters:
1. endometrial thickness (full-thickness measured from the myometrial-endometrial junction to the endometrial- myometrial junction)
2. endometrial layering (i.e., a 5-line appearance)
3. myometrial contractions (seen as endometrial motion)
4. myometrial echogenicity
5. uterine artery Doppler flow evaluation
6. endometrial blood flow
7. gray-scale myometrial blood flow
Each parameter is scored as follows:
1. endometrial thickness
a. < 7 mm = 0
b. 7 - 9 mm = 2
c. 10 - 14 mm = 3
d. > 14 mm = 1
2. endometrial layering
a. no layering = 0
b. hazy 5-line appearance = 1
c. distinct 5-line appearance = 3
3. myometrial contractions (seen as wave-like endometrial motion high-speed playback from videotape)
a. < 3 contractions in 2 minutes (real-time) = 0
b. > 3 contractions in 2 minutes (real-time) = 3
4. myometrial echogenicity
a. coarse/inhomogeneous echogenicity = 1
b. relatively homogeneous echogenicity = 2
5. uterine artery Doppler flow evaluation
a. PI > 3.0 = 0
b. PI< 2.5 - 2.99 = 0
c. PI < 2.2 - 2.49 = 1
d. PI < 2.19 = 2
6. endometrial blood flow within Zone 3
a. absent = 0
b. present, but sparse = 2
c. present multifocally = 5
7. myometrial blood flow internal to the arcuate vessels seen on gray-scale examination
a. absent = 0
b. present = 2
The values assume a technically adequate ultrasound examination with no abnormalities of uterine shape or development, no other gross uterine abnormalities (e.g., significant masses) and a normal ovarian cycle (e.g., without evidence of ovarian-uterine dyscoordination). A male factor component to the infertility is not present.
In our limited experience with this system, thus far, a USSR "perfect score" of 20 has been associated with conception 100% of the time. (The number of patients in which we predicted successful conception cycles based upon the UBP and USSR perfect score was 5. This group included 2 spontaneous cycles (non-IVF, non-IUI), 2 IUI and 1 IVF.) Scores of 17 - 19 (10 patients) have been associated with conception 80% of the time. Scores of 14 - 16 (10 patients) have a 60% chance, while scores of 13 or less (25 patients) have resulted in no pregnancies.
Absent endometrial flow, despite highest values for the other parameters, has always been associated with no conception.
My initial observations were based upon my experiences with both "normal" non-infertility patients and patients treated for infertility. The observations were categorized and then applied as a system to patients with diagnosed infertility -- all comers. I did not divide the patient population into sub-groups based upon treatment protocol, age, cause, etc.
No doubt, other factors apart from sonographic signs of "uterine receptivity" are at work in determining conception. I attempted to control for all factors which I could detect sonographically, plus male factors. Factors such as scoring of either embryos prior to transfer or ova at the time of aspiration, as some of our labs do, were not considered. I am sure that the quality of the transferee is important; however, I volitionally limited myself to the ultrasound findings.
Our results are preliminary and substantially more patients need to be evaluated. I have no illusions that the parameters and scoring numbers will remain the same and I suspect that the cut-off values and success rates will evolve over time, especially in the hands of other investigators. I suspect that the quality of the laboratory affects the values but have not investigated this, yet. I also do not believe that any group of findings will work perfectly 100% of the time. Such is not the nature of being human. Nonetheless, I do believe that there is a "normal" appearance to the "normal" mid-cycle which is ascertainable, the recognition of which can be applied to the benefit of our infertility patients.
I know of no way to predict, in the positive, the outcome of either an IVF, stimulated or transfer cycle. I do believe it is possible to provide information to the patient as to whether such cycles will fail and thus predict in the negative.
Normal things happen normally. In general, if the normally expected findings of the UBP are not present, a "normal" outcome (pregnancy) will not result. In general, if favorable values for the USSR are not obtained, a favorable outcome (pregnancy) will not be obtained. Perhaps further investigation will allow us to predict outcomes in the positive.
Copyright 1998-2008, Michael
Applebaum, MD, JD, FCLM. All rights reserved.
Suite 935 East, 845 North Michigan Avenue, Chicago, IL 60611- 2252, (312) 337-0732
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Copyright 1998-2008, Michael
Applebaum, MD, JD, FCLM. All rights reserved.
Suite 935 East, 845 North Michigan Avenue, Chicago, IL 60611- 2252, (312) 337-0732
Please send comments regarding this Web site to webmaster@drapplebaum.com