Sonography of the 1st Trimester: Another Look - SD
Sonography of the First Trimester
Hello, I'm Dr. Oksana Altaic from the Jefferson Ultrasound Research and Education Institute, in the Department of Radiology at Thomas Jefferson University.
And my topic for this session is sonography of the first trimester. Another look, there are things that are changing, as far as some of our criteria that we're using in the first trimester. I would like to introduce you to that.
I'd like to discuss the significance of some of these discriminatory levels that we have for diagnosis of miscarriage. I will describe in detail sonographic signs of a normal first trimester pregnancy, and describe signs of early pregnancy failure.
Normal First Trimester Pregnancy
First, let's go to the beginning. When the ovary releases an ovum, it is swept up by the fibrillated end of the tube. This occurs around day 14 of a menstrual cycle. And somewhere in the tube here, the sperm meets the ovum, there's fertilization, and then the conceptus tumbles down the tube, and it takes a week to implant. Day 21 is implantation day, and this is done in a very aggressive method manner, where the trophoblast burrows its way under the endometrial lining and sets up household. Starting then with very active, aggressive formation of the trophoblast.
We don't see any of this until four and a half weeks, from starting from dating by the first day of the menstrual period. Four and a half weeks menstrual age is the earliest that we could possibly see something with ultrasound.
Now, I always caution people that when they start doing first trimester scanning, and this is almost all vaginal approach, because these are early pregnancies. The first step before you start looking in the uterus is check the cervix and make sure that the gestational sac is in the uterus. Make sure that the cervix connects with the lower uterine segment, that the anterior cervical wall connects with the anterior uterine wall, that the posterior cervical wall attaches with the posterior uterine wall. That way you are sure that this is an indeed an intrauterine pregnancy. We certainly do not wanna miss abdominal pregnancies. We do not want to misinterpret an ectopic for an intrauterine pregnancy or vice versa.
Now, chronologically what we can hope to see if we scanned every day during a pregnancy, we would first see the gestational sac. Next comes the yolk sac. Then the embryo becomes visible, and then it's heartbeat.
The Gestational Sac
Now let's talk about the gestational sac. The gestational sac is a combination of the chorionic cavity in the amniotic cavity. It shows up as a cystic structure in the center of the uterus. And it's either round or oval in shape, has a very smooth border, has a thickened echogenic rim around it. The early little sacs will start being more than two millimeters in thickness, and later it gets a little thicker and thicker. It's like a very thick crayon line around the gestational sac. This, by the way, is the same the way they look in the adnexa, and ectopic has a thick echogenic rim. If you have a cystic structure with thin rim, that is not going to be a pregnancy, it's going to probably be an ovarian cyst or something. That thick border, the thickened chorionic reaction, is important.
Now, the sac usually implants in the fundus of the uterus or in the mid uterus. If it implants low in the lower uterine segment, that is not a normal kind of an implantation.
So the early sonographic signs of an intrauterine pregnancy are basically an intradecidual sac sign and a double decidual sac sign.
The Intradecidual Sac Sign
The intradecidual sac sign is the earliest sign of an intrauterine pregnancy. We can see it as early as four and a half weeks. It's not a very accurate sign because there are a lot of mimics, and we don't yet see a yolk sac, which would be more definitive, but it is helpful if it's present, and vice versa. If we do not see it, that does not rule out an intrauterine pregnancy.
So what we can see is below underneath the central line here, which represents a mucosa to mucosa. In the cavity underneath is buried this little small cystic structure with a thickened echogenic rim. Here's another one. This would be the central cavity line. And burrowed underneath is this little cystic structure with a somewhat thickened echogenic rim. We would be very suspicious that this is an early pregnancy, and we would follow this up. There are mimics, that's why this is not very reliable. You could have a little drop of fluid in the cavity. There could be endometrial myometrial, decidual cysts. It could be a degenerated myoma. So basically, we want to follow up to document development of the embryo.
Here's an example. This was a uterus. And as I was scanning this woman who had a positive pregnancy test and bleeding, I saw a little cystic structure and thought that that possibly could be the early pregnancy. But then I scanned the adnexa, looked around, I came back to the uterus, and it was gone. This was just a drop of blood or fluid in the cavity.
How about this one? This looked like it might be a little gestational sac buried under the endometrial line, but this lady is 65 years old. She's a postmenopausal, and this was a postmenopausal polyp. That's, again, very important for us to know. Age, parity, previous surgeries. These are important pieces of information about any woman being scanned.
Here's again, another one. This was a thickened endometrium, a little cystic area. Maybe that's an early IUP. It turned out to be a little decidual cyst, and an ectopic was found in the adnexa.
Here we thought there might be two gestational sacs. Eventually what happened? One of these grew as a pregnancy. The other one stayed the same. It was a cystic degeneration of a myoma. A lot of mimics of this early little sign, but still can be useful to us.
More and more we're hearing case reports and anecdotal discussions of patients that were given methotrexate when they were thought that maybe they had an ectopic and suddenly an intrauterine pregnancy shows up. And people are reporting this. Dubay and Benson have written about this, a warning to do no harm to early pregnancies. And one of their conclusions was that in a woman with a positive pregnancy test, any fluid area in the endometrial cavity is statistically likely to be an intrauterine pregnancy. It could be normal or abnormal, but still, statistically it's much more likely than to be related to an ectopic pregnancy. We should give the pregnancy the benefit of the doubt, follow it up and wait. All potentially harmful treatments such as methotrexate, or D&C should be avoided until an IUP is definitely excluded. We're going to look at some of the newer criteria later on in this talk.
The Double Decidual Sac Sign
Now let's talk about the other one, the double decidual sac sign. Now, this is another sign of intrauterine pregnancy. It's seen a little later at five to six weeks menstrual age. It's more useful with transabdominal sonography, but it can help us out periodically with the transvaginal scans. And basically what we see are two thick echogenic bands around the pregnancy. We'll see a thick band, which is surrounding the gestational sac itself. That's a combination of chorionic individual tissue. Then we see a thin lucent stripe, that's the collapsed potential cavity. And then another thick band on the other side, and that would be the decidua parietalis. Not around the entire sac, but certainly around a portion of it. If we see that, that's very helpful to guide us towards an intrauterine pregnancy. This sign helps to differentiate from that pseudosac, which only has one thickened border. This sign is highly reliable, but it's not absolute. Once we see a little yolk sac, it doesn't matter because then we would be sure that it's an intrauterine pregnancy. And if any suspicion or uncertainty arises, definitely follow up, make no clinical decisions based on that sign alone.
Here's a situation where there's some fluid in the uterus. Maybe it looks like a pseudosac related to an ectopic, but if you look, there are two thick bands of echogenicity, and that would push it towards the intrauterine pregnancy, probably a miscarriage in this case.
Doppler can be helpful. We know that trophoblastic blood flow has a typically normal low resistance arterial waveform. But I do wanna caution you that we should not be using doppler in any form, color, power, or spectral. We should not use it in a normal first trimester pregnancy unless there's an indication, because this does impart more energy to this little embryo undergoing embryogenesis. And we would not wanna do any harm if the pregnancy's abnormal and we want more information that would be justified.
The Yolk Sac
Now, the yolk sac, the yolk sac is a round little sphere that's next to its embryo. It's three to six millimeters in diameter, and no more than six millimeters. We should be seeing one yolk sac per embryo. It is technically found in the chorionic space. Here you have the embryo with the amnion, and out the chorionic space is the little yolk sac as we see here. The little embryo can never really play with the little ball because it's outside of the amniotic space. We don't see the yolk sac typically after 10 to 12 weeks. It just moves aside. It's compressed by the growing amniotic cavity. And it is connected to the midgut by a little vitelline duct, which occasionally you may identify.
The significance is that the yolk sac is the earliest embryonic landmark. There has been an attempt at formation of an embryo, and that reliably identifies an intrauterine pregnancy for us. It helps to locate the embryo when we're looking for a heartbeat. You look around the yolk sac, you don't see an embryo on the other side of the sac in the yolk sac on the other side. If that happens, that's probably a blood clot or some other debris, and it would not qualify for an embryo. When we see the yolk sac, the pregnancy has already reached at least five and a half weeks.
The Amnion
The amnion. Now this amnion is manifested by a thin membrane that surrounds the embryo. We don't see it really till about six and a half weeks. It grows linearly with the crown rump length. It starts out smaller than the chorion, and eventually outgrows the chorion. It's thinner than the yolk sac. Here is the amnion with a little embryo in it, and here would be the yolk sac. There is a point in time when the amnion is as big as the yolk sac, and it looks like a double bubble or a double bleb sign. At that point, you don't know what's happening. Is that a normal development with the equal sizes, or perhaps is it a pregnancy with a double yolk sac? The only thing you can do is follow it up. If the amnion grows with its embryo, it's normal. If the thing stays the same and does not change, it's probably abnormal, an abnormal pregnancy. Eventually, the chorion will fuse with the amnion, and you won't be able to differentiate them. This can happen anywhere between eight and 16 weeks.
The Embryo
Now, the embryo, the embryo technically exists between 5.1 weeks and 10 weeks menstrual age, and it is not a fetus until after 10 weeks. Menstrual age, lower than that, it's an embryo. The earliest that we can detect it vaginally is 5.7 weeks. The crown rump grows about 0.7 millimeters a day on the average in length. We used to say a millimeter a day, but now we know that some embryos can grow slower. This is a mean type of a growth. We should see the embryo in a sac that's 25 millimeters or bigger vaginally. Now, a year ago, I would've said 20. But now that we're starting to have more and more reports, we're moving this number up. And at this point, this is May of 2012. I would recommend that we start using 25 millimeters or larger by that time, should see an embryo. I'll address this a little more later in the talk. We also should see an embryo. We should see a visible heartbeat by the time the crown rump length is bigger than seven millimeters. Now, once again, this is sort of newer criteria. We used to use five millimeters in order to be more conservative and not to do any harm to pregnancies. There are recommendations to move this to seven millimeters and higher.
Now, there will be a large gathering, a consensus conference, sponsored by the Society of Radiologists in Ultrasound in October of 2012. At which time multiple specialists from different areas get together and hash out some of these discriminatory type criteria. Up until that point, I would recommend that we start using these more conservative numbers. It will take a little while. By the time they formalize the consensus, by the time it's published, it may be a year and a half to two years down the line. Therefore, in order to be safer for the general public, I think we should be using these more conservative numbers.
The earliest embryos that you see will be a little diamond ring sign, and here you have an array of different types and shapes of diamonds. The embryo grows from the little diamond shape, starts to look more like a peanut or a shrimp sign, and continues till 10 weeks when all structures are formed.
Now, there are two anatomic features that you should be very aware of, not to think that they're abnormal. There are two physiologic cystic spaces in the embryonic head. The anterior space is the precursor of the cerebral ventricles. The posterior cystic space is the precursor of the posterior fossa structures, and that's the rhombencephalon. That cystic space can look very prominent and very threatening, and you should not immediately think there's something wrong. You should not think that's a Dandy Walker cyst or something. It's normal. Follow it up, it'll disappear and will not be an anomaly.
Now, here's an example of someone not aware of these anatomic details. This was a young college student who was down in Florida in college, 19-year-old. She became pregnant, and had an ultrasound down there, and she was told that she had an anomaly, a double-headed embryo. She panicked. Her mother panicked. Her mother flew her up here to Pennsylvania, and through the emergency room, she was admitted. I happened to be around the sonographer, asked me to take a look. I looked at it, and all it was was a normal pregnancy. This was the embryo in its amniotic sac with a prominent cephalic end. And here is the yolk sac. This is not a double-headed embryo. This was a completely normal anatomy, which hopefully we'll all be familiar with.
Now, the other thing that is unusual in these early embryos is the physiological umbilical herniation that can be seen in a less than a 12 week menstrual age fetus. And it is a bulge. It's actually a herniation of some of the bowel contents into the base of the cord. It's a normal variant. It recedes back into the abdominal cavity by 12 weeks. Menstrual age, and it's considered normal anatomy. Here are some examples. You could see a little tuft or a little soft tissue mass protruding from the abdomen in these young pregnancies. Here's the embryo with more prominent herniation of the bowel into the base of the cord here. I was almost convinced this was going to be a gastroschisis or something. This was a 10 week fetus. We reexamined the fetus in a month. Everything was gone. All you can do here is wait. I recommend that you reexamine these not earlier than 14 weeks, because they recede by 12 weeks, but everything is always plus or minus couple weeks. Wait till a good 14 weeks to make sure that everything is back to normal.
The Heartbeat
Now, the heartbeat is seen vaginally around six weeks. You should see a heartbeat in an embryo with a crown rump length of seven or certainly more than seven. You may not see it in smaller embryos. The rate starts out slower with the tiny embryos, it may be something like around 90 or so. It continues to increase to about 150, and then kind of hangs around 140 or so through the pregnancy. A slow heartbeat is considered less than 80 beats per minute. That tends to be a poor prognosis for the pregnancy. It's a rule of thumb. There are charts that you can look at the size of the embryo and the heartbeat, as I said, there's slower early on. But any embryo with a heartbeat less than 80, you should follow that up in about three to four weeks and see how the embryo is doing.
The embryonic period lasts between six to 10 weeks, by which time all the structures are formed. And the fetal period begins in the beginning of the 11th week, which is like 10.1 weeks or so. All the organs are present. The only thing left is to reduce the midgut hernia. And by 14 weeks, we'll start seeing the external genitalia in a more mature form, and we will pick up four chambers. And then all the fetus has to do is grow.
I do want to just say one thing here. The difference between embryo and fetus is 10 weeks. The human embryo develops 56 days of embryologic development. 56 days is eight weeks, eight full weeks of embryologic development. But because we always talk in menstrual age, it would, we have to add two weeks. By the time the embryo is 10 weeks, that's when it becomes a fetus. Graduation day is at 10 weeks to becoming a fetus. That's just so that you know, we call things the way they are. We have such high resolution equipment. We see so many little anatomic details. Why not call it an embryo? People still call fetal pole. What is a fetal pole? This is a completely antiquated term. North pole, south pole. What kind of a pole? People say eight week fetal demise. It's not a fetus, it's an embryo. It's an embryonic heartbeat, not a fetal heartbeat. Early on, it's embryonic demise, not fetal demise under 10 weeks. Anyways, that's just a matter of terminology.
Abnormal First Trimester: Early Pregnancy Failure
Now, let's talk about the abnormal first trimester. And this is what we mean by this is basically spontaneous abortion. Spontaneous abortions occur in 15 to 20% of recognizable clinical pregnancies. Below that, subclinical pregnancies even have higher percentages of loss. This risk of loss increases with maternal age. It's quoted as 20% at age 35, and goes up to about 40% by age 40. The terminology that you'll hear is, I will be using early pregnancy failure. You'll hear first trimester pregnancy failure. This is the same thing as miscarriage, as spontaneous abortion. Same thing as being more specific or seeing an anembryonic pregnancy, similar as to seeing embryonic or early fetal demise. These terms like blighted ovum, I always wonder why, why is it an ovum that's blighted? Why wasn't it a sperm that was blighted? What is an empty sac? Which sac are we talking about? What's a missed abortion? People still use these terms. Who missed the abortion? What does that mean? These terms up here are more precise, and these terms down here are sort of more probably should not be used now that we have a better view as to what's going on in the uterus.
I would like to take another look here at some of this newer criteria. Like I say, these criteria will become more definitive within the next year or two, but up until that point, I think we should start being much more conservative with our numbers. We want to avoid any inadvertent termination of a normal wanted pregnancy. That would be the worst that could happen. We need safe cutoff values to define miscarriage in order to exclude errors in our diagnosis.
Discriminatory Beta hCG Level
Couple things about this discriminatory beta hCG level. This means that at what level of beta hCG is it abnormal not to see an intrauterine pregnancy with transvaginal sonography? At what level is it abnormal not to see an IUP? Many people have used a thousand and still do over the years. That was the first report. Then another report that people, well, that was actually Nyberg was first 2000 was recommended. Some people till this day still use a thousand. We've been using 2000 over the years. However, more and more reports are coming in to say that that may not be safe.
Here's a paper from 97 Mehta had 676 patients that he evaluated to rule out ectopic pregnancy. Out of those patients, 128 had no evidence of an intrauterine pregnancy. And 51 patients had betas over 2000 milli-international units per ml. Out of those 51 patients, one third eventually had a normal intrauterine pregnancy on a follow up ultrasound. Those, if methotrexate would've been given, those pregnancies would've been harmed. Using 2000 as an absolute cutoff will miss some normal intrauterine pregnancies. Therefore, we should push that discriminatory level higher.
Why will using 2000 as an absolute cutoff miss some normals? First of all, it could be a normal but twin or triplet gestation. The beta could be 3000. Yet it's a summation of the beta secretion from the two pregnancies. They could be very young gestations that are showing a higher number. Certainly that can happen with these pregnancy manipulations, which is even worse to destroy something that people have been working so hard at trying to get pregnant. There are variable beta hCG assays out there. Most people do not know what type of beta assay they have. There's variability. There's first international reference prep. There's the second international standard. There's a third international reference prep. And patients will go from an emergency room to an office to another emergency room. And these numbers are not always the same assay. Most even in our institution. It's even difficult to find out what kind of assay once you try to find out.
The other problem is different resolutions of different ultrasound scanners. Transducer frequencies give you different information. Manufacturers have different types of machines. There can be a lot of technical limitations, difficult exam with obesity. Fibroids can interfere. There could be operator and experience. There may be anomalies. Contractions can push the sac around sub chorionic bleeds interfere. Retroverted uterus is hard to examine. All of these can be confounding variables. There are statistical variations in anything that's reported, that has to be taken into account. A lot of the initial trials were from single centers, and they dealt with very small populations. A population of 100 patients is not the same thing as a population of 2000 patients. All of these have to be taken into account, including the fact that anything that is reported as a number, or especially with pregnancy, anything has plus or minus two standard deviations of normal in a population.
There have also been case reports of beta hCG levels over 4000 milli-international units ml before a gestational sac was seen recently, I heard of a case that was 4600 beta hCG level. Nothing was seen in the uterus. Two weeks later, twin sacs were identified. Until a new consensus is reached, 4000 should be used as the beta hCG discriminatory level, by which you should see an intrauterine pregnancy inside the uterus. Methotrexate should not be given below this level, and Dubay and Benson have come out with this publication. And perhaps it even should be higher. Perhaps it should be 4500, perhaps higher. We'll see what the consensus statement decides, but in the meantime, it's better to be safer.
Definitive Signs of Early Pregnancy Failure
There are some new discriminatory criteria for early pregnancy failure. The first one is, there's no heartbeat in an embryo that's bigger than crown rump length of seven millimeters. We used to say five millimeters, but now we have more information. And this mostly came out from Abdullah from the UK, where they did larger, more prospective studies. Second criteria, no embryo in a gestational sac with a mean sac diameter of greater than 25 millimeters. We used to say 20. Some people use 18, some people use 16. We should move this up to 25. The third criteria is no growth or appearance of an embryo in seven to 10 days on a follow-up. All these criteria that I'm talking about are based on vaginal scans. And if you're somewhere at the limit, if the embryo seven or the sac is 25, it's always a good idea to follow up with beta or do another ultrasound in seven to 10 days. That's important to follow these kind of pregnancies so that we do no physical harm to the pregnancy. And even though patients are anxious about the status of the pregnancy, and that's a significant consideration, but we have to be balanced against harming, potentially harming a normal pregnancy.
The first definitive sign is no heartbeat in an embryo with a crown rump length greater than seven millimeters. Then if the embryo's bigger, we can safely say, embryonic demise. This is a 10 millimeter embryo. No heartbeat. Definitely this is abnormal. The previous criteria that we were using a lot was embryos bigger than five millimeters, no heartbeat. Why did this change? We have to take into account standard deviations with measurement errors. And also another study out of the UK found that there was a 18.7 or 19, almost 20% inter observer variation on measurements. For a five millimeter crown rump length that they established as be five millimeters, they found that when they had other people measuring their measurements range from 4.1 to 5.9 millimeters. A five millimeter crown rump length could actually be measured close to six. And they found that if it was a six millimeter crown rump length, the measurements ranged close to seven. That's how they established this. Seven was a fairly safe was a safe number to use.
Before you make the diagnosis of embryonic demise, it's always important to make sure that you have a technically adequate examination. If there's problems, if the patient is obese, there's fibroids, retroverted uterus, et cetera, should not be so definitive. We should locate the embryo with certainty. It's always near its yolk sac, and we have to search the embryo thoroughly for its heartbeat. Sometimes patients are nervous, they're breathing, the embryo's moving. You have to take it in a quiet slow respirations so that you can do a thorough search. There's no harm in waiting and following with beta or ultrasound.
Another definitive sign, there's no embryo in a gestational sac with a mean sac diameter greater than 25 millimeters. We used to use this for transabdominal size. Now, we are recommending usage for transvaginal. So we have a sac. It's bigger than 25 mean sac diameter. There's no embryo in it. It's an empty sac. We can call it an anembryonic pregnancy, no problem to if it's around if it's at 25 or so, no harm in waiting and following with beta and ultrasound previously, the criteria for miscarriage were lower on average in the United States 16 millimeters is being used around the country. But Pex in his study found that there was a 4.4% false positive rate for diagnosis of miscarriage. When using 20 millimeter as a cutoff mean sac diameter, there was a 0.5% false positive rate of miscarriage. So even 20 didn't turn out to be safe. They ended up recommending 25.
How did they get to 25? They did inter observer variations. And when a sac was 20 millimeters, they found that the range was 16.8 to 24.5 millimeters. Some people measure it that size, therefore, they concluded 25 millimeters to be the cutoff. Here's a case. Here's a little embryo. It measures six millimeters in a crown rump length. It has no heartbeat. The mean sac diameter is 20. What do you do? We would recommend that. You do not use you wait till over seven over 25. You follow this with betas. You follow this with ultrasound in seven to 10 days. Here's an embryo that's 10 millimeters crown rump length. It has no heartbeat, mean sac diameter is 28 millimeters. Now we can say this embryo is dead. There's no heartbeat. It's big enough where sure, it's an embryo. And this pregnancy can now be dealt with properly. It's a miscarriage.
When we have an anembryonic pregnancy as a sac that's empty. What are the possibilities? Maybe the embryo never really developed, and the sac just accumulated some fluid. There could be a very early demise, and we just don't see the little tiny embryo, or perhaps the body has started resorbing the products of conception.
The third definitive sign is no growth or shrinkage, or actual disappearance of an embryo. That obviously would be a bad sign, or no appearance of an embryo or yolk sac on serial exams that are seven to 10 days apart. Nothing shows up. You see an empty sac, you wait, nothing happens. Then we can say that we have an anembryonic pregnancy. When we see an embryo with no heartbeat, we should scrutinize the embryo with sonography. We should look for some kind of abnormalities, structural abnormalities, because an underlying chromosomal abnormality supposedly accounts are about 50% of these losses. Here was a pregnancy that had conjoined embryos. Here are other examples of demise embryos or early fetuses.
A very popular sign is this nuchal translucency. So we would wanna look around and see if that's possible, which of course has a lot of negative implications. Look for absent nasal bone. Look for gross deformities of the embryos. These do not look anything like the normal embryos we talked about? Here's a knobby looking embryo. Here's some kind of strange formation. This one looks like, maybe like some bug or something. Anatomic features are not normal.
Suggestive Signs of Early Pregnancy Failure
There are many suggestive signs of early pregnancy failure. There's only a few definitive signs, but very many suggestive signs. None of these have been proven to be definitive in and of themselves in a large study, they're taken as a warning of a possible pregnancy failure. The more signs we have, the worse the prognosis. But nothing definite can be done. And so we must prove that the pregnancy has failed before any final action is taken.
The first sign is anembryonic bradycardia. The heartbeat depends on the gestational age, especially in the very early embryos. But a rule of thumb is that below 80 beats per minute would be a slow heart rate. That pregnancy should be followed, not within a week or two, probably three to four weeks to give it enough time to decide which way that heartbeat is going. Because you don't wanna be following a pregnancy every week and just waiting for something bad to happen that has a psychological trauma for the mother.
Another suggestive sign is a small gestational sac. This is that first trimester oligohydramnios. You have a small tight sac relative to the size of the embryo. The embryo can't seems like it can't roll over. And the reason it's not definitive is because at least there's at least a 35% survival rate with these type of pregnancies. If you want a number, if you want something more quantitative, you can take the mean sac diameter, which would be the three orthogonal measurements and average them. That would be your mean sac diameter. Let's say it's 12 millimeters. And then measure the crown rump length. Let's say it's 10 millimeters. The difference, 12 minus 10 is only two millimeter difference. The smaller the difference, if it's less than five millimeter difference, that's bad. Those end up many of them with subsequent demise. That's a quantitative number. But before you make that judgment, you have to examine the pregnancy in two perpendicular planes in a sagittal and transverse plane to decide about the fluid. If you just do it in one plane, you may be cutting through the embryo, but all the fluid is on the other side of the sac. You have to make sure that this is a three dimensional assessment. The embryo cannot roll over.
Now, here's another suggestive sign, slow growth of the embryo. We used to think that the embryo grew about a millimeter a day. Growth below 0.6 millimeters a day was considered to be too slow. From Abdullah's work, we find that we have to push that level down, at least down to 0.2 millimeters a day. If an embryo is growing, if the crown rump length is growing less than 0.2 millimeters a day, that would be likely to be a miscarriage. But like, if it's growing 0.4 millimeters a day, if it grew four millimeters in 10 days, that's 0.4 millimeters a day. We can't use that because we have found that with 0.6, that was a almost 45% false positive rate for miscarriage. The crown rump length growth can be very slow in pregnancies at the beginning, and subsequently, they turn out to be viable, and they grow normally. We have to move our criteria down.
As far as growth of the sac, growth of the mean sac diameter, it turns out that growth rates cannot be used at all. What happened here, and again, Abdullah looked at thousands of patients, and they found that a gestational sac could grow very slowly or may not grow at all, but that's not necessarily related, associated with miscarriage. We used to say that the sac grew about a millimeter a day, and also just like crown rump length. And we thought that less than 0.6 millimeter a day was too slow of a growth. Abdullah found that if we use that criteria, 10% were false positives for miscarriages, we would've made mistakes or probably did make mistakes. Now, we don't even talk about mean sac diameter growth. I'm not exactly sure how to explain this. I explain it to myself as the sac, the sac being a little big something like a first trimester polyhydramnios. And then maybe as the pregnancy advances, the whatever caused the accumulation of fluid in the sac stops the reason stops. And the sac doesn't grow or kind of even shrinks a little, but then eventually starts to grow as the amnion continues to grow. That is not reliable. There's too much overlap between the growth rates of viable and non-viable gestations.
Subchorionic bleeds are another threatening sign of a miscarriage. The size of the bleed has been related. Smaller bleeds, not so bad. Larger bleeds much more threatening, but this varies tremendously. The woman may have an episode of bleeding, and the sac stays intact other times she has an episode of bleeding in the sac, and everything comes out of the uterus. That's not very predictable. Sometimes we see blood clots inside the gestational sacs. We can see accumulations of fluid that sometimes fool us for whether it's a really a subchorionic hemorrhage, or is it a twin Here, in this case, we see an embryo, and this was a normal pregnancy here, but what is this? We don't see any embryonic parts. We don't see a round shape. We see points. We don't see good echogenic rim. This does not really meet criteria of a gestational sac. I would say that this is probably blood and hemorrhage in the cavity dissecting its way. In the cavity here, on the other hand, you see two fluid areas, and each one of these has a thick echogenic rim around it. They're both rounded. They were round in different projections. They even have possibly yolk sac in there. This would be twins.
Here is another example. We have three fluid areas, which what are pregnancies? What are bleeds? Here we have a gestational sac. There's an embryo on yolk sac, so that would be a pregnancy. It's probably abnormal in such a big sac and such a small embryo. Nonetheless, it's a pregnancy here. This has an oval shape. It has some kind of embryonic parts. It was oval in different projections. That's probably a twin sac that died off much earlier. But this area has some vague echoes in it. It has a point. It seems like it's fluid dissecting around the sacs, this would probably be hemorrhage. Sometimes we can't tell. We just follow these pregnancies. You can see blood clots in the pregnancy. Here's a blood clot that's actually smashing this poor little gestational sac off to the side. Sometimes you'll see membranes or linear echoes or some type of debris. All of this is probably manifestations of blood inside the cavity. Sometimes you'll see a fluid level. This is a transabdominal image. This was a fetal demise, and there was a layer of blood in the uterus on vaginal exams. The layer is seen in this fashion. It's an up and down kind of an appearance, because vaginally, this is anterior, this is posterior, this is caudal. And where the transducer is, this is cranial. That, yes, this is layering in a dependent fashion, but for the novice who's not used to transvaginal scanning this level does doesn't look like it's so intuitive like we have on transabdominal scans. But that's just something that one gets used to blood clots, may mimic embryos. Here was a live embryo, and here was another structure. It did not have a heartbeat. Is that a demise twin? What's going on? We were lucky that we rolled the patient around, and this fell to the other side of the uterus. Therefore, that's a little blood clot.
Here was a uterus with a structure that resembled an embryo. This was not an embryo. This was a blood clot. There was a single layer around this gestational sac. There was an ectopic pregnancy in the adnexa. This is one of those, what we call pseudosac accumulation of blood and fluid in the cavity with an ectopic. Same thing happened here. This was blood in the endometrial cavity. Somebody thought that was an embryo. This was not an embryo. There was an adnexal ectopic, and this was all just blood. That's a blood clot in the cavity.
Another suggestive sign, abnormal chorio decidual tissues, thin tissues, chorionic tissues losing their brightness, and their echogenicity gestational sacs with irregular outlines, losing the double decidual sac sign. All of these are abnormal, more abnormalities, very regular borders of the sac. Loss of echogenicity here. Some still retained echogenicity and loss here. Some retained echogenicity thinning, loss of echogenicity. There is something called a chorionic bump. Another sign that's been described in the literature. This is an echogenic area, rounded area along the border of a sac. It's uncommon. It's found in only 0.7% of pregnancies. Probably. It represents a hematoma, a hematoma that originally is echogenic and bulges into the sac. And some have been documented. They were followed, and they turned cystic, hypoechoic. It was a blood with temporal change. Some have surmised that this could be a resorbing twin. Nonetheless, the prognosis for the pregnancy becomes guarded. Here's a couple other examples of the chorionic bump. A small one here, a much larger one here.
Now, it's important to turn on Doppler because if these are hematomas, they should have no blood flow within them. The problem is if you have a mass like this and it has blood flow, now that's not a chorionic bump. We have to now suspect some kind of a tumor or some kind of a problem. And this turned out to be a hemangioma later on in pregnancy. Turn on the doppler.
Another sign increased perigestational venous flow. Here's a gestational sac, demise embryo. And now we have a lot of vascular spaces around the border. We can see little tiny movement of these little red blood cells. We turn on the Doppler, and we have increased flow, but sometimes we can't fill in all of the spaces because the flow is so slow. Nonetheless, it's coming in and trying to resorb the pregnancy yolk sac abnormalities are a harbinger that something may go wrong. We should have one yolk sac per embryo. We shouldn't have two embryos per one yolk sac. A yolk sac that's enlarged. This one was 10 millimeters. Yolk sac should be no more than six millimeters. This is abnormal, seeing in this case, three yolk sacs and only one amnion. Seeing a solid looking yolk sac or seeing a calcified yolk sac, all of these are abnormal and pregnancies should be followed.
There's something called a yolk stalk sign. This was described as another suggestive sign of pregnancy failure. I told you that the embryo should be near its yolk sac. When we start seeing the embryos separate from its yolk sac, that implies the presence of this yolk stalk, which is a later development with a pregnancy. By that time, by the time it starts to move away, there should be a heartbeat visible. If you have a yolk stalk, a little stalk, separating the yolk sac from the embryo, that means that the embryo should have a heartbeat by that time, or at least that's how the Philly and his group described it. If you don't see it, that means the embryo. If you don't see a heartbeat, the means the embryo is demised. You can use this in tiny embryos, but nonetheless, it's not a definitive sign, it's just something that we follow.
Another sign is an enlarged amniotic cavity. An enlarged amnion predicts possibility of embryonic death. It's large in relation to the size of the embryo. The amnion normally should grow in direct linear proportion to the crown rump length. Other abnormalities of the amnion, such as a wavy amnion or a thicker than normal amnion. Those can be abnormal signs. Some authors have talked about this enlarged amniotic cavity. The amnion is seen at six and a half weeks menstrual age, and that's about the time the crown rump length is seven millimeters. That's where they deduced that this should have a heartbeat, an embryo on a heartbeat. By that time, by the time you see an amnion, seeing the amniotic cavity implies that there should be an embryo with a heartbeat. If that's empty, or if the embryo does not have a heartbeat, then this is a strong possibility that this pregnancy will not develop normally a another suggestive sign, low position of the sac in the uterus. I have to be careful with that because we know low implantation site is not really a good idea for this pregnancy. But there could be a couple other things going on. For example, an abortion in progress. We need to make sure that's not what's going on. Sometimes the sac is completely normal, but there's a contraction that kind of looks like it. It pushes it down. As soon as the contraction releases the sac goes back into normal position. Same thing with fibroids. Nabothian cysts can fool us. Cervical ectopic can look like a low position. All these things have to be taken into account.
Here is a gestational sac with an embryo that implanted in the lower uterine segment. Here's the cervix, and it's in the, and this one miscarried. Here's an another one, low implantation. Eventually this pregnancy failed. This embryo is without a heartbeat. And this gestational sac is sliding out. It's an abortion in progress. We have to make sure that that's not what's going on. More and more we see abnormal ectopic pregnancy. Here's an intrauterine pregnancy, a diamond ring sign in the uterus. But look down here. There's another little gestational sac with another diamond ring sign. And this was a cervical ectopic. We have two sacs. It's a heterotopic type of pregnancy. And this has to be handled very carefully.
There are more signs, some of the older signs using sacs of 12, 16, 18, 20. Any of those are should be viewed suspiciously. Any embryo without a heartbeat, even a little one should be viewed with suspicion and followed, no yolk sac in a gestational sac, bigger than 25. That's also something that you can look for. In general, we have many suggestive signs that I've gone through. We have very few definitive signs.
Conclusion
In conclusion, we wanna be familiar with the sonographic findings of a normal first trimester pregnancy. We want to understand the significance of discriminatory signs of early pregnancy failure. We wanna be very conservative, not to harm any pregnancies. I would recommend that for now until the consensus statement is out, that you use crown rump length of bigger than seven millimeters as the discriminatory level, by which time an embryo should have a heartbeat. Also, it would be a good idea to start using mean sac diameters of greater than 25 millimeters should have an embryo with a heartbeat. Always correlate with beta and follow up with another ultrasound. Don't just use betas. Use ultrasound also because many odd things can develop. Hopefully in the future we'll have another talk where the consensus statement is more definitive. But for now, I recommend that we use these criteria.
Thank you very much for your attention.
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