Ultrasound of Failed First Trimester Pregnancies and Ectopic Pregnancies - HD

Introduction

Hi, I am Douglas Brown, a radiologist at the Mayo Clinic in Rochester, Minnesota. And I'm gonna be talking about ultrasound of the failed first trimester pregnancy and ectopic pregnancy.

So today we're gonna review normal first trimester pregnancy milestones. We will talk about an approach to how to diagnose ectopic pregnancy and then review ultrasound features of failed first trimester pregnancy, and for that was failed pregnancy criteria. We will talk mainly about those in the SRU Consensus conference on diagnostic criteria for non-viable pregnancy early in the first trimester. That was published in New England Journal in 2013.

Normal First Trimester Pregnancy Milestones

So first, we see the gestational sac at around five weeks after the last menstrual period, perhaps a little bit earlier in some patients, but it's generally at about five weeks after the last menstrual period before we see a gestational sac. And that's usually about an hCG level of about 3000. And notice that said usually, and we'll come back to that topic in a moment, the discriminatory level of serum HCG is the level above which a gestational sac should always be seen in a normal pregnancy.

And so the traditional teaching was that if the HCG was above that level and no gestational sac was seen, then the patient did not have a normal intrauterine pregnancy and either had a ectopic pregnancy or an abnormal intrauterine pregnancy, and therefore you could treat with methotrexate or do it DNC. One to 2000 was commonly used discriminatory levels.

But we now know from multiple sources that this number is really too low. Again, 2000's a commonly used number, but it's certainly too low. A number to use for the discriminatory level. One study found that about a third of the patients without a gestational sac at an hCG above 2000 went on to have a normal intrauterine pregnancy. Another study found that the highest HCG without a gestational sac seen by ultrasound that then resulted in a normal pregnancy was a little over 4000.

So there's increasing evidence that we really should not rely on a discriminatory level when no ectopic pregnancy is seen, at least in a stable patient, and that we should follow that patient with ultrasound and serial HCGs.

Another question that comes up sometimes is a low HCG level, is it even worth doing the ultrasound? And really ectopic pregnancy can occur with very low HCG levels. So a low HCG should not preclude an ultrasound. It's not a reason to not do the ultrasound.

So first we see the gestational sac. The next thing we see in the gestational sac is the yolk sac as indicated here by the arrow. And this is what we need to at least see that the fluid collection we're seeing is definitely intrauterine pregnancy is to see a yolk sac or embryo. And we'll see the yolk sac at around five and a half weeks since the last menstrual period. We usually see the yolk sac by a mean sac diameter of eight millimeters. Again, notice I say usually, so that can be a guideline, but it's not a definitive criteria.

The embryo we see at about six weeks, it's indicated here at the edge of the yolk sac. It just looks like a little thickening when we first see it again, usually by mean sac diameter of 16 millimeters. We will see the embryo, not always, but usually by 16 millimeters.

And then cardiac activity once we see the embryo, you should see cardiac activity, at least in most patients. And so again, at any crown rump length, we expect to see cardiac activity, but you should at least see it by seven millimeters. And we'll also come back to that a few minutes. And you'll notice here the gestational sac, the yolk sac, here's the little embryo with the flicker of cardiac activity.

Features to Identify Intrauterine Pregnancy

So before we see the yolk sac and know that the structure we're looking at is definitely a pregnancy, what other features can we identify that may help us? Well, these are all findings, again, that may help you. It's important to know they're not required to diagnose an intrauterine pregnancy. It's just signs that may be of help.

One that's been written about for many years is a so-called double decidual sac sign. As indicated by the two arrows. Here we see two layers of the decidua. And this has been talked about a lot, in my opinion, it's not very helpful. It tends to cause more confusion than help. Generally when you see it, you've already seen a yolk sac, so it doesn't really help you that much. So I don't find the double decidual sac sign to be that helpful. If you do want to use it again, you do not want to require its presence before you identify an intrauterine pregnancy.

Then the intradecidual sign, it makes great embryologic sense because by the time we see the gestational sac, it's certainly no longer in the endometrial cavity and a normal pregnancy. It's beneath the endometrial cavity line. And so the idea here is that the sac that we're seeing, if we can see the thin white line down the middle and tell that the fluid collection is deep to that white line, it's in the decidua. Now the decidua is the pregnant endometrium. And so if we can tell it's deep to that line, then it should be an early pregnancy rather than just fluid in the cavity.

Here's a video clip. You see the white line down the middle, there's the little tiny gestational sac at around five weeks. Again, here's the sac just deep to that central echogenic line that delineates the endometrial cavity itself. So this is a nice intradecidual sign. Makes you very much more confident that this is a true gestational sac. Again, we don't always see the intradecidual sign. Sometimes it's hard to identify that central echogenic line down the middle. So I think it's more helpful as a positive finding. And again, you do not always have to see this to confirm that it's intrauterine pregnancy.

Now, when we don't see the intradecidual sign, chorionic rim has been discussed, there's been some articles on this. And it refers to the hyperechoic rim of tissue around the gestational sac. Whereas a lot of the older, so-called pseudo sacs didn't have this hyperechoic rim. It's helpful, again, not a requirement. And most fluid collections we see in the uterus, again, regardless of their appearance, do turn out to be intrauterine pregnancies.

The pseudo sac itself is elongated fluid within the endometrial cavity as opposed to the more spherical shape of the true gestational sac. So most of these pseudo sacs are such an elongated shape of the fluid that it's easy to distinguish 'em from the true gestational sac that is more spherical to slightly ovoid. And in this case, on the sagittal view of the uterus, this fluid is very elongated, really looks like fluid in the endometrial cavity, what would've been called a pseudo sac and is not a true gestational sac.

Doppler in Early Pregnancy

Now what about doppler and early pregnancy? Just wanna mention that. It really doesn't help you identify an early pregnancy. There were some studies that looked at seeing the flow around these, but we tend not to do doppler anytime we think this is a normal early pregnancy, it puts more energy in for no proven benefit. So in my opinion, there's rarely a reason to do doppler in early pregnancy. Even when we document cardiac activity, you can do that with m mode or video clip. And that uses lower energy than the doppler methods.

Decidual Cysts and Pseudo Sacs

Now another reason besides true gestational sac and the fluid in the cavity, that again has been called a pseudo sac or decidual cyst. They don't seem to be real common, but they're not rare. They refer to these tiny cystic areas in the endometrium. They do not have that hyperechoic rim. Now these are deep to the endometrial cavity line. If we look at this patient, here's that thin white line. So these are deep, but there's a couple of 'em. They do not have a hyperechoic rim around them. So this is the typical appearance of decidual cyst. And occasionally they may be problematic in distinguishing from a true gestational sac, but still they're uncommon enough. Intrauterine pregnancies are much more common. So most of the time, again, when we see fluid in the cavity, that's not an obvious pseudo sac that is elongated in the cavity. It's much more likely to be a true gestational sac.

Now here's a video clip from another patient. In it, you're gonna see all three of these fluid collections. You're gonna see fluid in the endometrial cavity. You're gonna see the true gestational sac, and you're gonna see some decidual cyst. Here's the fluid in the cavity. Pretty obvious there's the true gestational sac. Here's a little decidual cyst over here. There's another one out here. Many of these decidual cysts, in my experience, are near the outer border of the endometrium that is the border of the endometrium with the myometrium. So they tend to be further away from that central cavity line. And in my experience, so when we're scanning these patients, we need to, when we report them, we need to decide how are we gonna report these.

Reporting Categories for Intrauterine Pregnancy

Can we say for sure that there's definitely intrauterine pregnancy present? And I think you can put 'em in these categories. That is, there's definitely an intrauterine pregnancy. So when you see a yolk sac or embryo inside the gestational sac, you know for sure if that's an intrauterine pregnancy. Then there's the ones that are probably an intrauterine pregnancy. And these you generally are gonna wanna follow. So any fluid collection that's not an obvious pseudo sac is likely a gestational sac. The intradecidual sign or seeing that echogenic chorionic rim is certainly supportive evidence, but it's not required. Decidual cyst are occasionally a problem, but are uncommon, and are much less likely to be a cause of the fluid collection than a true gestational sac.

And certainly if it's not clear any of these categories in this group, even if you're not sure if it's a true gestational sac, you don't want to ignore these. You want to at least mention the possibility that what you're seeing could be a gestational sac because otherwise the patient may get inappropriate treatment with a DNC or methotrexate and potentially harm a normal wanted pregnancy.

And then lastly, there are patients where we don't see anything in the uterus that could be a gestational sac. So there's no evidence of intrauterine pregnancy. And in these patients who have a positive serum pregnancy test, these fit into the category of pregnancy of unknown location. That is, we know they're biochemically pregnant, but by imaging we have not identified the location of that pregnancy.

Ectopic Pregnancy

So now we'll talk about ectopic pregnancy. As you're probably aware, the vast majority or tubal pregnancies, most commonly in the ampullary portion of the tube, less common locations are what so-called cornual or interstitial pregnancy. Many people do refer to these as cornual. We won't debate the best name, but many people are preferring the term interstitial pregnancy over cornual pregnancy at this point. Then you have cervical pregnancies and then c-section scar pregnancies, which someone would consider not true ectopics 'cause they are in the uterus, but still they're not in the normal position. Then you can have abdominal or rudimentary horn pregnancies that are quite rare. Unfortunately, ovarian ectopic seem to be very rare. And this is important because as we'll discuss when we're looking at the adnexal mass of a tubal ectopic pregnancy, it's important to determine the location. Unfortunately, location in the ovary is very rare.

If we look at the ultrasound criteria of ectopic pregnancy, this status from a meta-analysis a few years ago, and certainly if you require the presence of a living embryo to be the only absolute criteria for ectopic pregnancy, your sensitivity is only gonna be in the neighborhood of 20%. But if you move up to the so-called tubal ring appearance, which we'll review in a minute, you're up to about 65% sensitivity. And then if we take any mass in the adnexa, that's not a simple cyst or in the ovary, you're at about nearly 85% sensitivity and your specificity is still high at about 99%.

So here's a living embryo. If we look at this video clip through the adnexa, here's the gestational sac. This is outside of the uterus. The uterus is not shown in this clip, but is elsewhere. So here's the gestational sac with the embryo. Here's a resub view of the embryo. And you can see the cardiac activity. So these are generally easy, straightforward diagnosis. Unfortunately, they occur in the minority of all ectopic pregnancies.

So then if we go up to the so-called tubal or adnexal ring appearance, and you can imagine this looks like if you just took that gestational sac in the uterus and put it outside, you see that hyperechoic rim central fluid cavity. And this is that so-called tubal ring appearance. Here we see it in the right adnexa. Here's another patient where you see the ovary and here's this tubal ring appearance. This one probably has a little yolk sac in it too, but you can still see that hyperechoic ring appearance of a mass separate from the ovary.

Another patient ovary here. This is the corpus luteum inside the ovary. 'cause you can look at these and see that the corpus luteum and the tubal pregnancy look a little bit similar. They got a central anechoic cavity, a little bit of a thick rim around it, but the corpus luteum lives in the ovary. Tubal pregnancy obviously is outside the ovary, and that's the distinction that you're trying to make in these patients.

And then you have another category mass complex or solid looking mass that is, it's not a simple cyst. It doesn't have the obvious tubal ring or gestational sac appearance to it. And while admittedly, it's not specific by itself in the right clinical setting that is a patient with a positive pregnancy test, no evidence of a pregnancy in the uterus. And you see this mass that's outside the ovary in the adnexa, it becomes highly predictive of a tubal pregnancy. Admittedly, there are a few pitfalls. Pedunculated fibroid might occasionally be a problem, but most vast majority of the time these masses outside the ovary in this clinical setting are gonna be a tubal pregnancy.

So here's a patient with ovary here. Here's this kind of heterogeneous hypoechoic mass adjacent to the ovary. Here's the video clip in the same patient. Again, we see the ovary with normal follicles. Here's the mass over here. Admittedly, you don't see a definite gestational sac in it, but in this case, positive pregnancy test. There was nothing in the uterus. This mass becomes highly predictive of a tubal pregnancy, which this was.

So again, location of the mass is key. You're really looking for that extraovarian location. Corpus luteum is the big fooler. It can fake you off, but the corpus luteum is inside the ovary, whereas the tubal pregnancy, again, is outside the ovary. So sometimes is in the case that we just looked at. It's obvious that it's outside the ovary. There admittedly may be other times where it's hard to tell. So if you're not sure when the scan's being done, it's helpful in many cases to try palpation with your hand, with the non scanning hand during the transvaginal exam, or use gentle pressure with the transvaginal transducer. And with one or both of those, you can often separate the mass from the ovary or tell that it really is part of the ovary and that will help you in making the distinction. Occasionally it's still problematic, so you may have some problem cases every now and then, but this pressure with the transducer or palpation is often helpful in making the distinction.

Color Doppler and the Ring of Fire

Now what about color Doppler? The ring of fire gets talked about. You see this flow around the periphery. But in my experience, the ring of fire doesn't really help you very much. Both the corpus luteum and the ectopic pregnancy can have abundant vascularity. Some tubal pregnancies even don't have that much. But here's a patient with the corpus luteum. This was inside the ovary. It's got a lot of flow around the periphery. Looks like the ring of fire, but this is inside the ovary. And this is typical of a corpus luteum.

Here's a tubal pregnancy with maybe a little mild ring of fire. But again, it's really the location of the mass that's most helpful, not whether it has the ring of fire appearance. So I personally don't use this and don't find it very helpful in making the diagnosis of ectopic pregnancy.

Intraperitoneal Fluid

Now, what about intraperitoneal fluid? Occasionally you do a scan, there's nothing in the uterus. You don't see a mass in the adnexa that looks suspicious, but maybe you got a little more free fluid than normal. How predictive is that? Well, part of the problem with some of the articles in the literature is that they don't allow for the normal small amount of fluid in the posterior cul-de-sac. That's common in premenopausal women. So certainly larger amounts of fluid or internal echoes in the fluid that are often due to blood or worrisome.

I think in this patient. This is a transabdominal scan. Here's the uterus. Here's a moderate amount of fluid with internal echoes in the pelvis. Here's the same patient, transvaginally, sagittal view of the uterus, no evidence of a pregnancy in the uterus. And we've got this fluid with echoes in the cul-de-sac. Certainly, I think we're all gonna be concerned that is a tubal pregnancy is a potential cause even if we don't see the mass. But unfortunately there's a lot of data on this as the sole criterion for ectopic pregnancy, particularly when you don't have an adnexal mass. So larger amounts of free fluid, yeah, we're gonna be worried, but it's still difficult to sort out in that case as there are other potential causes of the fluid, such as a ruptured hemorrhagic cyst.

Pregnancy of Unknown Location

Now the concept of pregnancy of unknown location we referred to earlier, it's a patient with a positive pregnancy test, and the ultrasound does not show the location either in the uterus or outside. This occurs in about eight to 20% of patients presenting with positive pregnancy tests and pain or bleeding. What are most of these patients gonna end up having? Well, the majority are gonna have intrauterine pregnancies, but unfortunately most of these are miscarriages or failed intrauterine pregnancies. About five to 15% of patients with this pregnancy of unknown location will turn out to have ectopic pregnancies and stable patients can generally be followed conservatively with serum HCG and ultrasound.

Non-Tubal Locations of Ectopic Pregnancy

Now, non tubal locations of ectopic pregnancy. Again, interstitial perhaps is the better term, though cornual is still used in many centers. Are there numbers you can rely on how much myometrium is around it? Well, unfortunately, I don't think so. There are a couple of numbers that have been mentioned in the literature. They seem to be arbitrary. Neither has really been proven in my experience. There's some studies that talk about an eccentric sac within five millimeters of the serosa or more than a centimeter from the lateral edge of the endometrium. And perhaps these are true but have not been validated in my experience. And I don't know of a number that you can absolutely rely on.

These interstitial pregnancies may present later in gestation than the usual tubal pregnancy. I think the eccentric location of the gestational sac is key. It's up in the cornual region of the uterus separate from the endometrial cavity, and there's little to no surrounding myometrium. And I think transverse or coronal views are really important. And this is a case where 3D ultrasound may be helpful too.

Another thing to remember with these interstitial pregnancies is that sometimes you just see heterogeneous hyperechoic tissue in this region of the uterus. You may not see a well-formed gestational sac. So here's a patient with interstitial pregnancy. Here's a sagittal clip through the uterus. In the endometrium, we don't really, we see a little heterogeneous fluid, no definite gestational sac. But if you noticed on that clip, as we get out to one side, you'll see some in this region heterogeneous hyperechoic tissue. Here's the transverse or coronal view in the same patient. So here's the mass, some heterogeneous hyperechoic tissue, not an obvious gestational sac, but this is trophoblastic tissue. And this patient did have a proven right interstitial pregnancy.

Now, gestational sacs can be eccentric in the uterus. It just being eccentric by itself doesn't prove it's a cornual interstitial pregnancy. You can have mullerian anomalies such as a septate bicornuate uterus, where this gestational sac can be to one side. The fibroid can displace the gestational sac to one side and cause eccentric location. And sometimes, as in this case, as this is a transverse or coronal view up toward the fundal region, the gestational sac is just more toward one side. And that's okay, as long as you clearly see the myometrium going around it, that's still normal.

Cervical Pregnancy

Now, cervical pregnancy, when we see a gestational sac in the uterus, the main differential diagnosis that you've gotta make is whether this is implanted there. So a true cervical pregnancy versus is this a spontaneous abortion or miscarriage in progress? So we may have just performed the ultrasound when the gestational sac is passing through the cervix and which is gonna be more common? Well, certainly by far a spontaneous abortion or miscarriage in progress is gonna be more common than a cervical pregnancy.

So here's a patient with a gestational sac down in the cervical region. This was just a spontaneous abortion in progress. Here's one gestational sac in the cervical region, the sagittal view of the cervix. In this case, we can actually see the endocervical cavity line and tell that the gestational sac is deep to it. So in a sense, this is sort of the cervical equivalent of the intradecidual sign, if you will. And I think if you see that it's helpful in confirming that this is a cervical pregnancy.

But as far as which finding sonographic best helps you distinguish, it's hard to know. There's not really been a study, to my knowledge that's looked at all these features. Ones we could consider to help us tell the difference or embryonic cardiac activity. Certainly if you see it would be more concerned, it's implanted there. But I have seen a few cases where the gestational sac and the cervix had cardiac activity. We re-scanned the patient the next day and it was gone. So I think there may be a short window during a spontaneous miscarriage where you still might see cardiac activity even though it's not implanted there. So that's certainly not totally reliable.

Could you do color or power doppler? I mentioned that we don't do it in a normal pregnancy, but if the gestational sac is truly in the cervix, it's not gonna be a normal pregnancy. And I think if you did it and you saw flow around it, it would suggest it's implanted there. But I'm not aware that this has been evaluated to know how reliable it is. I just mentioned the intradecidual sign equivalent, which we showed an example of.

Another thing that can be helpful is movement of the gestational sac during the scan. And you may see this passively if you're noticing perhaps you do a transabdominal scan first, then the transvaginal. And if you are paying careful attention, you may see that it's actually in a different part of the cervix or lower uterine segment during the two portions of the scan. But you can also do this with a little active maneuver by applying pressure with the endovaginal transducer. And if you can show that that gestational sac moves that is slides within the cervix, then that suggests it's not implanted there and that you're dealing with a patient with a spontaneous miscarriage in progress.

So if you're still not sure after considering these signs, and admittedly there are times where it's hard to be sure if the patient's stable and often they are, I think the most reliable thing to do is to re-scan the patient the next day. And that's often helpful in clarifying it. If you do the scan the next day and the gestational sac is gone, you obviously have your answer that it was a miscarriage in progress. If it's still there and looks the same, then I think you have to be more suspicious that you're truly dealing with a cervical pregnancy that it's implanted in the cervix.

And the other differential is that blood clots in the cervix, they're quite common, but I think most of these are simple or very low level echoes, and they're not generally an issue in the differential diagnosis pregnancy.

C-Section Scar Pregnancy

In a cesarean section scar, here's a patient sagittal view of the uterus. Here's the cervix, endocervical canal. Here's the gestational sac, right where we'd expect most c-section scars to be. That is anteriorly in the lower uterine segment. These have also been called intramural or myometrial pregnancies. And these again are gestational sacs implanted in the c-section scar. Ovary ectopics are quite rare. This is certainly the only case I've ever seen.

Ovarian Ectopic

I thought it was gonna be the corpus luteum. It looks like a little heterogeneous area inside the ovary. No obvious gestational sac. And I think these will be a difficult diagnosis to make unless you see a clear cut gestational sac with a yolk sac or embryo inside the ovary. I think it would be difficult to make this diagnosis. Unfortunately, ovarian ectopics, as we mentioned earlier, are quite rare. So this location inside the ovary or outside is again usually quite helpful in making the distinction between ectopic that is tubal pregnancies anyway. And the more common corpus luteum.

Abdominal or Rudimentary Horn Pregnancy

You can also get pregnancies in the abdomen or in a rudimentary horn that is a uterus that's unicornuate with the rudimentary horn. And you should especially consider this when you've got an embryo or that is a pregnancy outside the uterus that's a little bigger as in this case. On first glance here we see amniotic cavity placenta. Here's the embryo. It correlates in crown rump length with about 13 weeks. Now we don't usually see tubal pregnancies that get quite that far. Tube isn't gonna extend that much. So in this case you have to consider abdominal or rudimentary horn pregnancy. And when we look closer, you see that actually the uterus is below this. You can't tell from this image, but this fetus here is not in the uterus. It's separate from, it was actually superior to this uterus. And it turns out that this pregnancy was in the rudimentary horn of a patient with a unicornuate uterus.

So that's ectopic pregnancy. We're gonna move on here to the ultrasound signs of early pregnancy failure.

Ultrasound Features of Failed First Trimester Pregnancy

I like to separate these into three groups. The definite ones that when you see them, you know, it's a failed pregnancy. The ones that are worrisome, you want to pay attention to these. We're not gonna ignore them, but you can't totally rely on them. And then there's a few that will mention that I think are less predictive and are hard to apply. They've been talked about a bit in the literature, but I don't find them helpful and you certainly would not rely on them.

Definite Signs of Pregnancy Failure

So what's the definite signs of pregnancy failure? Well, on a single transvaginal ultrasound of adequate quality, it's no heartbeat in the embryo when the crown rump length is seven millimeters or more or no embryo when the mean sac diameter that is the mean diameter of the gestational sac is 25 millimeters or more.

So absent cardiac activity by transvaginal ultrasound for many years most people use five millimeters or more. That is if it was five or more and no embryonic cardiac activity, we could confidently call it a demise. But there is new evidence in the last few years that we need to raise that number to seven. And that was used in the consensus conference that I referred to at the beginning of the talk.

Now it is important to know that even at less than seven millimeters, you should see embryonic cardiac activity in a normal pregnancy. So if you don't see cardiac activity even less than seven, you should be very worried. You know, here's a patient small embryo, no heartbeat. And this did go on to be a failed pregnancy.

So if it's seven millimeters or more adequate quality, transvaginal ultrasound, no cardiac activity, you can confidently call that a demise. If it's less than seven millimeter crown rump length and no heartbeat, you should be very worried and should get a followup ultrasound in seven to 10 days. And then if there's still no heartbeat, you can diagnose that as embryonic demise.

A couple of pitfalls, make sure you're really looking at the embryo. The early embryo is at the edge of the gestational sac at around six to seven weeks. Sometimes you'll see a little lobular thickening like here along the edge of the gestational sac. Yeah, you can put calipers on that, come up with a pseudo crown rump length and an age. But the early embryo is not over here. It's at should be at the edge of the yolk sac. So this has been referred to in some articles as the chorionic bump. Sometimes those do have a poor outcome, but as an isolated finding, most seem to do pretty well. But I think it's also potential pitfall that you don't mistake that irregularity along the wall, that chorionic bump for an embryo and make decisions based on the length of that. So be sure it's the embryo being imaged.

Another definite sign of early pregnancy failure is that empty gestational sac. How large before you can be certain that it's not a normal pregnancy. Here's a patient again, when you measure the mean sac diameter, you find the longest dimension of the anechoic fluid filled space. We're not measuring the wall, the echogenic chorion, just the anechoic fluid filled space. And then the two perpendicular dimensions and average them. This one was right at 25 millimeters and nothing in it.

So generally, as I mentioned before, we'll see a yolk sac by eight millimeter mean sac diameter an embryo by 16. Now these are worrisome if they're over those size thresholds and you don't see a yolk sac or an embryo, but they're not definitive. The old rule was 20 some might've used 16. That is if it was over, if it was 20 millimeters or more mean sac diameter without an embryo, you could diagnose a failed pregnancy. But similar to the change we had with the crown rump length criteria, and this largely relates to measurement variability that is present, we should use 25 millimeters now.

So if you're 25 millimeters or more mean sac diameter without an embryo, you can definitely diagnose a failed pregnancy. One problem with this criteria is it has low sensitivity. The vast majority of failed pregnancies are not gonna reach this gestational sac size. But if it is over this, then you can be confident that it's a failed pregnancy.

If there's no embryo seen, you'll notice the SRU guidelines did not use any criteria related to the absence of a yolk sac based on mean sac diameter. The criteria we're talking about here is in regards to an absent embryo with the mean sac diameter of 25 millimeters or more.

Worrisome Signs

Now, there are some worrisome signs. All these generally require follow up. They're not definitive by themself. A large gestational sac in the gray zone that we've talked about, that is a mean sac diameter of 16 to 24 millimeters without an embryo is worrisome but not definitive for a failed pregnancy. The others are small gestational sac size, empty amnion and bradycardia.

So small gestational sac size is often quantified by subtracting the crown rump length from the mean sac diameter. And there are studies that have shown if that difference is less than five millimeters, that there's an increased risk of pregnancy failure. It certainly does increase the odds, but we still wanna follow these. It's not totally reliable based on some follow up studies. And it's also uncommon that is of low sensitivity in patients with failed pregnancy. But if you do see it, and you can quantify it, take the mean sac diameter, subtract the crown rump length less than five, be worried about a failed pregnancy and follow that. But it's not a definitive criteria for pregnancy failure.

Another's the empty amnion sign that is here we have a gestational sac. Here's the yolk sac and here's the embryo and no embryo, I'm sorry. Here's the amnion, the yolk sac and the amnion. And no embryo was seen inside the amnion, so so-called empty amnion sign. There's good evidence that this indicates a failed pregnancy, but it's not a definite criteria. So again, this is a feature where if I saw what I'd be very worried, but I'd still wanna follow the patient before diagnosing a definite failed pregnancy bradycardia.

When a crown rump length's less than five, if your heart rate's less than about 80, you have a very slim chance of survival. Even less than 90 is poor survival. If your crown rump length's five to nine millimeters, very poor survival if it's less than a hundred. So it's nice when these early embryos have heart rates over 110, 120. If you're less than 80 or less than a hundred depending on the crown rump length, that's a poor prognostic sign. But again, as long as you have that cardiac activity present, you're gonna follow that pregnancy rather than intervene at that time.

So those are findings that are worrisome that you're gonna pay attention to and not ignore, but not make decisions based on one ultrasound.

Less Predictive Features

Other features that I think are even less predictive harder to apply are yolk sac. Yes, you can have a large yolk sac with failed pregnancies and there's other parameters about the yolk sac that have been evaluated, but in general, they're not totally reliable. Irregular shape of the gestational sac. You can certainly see that with failed pregnancies, but sometimes they're just a little lobular. And I think there's the potential to over call or be overly worried based on just a slightly irregular gestational sac. So I don't find that as useful unless it's just grossly distorted. And even then I'd wanna see some of the other findings that we talked about.

And then there's the hematoma, so-called subchorionic hematoma. Different terms have been used for this implantation bleed, perigestational bleed or intrauterine hematoma. And here's two different patients. Here's one gestational sac here with a little fluid next to it with echoes. Another patient with gestational sac, yolk sac. Here. Here's a little fluid collection with internal echoes along the edge. Typical small subchorionic hematomas. The ones that are small, which in some studies has been defined as less than two thirds of the sac circumference are common. They're usually not clinically significant.

There is an increased risk of miscarriage if they're larger hematomas, which has been defined in one study, is greater than two thirds of the sac circumference if it's younger gestational age or older maternal age. But these small hematomas, again, are quite common. Usually a little clinical significance. If they're very tiny and you're even trying to decide whether they're real or trying to even report them, I wouldn't even worry about calling them. 'cause sometimes what you're seeing is probably just the early intervillous space of the placenta with slow flow that may even simulate a small hematoma.

Gestational Trophoblastic Disease

I wanna briefly mention gestational trophoblastic disease. The typical two most common forms are complete molar pregnancy and partial molar pregnancy. We certainly are more sensitive on ultrasound for identifying complete compared to partial molar pregnancy. The sensitivity of ultrasound for complete molar pregnancy is around 95%, but for partial molar pregnancy overall, it's only about 20%. However, with partial molar pregnancy, it really depends on the gestational age. If you're less than about seven weeks, we tend to do very poorly with ultrasound at identifying partial molar pregnancies. We get better as we increase in gestational age as illustrated here, about 13% sensitivity at seven to 13 weeks, around 40 to 50% as you get to 13 to 15 weeks. So we do a little better with those at a higher gestational age.

Typical ultrasound appearance of the complete molar pregnancy is a hyperechoic mass with small cystic space, as in this case, resub view in the uterus, transverse and sagittal. You see a lot of this hyperechoic tissue, multiple small cystic spaces. This is the typical appearance of a complete molar pregnancy.

There is some evidence that early in the first trimester some of these patients will not have this classic ultrasound appearance. A couple of studies that looked at this found a little bit different incidence of how often this atypical appearance happens. 18% in one study, about 50% in another, and this patient had a complete molar pregnancy, a little heterogeneous tissue, a little fluid, maybe that's a gestational sac. Hard to be sure little heterogeneous tissue. Maybe there's a few little cystic areas in retrospect, but certainly not that classic complete mole appearance that we looked at in the earlier example. And this did turn out to be a complete molar pregnancy.

Sometimes it may be hemorrhage into the tissue that obscure some of the normal findings or the expected findings that we talked about earlier. And also it seems to be that this probably is more common at an earlier gestational age, that is to see this atypical appearance of complete molar pregnancy.

Now with partial molar pregnancy, we expect to see some embryonic or fetal tissue. Unlike the complete molar pregnancy that we looked at, you do not see embryonic or fetal tissue. But with partial molar pregnancies, you do at least by pathology and generally by ultrasound. Many of these partial molar pregnancies, the majority have triploidy, most will die in utero. If they do survive the first trimester, they typically have intrauterine growth restriction or dysmorphic partial molar pregnancy can be problematic because the appearance overlaps with non molar pregnancies that fail and go on to have some hydropic change in that non molar early placenta.

So when we see cystic spaces in the early placental tissue, that's main or two main differential diagnoses are partial molar pregnancy versus hydropic change in a non molar failed pregnancy. And they can look quite similar. Here's a patient with hyperechoic placental tissue, little cystic change, another patient, little heterogeneous placenta with cystic spaces. This was a partial molar pregnancy. This was hydropic change in a non molar failed pregnancy. And they can be difficult to distinguish from one another.

I think when you see this appearance, it's fine to raise the possibility of a partial molar pregnancy, but it'll often take pathologic examination of the tissue to make the distinction. Another patient with partial molar pregnancy. Some of these patients that we identify that have failed pregnancies early on without even identifiable changes in the early placenta will turn out to have partial molar pregnancies. And that happened in this case. Here's an embryo. No heartbeat looked like just a failed pregnancy, but it ended up being a partial molar pregnancy. Now you can see the cyst in the placenta, and that this is a 17 week triploid pregnancy with a partial molar pregnancy. And I think that cystic change becomes more obvious later in gestation, as in this case.

So main differential diagnosis of a complete molar pregnancy, you could potentially have a polyp with cystic change, but if you've got the positive pregnancy test, particularly with a really high HCG level, then you'd be more concerned about a complete molar pregnancy differential diagnosis for partial molar pregnancy, as we mentioned, the main one is just hydropic degeneration of a non molar failed pregnancy. Later on you might consider Beckwith-Wiedemann syndrome with placental hydrops. You can rarely have a twin pregnancy where one is a complete molar pregnancy and one's a normal fetus can usually make that distinction between a partial molar pregnancy because the true partial molar pregnancy, even later, the entire placenta is gonna have that cystic appearance. Whereas if you did encounter that rare coexistent, complete molar pregnancy and normal fetus, you're gonna have a normal area placenta for the fetus. And then a separate area that has the cystic change for the molar component.

Theca Lutein Cysts

Theca lutein cysts tend to appear as bilateral multiloculated cystic masses. These theca lutein cysts are the classic adnexal finding in patients with gestational trophoblastic disease, and they seem to be a marker for these high hCG levels. Traditionally these are seen more commonly with complete molar pregnancies as compared to partial molar pregnancies. In my experience, we see these less frequently. Now even with complete molar pregnancies, I don't see these as often as we did many years ago. If you do see them, realize that it may take several months for these to resolve after treatment For the molar pregnancies, they often get D&C and chemotherapy, and they, these theca lutein cysts may take a little time to resolve. The fact that they don't go away within a month or two does not mean treatment failure.

Summary

So in summary, I think the key points like us to remember or that we generally do not wanna rely on a discriminatory level based on a single HCG, when no ectopic pregnancy is seen, most of these patients are stable, and if they are, it's better to follow them with ultrasound and HCG, any fluid collection in the uterus, that's not an obvious pseudo sac or decidual cyst. Mid, occasionally decidual cyst may be problematic, but most of these fluid collections that are not an obvious pseudo sac that is elongated fluid in the cavity are very likely an intrauterine pregnancy. Even if you're not completely sure, you do not wanna ignore these small fluid collections because otherwise the patient may be inappropriately treated with methotrexate or a D&C and have a normal pregnancy.

And for ectopic pregnancies, that extraovarian location of the adnexal mass is the key feature you wanna make in diagnosing ectopic pregnancy. The corpus luteum obviously is very common in these patients. It's inside the ovary and you don't wanna mistake it for the mass, the tubal pregnancy. So look for the location of that mass and try to determine whether it's inside the ovary or out. That's the key distinguishing feature. Thank you.