Sonographic Evaluation of Ectopic Pregnancy - SD

Introduction and Objectives

Hello, my name is Dr. Leslie Scout and I'm chief of ultrasound at Yale New Haven Hospital. I'm going to talk to you today about the ultrasound evaluation of ectopic pregnancy.

We are going to be talking about the sonographic evaluation of ectopic pregnancy in the next 30 to 45 minutes. The outline and objectives of this presentation are to discuss the ultrasound technique for the evaluation of ectopic pregnancy, to review the ultrasound findings and discuss common pitfalls as well as unusual locations for ectopic pregnancies.

Patient Presentation and Initial Evaluation

The way that these patients present typically is with pain and vaginal bleeding in the first trimester. Whenever such a patient comes into the emergency room or the clinic with pain and vaginal bleeding, the first question that you need to ask is, is the patient pregnant? If the answer to that is yes, the primary thing that you need to exclude is whether or not she harbors an ectopic pregnancy.

If she is not pregnant, you will then evaluate her for the following etiology, such as hemorrhagic ovarian cyst, ruptured ovarian cyst, ovarian torsion, or pelvic inflammatory disease. These topics have been covered in other lectures on the website.

Incidence and Risk Factors

Regarding ectopic pregnancy in the United States, it accounts for approximately 2% of all pregnancies, and this incidence has been increasing over recent decades. The reason for this is that there has been an increase in the size of the patient population with risk factors for ectopic pregnancies, but also because we are now diagnosing these pregnancies earlier with endovaginal ultrasound. Therefore, we likely identify ectopic pregnancies that would have resolved spontaneously without coming to medical attention before the advent of use of endovaginal ultrasound.

The risk factors for ectopic pregnancy are listed on this slide, and the most important include any history of prior ectopic pregnancy, pelvic inflammatory disease history or treatment for infertility and tubal surgery. But if a patient has an IUD or endometriosis or in the older woman or a woman who has had a prior cesarean section, the risk of ectopic pregnancy is also substantially increased.

Mortality Trends

Now while the incidence is increasing, the mortality of patients with ectopic pregnancy has been decreasing. This is also due to the fact that we are now making the diagnosis earlier with endovaginal ultrasound, and therefore these patients are coming to medical attention before they become hemodynamically unstable. Nonetheless, ectopic pregnancy remains the leading cause of pregnancy related death in the first trimester.

Ultrasound Technique

In terms of technique, the gold standard for evaluating the patient to exclude ectopic pregnancy is endovaginal ultrasound. The reason for this is that this gives the best spatial resolution for evaluation the adnexa. That being said, you do have to pay careful attention to optimizing your technique, and you want to use the highest frequency transducer that is available. You want to optimize the focal zone so that it is just at the level or just below the area that you are interrogating with the ultrasound beam. You want to use any tricks that your high end equipment might have that would improve spatial resolution such as harmonic imaging or spatial compounding. Don't forget to magnify the images, particularly if you're looking at the endometrial stripe and the adnexa.

We suggest using a bimanual approach when you're evaluating the female pelvis. By that what I mean is that you want to palpate the anterior abdominal wall with one hand as you're holding the endovaginal probe with the other. This will help move the gas and the artifact from the gas and the bowel out of the way so that you can visualize the organs in the pelvis better. It pushes the area of interest towards the transducer, which will improve visualization. It also helps to identify the area of the patient's pain, which is where the pathology is likely to be. It is a very useful technique to try and separate a tubal mass or ring from the ovary. If you can identify that these two structures are separate, you can be sure that the tubal mass is in fact an ectopic pregnancy and not simply a corpus luteal cyst arising from the ovary.

In addition to evaluating the endometrial stripe and the adnexa, you always want to examine the cul-de-sac carefully as this is the most dependent portion of the pelvis and therefore where ectopic pregnancies not infrequently drop. You want to use doppler selectively in the first trimester as a last resort for evaluating the adnexa and occasionally the endometrial stripe.

Now, while we focus our exam on the endovaginal component, transabdominal scanning is a required part of the protocol. The reason for this is that you need transabdominal scanning to assess the upper abdomen for the presence of free fluid. This will help quantitate any hemoperitoneum that you might have identified in the pelvis. This is extremely important in terms of determining the hemodynamic stability of the patient.

In addition, you want to use transabdominal scanning to look for any adnexal mass that might have been missed on endovaginal scanning, particularly masses that are higher, perhaps displaced out of the pelvis. Anytime you've not been able to visualize the ovaries or the area of the patient's pain on endovaginal exam, it is worth looking with transabdominal imaging in order to more fully appreciate the upper pelvis and the adnexa.

Lastly, after you've done your ultrasound, it is extremely important that you correlate your findings with a date of the patient's last menstrual period, the serum beta HCG level, as well as her symptoms. We all must recognize that occasionally ultrasound will be negative and follow up examination may be required to confirm the diagnosis.

Diagnosing Intrauterine Pregnancy

In a patient who presents with pelvic pain or vaginal bleeding who is pregnant, you must consider the diagnosis of ectopic pregnancy. But the fact of the matter is that when you do your ultrasound examination in these patients who have a clinically suspected ectopic pregnancy, most of the time what you end up doing is documenting the presence of a normal intrauterine pregnancy. It's estimated that about 70 to 90% of all patients with clinically suspected ectopic pregnancies in fact turn out to have an intrauterine pregnancy.

So it's extremely important that you understand how to make the accurate diagnosis of an intrauterine pregnancy in the first trimester because if you can make this diagnosis, this makes the likelihood of a concomitant or heterotopic ectopic pregnancy extremely unlikely in the general population. This occurs in probably only one in 7,000 pregnancies. But you must understand in patients who've undergone assisted reproductive techniques, the incidence is much higher and may in fact reach an incidence of approximately one to three in a hundred pregnancies. But in the normal population, if you identify and diagnose an intrauterine pregnancy, it pretty effectively excludes the diagnosis of an ectopic pregnancy.

So while I know this has been covered in prior lectures, just to review very quickly how you diagnose an intrauterine pregnancy. The first thing that you're going to be looking for temporally is the presence of the intradecidual sign. This is the presence of a cystic structure within the endometrial cavity. It will have an echogenic rim as you see in these two cases, and it will be located eccentrically not within the endometrial cavity, which is identified by this linear central echogenic line, but it will have burrowed into either the anterior or posterior layer of the endometrium, and therefore it will be eccentric. This has been determined or termed the intradecidual sign.

While it is suggestive of an intrauterine pregnancy, it is recommended that you do get follow-up to document the appearance of the yolk sac because it's really only once you see the yolk sac that you can have a hundred percent confidence that that little cystic structure in fact represents an intrauterine pregnancy.

Later you might identify the double decidual sac sign, and this is a description of the following appearance where you have concentric echogenic rings. The innermost ring, which will be a 360 degree echogenic ring, represents the chorion or the decidua capsularis. The outer echogenic ring indicated by the red arrow here is typically incomplete, not 360 degrees, and that represents the decidua vera. In between these two echogenic rings, you'll see a little bit of echogenic or hypoechoic material representing either the endometrium or some fluid within the endometrial canal.

Once the beta HCG is greater than 1000 to 2000 units, using the international reference preparation, you ought to see an intrauterine pregnancy on endovaginal examination. This corresponds to approximately a five to six weeks gestational age.

So if you are left with a situation of a patient who has a positive beta HCG with a level greater than 2000 and an empty uterus, an intrauterine pregnancy is therefore extremely unlikely unless the patient has multiple gestations or the examination is technically limited, and therefore you need to correlate with the dates to make sure that you're not dealing with a very early intrauterine pregnancy with multiple gestations. Of course, patients with multiple gestations will have a higher beta HCG level for any given gestational age. You also want to check for history of vaginal bleeding. If there is no history of vaginal bleeding, miscarriage is unlikely.

So again, to reiterate, if your beta level is greater than 2000, the uterus is empty, there's not significant risk for multiple gestations, you have a good exam, probably you're dealing with an ectopic pregnancy.

Ultrasound Findings in Ectopic Pregnancy

Pseudo Gestational Sac

So what are the features on ultrasound that you look for? You're going to start by looking at the endometrial canal, and of course you won't see an intrauterine pregnancy, but very often you may see some fluids centrally within the endometrial cavity. This has been called a pseudogestational sac. This fluid will always be central. It will not be eccentric in location, it will not have an echogenic rim, and you will not see a double decidual sac sign. The fluid can be round or oval as you see here.

It is not uncommon that a little bit of decidua may fragment into the endometrial canal and mimic the appearance of a yolk sac or an embryo. But in this case, although it looks like there's a little embryo here, that fluid is central, there's no surrounding echogenic rim. Here is the patient's ectopic pregnancy. All this was was a pseudogestational sac with a fragment of decidua mimicking a little embryo within the fluid.

If you use color doppler or pulse doppler, this has will have been described in another lecture. In general, we try to avoid using doppler evaluation of the endometrium in the first trimester. But if you happen to do this, and occasionally it can be helpful, if you really need to try and exclude an ectopic pregnancy, there will be no evidence of trophoblastic flow. So in this example, you can see the central fluid with color flow in the myometrium, but no flow within the endometrial stripe.

Extra-Uterine Gestational Sac

The diagnostic finding of an ectopic pregnancy is of course the presence of an extra uterine gestational sac. This can be identified as an echogenic ring-like structure in the adnexa here next to the right ovary containing a embryo. Here you can see an embryo of about 10 weeks gestational age. You can even see the rhombencephalon very often it's, you see these much earlier. The little embryo will be very tiny as you see in this case, just between the yolk sac and the echogenic trophoblastic tissue. Occasionally you can see cardiac activity here, it's measured with the M mode, and you can see that there's a heart rate of 105 beats per minute.

You may not see the embryo, you may only see the yolk sac, but if you see an echogenic ring-like structure with a yolk sac within it, cardiac activity or an embryo, you have a hundred percent positive predictive value that you are looking at an ectopic pregnancy.

Adnexal Tubal Ring

Now, the next most likely finding, but a little bit less specific, is the presence of an extra ovarian tubal ring. This is, again, a ring-like structure with an echogenic rim that is separate from the ovary, but you cannot see the yolk sac or the embryo within it. The ring might or might not be vascular, and it's typically located as you see in these two cases between the ovary and the uterus. However, it is contralateral to the corpus luteal cyst in approximately a third of the cases. Another common place to find the tubal ring is in the cul-de-sac. As I mentioned, this is the most dependent portion of the pelvis. This is a common place for ectopic pregnancies to fall.

So in this example here you see the lower uterine segment, the empty endometrial stripe, and here is the echogenic tubal ring with in fact a little yolk sac in the cul-de-sac.

When you are looking at the tubal ring, it is extremely important to optimize your technique in order to make every effort to determine whether or not there is a yolk sac or an embryo within the echogenic tubal adnexal structure. The reason for this is that when you see simply a tubal ring, while the specificity is high, it isn't a hundred percent. However, if you can identify the yolk sac or the embryo within the tubal ring, your positive predictive value will become a hundred percent, and you will have a hundred percent specificity for the diagnosis of ectopic pregnancy. So it is extremely important to do everything you can to optimize your technique.

Just to review the things you can try and do. You want to again, check your focal zone to make sure that it is right at the level that you're trying to interrogate, or just below you want to make sure you're using the highest possible frequency transducer, which will improve your resolution. You want to use harmonics and spatial compounding if available because those features will also increase spatial resolution. But a very important thing to try as well is to simply magnify the image.

So in this particular case of a woman who was pregnant with pelvic pain and had an empty endometrial stripe, you can see that there is an adnexal mass. It's relatively amorphous. The ovary is here, there's some hemorrhage here, a suggestion of a tubal ring and some adjacent free fluid. Certainly you're very concerned about the possibility of an ectopic pregnancy, and this would fall into that tubal ring category of high, but not a hundred percent specificity. However, when you magnify the image, you can see the echogenic tubal ring to much better advantage. In fact, you can clearly identify that there's a yolk sac within this, and this makes this examination or it changes the impression from this examination to be highly likely or suspicious for ectopic pregnancy to an impression where you can safely say diagnostic of ectopic pregnancy.

So remember, magnifying the image is a very, very important technique to help improve the specificity of your examination.

As I said, it is not uncommon for the echogenic tubal ring to be surrounded by hematoma. This is another example of a patient who was pregnant. She had already had a prior tubal ligation, so we were quite concerned that in fact she likely had an ectopic pregnancy. You can see that there is no evidence of intrauterine pregnancy within the endometrial cavity and adjacent to that right ovary, you can see this echogenic tubal ring. We couldn't see a yolk sac or embryo, but note this amorphous material surrounding it. It has a typical geographic appearance with these triangular margins or pointed margins as that hematoma interdigitate between the loops of bowel. This is a very classic appearance of hematoma surrounding the echogenic ring of the tubal pregnancy.

When you see an adnexal hematoma, as in this case, another thing that you can do that will optimize your technique and improve your visualization of the ectopic pregnancy is to use color and power doppler so that you see in this case, when you use the color doppler, the color clearly outlines that echogenic tubal ring, and it may increase the conspicuity of this finding within the adnexal hematoma.

Adnexal Hematoma

Now, the next most specific finding though, probably the most common finding is the presence of adnexal hematoma. This is due to bleeding from the ectopic pregnancy. The appearance can be very, very variable depending upon how recently the patient had the episode of bleeding, how often the patient has bled, and how much bleeding of course has occurred.

So these adnexal hematomas appear complex, amorphous, the echogenicity can be very variable. The slide on your left demonstrates a relatively hypoechoic hematoma. Again, note those pointed or triangular margins. On the right you see a very echogenic hematoma in a patient who's had a more recent episode of bleeding from the ectopic pregnancy.

These hematomas may be free within the pelvis, but also may be within the tube. When they're within the tube, they're of course confined by the limits of the tube and therefore will be tubular in configuration. So if you see a round like heterogeneous structure and you're wondering if it is a hematoma, don't forget to turn 90 degrees on it. Very often you can see that it will elongate and look tubular or sausage like in configuration, confirming that this is hematoma within the fallopian tube.

The vascularity of these hematomas can be quite variable. Sometimes you don't see much vascularity at all, but if you see vascularity with a color doppler, this of course convinces you that this is more than just bland hemorrhage. There is likely a trophoblastic tissue within the hemorrhage and can again be a useful finding to help you differentiate bland hemorrhage from a ruptured corpus luteal cyst from hemorrhage from trophoblastic tissue from an ectopic pregnancy. So color doppler is helpful. It may not always be present in an ectopic pregnancy, but when you see it, it will help you confirm the diagnosis.

Free Fluid

The next thing that you want to look for is a presence of free fluid. This is a very, very important finding, although not specific. It may be the only ultrasound finding in as many as 15% of all ectopic pregnancies. In addition to being a diagnostic finding, it also has management implications because it's a very important clue to helping to assess patient stability.

These patients come to the ER often a very early nowadays, and so often they are hemodynamically stable and the referring physicians are therefore have a lower index of suspicion that these patients may have a large amount of hemoperitoneum in their belly or that they may need surgery. Very often by identifying a large amount of hemoperitoneum, you perform a very important service to the patient because you may be the first physician to realize that the patient, while hemodynamically stable now in fact, has a large hemoperitoneum and is just one step away from being hemodynamically unstable.

So again, it is very, very important to look for this free fluid, not just to make the help you make the diagnosis of ectopic pregnancy, but to assess the patient's hemodynamic stability.

A couple of things to remember about this fluid is, number one, it is free. So when the patient walks into the ultrasound suite, the fluid is likely going to be in the cul-de-sac because that is the most dependent portion of the pelvis. But once the patient lays down on the examining table and they lift their buttocks in order to get into the stirrups of the GYN table, or sometimes they lift their buttocks because you put a few towels underneath in order to help you visualize the pelvis better, that the cul-de-sac will no longer be the most dependent portion of the pelvis, and that fluid will move down into the upper abdomen around the liver.

So it is very important to not just scan the cul-de-sac, but also to look in the upper abdomen around Morrison's pouch for free fluid. So in this case, you see fluid outlining the liver and between the liver and the kidney. Not only again does this help you identify the fluid that you might no longer see in the pelvis, but also helps you quantitate the fluid because if there's enough fluid that you can see it in the upper abdomen, it usually means there's been a fair amount of bleeding in the pelvis, and that patient may not be stable for long.

The other thing is that this fluid is hemoperitoneum. So it is echogenic, it is not bland anechoic fluid. It is important to look for clot and echoes within the fluid. Sometimes it's very easy to identify. You can see layering as you see in this slide on the left. But sometimes when you see internal echoes within the fluid, it may be difficult to determine whether or not these echoes represent true blood particles or whether or not it represents artifact.

So it's important to make sure that your gain settings are correct. If you turn the gain up too high, you can create artifactual echoes in all fluid, but if the gain settings are too low, you can lose the echoes from true particles. So what we recommend that you do is that you start by looking at the bladder, you adjust your gain just so that you start to see some artifactual echoes. Then you back off from the gain till the fluid is anechoic. At that point, you know your gain settings are correct and you don't adjust them as you examine the rest of the pelvis.

Another thing that you can try and do is to have the patient roll or to actually poke the fluid with a transducer. If those particles are real and are artifactual, they will move as you have the patient move or as you poke them with the transducer.

Another thing to remember is if there has been a lot of bleeding or if the bleeding has been very rapid, clot may occur. When you have clot in the pelvis, the echo texture is very heterogeneous and very similar to bowel. In fact it can silhouette with a bowel and can be hard to see. It sometimes can even silhouette with a uterus. So it can be hard to identify the serosal surface of the uterus.

So in this patient on the right, you can see that there's a lot of amorphous material in the cul-de-sac and it looks a lot like bowel. How can you differentiate bowel from clot? Again, clot would be a very worrisome finding. You can turn on it. If it's bowel, it ought to be tubular. You can again poke it with a transducer. If it's bowel, it ought to peristals. But again, I just demonstrate this finding to you because occasionally clot can look a lot like bowel and clotted blood implies that there's been a relative large amount of rapid bleeding, and again, is a worrisome finding in terms of the patient's hemodynamic instability.

However, there's some problems with looking with free fluid because it's a non-specific finding. First of all, there are other causes of hemoperitoneum. This is a patient who had undergone assisted reproduction. So her dates were very good. We knew she was only about three weeks pregnant. Therefore, although we could not see any evidence of an intrauterine pregnancy within the endometrial stripe at this early gestational age, that might be a completely normal finding.

But she presented because of acute pain, and you can see her ovary here, and you can see a large amount of amorphous clotted blood around the ovary in the cul-de-sac, some free fluid as well, some as some clot, and also some clot in the anterior cul-de-sac as well. When you see this much hemoperitoneum within the belly, this patient was actually hypotensive as well as having severe abdominal pain. There is no evidence of intrauterine pregnancy. You do need to say you can't exclude an ectopic pregnancy.

This patient went to the operating room at the operation, they found that all this was bland hemorrhage from a ruptured corpus luteal cyst. In fact, the patient had a very early intrauterine pregnancy that was below the level of our ability to discriminate it on endovaginal imaging. So remember that hemorrhage from a corpus luteal cyst is the most common false positive diagnosis of ectopic pregnancy. Hemoperitoneum is not a specific finding for ectopic pregnancy.

Now, it was not a mistake to send this patient to the operating room, even though we said we couldn't exclude an ectopic pregnancy because she was hemodynamically unstable and needed the operation in order to stop the bleeding. But again, it is a non-specific finding.

Accuracy of Ultrasound and Pregnancy of Unknown Location

What about our accuracy of ultrasound? I've described to you all the things that you would look for in terms of trying to make the diagnosis of ectopic pregnancy on endovaginal and transabdominal imaging. So the question is how good are we? This is a study that was published from the Brigham and Women's Hospital in the early 1990s. This is a meta-analysis of 10 other earlier studies.

When they used as a criteria or criterion for diagnosing ectopic pregnancy as the presence of any non-cystic extra ovarian adnexal mass, they found that their specificity was very high, close to 99%, but their sensitivity was only about 84%. What are the reasons for this? One of the primary reasons for this is that we examine patients too early within their gestation before we can identify either an early or an extra uterine early intra or extra uterine pregnancy.

Now, when they looked specifically at the findings that I've just reviewed with you, again, it is the presence of that extra uterine gestational sac containing the yolk sac or the embryo that has the highest positive predictive value for an ectopic pregnancy. However, if you have any adnexal mass and a large amount of free fluid in these earlier studies that constellation of findings also had a hundred percent positive predictive value.

The other features that I've described, namely the presence of an adnexal hematoma, free fluid or fluid, a small amount of fluid in a mass has, as you can see here, much lower positive predictive values for this diagnosis. But the key is that even when we put all of these features together, we're still only about 84 or 85% accurate in identifying ectopic pregnancies on endovaginal ultrasound.

Approximately 15% of the time you have a patient that's pregnant, you have a patient who is symptomatic, and the endovaginal ultrasound is negative. This happens so commonly that recently this has been given its own descriptive term, namely pregnancy of unknown location or PUL as it is abbreviated.

What this is defined as as a patient who is pregnant, who has a positive beta HCG, but no evidence of either an intrauterine or a ectopic pregnancy on endovaginal imaging, no evidence of retained products of conception on endovaginal imaging, the patient is hemodynamically stable and there's no sign of hemoperitoneum on ultrasound. In most labs, this happens commonly in a recent gynecologic consensus conference. The incidence of this occurrence was estimated in different labs at about eight to 31% of the time.

It depends basically on two factors. First of all, it depends on how early one is asked to image the patient, because if you're asked to image the patient at about three weeks gestational age, of course your sensitivity for finding either an intrauterine or extrauterine pregnancy will be much lower than it will be at a later gestational age. But it also depends on how well you do your examination. Clearly in laboratories that have less experienced sonographers, the number will be higher than in a laboratory that does a very extensive complete protocol with very experienced sonographers.

Now, when this group looked at the ultimate outcome of these pregnancies of unknown location, they determined that most of these are either failing intrauterine pregnancies or ectopic pregnancies, but as many as a third of these pregnancies of unknown location in fact turn out to be early normal intrauterine pregnancies.

So the question is how do you manage these patients? Their recommendation is that what you need to do is to correlate with serial and follow-up beta HCG levels. Again, to remind you that one of the criteria for making the diagnosis of the pregnancy of unknown location is that the patient is hemodynamically stable.

So what they recommend is that if the patient is stable and there is no intrauterine pregnancy or ectopic pregnancy identified on the endovaginal and transabdominal exam, it is safe to watch the patient and repeat the beta HCG in 48 hours. When they repeat the beta HCG, there are of course three possibilities.

If the beta HCG is increasing and increasing at the expected rate, you are probably dealing with an intrauterine pregnancy, just a normal early intrauterine pregnancy. They will watch that patient. If the beta HCG plateaus doesn't increase or drop and they don't see an intrauterine pregnancy, then you are most likely dealing with an ectopic pregnancy. If the beta HCG is dropping, you are likely dealing with either an ectopic pregnancy or a failing intrauterine pregnancy.

So in both of those scenarios, a beta HCG that is plateauing or dropping and on repeat ultrasound, there's no evidence of intrauterine pregnancy, you're likely dealing with either an ectopic pregnancy or a failed intrauterine pregnancy. In either clinical scenario, it would be safe to treat with methotrexate.

Some of the people at the Consensus Conference were concerned about treating a patient with methotrexate without identifying a pregnancy. Some people would actually recommend that laparoscopy and or DNC be performed in order to clearly identify trophoblastic tissue in order to exclude the possibility of a beta HCG secreting germ cell tumor. But there was not ultimate consensus on that.

Pitfalls in Diagnosis

Early Gestation and Visualization Issues

What are some of the pitfalls in the diagnosis of ectopic pregnancy? I've just described probably the most common, which is the problem that you have diagnosing an ectopic pregnancy at a very early gestational age. Another problem is poor visualization, and this can be due to obesity. The presence of fibroids in the uterus or retroverted uterus, myometrial contractions, artifact from bowel gas, and also inexperience of the examiner, the presence of coexistent adnexal pathology can also decrease your ability to evaluate the pelvis and identify an ectopic pregnancy.

So a patient who has a dermoid or some sort of adnexal mass, again, it's just harder to visualize any other adnexal structure. But another very common problem is the difficulty in differentiating a corpus luteal cyst from an ectopic pregnancy.

Differentiating Corpus Luteal Cyst from Ectopic Pregnancy

There are several things though, that you can use to help you make that differentiation. First of all, the corpus luteal cyst is intraovarian in location. So you ought to see a rim of ovarian tissue around the corpus luteal cyst. This has been determined or described as the claw sign, as opposed to an ectopic pregnancy, which is adjacent to the ovary. Therefore the structure should have an acute angle with the adjacent ovary.

Another thing that has been described is that in general, the wall of the corpus luteal cyst is thicker, more regular and more hypoechoic than the wall of the ectopic pregnancy, although there is certainly overlap with the ring of the ectopic pregnancy, which tends to be a little bit more echogenic, similar in echogenicity to the endometrial stripe or the ovarian stroma. But again, while those are tendencies, there is overlap between the two appearances.

The last thing that you can try and do is dynamic scanning, namely to try with your hand pushing on the anterior abdominal wall, try to separate the two structures, and if you can separate them, you know that you're dealing with an ectopic pregnancy and not a corpus luteal cyst, because the corpus luteal cyst, of course, is part of the ovary and therefore will not be separable from it.

Here are some apparent examples of the typical appearance of a corpus luteal cyst. You see a very homogeneous, thick walled structure, often very vascular and relatively hypoechoic. Sometimes it contains some hemorrhage or debris. You can see some fibrin stranding or some internal echoes within it. Here are another couple of examples showing that you sometimes can see free fluid around the corpus luteal cyst, but again, a very homogeneous thick, almost cyst like appearing hypoechoic ring-like structure. Notice it can be extremely vascular.

Although the term the ring of fire was initially described or proposed as a description of an ectopic pregnancy, in fact, it's been my experience that you can see this completely circumferential ring of blood flow that's much more common to see in a corpus luteal cyst than in an ectopic pregnancy. In my experience in an ectopic pregnancy, that color flow tends to be a little more segmental.

The other thing is that you sometimes see this stellate or starlike appearance of a crenated corpus luteal cyst. When you see the inside, again, having this pointed or triangular margins is that cyst wall seems to collapse on itself. That's, again, a very classic appearance for the corpus luteal cyst.

This is an example of the claw sign. This patient was pregnant, had an intrauterine pregnancy, but had some left-sided pain. Here you can see the left adnexa here is the ovary. There's obviously a cyst here with a lot of hemorrhage and debris within it. You note that there is a lot of vascularity within the cyst wall, not as thick as those other corpus luteal cysts. But the reason that I'm confident that this is a corpus luteal cyst and not a heterotopic ectopic pregnancy is that I can see this claw of ovarian tissue or ovarian parenchyma surrounding part of that cyst that confirms that that cyst arises from within the ovary.

If I can tell for sure that the cystic structure arises from the ovary, I am virtually certain that this is a corpus luteal cyst as intraovarian ectopic pregnancies are extraordinarily rare.

Here are two different patients demonstrating the classic difference between the corpus luteal cyst and the ectopic pregnancy. Notice that the corpus luteal cyst, while it has a vascular wall, it's relatively hypoechoic. There's ovarian tissue around it. You can see this crenated appearance with some debris within. The patient on the right that has an ectopic pregnancy, you can see that the trophoblastic tissue is extremely echogenic, much more echogenic than the corpus luteal cyst. You can see an acute angle between the ectopic pregnancy and the adjacent ovary, although there's a little hemorrhage between the two structures. There's no claw of ovarian parenchyma surrounding the ectopic pregnancy.

So again, in general, ectopic pregnancy is much more echogenic than the corpus luteal cyst, although there is overlap. The last thing you might try and do is dynamic scanning, and you push on the anterior abdominal wall and you see if you can separate the cystic structure that you see here on the left hand side of the slide from the ovary here on the right hand side. With your hand, and this is a video clip demonstrating that as we push anteriorly, you can see that the ectopic pregnancy, which is very echogenic, moves quite separately from the ovary here, which is hardly moving at all, implying that this structure is separate.

As if you look carefully on this video clip, you can see the edge of the ovary actually here. This is just some hematoma between the edge of the ectopic pregnancy and the edge of the ovary. Dynamic scanning can be extremely helpful in determining whether structures are separate from each other within the adnexa.

However, color flow imaging and the pulse doppler waveform characteristics are not helpful in differentiating the exophytic corpus luteal cyst from an ectopic pregnancy. Both will demonstrate increase in peak systolic velocity and increase in end diastolic velocity, the so-called trophoblastic flow, and both may demonstrate that ring of fire. So again, the doppler, either pulse doppler and color flow characteristics are not helpful in differentiating those two structures.

To reiterate, as many as eight to 25% of patients with ectopic pregnancies will have a normal endovaginal ultrasound initially, particularly if you evaluate them early in gestational age, these are those so-called pregnancies of unknown location that we've talked about earlier. It's important to remember that follow up imaging serial beta HCG levels may be required in order to make the diagnosis.

Unusual Locations of Ectopic Pregnancy

I want to end by talking about some unusual locations of ectopic pregnancy. Most ectopic pregnancies occur within the ampullary portion of the fallopian tube, but occasionally you'll see ectopic pregnancies in the interstitial portion of the tube, which is the portion of the tube that travels through the myometrium to the endometrial cavity, occasionally within the cervix here, occasionally within the ovary, and occasionally you may see abdominal pregnancies as well.

Of these pregnancies in unusual locations, it's the interstitial pregnancies that are the most problematic. These account for about two to 4% of all ectopic pregnancies. The reason that these are of concern is that they're associated with a much higher morbidity and mortality, probably because these pregnancies have a better blood supply from the uterus and therefore can grow larger before they rupture. The end result is that very often these patients present late in gestational age with massive hemorrhage and so significant morbidity and mortality to the mother. In addition, medical treatment, much less successful than in pregnant ectopic pregnancies in other locations.

Interstitial Pregnancy

So how do you make this diagnosis? First of all, you look for an eccentric location of the sac, and you can see that either the surrounding myometrium is completely absent on the serosal side of the ectopic pregnancy. So here you see myometrium on the right surrounding only about half of this gestational sac. The rest of it protrudes beyond the serosal surface of the uterus, or you see significant thinning of the surrounding myometrium.

People have suggested that if you measure from the serosal surface to the edge of the trophoblastic tissue, if that myometrial rim is less than five millimeters, then you probably are dealing with an interstitial pregnancy.

Here is another example where you can see that the endometrial stripe is empty, no evidence of intrauterine pregnancy. Here is the ectopic pregnancy here you can see how vascular it is, and you can see that it's surrounded about 50% by the myometrium, but again, the serosal surface of it, there's no myometrium around it at all. So again, an interstitial pregnancy, a finding that's been described in the literature is an interstitial line sign, which means that if you look between the edge of the interstitial pregnancy, you can see a little echogenic line that connects it to the endometrial stripe. This is an example from the literature.

But what I think is actually, and I should say that that little echogenic line is believed to represent the residual of the interstitial portion of the tube. But what I actually think is more helpful is actually looking for a bit of myometrium that separates the edge of the gestational sac from the endometrium. If it is you see normal myometrium between these two structures, you know for certain that that little gestational sac cannot be within the endometrial cavity. If it's surrounded in part by myometrium, it must be an interstitial pregnancy.

Here's another example where you can see the endometrial stripe. Here you can see the gestational sac. It is surrounded clearly by myometrial tissue. But note that there is about five millimeters of normal myometrium between the edge of the sac and the endometrium. This confirms that this eccentric gestational sac cannot be within the endometrial cavity, and it must be within the interstitial portion of the tube.

Sometimes color flow imaging can be helpful because it demonstrates that you can see blood vessels directly feeding the gestational sac arising from the myometrial tissue. Again, confirming that this is within the myometrium and not just adjacent to the uterus.

There is a differential diagnosis, and that would include a cornual pregnancy. Here is the eccentric gestational sac in these two cases, and you can see that the endometrial stripe clearly comes up to the edge of the gestational sac, and in fact engulfs the gestational sac. That means that while this gestational sac in both of these cases is eccentric in location, it is clearly within the endometrial cavity and therefore in both of these cases within the right cornua, and this is something that you might see in a patient with a septate or bicornuate uterus.

Occasionally fibroids or myometrial contractions can also displace the intrauterine gestational sac and make it appear eccentric and sometimes can mimic an interstitial pregnancy.

Cervical Pregnancy

Cervical pregnancies are also important to identify because they too have an increased risk of bleeding. These are an uncommon location of ectopic pregnancies. Risk factors include in vitro fertilization, prior DNC or C-section presence of an IUD asherman's syndrome or endometrial adhesions as well as fibroids. But occasionally, no predisposing factor can be described.

The problem with the cervical pregnancy is that if you think the patient is miscarrying and you do a DNC, the patient may end up with life-threatening hemorrhage. So in the past, these patients had to be treated with hysterectomy. Current options include systemic methotrexate, local injection and methotrexate or potassium chloride or occasionally DNC with careful control of local bleeding, uterine artery embolization or tamponade with balloon catheters.

So again, there are some current treatments that can be performed that potentially could preserve fertility, obviously a much better situation than having to do a hysterectomy.

These are some older cases because again, this is not that common. What you are looking for is an intracervical location of the sac. So the uterine fundus will be empty, the cervical os will be closed, and you'll see the sac embedded within a wall of the cervix. You can see the embryo, the amnion, and the trophoblastic tissue. This often causes the cervix to increase in size and it almost approximates the size of the uterine fundus with a waist at the level of the internal os. That appearance has been described as the hourglass uterus.

Here are a couple of other older cases. Again, you can see this gestational sac within the cervix, eccentric trophoblastic tissue embedded into the cervical wall. Here you see the little embryo and amnion with this very irregular gestational sac within the cervical wall.

Early on it can be very difficult to differentiate a cervical pregnancy, however, from a miscarriage. Here is a patient who came in with vaginal bleeding. You can see on the sagittal view of the uterus, the endometrial stripe is completely empty. Here is the gestational sac within the cervix. We were pretty certain, or my residents were at night that this was a cervical pregnancy because you can see it's eccentric, it's actually embedded in the posterior wall of the cervix. You can see it's quite close to the outer margin and separate from the endocervical canal, but in fact, it can be hard to differentiate this from a sac that is aborting within the endocervical canal.

One thing that might've been helpful for them to have done would've been color flow, looking to see if they could see a feeding vessel implanting into the cervical wall.

Here is a patient that came to us. We wondered if there was a cervical pregnancy. Here you can see on the sagittal view, the endometrial stripe is empty. Here you can see the endocervical canal. You can see the external os is clearly shut, and here is the gestational sac. It's clearly eccentric not within either the endometrial stripe or endocervical canal, but it's actually just above the level of the internal os. So here's the external o the internal os. This is actually in the anterior embedded in the anterior wall of the uterus just above the level of the internal os.

Here you can see it better on this sagittal image with the uterine fundus here, the endocervical canal here. Here is this gestational sac embedded into the anterior wall of the lower uterine segment. This is exactly where a c-section scar is located. This in fact is an ectopic pregnancy that has implanted in the C-section scar. This location of ectopic pregnancies is becoming increasingly common as the rate of c-sections increase.

This is important to diagnose because it is associated with an increased risk of uterine rupture and severe hemorrhage. In these patients, just like in a cervical ectopic pregnancy, DNC would be contraindicated and these patients should be treated with either local injection of potassium chloride or methotrexate or perhaps systemic methotrexate or even surgery.

Here is another example. You can see some fluid in the cul-de-sac. Here is the ectopic pregnancy that's located just above the level of the internal os. You can see the edge of this ectopic pregnancy going all the way to the serosal surface of the lower uterine segment. So again, another ectopic pregnancy implanted in a c-section scar.

Abdominal and Ovarian Pregnancies

Now, this patient initially we thought was a pregnancy of unknown location. She came in complaining of pelvic pain. We did an endovaginal ultrasound. We saw no evidence of intrauterine pregnancy, and we saw no evidence of an ectopic pregnancy at all. This patient, we told her that we weren't sure where the pregnancy was, but it could easily be an early intrauterine pregnancy. She was not sure of her dates, and we advised her that she should come back for follow up in a couple of days.

She looked at us and said, I don't really understand why you spent all that time examining my pelvis, because really I hurt up much higher up by my in the, by my left kidney. Pointed to an area that she hurt just below her rib cage. So sure enough, we looked up there and this is what we identified a hematoma right in the region of her pain in the left flank. This is a patient who had an intraabdominal pregnancy in the left flank. This looks like a pregnancy in the adnexa, just looks like an adnexal hematoma, but it was in the upper abdomen.

So again, intraabdominal ectopic pregnancy is extremely rare, but it is absolutely critical that you always examine the area of the patient's pain because that is where the pathology is likely to be.

The least common location of ectopic pregnancies is the intraovarian ectopic pregnancy. This is a patient who was pregnant, had some bleeding. You can see that there's some fluid within the endometrial canal with a little, you can see the echogenic endometrium around it. This would be consistent with a pseudogestational sac. When you looked at her ovary, you can see this echogenic tubal structure within you can actually see a yolk sac in it. It clearly is surrounded by the ovarian parenchyma.

The only way that you can differentiate this from a corpus luteal cyst is by this identification of the yolk sac. Now, I have said earlier that occasionally you can have fibrin stranding or debris that could mimic a yolk sac or an embryo. So again, hard to know for certain, but this was surgically proven to be an intraovarian ectopic pregnancy.

Heterotopic Pregnancy

The last thing one needs to talk about in terms of location of ectopic pregnancies is of course the heterotopic pregnancy. In other words, two pregnancies, one within the endometrial cavity, a normal intrauterine pregnancy, but an additional pregnancy within the adnexa. So both an intrauterine and an extrauterine pregnancy.

As I said at the outset of this lecture, this incidence is extremely low in the general population, estimated to range from one in 7,000 to one in 30,000 pregnancies. But the incidence is substantially increased in women with multiple risk factors for ectopic pregnancies. So women who've undergone in vitro fertilization, ovulation induction, PID and tubal surgery, and these risk factors are additive. So in a woman with multiple risk factors, her risk for having the intrauterine and extrauterine pregnancy may be quite high, as high as one in three per 100 pregnancies.

This is a patient who'd undergone assisted reproductive techniques, gotten pregnant. You can see here there's a little intrauterine gestational sac. You can see the embryo and the yolk sac. It's eccentric. You could even describe this as a cornual pregnancy, but if you look carefully, in fact, there is a second gestational sac here in the left interstitial region. Notice there's myometrial tissue around part of this second gestational sac, but part of it is beyond the serosal confines of the uterus. You can see a little bit of normal myometrium between the edge of the gestational sac and the edge of the ectopic pregnancy confirming that this is a heterotopic pregnancy with the ectopic being interstitial in location.

This is a patient who had an IUP. Here you can see the yolk sac had an ectopic pregnancy here in the left adnexa also with a yolk sac. Both of these gestational sacs contain little embryos and both of them demonstrated cardiac activity.

Another patient having a little gestational sac within the uterus, and actually a much larger gestational sac in the left adnexa. Here you can see the yolk sac, and here the little embryo consistent with heterotopic pregnancies.

Another case where you can clearly see an intrauterine pregnancy, the yolk sac and the embryo here is the uterus. Here is the endocervical canal, but when you look where she hurts between the right ovary and the fundus of the uterus, notice we could only see this on transabdominal imaging. You see this echogenic tubal ring. Again, another patient with a heterotopic pregnancy.

I believe one last one to show you. Here you can see an intrauterine pregnancy. That's number one. Number two is this interstitial pregnancy here. Number three is an ectopic pregnancy within the tube between the right ovary and the fundus of the uterus. One more an intrauterine pregnancy. Here you can see the yolk sac. Here you can see the corpus luteal cyst, the ovary, the fundus of the uterus. But way up high you see another tubal ring. So again, a patient with a heterotopic pregnancy.

It's been my experience that the incidence is actually probably increasing a little. Not all of these seem to be related to assisted reproductive technique, but certainly in those patients you need to be particularly careful to look for both an intrauterine and extrauterine pregnancy.

Conclusion

In conclusion, when you have a patient who is pregnant in the first trimester and presents with pain and vaginal bleeding, you do need to evaluate the patient for an ectopic pregnancy. But you should remember that about 70 to 90% of all of such symptomatic patients actually turn out to have an intrauterine pregnancy.

In terms of making the diagnosis of an ectopic pregnancy, you need to use both endovaginal imaging and transabdominal imaging. Remember to magnify the images and be particularly careful to look where the patient hurts. In terms of the ultrasound findings that will help you make the diagnosis look for the extra uterine gestational sac. You can be a hundred percent positive of your diagnosis if you see that echogenic tubal ring containing the embryo cardiac activity or yolk sac.

But you can be fairly certain of the diagnosis, even if you see just an echogenic tubal ring. The next most likely or next most specific finding will be the presence of the adnexal hematoma, which will be a much more amorphous and variable in appearance. Turn on it 90 degrees to see if you can identify the tubular configuration. Magnify it. Use color to see if you can see the yolk sac. Use color doppler to see if you can see trophoblastic flow.

Don't forget to look for free fluid both in the pelvis and in the upper abdomen. Remember, that may be the only finding of ectopic pregnancy in some patients. It's also very, very important in terms of assessing patient hemodynamic stability.

In all cases, you need to correlate your ultrasound findings with the serum beta HCG level, the date of the last menstrual period. In many cases, you may need to do a follow-up ultrasound examination or beta HCG level in order to confirm your diagnosis. Thank you very much.