Solving the Dilemmas of PUL (Pregnancy of Unknown Location) - HD

Introduction

My name is Dr. Teco. I'm from the University of Arkansas for Medical Sciences in Little Rock, Arkansas. I'm a professor of radiology, obstetrics, and gynecology, and my topic today will be solving the dilemmas of pregnancies of unknown location.

Solving the dilemmas of pregnancy of unknown location is a common day-to-day problem among radiologists who deal with emergency room patients who only come with a history of a positive pregnancy test, but no other knowledge of past history or patient findings on physical examination.

For this talk I have no disclosures to make, and this is a screenshot of a blog of women who reported problems of pregnancy of unknown location. This particular woman for sure was told that she had this diagnosis and she wasn't quite what it meant. All she was told was that she's pregnant by her blood tests, but they could not find the pregnancy either in her uterus or outside her uterus. So they decided to do a laparoscopy, hoping that it was an ectopic pregnancy and that they could remove the ectopic. But when they went in, they did not see an ectopic pregnancy, so they called it pregnancy of unknown location and they gave her methotrexate afterwards.

So as you can see in the second paragraph, this has left the patient with a lot of very equivocal findings and feelings about what happened to the pregnancy that she's supposed to have. And as you can see, this anxiety is very common among women with this problem.

So it is the hope that after we know a lot more about this entity, we can lessen the anxiety among these patients and hopefully decrease this diagnosis or maybe even in the future, completely eliminate from our diagnostic choices.

Definition of Pregnancy of Unknown Location

A pregnancy of unknown location is defined as a case where there is a positive pregnancy test, but there is no sign of a pregnancy inside or outside the uterus on a good transvaginal ultrasound in the United Kingdom where there are no sonographers that are available to do this routine. Pelvic ultrasounds, A paper that often quoted about pregnancy of unknown location is from Sili etal who claimed that in the United Kingdom, up to about 31% of women with had positive pregnancy test present where the diagnosis of pregnancy of unknown location. However, they admit that given a good sonographer who can have good technique in doing transvaginal sonography in these women, this number can be reduced easily to 10%, which gives us an advantage here in the United States where we have the luxury of having well-trained sonographers who can do our transvaginal examination from day to day in a reproducible, accurate and very high quality type of work.

Solving the Dilemma

Now, how do we solve the dilemma of a pregnancy of unknown location? In the first trimester, most patients will present with a common complaint of pelvic pain and physical finding of vaginal bleeding. The very first priority that any clinician, radiologist or emergency physician should look into is the hemodynamic stability of the patient. The second most important thing that we have to pay attention to will be determining the location of the pregnancy. Is it intrauterine or outside the uterus? Because the decision on whether it is intrauterine or an ectopic pregnancy will guide the remainder of the evaluation and management of this patient after the examination.

Possible Outcomes

There are four possible outcomes for pregnancies of unknown location. The most important, of course, is the confirmation of a normal intrauterine pregnancy. The second is the diagnosis of a failed or failing pregnancy resulting in the eventual disappearance. The third category will be those that present with ectopic pregnancies. And the fourth category, which will probably never be solved are the 2% of patients who are defined as those where the HCG levels in the blood will not decrease. There are no signs of tol disease and the location of the pregnancy cannot be identified in spite of multiple imaging sessions or workup.

So because of these four outcomes, it is important for us to determine the difference between a normal pregnancy, a failed pregnancy, or an ectopic pregnancy, and those will be the focus of this presentation.

Determining Viability Versus Non-Viability

So how do we know that a pregnancy is viable versus non-viable? I will be quoting heavily on this article that just came out of the New England Journal of Medicine last week, October 10th, 2013, and it was a consensus conference of the Society of Radiologists in ultrasound led by Dr. Peter Dubay from the Brigham Women's Hospital in Boston. And it defined the diagnostic criteria for determining what a non-viable pregnancy is early in the first trimester.

This is a table from that article that defines viable versus non-viable pregnancy. A viable pregnancy is one that can potentially result in a live born baby. A non-viable pregnancy is when it cannot possibly result in a live born baby. So ectopic pregnancies and failed intrauterine pregnancies are considered non-viable and belong to this category.

When there is intrauterine pregnancy of uncertain viability, then transvaginal sonography would show an intrauterine gestational sac with no definite embryonic pole or a heartbeat. And at this point you are not really sure that you are dealing with a definite pregnancy failure. That is why it's called intrauterine pregnancy of uncertain viability.

The next category is the pregnancy of unknown location, whereas I have stated before you have a positive urine or serum pregnancy test, but on ultrasound done transvaginally, no intrauterine or ectopic pregnancy is seen.

The diagnostic tests usually employed in these instances will be the human chorionic gonadotropin levels and we use the third or the fourth international standard. And using the standard, a positive serum pregnancy test is usually defined as one that is above the positive threshold of 5 million international units per ml. And of course our mainstay for diagnostic testing will be pelvic ultrasonography performed transvaginally.

So we have to answer this question, is there a chance of a viable pregnancy in cases where there's intrauterine pregnancy of uncertain viability? The next question will be, should the uterus be evacuated in pregnancies of unknown location? The question is changed into should treatment for the presume ectopic pregnancy be initiated? And these are two questions that will lead to eventual management of the patient.

Value of HCG Monitoring

So what is the value of HCG monitoring? In the olden days, we used the levels of data HCG in the woman's blood to determine whether or not the pregnancy is normal or abnormal. However, we have found out recently that approximately 70% of women with ectopic pregnancies will have a rise in HCG that is slower than what is minimum for a normal pregnancy, which usually is doubling in 48 hours or they will fall slower than the minimum for spontaneous miscarriage.

So the actual level of beta HGS cannot predict or tell the difference between a normal intrauterine pregnancy or an ectopic pregnancy. Also, 15% of normal pregnancies will have an abnormal doubling time, which should have occurred every 48 hours.

So as you can see, using beta HCG as your means of monitoring will be impossible to differentiate the failing intrauterine pregnancy from a healthy intrauterine pregnancy or from an ectopic pregnancy. So we do not advocate the use of a single level of HCG monitoring as the differentiating test.

Consequences of False Diagnoses

So what are the consequences if we make false positive or false negative diagnoses this early in the first trimester for a non-viable pregnancy, a false positive diagnosis would result in medical or surgical intervention that will eliminate or severely damage a viable pregnancy. On the other hand, a false negative diagnosis will delay intervention for a failed pregnancy. So obviously the false positive diagnosis has more dire consequences than a false negative diagnosis In women with pregnancy of unknown location, the false positive diagnosis can cause potential harm to a normal intrauterine pregnancy, whereas a false positive diagnosis will delay in treatment of an ectopic pregnancy.

So how do we rule out a viable pregnancy? We have several accepted criteria that we have been using in the past, but they were found not stringent enough to avoid the false positive results. And so therefore, the consensus panel that resulted in this publication that I cited a few minutes ago is hoping that this new information that has been decided at this consensus conference will lead to a standardization of practice protocols that is currently challenged because of the multispecialty nature of diagnosis and management of women in early pregnancy.

Not only are radiologists involved in this diagnosis and management, but also obstetrician gynecologists, emergency medicine physicians and family medicine physicians who all see women in the early first trimester.

Signs of Pregnancy Viability

So how do we determine the viability of a pregnancy? The first sign of a pregnancy is a gestational sac within the uterus. We usually see it at five weeks menstrual age. We rely upon signs like the intraprocedural sign, the double deral sign, or the double gestational sac sign, which could be absent in 35% of gestational sacs.

However, because the vast majority of these intrauterine fluid collections eventually end up in normal gestation, we propose that any round or oval fluid collection in the uterus of a woman with a positive pregnancy test should be assumed as a normal intrauterine gestational sac until proven otherwise.

There are two mimics to this finding. One is the pseudo gestational sac that we can see in an ectopic pregnancy, and the other is a benign residual cyst that could be mistaken for an early intrauterine gestation.

When we see a yolk sac, we usually see a circular structure at about three to five millimeter size, and we usually see this at about five and a half weeks. We usually do not see an embryo until about six weeks. And initially our standard said that five millimeters crown rum length for an embryo was the cutoff for visualizing cardiac activity. So everybody used the term five alive to mean that if you have a five millimeter embryo, you should see cardiac activity, otherwise the pregnancy is abnormal.

There have been recent studies that described embryos with five millimeters and no heartbeat resulting in a normal pregnancy which triggered the reason for the consensus conference. In addition, inter observer variation in measuring the crown rum length, given that it's just a few millimeters plus or minus is about 15%.

So therefore the new standard proposes that it is more prudent to use seven millimeters as cutoff for visualizing heart motion in an embryo instead of the previous five millimeters.

What about mean sac diameter? In the past, our criteria for visualizing an embryo was 16 to 17 millimeters mean sac diameter, which is obtained by adding the length, the width, and the height of the mean, the sac diameter dividing it by three and coming up with a mean sac diameter number. For this particular measurement, we have inter observer variability as high as 19% resulting in a range of 21 to 25 millimeters variation.

So therefore the consensus conference has recommended a more prudent cutoff criteria of 25 millimeter mean sac diameter before an embryo can be seen. And beyond that, then the suspicion for a non-viable pregnancy can be made. If you have a mean sac diameter below 25 millimeters, let's say in the range of 16 to 25 millimeters, you can say that it is suspicious for a failed pregnancy, but it's not diagnostic until 25 millimeters.

Diagnostic Findings for Pregnancy Failure

So what are the findings that are diagnostic of a pregnancy failure? You have to see a crown ramp length that is equal or greater than seven millimeters without a heartbeat. You have to see a mean sac diameter or a gestational sac equal or greater than 25 millimeters without an embryo. You should have an absence of the embryo without a heartbeat two weeks after seeing a gestational sack with or without a yolk sack or 11 days after seeing a gestational sack with a yolk sack.

The non visualization of a gestational sack with a yolk sack and an embryo with a heartbeat after six weeks after the last menstrual period is also diagnostic of pregnancy failure.

Suspicious Findings for Pregnancy Failure

What are the signs or findings that are not diagnostic but suspicious of pregnancy failure? Obviously any crown rum length of an embryo less than seven millimeters with no heartbeat is one because we can sometimes see embryos at two millimeters without a heartbeat, but we have to wait until the measurement of seven millimeters is reached before we make this sign. Diagnostic mean sac diameters of 16 to 24 millimeters with no embryo is also suspicious but not diagnostic.

And if you've see an embryo with a heartbeat seven to 13 days after gestational sac with or without a yolk sac, if you don't see an embryo then it is also suspicious for pregnancy failure. Time-wise, six weeks is presumed to be a time when an embryo should appear based on the woman's menstrual dates. So if you don't have an embryo by six weeks after the last menstrual period, that is suspicious for pregnancy failure.

Also, the amniotic membrane, which can be seen earlier than the embryo can be measured and if you don't see the amnion or if you don't see the embryo, when you see an amn adjacent to the yolk sac, then it's also a suspicious sign. Some people claim that a large yo sac meaning greater than seven millimeters, is highly suspicious for pregnancy failure and a small gestational sac, meaning if you subtract the crown rum length from the diameter of gestational sac and the result is less than five millimeters, then you have a small gestational sac.

All of these are suspicious, but again, not diagnostic for pregnancy failure. So basically we are asked to be more conservative and wait until we know for sure that we are dealing with either a viable pregnancy or a non-viable pregnancy.

Assessing Pregnancies of Unknown Location

How do we assess pregnancies of unknown location? Obviously ultrasound is our first and the most useful imaging modality. We always have to do a transvaginal ultrasound. It allows for earlier and more reliable detection and especially when the detection of a heartbeat becomes crucial. Our transvaginal probes range in frequency from five to 12 megahertz and obviously the higher megahertz gives you the better resolution.

We only do transabdominal imaging to get an overview of the pelvic anatomy just in case there are findings that are beyond the reach of the transvaginal probe. And for that purpose we use a transabdominal frequency of about two to five megahertz transducer.

We seldom do 3D ultrasound imaging, but it could be helpful in unusual pregnancies like interstitial pregnancies, but it generally is not helpful in detecting ectopic pregnancies. Doppler ultrasound has been used but is of limited value. It shows you high trophoblastic flow with high velocity and low impedance, but the absence of flow in masses that you detect does not exclude an ectopic pregnancy.

Again, doppler ultrasound cannot differentiate an ectopic pregnancy from a corpus lium cyst because they both can show ring of fire. In fact, this so-called ring of fire, which is increased flow around the mass in the pelvis, has been shown to be more common in corpus lutetium cysts than ectopic pregnancies.

The primary contribution of doppler is sometimes if a mass is not seen with conventional 2D imaging, the doppler might show the mass because it has different patterns of blood flow at ectopic sites. So some people would turn on the doppler if no mass or ectopic pregnancy is detected.

MRI is useful if ultrasound is not able to locate the pregnancy, for instance, in interstitial or cervical pregnancies where MRI may contribute to the localization of the pregnancy more accurately. Computed tomography generally has no role because of its limited resolution of soft tissue planes and of course the use of radiation in pregnant women.

Management in the Emergency Room

Now when women come to the emergency room for this problem, 15 to 26% of them have normal or negative initial ultrasound examination. So a normal pelvic examination at presentation does not exclude an ectopic pregnancy. Again, we need to assess the hemodynamic stability of the patient and in a stable patient we could repeat the ultrasound until the HCG reaches the discriminatory zone, which has now been pegged to 3000 million international units.

It used to be that if there's no gestational sac within the uterus by 2000 million international units, then we assume that we are dealing with a failed pregnancy. But now there is the new standard that says you have to wait until 3000 million international units before you could declare the a pregnancy as having failed.

If no intrauterine gestational sac is seen when a discriminatory zone has been met, then a follow up ultrasound examination and HCG level is performed 48 hours for confirmation. You can also repeat the ultrasound in three to four days because a normal gestational sac grows at a rate of one millimeter per day and we can usually see a three millimeter sac and therefore waiting three to four days should be enough to show you an intrauterine early gestational sac.

When you do follow ups, about 11 to 16% of women we'll be diagnosed with an ectopic pregnancy on the follow-up examination when the initial ultrasound is negative. Bottom line, you should never treat with methotrexate, systemic methotrexate or DNC based only on the HCG levels without doing an ultrasound follow-up examination.

Normal Intrauterine Pregnancy

So here's what a normal intrauterine pregnancy should look like. And when you refer to this diagram obtained from Moore's Human Embryology, you can see how the potential endometrial cavity and the relationship of the cavity to the early pregnancy would lead to the eccentric appearance of the gestational sac.

So for every endo vaginal ultrasound done for this diagnosis, you have to always look for this line. This line marks the endometrial cavity. It might contain some fluid sometimes in women with a small implantation hemorrhage, but the whole idea is that you should see the gestational sac in an eccentric location relative to the endometrial cavity.

Sometimes you can see what we call a double deral sign. There is the decidua that surrounds the developing pregnancy. The decidua capis is seen on this diagram from Moore's embryology. That is the decid layer immediately surrounding the fluid collection. On the other side of the potential endometrial canal is the decidua vera or parital, and the two will form two very echogenic rings, which we designate as the double deral sign.

Now at three to five weeks you might see a fluid collection, which we said is suggestive of pregnancy in the vast majority of women. The yolk sac, however, has to develop for you to confirm that it is indeed an intrauterine pregnancy.

The eccentric intraprocedural sign is only sensitive in 48 to 68% of cases and the double decidual sign may be seen at four to nine weeks, but more helpful at an earlier time because the embryo is not typically seen at this time. So these two signs are important before you can demonstrate a yolk sack or an embryo. And when you see these two signs, you can feel pretty confident that you are probably dealing with a normal intrauterine pregnancy before you see a yolk sack or an embryo.

Ectopic Pregnancies

What about ectopic pregnancies? The pseudo sac is a fluid collection inside the urine cavity seen in about 20% of women with ectopic pregnancies. It is centrally located so the endometrial stripe or the endometrial cavity leads up to the collection. It is surrounded by desa and not by the chorionic ring that typically surrounds a developing gestation. So this is all deral echogenicity you see and at the chorionic ring. So you don't have the double decidua sign.

If you try to compress the sack with your probe, it can change in shape and sometimes when they contain blood, as you see here, it might a pain, it might appear complex because of the blood products within it.

Ectopic pregnancies can occur in many places and if you say that the vast majority of ectopics are tubal in origin, you'll be right about 95 to 97% of the time. And as you can see, the most common site will be the ampullary region of the tube. But it can also occur in the ovary in the cervix, although they're rare and we of course have specific types of tubal pregnancies, the most, disastrous of which will be the interstitial or corneal pregnancy.

Another diagram barred from Dr. Philippe Gent with his permission shows you the different location of the unique or unusual pregnancies. We have the angular pregnancy, which is really an intrauterine pregnancy, but implanted right at the angle before it becomes the interstitial portion of the tube. We have different kinds of tubal pregnancies, so an interstitial is one of them then followed by the isthmic and the ampullary and the fibrile.

A very unusual pregnancy is the abdominal pregnancy that can implant anywhere in the abdomen or pelvis. So you might have a pregnancy develop under the liver under the spleen in the mesentary attached to bowel in the fundus of the uterus. And these are pregnancies that either resulted from a rupture in the tube and the fertilized egg basically escapes out of the tube to implant in other places.

Or there's also a theory where the fertilized egg instead of proceeding towards the uterus, can have reverse peristalsis and exit the tube through the fia and therefore the fertilized egg is free to roam around a peroneal cavity looking for a nurturing environment on which to grow.

So in a patient that appears to have a perfectly normal pregnant, intrauterine stripe and has no signs of intrauterine or a nal mass, both trans abdominally and endo vaginally, you could see a thin stripe. And if the pregnancy test is positive, you know that this uterus does not look like it could nurture or provide a good environment for a developing pregnancy.

So this is where you have to come into the algorithm of the pregnancy of unknown location. In this particular case, there is no free fluid in the cul-de-sac, so that does not support the possibility of a ruptured ectopic pregnancy.

The next thing you should do is to look for the ovaries or look at the ad nexa. So these are your normal images of the left ovary where the patient was symptomatic and for all intents and purposes, this left ovary appears normal. However, if you continue to evaluate the left and nexa, you'll appreciate the fact that in a place where there is no ovary, there is a developing gestational sac with a very thick rim of chorionic tissue.

And as you can see, the probe that passes from front to back that assesses the whole left. A nexa will usually find the ectopic pregnancy unrelated to the uterus or the normal left ovary that we have previously demonstrated. Again, there is no free fluid in the pelvis suggesting that this ectopic pregnancy is intact.

How about this patient that has a very thick deidra that looks like it is well prepared to provide a good environment for the development of a gestational sac? You would think that there will be a normal pregnancy that will result from this. However, this is always not a guarantee because in this patient a beautiful tubal pregnancy is seen between the uterus and the normal appearing ovary and it has the so-called ring of fire, which is increased flow around the chorionic ring.

And in fact, the embryo, if you can see on this real time, has a heart motion that you could document on M mode at a normal rate of 114 beats per minute. So the appearance of the uterus does not predict whether or not you'll have an ectopic pregnancy or a normal intrauterine gestation.

The fallopian tubes when the ectopic pregnancy settles within the cavity of the tubes could be the site of up to 98% of all ectopic pregnancies. And as I said earlier, the vast majority of tubal pregnancies will settle within the ampullary portion of the tube as the tube widens.

So on a real time clip, you will see the intact tubal pregnancy typically between the ovary and the tube, and that is where you visualize the vast majority of tubal pregnancies and when they're intact you can see a mass right next to the uterus and an intact ectopic pregnancy upon surgery.

Signs Suggestive of Ectopic Pregnancy

What about other signs that could suggest that you're dealing with ectopic pregnancy? We have the tubal ring sign, which is really the thick echogenic ring made up of cho tissue that when seen provides a 100% positive predictive value if you see a yolk sack within the fluid collection or a dead embryo, however, if it is empty, the positive predictive value falls to about 95%.

So therefore the finding of the tubal ring sign is highly suggestive, but again, not diagnostic of a tubal ectopic, without the presence of an embryo or a yolk sac.

What about masses? Extra ovarian masses could be complex, predominantly cystic or complex, predominantly solid and be 84% sensitive and 99% specific for tubal pregnancy. However, follow up is required until the status of the pregnancy or the location of the pregnancy has been confirmed because these by themselves are not accurate in predicting the ectopic pregnancy.

Sometimes the adnexal masses may be hyper coic. They could even look tubular, especially in those with hemato cell pinks. But again, the appearance of these adnexal masses are nonspecific and therefore may only be suspicious or suggestive of an ectopic pregnancy, but without the finding of a sac with an embryo or yolk sac, they are not confirmatory.

Perennial fluid when seen is highly suspicious for an ectopic pregnancy, but it doesn't always mean a ruptured ectopic because it's usually or could be seen in 37% of intact tubal pregnancies. This is why you should always look for fluid or free fluid in the upper abdomen under the liver, under the spleen, under the diaphragm, and you should especially be suspicious if it appears echogenic, which means it has blood or occasionally puss within it.

In women with pregnancies of unknown location, echogenic fluid has 56% sensitivity and 96% specificity. So again, by themselves, without the actual finding of an ectopic sac with a yolk sac or an embryo, it's not a hundred a hundred percent reliable.

When you see hemorrhagic peroneal fluid, we need to evaluate the hemodynamic stability of the patient because if they're unstable then they should proceed immediately to surgery. However, if they are stable then a follow up ultrasound should be performed until the location of the pregnancy has been determined.

So here are examples of hemorrhagic peritoneal fluid. You can see real thick are echogenic content suggesting the presence of blood within the free fluid in the abdomen.

Rare Ectopic Locations

Now there are the rare ectopic locations. The first one is what we call interstitial ectopic pregnancy. This could be misdiagnosed as normal interuterine pregnancies because they implant within the first two centimeters of the tube. They're still within the limits of the outline of the uterus, but they really are located in the proximal portion of the tube. They're partially implanted in the endometrium and they are usually discovered at an advanced gestational age.

In a patient presents with pelvic pain, they're surrounded by myometrium and the pregnancy is seen very close to the cirr. They have to be differentiated from the corneal pregnancies that are seen by cornal uterine and the angular pregnancies that I showed you earlier that are literally in the uterine cavity but very close to the IC or the inter interstitial portion of the tube.

So interstitial pregnancies comprise about 2% of all ectopic pregnancies. When you look at the coronal image of the uterus, you can see the normal endometrial canal and you can see the gestational sac that bulges beyond the fundal margin of the uterus. You can see here if you trace the myometrium surrounding this interstitial pregnancies, you can see there's less than five millimeters of myometrium because the developing pregnancy bulges around the posterior portion of the sac.

These are specimens of interstitial pregnancies that were intact at the time of surgery and as you can see, they bulge outside the fundus of the uterus because they are literally within the first two centimeters of the fallopian tube.

Another sign that we follow in interstitial pregnancy is the so-called interstitial line sign. If you follow the endometrium and follow it to its termination in the region of the urine cornea, you will see that the line points to the ectopic pregnancy. They usually rupture at less than 12 weeks, but when they do rupture, they're often fatal because they can result in massive hemorrhage.

Here is an example from my institution of an interstitial pregnancy that was difficult to diagnose an ultrasound because of complicating fibroids. However, this was clearly outside the borders of the uterus. And when you turn your collar doppler around a suspicious sac, you can see a very elaborate network of vascularity called the ring of fire.

This is the MRI in the same patient. And as you can see, the ultrasound had such difficulty finding the endometrial cavity in the lower half of the uterus because of multiple uterine myomas that deformed the uterine contour. But here is the endometrial cavity on a coronal plane and you can see that the cavity points to this gestational sac in the corneal portion of the uterus. And so this is the so-called interstitial line sign as interpreted on an MRI exam.

Angular Pregnancy

The angular pregnancy, as we already mentioned, is really an endometrial pregnancy. It is not within the tube yet, but it is at the angle of the endometrium. It is not interstitial in location. It has a thick myometrium around it, definitely more than five millimeters, but it could be easily mistaken for an interstitial pregnancy.

It implants at the lateral angle of the uterine cavity, so it is technically within the uterine cavity, but it is high risk for spontaneous abortion because of its abnormal location. It can result in uterine rupture in 23% and also has a high incidence of placenta accreta.

Here are two examples of angular pregnancies and as you can see there's a thick myometrium surrounding the pregnancy and it is literally within the extreme lateral portion of the fundal endometrial cavity.

Ovarian Ectopic Pregnancy

What about ovarian ectopic pregnancies? These are very rare, extremely rare and may only be diagnosed at surgery. Sometimes the diagnosis could be difficult At laparoscopy it's usually mistaken for a corpus lithium cyst or an ovarian malignancy. And when the pregnancy is excised, the ovarian tissue is seen to attach to the wall of the gestational sac.

So you usually will have a rim of normal ovarian tissue right next to the gestational sac. So here are two examples. This is the pregnancy, this is the ovary and it's growing right at the edge of the ovary. And you can still see follicles here, the same thing here, gestational sack ovary, and you can see the rim of the ovary going around the sack.

So you will find this gestational sac within the normal location of the ovary surrounded by ovarian tissue and attached to the uterus by the ovarian ligament.

Heterotopic Pregnancy

What about heterotopic pregnancies? Heterotopic pregnancies are pregnancies where you have a concurrent intrauterine, an extrauterine pregnancy. So in this particular example, you have an embryonic pole within the uterus and another one in the adexo, which is ectopic.

We are seeing more and more of these lately because of increasing in vitro fertilization and therefore even if you see an intrauterine pregnancy, you should always investigate the adnexa just in case you might be dealing with a heterotopic pregnancy. The presenting symptoms are the same as other ectopics.

Another case of heterotopic pregnancy, here's a yolk sac within the uterus and a yolk sac within the adnexal mass that turned out to be the ectopic pregnancy. In this particular case, there is an intrauterine pregnancy where is that is larger than the ectopic pregnancy. Because the ectopic pregnancy has died, she can see there is no blood flow around this developing sac or within the embryo, whereas the embryo within the intrauterine cavity was viable.

In this particular case, the obstetricians chose to do a laparoscopy and excise the dead, a tubal pregnancy and allowed intrauterine pregnancy to continue. So if detected early, it is possible to save the normal intrauterine pregnancy.

Cervical Ectopic Pregnancy

What about cervical ectopic pregnancies? They could be difficult to differentiate from a pregnancy that is undergoing spontaneous abortion because you can see the gestational sack in the cervix and it could be mistaken to be within the cervical canal, but you can see a yolk sack within the fluid collection and therefore that is definitely an intact gestational sack and not an incomplete abortion or an abortion in progress.

They could be subtle like in this particular transabdominal ultrasound. All you see is a very small suggestion of a fluid collection in the cervix. And when you do the endo vaginal examination, then you can see actually that there is a yolk sack in an embryo where the heartbeat was 112 beats per minute.

So an intact gestational sac implanting in the region of the cervix is a cervical pregnancy versus an incomplete abortion or an abortion in progress. And as you can see, the difference in resolution between the transabdominal images and the transvaginal images is quite significant.

Hysterectomy Scar Pregnancy

A very unusual case is the hyster ostomy hysterectomy scar pregnancy or the cesarean section pregnancy. This particular case when done transabdominally created a confusing picture because this patient has never had a prior ultrasound examination before she got pregnant. So we did not know that her uterus is severely retroflexed and that we were really looking at the fundus of the uterus over here and where we thought the pregnancy was here was not within the uterus but bulging out of the uterine scar.

So this is the sagittal view endo vaginally. You can see the intact gestational sac with blood flow around it protruding out of the caesarean section scar. This is the uterus with hemorrhage within the uterine cavity and this was initially felt to be an adnexal hematoma with an intrauterine pregnancy, but when the real time syn eclipse were obtained, you can see cardiac activity in this intact gestational sac and you can see how the gestational sac is documented to protrude from the site of the cesarean section scar.

And the hematoma within the uterine cavity is more posterior since it's in a retroflexed uterine fundus. So it could create a very confusing picture, but just bear in mind that women with prior cesarean sections can develop a hysterectomy scar pregnancy.

This patient did not have an ultrasound. She went straight to have an MRI examination. But as you can see, it's the same finding. You have an empty uterus, uterine fundus and a pregnancy that protrudes anteriorly through the cesarean section scar. This is the coronal view given the expanded, lower uterine cavity secondary to the site of implantation.

Abdominal Pregnancy

What about abdominal pregnancies? I told you earlier that these are special ectopic pregnancies because the fertilized egg finds a nurturing environment in the abdomen, upper abdomen, lower pelvis to develop normally if it has found a good supporting structure.

So at 10 weeks this patient presents with vaginal bleeding and pain. You can see there's a lot of fluid posterior to the uterus in the cul-de-sac. The uterine cavity has decidua surrounding a fluid collection that is not eccentric. So this really satisfied the criteria for an ectopic pregnancy.

And if you look outside of the uterus, you can see this mass which is superior to the uterine fundus. If you look at the real time clip here, you're gonna pre appreciate the body of the fetus and the head of the fetus lying completely outside of the uterus. And the sonographer who performed the examination placed an arrow to point out to the cardiac activity that is very faintly seen on this real time clip, but it again demonstrates the extrauterine nature of this pregnancy that was intact at the time of examination.

Even if you do see a little bit of fluid within the cul-de-sac, this is the corresponding MRI examination for confirmation. You can see the vagina, the cervix, the uterus, the uterine fundus ends here and above the uterine fundus, you will see the head of the fetus, the body of the fetus, and the surrounding mass around the developing abdominal pregnancy.

Summary

So in summary, when encountered with a problem of pregnancies of unknown location, ultrasound remains our most useful imaging modality. In the 15 to 26% of women with pregnancies of unknown location, we have to remember that the ultrasound may be negative. Initially, the discriminatory zone for the level of beta a CG were to expect a gestational sac has now been increased to 3000 from the prior, limit or level of 2000 million international units.

And finding a gestational sac is suggestive but not diagnostic of a viable pregnancy because sometimes you could mistake the pseudo sac of an ectopic for a gestational sac. So therefore follow up examination or conservative treatment has to be done to make sure that we are dealing with a viable pregnancy.

Also, the findings of tubal rings at nexel masses whether cystic or solid are suspicious. But again, not diagnostic of ectopic pregnancy together. However, the finding of an adnexal mass and echogenic fluid have a higher positive predictive, detection rate than either one of these findings alone.

And we always have to remember that only finding a yolk sac or an embryo within a fluid collection are confirmatory signs of an intrauterine pregnancy. Without these two structures, we couldn't be sure that we are dealing with a true developing pregnancy.

So in summary, the pregnancy of unknown location consist of cases where you have a positive pregnancy test and a negative ultrasound. The management should be expectant and conservative until we can tell for sure where the pregnancy location is. Some of them can resolve spontaneously, as in abortions and intervention will only be indicated when the beta HCG does not decline after meeting all of the criteria that we have talked about earlier.

So statistically, the 8% of pregnancies that are diagnosed as pregnancies of unknown location, vast majority of them will resolve spontaneously. 27% will end up being normal, 14% will resolve ectopic pregnancy and about 9% will develop into spontaneous abortions.

And finally, the new guidelines presented by the society radiologist and ultrasound consensus panel should be promulgated to all specialists of various disciplines who diagnose and manage problems in the first trimester. If we could do this, we would definitely improve patient care and reduce the risk of inadvertent harm to potentially, viable or potentially normal pregnancies.

As we have learned in medicine the mantra of premium non-natural, or first do no harm, we should always remember that our primary purpose is to not prevent the development of a viable pregnancy by being very aggressive in our management.

So with that, I hope we have decreased the incidence of pregnancies of unknown location, which can result in a lot of anxiety and false positive diagnosis in women in the first trimester gestation. Thank you.