Ultrasound in the Evaluation and Management of Ectopic Pregnancy - SD

Introduction

Hello, I'm Dr. Jim Schweder. I'm an associate professor at the University of Louisville School of Medicine and the director of gynecology and the director of the fellowship in minimally invasive surgery.

Today we're gonna talk about the use of ultrasound and the evaluation and management of ectopic pregnancy.

Objectives

The objectives of this discussion are really to discuss some of the new nomenclature, which we deal with the value of various diagnostic tests including ultrasound, HCG, and progesterone.

Periodically discuss some of the risk factors associated with ectopic pregnancies, and we're gonna do this by way of patient presentations.

To actually summarize what we're gonna talk about though there are some learning points that are critical and will be covered throughout this lecture.

Key Learning Points

The first is that ultrasound's an appropriate test even if the HCG is below the threshold value.

And the reason for this is that if the endometrial thickness is less than or equal to eight millimeters, it's associated with an abnormal pregnancy in 97% of cases.

Secondly, 50% of ruptured ectopic pregnancies have an HCG less than 1000.

The next point is that any complex mass separate from the ovary has a 92% likelihood of being an ectopic pregnancy.

This will be valuable in our initial evaluation of patients.

Finally, careful selection is necessary for the use of methotrexate.

The reason is that patients who have HCG levels above 5,000 have an increased risk of failure with methotrexate.

Those whose HCG levels are above 10,000 have a higher risk of failure as well as rupture.

And their increasing numbers of intrauterine pregnancies have been treated with methotrexate.

My caution is that careful observation is appropriate even with suspected ectopic pregnancies with lower HCG levels.

Nomenclature

Let's get into nomenclature.

In the past we typically looked at ectopic pregnancies with three diagnoses.

Either it was an intrauterine pregnancy and ectopic pregnancy or it was inconclusive.

More recently, a consensus group discussed the issue and changed nomenclature so that there are five ways to discuss and categorize ectopic pregnancies or pregnancy in general.

And we're gonna go through each one of these.

The first is that the presence of a gestational sac with a yolk sac, with or without an embryo and the embryo either or having cardiac activity or not, is definite for a gestation definite for pregnancy.

Where it's located denotes whether it's gonna be a definite ectopic pregnancy.

In other words, the sac yolk sac and or embryo are in the adnexa or not in the uterus.

Or if it's just a gestational sac or sac like structure in the adnexal area or a mass in the adnexal area, then it would be a probable ectopic pregnancy.

Conversely, if the sac is present within the uterus or there's an embryo with or without cardiac activity inside the uterus, this is a definite intrauterine pregnancy.

However, any intrauterine sac like structure could potentially be an intrauterine pregnancy.

So that's listed as a probable intrauterine pregnancy.

If none of these criteria are met, then we consider this a pregnancy of unknown location.

It means we just can't determine is this an extrauterine or an intrauterine pregnancy.

Case Presentations

Case 1: 28-Year-Old Patient

Let's start with the first case.

This 28-year-old gravida one para zero presents with pelvic pain and scant vaginal spotting.

Her last menstrual period is four to five weeks ago.

She has a positive urine pregnancy test at home.

Her exam is essentially normal and her HCG level is 874.

Now there are many options in how to manage this patient ranging from serial HCG levels to an ultrasound.

At this time, likely this patient would not be a candidate for surgery with no further evaluation, but it's elected to follow the patient with serial HCG levels.

Now to do that, one has to have some established concept of what happens with HCG levels.

Early studies by Nick Qar indicated that the sampling interval should be about two days and during that time period you would expect the HCG to go up 66%.

But a key thing in that study that has not been really focused or emphasized enough is that the doubling time he determined was 2.98 days.

But what I found very interesting with this study is that 15% of normal pregnancies had abnormally rising HCG levels.

Again, 15% of normal pregnancies can have an abnormal rise in the HCG level.

Now Kurt Barnhart's group looked at this more recently and what he determined is if you sample in two days that on the average it should rise about 2.24 times.

But note there's a range from 1.5 to 3.3 times.

So even in the more recent study, we can see that at two days, a normal pregnancy may not have a doubling of the HCG level.

Now you may hear a discussion about a term called HCG ratio and this arises from work from Europe.

And in essence what they did is they looked at the HCG levels 48 hours apart and made a ratio out of them.

And similar to what we found in the studies reported in the United States is if the ratio is above two or if it doubles in that 48 hours, that predicts a good outcome.

If the ratio's less than 1.2 or it only rises 1.2 times or less, that's a predictor of a lack of viability.

So let's continue with our case presentation.

Day one, the HCG was 874.

On day three it's 1056, so it did not double normally.

Now to confirm this abnormal rise, they obtained another HCG level, which is 1100.

Again, not normal.

So now they decide to do an ultrasound and the importance is when you do an ultrasound, what should you expect to see?

And there's two concepts we need to discuss the threshold level and the discriminatory level.

The threshold level is that lowest HCG level at which a normal intrauterine pregnancy can be detected.

In other words, when you first think you can see the pregnancy on ultrasound as opposed to a discriminatory level, which says above this level of HCG, all normal intrauterine pregnancies should be seen.

Which means if you don't see it at that level, then we are dealing with an abnormal pregnancy.

Now in the past, these levels were much, much higher than they are today.

David Berg looked at this in the late eighties and determined it the discriminatory zone or that level above what you should see, all intrauterine pregnancies was 1800.

Today, with advanced equipment and newer technology and change in preparations for management and diagnosis of the HCG levels, these levels are actually much lower.

And we see the threshold level is probably in the four to 500 range by the first international reference preparation.

And the discriminatory level is probably in the 1000 to 1500 range depending on the lab.

Then there are other things that affect our ability to see the pregnancy adequately.

What frequency of transducer are we're using, what's the uterine position, particularly a mid axial or midplane uterus is much more difficult to see.

Is the patient obese or not?

The other fibroids that are present and then clearly operator experience and ability play into our ability to evaluate these pregnancies.

So this is the ultrasound of this patient and what we see is that the endometrium is 3.3 millimeters thick.

What's the significance of this?

We're gonna address that after looking at her adnexa.

We see here that the ovary on the right side is normal.

On the left side we see a complex lacy particular mass in this area here that is associated with a corpus luteum.

There are no adnexal masses seen.

So in essence in this particular ultrasound, we see no evidence of an intrauterine pregnancy, a corpus luteum on the left, normal right ovary, and no adnexal pathology.

In the past I would've called this a probable diagnosis of ectopic pregnancy or a presumptive diagnosis of an ectopic pregnancy.

Today the proper terminology is pregnancy of unknown location and then management depends on several issues.

Some people advocate doing a DNC beforehand to look for chorionic villi and if found, it would be indicative of an abnormal intrauterine pregnancy.

Some people have advocated in this situation with serial HCG levels and a normal ultrasound that you can proceed with treatment.

And in this particular instance, they elected to treat the patient with methotrexate at an appropriate dose.

Case 2: 24-Year-Old Patient

The second patient is a 24-year-old gravida two para 0010 who presents with scant vaginal spotting and pain, her last period was five weeks ago and she has a normal examination.

Now her initial HCG was 710.

Repeat two days later is 980. It's abnormal.

Now as we've noted, this may or may not be at the threshold level of many laboratories and the question is what should we see if the endometrial stripe or more properly the endometrial thickness in ectopic pregnancies?

Why would we wanna do an ultrasound if the HCG is below the discriminatory zone?

And this is answered I believe by Kurt Barnhart's study in the mid nineties where they looked at different types of pregnancies and what's the mean thickness of the endometrium, something I never used to look at before.

And what they found was if the endometrial thickness was eight millimeters or less, that was associated with an abnormal pregnancy 97% of the time.

Now the pregnancy could be an abnormal pregnancy inside the uterus or an ectopic pregnancy, but an abnormal pregnancy.

So when I look at a thin endometrium, one less than eight millimeters, I think of abnormal pregnancy and my index of suspicion for an ectopic rises.

Conversely, if one looks at the endometrium and it's thicker, we see here the average for an intrauterine pregnancy was 13.4 millimeters.

Then I think more on the lines of this being possibly an intrauterine pregnancy.

So in this patient, an ultrasound is done in the endometrium is 7.4 millimeters.

This is in that range of less than eight millimeters, less than or equal eight millimeters.

So this is associated with an abnormal pregnancy 97% of the time we see a scant amount of fluid in the cul-de-sac in this region here.

And we look in the adnexa here, we see the right ovary, which appears normal.

We see the left ovary that has the probable corpus luteum.

And when we look at this more carefully, we see that there's a mass immediately adjacent to the left ovary.

Now this mass measures about 2.3 centimeters in size.

There's no obvious pregnancy here.

This is just a solid mass or a complex mass next to the ovary.

And we certainly see central flow with doppler, which would indicate to us that this is a solid mass and certainly has vascular flow.

This patient subsequently became more symptomatic and proceeded to laparoscopy shortly after this ultrasound.

And what we see is the scant amount of fluid in the cul-de-sac, the blood that we see in the posterior cul-de-sac.

And here we see here ectopic pregnancy on the left side, which is unruptured technically at the current time.

So this depicts exactly what we're seeing on ultrasound with the laparoscopic appearance.

Case 3: 30-Year-Old Patient

Now this 30-year-old gravida one para zero presents with scant vaginal spotting, her last period was about five weeks ago.

Again, she has a normal examination.

Her initial evaluation showed an HCG of 3,100 and the clinician decided to obtain a second HCG that was 4,235 with an abnormal rise.

This prompted ultrasound evaluation at this time, which reveals the following.

We have to first consider what should we expect to see.

This patient was about five to six weeks out from her last menstrual period, but says by vaginal ultrasound we should probably even see cardiac activity.

Her HCG certainly is above the 2000 level that's quoted in this reports that we see.

And so we would expect to see fetus, perhaps cardiac activity and with an HCG of this nature certainly expect to see those.

Let's see what we find when we look at this endometrium.

This is actually measuring two sides of the endometrium, which measures 9.5 millimeters.

It appears to me personally that there may even be a small yolk sac present, which would be highly indicative of an intrauterine pregnancy, but one cannot definitively state this without further investigation.

We see in the cul-de-sac that there's a small amount of fluid present.

When we look in the, at the left ovary, we see a left ovary which appears normal with a corpus luteum.

Here we see the left ovary, we see the uterus.

But note in between the uterus and the ovary is a mass effect, is a mass effect.

And in fact, when investigated further, we see there is some flow in this mass.

And then when we see this mass as 2.3 by 2.9 centimeters, note the presence of two gestational sacs.

This actually represents a twin ectopic pregnancy.

There was no evidence of an intrauterine pregnancy on dilatation and curettage.

This patient ultimately had methotrexate therapy for the twin ectopic pregnancy.

Case 4: 28-Year-Old Patient with Pelvic Pain

The next patient is a 28-year-old who presents with pelvic pain and spotting with the last menstrual period seven weeks ago.

Her uterus is top normal size and she has mild adnexal discomfort.

Her HCG is 4,634.

Now when we look with ultrasound, we see that the endometrium is 11 millimeters thick.

And here we can see what appears to be a sac like structure and yolk sac within the endometrial cavity.

Again, this would be highly indicative of an intrauterine pregnancy.

I even measured this anticipating this was going to be a yolk sac.

We have to be cautious.

Sac like structures have been mislabeled misread on an exhaustive basis.

And there's two studies. There's one by Rory Philly, the other by Peter Dubay and Carol Benson.

They caution us that the things we've described intrauterine pregnancies or ectopic pregnancies with, we need to be careful because we can certainly see what appears to be gestational sac like structures with ectopic pregnancies.

Here we know to scan out of fluid in the cul-de-sac, but as we scan into the left adnexal region and what we see is a mass that measures about 5.8 by 3.1 centimeters, if we put power doppler on, we see there's no central flow indicative that this is not a solid mass and this is highly suspicious for perhaps a clot in the cul-de-sac.

When we look in the right adnexa, we could clearly see the right ovary and we saw this mass next to the right ovary measuring 3.8 by 2.7 centimeters.

It's a somewhat solid mass in appearance.

And the question is how likely is this to be an ectopic pregnancy?

Peter Dubois's group at Harvard looked at this and what they did is reviewed 10 studies with over 2000 patients of which one fourth of them had ectopic pregnancies.

And what they decided was that their inclusion criteria for ectopic pregnancy was a clinical suspicion.

All those patients underwent ultrasound and all the cases were confirmed by surgery.

And no adnexal masses were excluded except simple cysts.

And these were the criteria they used for an ectopic pregnancy.

All four of these were gonna go over individually, so I'm not gonna address them on this slide, but what we see is if you see an extrauterine embryo with a heartbeat, that's a hundred percent likelihood of an ectopic.

Any adnexal mass with a yolk sac or an embryo without a heartbeat is a hundred percent.

The way I look at this is if you see a yolk sac or an embryo with or without a heartbeat, that is a hundred percent.

If you see a tubal ring, which sometimes people call the bagel sign, and I'll demonstrate that shortly, that's got a 95% likelihood of an ectopic.

And if you see any complex or solid adnexal mass separate from the ovary, that's not a simple cyst that has about a 92% likelihood of an ectopic pregnancy.

So as we look at this, what we see is as we see an adnexal mass, this is the uterus.

Here's the adnexal mass.

And we have to look very carefully here where we're gonna see a small little flicker right above the marker.

And when you look there, what you see is this small little flicker cardiac activity.

This is an ectopic pregnancy definitively because we have cardiac activity that's 100%.

In this instance we see an embryo, but there's no cardiac activity denoted on doppler study, but that is a 100% ectopic pregnancy.

Now here we see an adnexal mass with the yolk sac.

That is a hundred percent.

Here's one that's even clearer, that's adnexal mass.

We see the uterus here. We see the yolk sac here.

That's 100% definitive for a diagnosis of an ectopic pregnancy.

Conversely, the tubal ring, or as you can see now, the bagel sign has about a 95% association with an ectopic pregnancy.

And here we have another demonstration of this hyperechoic ring of tissue with a sonolucent center considered a tubal ring, 95% association.

We can see the ovary separate from this.

And ultimately when we see any complex mass separate from the ovary, it's got a 92% association with ectopic pregnancy.

That's what we're dealing with in this case.

So when we look at this, ultimately we say this person has an ectopic pregnancy, so let's look and see what we found.

But laparoscopy, we can see blood in the anterior cul-de-sac as we look in the posterior cul-de-sac.

This is actually where the clot was that we were visualizing.

Here's the patient's right ovary and here's ectopic pregnancy.

Now, what precautions did we take with this surgery?

Because of the concern about a possible intrauterine pregnancy, we were concerned that this may be a heterotopic pregnancy.

We elected not to use any intrauterine manipulators.

We removed this tube and ultimately the patient's HCG levels resolved and went to zero.

So that was apparently not an early intrauterine pregnancy despite our suspicion.

Strategies for Evaluating Ectopic Pregnancies

Now Kurt Barnhart looked at several different strategies on how to evaluate ectopic pregnancies and they said, let's look at six strategies.

One is to just do an ultrasound.

We have a positive pregnancy test, do an ultrasound first, and if it's not definitive, let's get quantitative HCGs till they reach a threshold or discriminatory zone and make our decision.

The second option was to get a qualitative HCG first and if a level of threshold or discriminatory zone met, look with ultrasound.

They also discuss the use of progesterone followed by either ultrasound or HCG in the two different steps that we saw before, serial ultrasounds or just clinical exam.

Progesterone Levels

Now I'll summarize the status in the following way.

Progesterone levels, although some people still use them, have less value.

And I think the reason for that is, when you look at the numbers and you look at the different diagnostic regimens, there's a great deal of overlap with the various diagnosis we deal with.

As an example, a serum progesterone less than five is abnormal.

We looked at the threshold level for being indicative of an intrauterine pregnancy is 15 and above.

25 was terrific. That was great.

That should be a normal pregnancy in 97% of patients.

The problem with it is when you look less than five, 11% of patients with a normal intrauterine pregnancy had a progesterone less than five above 25, 0.1% of the patients had an ectopic pregnancy.

And at the threshold level of 15 nanograms per milliliter, 18% of patients had an ectopic pregnancy.

So it's not particularly specific.

The other difficulty is it usually takes longer to get back.

In my particular lab, it's 24 hours, whereas I can have a quantitative HCG in two hours.

So I don't use progesterone in my diagnostic regimen.

Now Dr. Barnhart looked at all these different regimens and said, what are the outcomes?

And what they found is if you did the ultrasound first followed by HCG or HCG followed by ultrasound, they didn't miss any ectopic pregnancies, but they did interrupt in this theoretical cohort, which they expanded to 10,000 patients, you did interrupt some intrauterine pregnancies.

Ultimately what they decided was that when you look at the overall merit of this and you look at the number of blood draws, the total charge per patient, the days to diagnosis, they found that the two regimens involving ultrasound followed by HCG or HCG followed by ultrasound were essentially equivalent.

They did not recommend using the progesterone protocols because they missed more ectopic pregnancies.

They indicated the ultrasound, serial ultrasound may be helpful with poorly compliant patients.

However, I question those patients still need to come back for their ultrasounds.

So poor compliance may not be the best indicator and certainly clinical exam only was not recommended.

Case: 41-Year-Old Patient

So let's put this in action.

This 41-year-old presents to the emergency department with a period three weeks ago, complaints of bleeding and abdominal pain.

She's had unprotected intercourse for 10 years.

Now this patient ultimately had a urine pregnancy test that was positive and unprotected intercourse for 10 years in itself is a risk factor for ectopic pregnancy because infertility is a risk factor likely secondary to underlying tubal disease.

This patient had a positive urine pregnancy test.

We placed an ultrasound and saw the bagel sign, which has a 95% association with an ectopic pregnancy.

We measured it and it was approximately 2.6 by 2.3 centimeters in size.

And then we awaited her HCG level to determine further management which returned at 78 or rather low level.

This actually gives us a number of options in management.

We don't have a definitive diagnosis of ectopic pregnancy yet.

Yes, we have a 95% suspicion of it, but I would suggest it would be better to get at serial levels before we intervene with either methotrexate or surgery.

The question is, is it safe to observe these patients?

And in fact, this was answered in a study out of Helsinki, Finland where they looked at 118 patients with an ectopic pregnancy and looked at the rate of spontaneous resolution without treatment.

Now the entry criteria, and this is critical is that they had a stable or decreasing HCG level.

There was no signs of an intraperitoneal hemorrhage.

The mass itself was less than four centimeters in size and no cardiac activity was present.

And their protocol involved doing ultrasound every one to three days, serial HCG levels until they were less than 10 IUs per liter.

And then laparoscopy if the patient had increasing HCG levels, abdominal pain or signs of intraperitoneal hemorrhage.

Now this is slide. I would actually like to emphasize two points and that is if you looked at the patients who resolved spontaneously, the initial HCG was about half that of the patients with laparoscopy.

So the lower HCG levels had a higher rate of resolution.

In fact, if the HCG was less than 200, there was an 88% rate of spontaneous resolution.

And I was surprised to see that even with an HCG over 2000, the rate of spontaneous resolution was 25%.

So in our patient, certainly cautious observation would be appropriate 'cause we could expect that more likely than not she's gonna resolve some spontaneously.

Now a key thing with this is to know what direction is the HCG going.

If you recall, the entry criteria were stable or decreasing HCG levels.

So a level of 2000, if you're following the yellow line and it's dropping, those will resolve spontaneously.

If it's the green line and they continue to rise, then obviously this is not gonna be a spontaneous resolution.

Now if the initial HCG is 200, fairly good likelihood that this could resolve spontaneously.

Case: Patient with Spotting and Abdominal Discomfort

Now this next patient is seen in the emergency department complaining of spotting and mild abdominal discomfort.

Her uterus is top normal size with no definitive adnexal masses.

Her HCG was 357.

Her crit was stable at 36.4 and was elected to discharge the patient home to follow up in two days in what's called the woman's care clinic.

Now on her return visit that morning, she got an HCG level and was to be seen in the afternoon and when she arrived she was complaining of increasing pain and weakness prior to her HCG level returning, we elected to ultrasound the patient and we found this, we found blood in the abdominal cavity.

She had a hemoperitoneum, her quantitative HCG returned at 465.

This is below most people's threshold level and certainly below a discriminatory zone.

So if we were just following HCG levels and wait for them to get above a threshold level before we did an ultrasound, we'd not even performed an ultrasound on this patient and she went to surgery and immediately was found to have this and hemoperitoneum with an HCG of 465.

I found this quite surprising until I reviewed this study by Saxon and what they showed is that when you look at HCG levels in tubal rupture, 50% of the patients with a ruptured ectopic pregnancy had an HCG below 1000.

So when we look at the methods of following and evaluating patients based on Dr. Barnhart study in this study, I would surmise that an ultrasound would be very appropriate early on to make sure the patient isn't ruptured and then we can follow HCG levels appropriately.

Case: 27-Year-Old Patient with Diarrhea and Chills

Now ultimately this 27-year-old comes to the emergency department complaining of diarrhea and chills since the morning she thinks she even ate bad shrimp the prior evening and has diffuse abdominal cramping.

I think most of us would think this is probably a gastrointestinal process except for the fact she reported a positive home pregnancy test two weeks prior to presenting to the ED.

Now her history is significant in the fact that five years ago she had gonorrhea which was successfully treated.

She'd had a prior laparoscopic appendectomy which rules out appendicitis as an etiology for pain and discomfort and ultimately they decided to examine her, found that she had a diffusely tender abdomen with no rebound or guarding.

Her pelvic exam was essentially normal with only a retroverted uterus, no cervical motion tenderness and really no masses or fullness noted.

Her HCG level returned 17,507, which prompted an ultrasound.

And the ultrasound revealed the following, a retroverted uterus.

The endometrial thickness was less than five millimeters.

Remember endometrial thickness less than or equal to eight millimeters associated with an abnormal pregnancy 97% of the time the right ovary was normal, but next to the right ovary was a complex mass measuring about 2.3 by 2.2 by 2.7 centimeters.

The left ovary was normal and there's a small amount of fluid in the cul-de-sac.

This was read out as an ectopic pregnancy.

Now how would you treat this patient?

Should we treat her with surgery?

Should we treat her with methotrexate?

I don't think I would observe this patient as we talked about before, this particular person was seen by a clinician who said, this is a definite ectopic pregnancy was clinically stable and elected to treat the patient with methotrexate.

We have to look at the value of treating this pregnancy with methotrexate.

This study by Jobspra, and I would caution you not to read every one of these, but to get a sense that there were a number of parameters that they looked at as risk factors for tubal rupture.

And what they determined was the overall rate of rupture in their population was 18%, but the rate was 2.9 times normal if the HCG was above 10,000.

So in this patient, she has a significantly increased risk of tubal rupture because her HCG is over 17,000.

In addition, studies have shown us that when it's above 15,000, the rate of failure may be quite high.

This initial study by Potter said 32%.

A subsequent study said anything over 10,000 had about an 18% chance of failure.

So we have a risk of rupture, a risk of failure.

I think this patient was better managed by surgery rather than methotrexate.

Let's see what happened.

The patient unfortunately didn't present for a HCG until day seven.

One of the key things with methotrexate therapies is the patient compliance is critical to successful treatment.

Someone who is non-compliant is not a good candidate for methotrexate.

The methotrexate therapy on day seven, she returns and her HCG is 9,000.

That's an adequate decrease and actually quite good.

She came back on day 11, it's now 3,630, but then she presents to the emergency department on day 16 with 10 out of 10 right lower quadrant pain, which begins in her right flank and radiates to the suprapubic region.

Her hematocrit is 35.3 and her HCG is now 1,286.

An ultrasound is repeated that basically says that there's a disorganized mass adjacent to the right ovary.

No size was given but the report states that it likely had not changed greatly and there's a small amount of fluid which is complex in nature seen within the pelvis.

The assessment by the same clinician who saw her earlier was that she had an appropriate decrease in her HCG.

They interpreted that the pain the patient was experiencing was consistent with methotrexate and a degenerating ectopic and gave her Vicodin and told to follow up in clinic.

Let's see what happens. She didn't keep her clinic appointment again, a non-compliant patient.

She had to be sent a registered letter to come in on day 23, she came in for an HCG on day 25, which was 948.

And ultimately she came in 32 days over one month from her first injection of methotrexate, is finally seen clinically as an outpatient.

And at this time she has a painful right adnexal mass.

An ultrasound is performed and what it reveals is about a five centimeter adnexal mass on the right adnexa.

It was elected to take the patient to surgery.

At this point in time, we found a small amount of blood in the cul-de-sac, some brownish lesions which can be consistent with endometriosis.

Another potential risk factor for ectopic pregnancy.

And here is her dilated fallopian tube with her normal ovary.

Another picture of this dilated fallopian tube.

And I'd submit to you that this is not gonna be a normal functioning tube.

Now with an HCG above 17,000, if this patient had surgery initially this would've been resolved.

The patient would've been essentially cured after her first day of surgery and we would've avoided the multiple emergency department visits, the multiple HCG levels and the lack of followup that we saw.

So good patient selection for methotrexate is critical.

Case: 21-Year-Old at Six Weeks

Now this 21-year-old is at six weeks, three days.

By her last menstrual period, she had a home pregnancy test three days ago she was on progestin, oral contraceptives, progestin, oral contraceptives, progestin, IUDs, et cetera.

Anything using progesterone as a contraceptive agent actually has a greater risk of ectopic pregnancy.

She had a negative past GYN history and her quantitative HCG is 25,340.

What we do an ultrasound and what we see is a yolk sac with an intrauterine gestation.

This is a definite IUP, but we're not done yet because we have to thoroughly evaluate the pelvis because as we start to evaluate her further, what we see is the intrauterine pregnancy in this area.

But immediately adjacent to that is another hyperechoic ring with a sonolucent center consistent with a pregnancy.

This patient has a heterotopic pregnancy.

Now the incidence of heterotopic pregnancy probably approximates about one in 30,000, but with assisted reproductive technology, it may go as high as one in 100.

So in today's world, with greater use of reproductive endocrine and ART, we have to be more cautious about the finding of a heterotopic pregnancy.

Now this patient undergoes surgical treatment.

These are not candidates for methotrexate because you wanna preserve the intrauterine pregnancy.

They're not candidates for salpingostomy or linear salpingostomy because you can't follow the HCG levels adequate.

So these patients who are actually candidates for salpingectomy as definitive treatment.

So this patient underwent salpingectomy and ultimately carried to term this 28-year-old presents with pelvic pain and vaginal spotting in her last period was seven weeks ago with a positive HCG.

And we look at this and I wanna give credit to Dr. William Brown at Denver Health in Denver, Colorado.

One of my colleagues there for these images, the endometrial thickness is 4.5 millimeters.

Again below that eight millimeters that I look for, we look transversely.

There's no evidence of an intrauterine pregnancy.

But as we look out in the adnexa, what we see is near the uterus.

We see this hyperechoic with the lucent center.

This is consistent with either a cornual or interstitial pregnancy.

And this is a place for 3D.

Evaluation is critical if you're dealing with a pregnancy that you can't determine if it's a cornual or interstitial pregnancy or just a marginal implantation or or an eccentrically located pregnancy.

3D is invaluable.

So you take a 3D sweep and with multiplanar reconstruction, what we can see here is that clearly this is not an intrauterine pregnancy, that this is a cornual pregnancy.

Now the criteria for an interstitial pregnancy or what some people call a cornual pregnancy is that there's an empty gestational sac.

That the chorionic sac is greater than one centimeter from the lateral edge of the endometrium and that there's a thin myometrial layer surrounding the chorionic sac.

This patient ultimately goes to surgery.

We see this here in our 3D multiplanar reconstruction.

Again, we take her to surgery and this is exactly what we see.

We see the bulging from the left cornual region with a distal normal fallopian tube and ovary.

These patients are treated with a salpingectomy and then a cornual resection removing this area.

And this is the ultimate result based on laparoscopy.

So appropriate preoperative diagnosis allows preparation for appropriate operative management in a minimally invasive surgical manner.

Case: 23-Year-Old with Spotting and Cramping

Let's put all of this together with a more difficult case that we can work through.

This 23-year-old gravida two para one enters with slight spotting and cramping.

She has no idea when her last menstrual period is, but has a positive urine pregnancy test.

Her HCG is 2,392 and we elect to get an ultrasound.

Now her ultrasound initially reveals an endometrium, which is 17.84 millimeters.

That's thicker. Again, remember thicker, more commonly associated with an intrauterine pregnancy.

But her HCG is 2,392. We look transversely.

We see no evidence of an intrauterine pregnancy.

We look at the adnexa.

Here's her right ovary, which has a small corpus luteum present.

We look at her left ovary. It looks normal.

We do see a small amount of fluid in the cul-de-sac.

It's anechoic fluid.

And we see a right paratubal cyst, which is serous.

So this patient has no definable intrauterine pregnancy.

She has a true pregnancy of unknown location.

However, due to the increased endometrial thickness, I have an index of suspicion that this could be an intrauterine pregnancy.

Now interesting. Peter Dule and Carol Benson out of Harvard recently reported on the concept that if we don't see a pregnancy initially, what happens with that?

And they did a retrospective review of every case that they had where they did not see the intrauterine gestational sac or pregnancy to start with.

But ultimately the patient was proven to have an intrauterine pregnancy and they had ultrasounds and HCG levels on the same day.

And what they found were this data below the threshold level of a thousand.

About 80% of the time they did not see a intrauterine pregnancy.

But interestingly above 1500, which is at many centers discriminatory level, almost 11% of those patients had an intrauterine pregnancy, but they did not see an intrauterine gestational sac.

So the cautious physician, the caution we would recommend is if a patient's hemodynamically stable and the diagnosis is not definitive, defer treatment and follow the patient carefully.

So this is on December 30th.

A bad time to have this is over New Year's Eve weekend, but on December 30th, our endometrium is 17.84 millimeters.

We get serial HCG levels and what we see is 48 hours later, it's now 7721, it is doubled appropriately and we elect to repeat our ultrasound.

And what we now see is the hyperechoic ring with a lucent center consistent with an early intrauterine pregnancy.

So why are her HCG levels so high?

Here we see in the transverse view the eccentrically implanted normal intrauterine gestational sac.

Here's our explanation where we see not one but two gestational sacs.

This is a twin intrauterine pregnancy, which now explains why her HCG level was higher and we didn't see a definitive IUP initially.

Now we follow this patient and what we see is three days later now we see a definitive intrauterine pregnancy and we see the smaller gestational sac now is starting to wither away.

This would be consistent with an early vanishing twin syndrome.

The clinician elected to get another HCG, which is now 16,000.

I would submit once you make the diagnosis of an intrauterine pregnancy, that you can follow them with ultrasound.

And we see a change from the fourth to the 18th, where now we see early pregnancy, seven weeks, three days, cardiac activity at 140 beats per minute.

Summary

So let's summarize this discussion.

Ultrasound is justified prior to obtaining your quantitative HCG.

Why? Because 50% of ruptured ectopics have an HCG less than a thousand, which is below the discriminatory zone in virtually every lab.

If you're HCG is below the discriminatory level and you get an ultrasound, the endometrial thickness is critical.

If it's less than or equal to eight millimeters, it's associated with an abnormal pregnancy 97% of the time.

If you find an intrauterine pregnancy, it essentially rules out an ectopic pregnancy except with the caution of a heterotopic pregnancy.

And as we see more use of assisted reproductive technology, we have to be careful 'cause it could be as high as one in a hundred.

If you find an embryo with or without a heartbeat or a yolk sac in the adnexa, that's a hundred percent diagnostic of an ectopic pregnancy.

But if one finds just a complex or solid mass separate from the ovary, very high index of suspicion because it's got a 92% likelihood of being an ectopic pregnancy.

And I tend to summarize my management of these patients this way, if the initial HCG is less than 375, perfectly appropriate to observe these patients.

And I would say unless you have serial HCG levels documenting abnormal rises or you have definitive diagnosis on ultrasound, I would avoid treatment with methotrexate or if the patient's hemodynamically unstable, go to surgery.

So when we use methotrexate, you have to have a hemodynamically stable patient who is well versed, well-informed, and compliant and follow up.

The pregnancy should be under 3.5 centimeters in diameter and I recommend an HCG less than 5,000, although recommendations can be as high as 10,000 one has to put it in clinical perspective.

Certainly patients who've had multiple surgical procedures may have levels slightly above this and you may wanna avoid surgical intervention.

Note that in Dr. Stovall original study, they did not exclude cardiac activity.

I think many people today, however, feel cardiac activity is a relative or strong contraindication to methotrexate.

I reserve surgery primarily for the unstable patient, the poorly compliant patient high HCG levels because of their increased risk of rupture and failure.

And if the patient's had a history of tubal damage, particularly prior tubal ligation or ectopic on the same tube, I would recommend surgical treatment because even if they're successfully treated with methotrexate, you know you still have a tube that's patent on a side and may cause problems in the future.

I'd like to thank you very much.

I welcome you to come to Louisville, Kentucky at any point in time and join us in the Kentucky Derby.

Thank you very much.