Solving the Dilemmas of PUL (Pregnancy of Unknown Location)

Consequences of False Diagnoses

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.

Ruling Out Viable Pregnancy and Standardization

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 multi-specialty 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.

Determining 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 deral 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.

Mean Sac Diameter

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 sac with or without a yolk sac, or 11 days after seeing a gestational sac with a yolk sac.

The non-visual of a gestational sac with a yolk sac 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 don't, but we have to wait until the measurement of seven millimeters is reached before we make the sign.

Diagnostic means act diameters of 16 to 24 millimeters with no embryo is also suspicious, but not diagnostic.

And if you 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 amnion adjacent to the yolk sac, then it's also a suspicious sign.

Some people claim that a large yolk 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 the 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 failures.

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 a 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 cyst 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 if it's limited resolution of soft tissue planes and of course the use of radiation in pregnant women.