Chapter 4. First Trimester.

Pregnancy of Unknown Location/Ectopic

and Trophoblastic Disease

Women’s Point of Care Ultrasound

Welcome to the Chapter on Pregnancy of Unknown Location (also called PUL) and Ectopic pregnancy. This is one of the most critical conditions for a woman’s health provider to either detect or rule out, since the early detection of an ectopic has the potential to save a woman’s life. Also included in this chapter is a section describing trophoblastic disease or molar pregnancy, which can also cause significant morbidity.

Objectives

By the completion of this Section the participant will be able to:

Describe the clinical significance of early detection of a PUL or confirmed ectopic

Describe typical locations of ectopic pregnancy

Scan through a uterus to identify a gestational sac

Recognize a “ring of fire” on an ultrasound, and discriminate between a “ring of fire” associated with a corpus luteum cyst versus an ectopic pregnancy

Recognize the clinical signs and sonographic findings associated with trophoblastic disease (molar pregnancy)

Clinical significance of PUL and ectopic¹

Ectopic pregnancy (EP) is any pregnancy that implants outside of the normal uterine location. A PUL (pregnancy of unknown location) is a pregnancy not located in the endometrium, but not yet detectable in another location in the pelvis.

Incidence: approximately 2% of all pregnancies²

Ectopic pregnancy is a medical emergency and is the leading cause of maternal death, second to hemorrhage. Complications of EP account for 3- 6% of all maternity-related deaths in the United States³.

EP also significantly impacts future fertility in women; 50% fail to achieve pregnancy again.

Accurate diagnosis is crucial because:

1. Failure to diagnose could lead to rupture and possible maternal death.

2. Incorrect diagnosis (where there is NOT an ectopic) can lead to inappropriate evacuation of a desired pregnancy.

NOTE: Pregnancy of unknown location (PUL) is not a diagnosis but is treated as a suspicious finding, while waiting to confirm the precise location of the pregnancy (IUP or ectopic).

Risk Factors for Ectopic Pregnancy⁴

This table identifies the various risk factors for ectopic pregnancy

--Previous Ectopic Pregnancy –the highest risk of all is a history of having 2 or more prior ectopics

--Prior tubal surgery

--History of infertility

--History of pelvic inflammatory disease

--Endometriosis

--Smoking (risk increases with the number of cigarettes smoked per day)

--Maternal age – increases after age 35

--Prior pelvic/abdominal surgery

--Prior termination of pregnancy

--Previous early pregnancy loss

--Assisted conception – IVF or Clomid

--Conception with IUD in place has been implicated in the past as a risk factor, but Schultheis, et al,⁵ reported findings from the CHOICE project* (including 9,256 women) that those who used LNG-IUD, copper IUD, DMPA, implant, and OCs, contraceptive patch, or vaginal ring had a significantly lower risk of ectopic pregnancy compared with women using no contraception or barrier method of contraception.

*The Choice project was a study where women were offered free contraception of their choice and were followed for 2-3 years.

However, keep in mind that almost 50% of women with an EP do NOT have any risk factors.²

Table 1. Ectopic risk factors.²

Clinical signs:

Positive pregnancy test, and/or pregnancy symptoms

Pain (unilateral pelvic, abdominal)
Bleeding

Adnexal mass on bimanual pelvic exam

Other possible symptoms:

--hypotension (due to blood loss)

--shoulder pain (due to hemoperitoneum – blood or fluid accumulation in the peritoneum impinging on the diaphragm)

Table 2. Classic ectopic imaging findings.

Lab findings:

Slower than expected rise in serial B-hCG levels, or plateauing levels

Differential diagnosis⁶

Table 3. Differential diagnosis for first trimester pregnancy and BhCG levels, including diagnostic clues for ectopic pregnancy.

Some “tips” to consider when trying to determine if a pregnancy may be ectopic are: ⁷

Do not use a single threshold or discriminatory level for TVUS IUP detectability.

Serial BhCG levels in PUL may be helpful to distinguish normal versus abnormal pregnancy. The ‘discriminatory cutoff ‘ for BhCG levels predicting an EP can be as early as 800 to1000 mIU/ml (according to some sources), especially if a woman has pelvic pain. But since a gestational sac may not be visible until BhCG is from 1500 to 2000 in the uterus; if it is not seen in the uterus, it is unlikely to be seen in the adnexa either. So a cutoff of 1000 may not be appropriate. At this level it would simply be a PUL rather than a confirmed ectopic. These levels vary due to the sophistication and resolution of the ultrasound machines being used.

NOTE: Even above 3000 mIU/ml and no sign of IUP, there is still a chance for viable IUP.

2. Normal IUPs have mean doubling time of 1.4 to 2.1 days.

3. An EP with visible yolk sac, embryo, or cardiac activity typically has higher levels of bHCG. Higher BhCG levels increase risk of nonresponse to medical therapy, requiring multiple treatments.

In general, observing BhCG level plays a limited role, underscoring the need for accurate ultrasound evaluation.

Rule outs:

--Retention of products of conception post miscarriage

-- Trophoblastic disease. BhCG levels in an early molar pregnancy, greater than 100,000 mIU/ml, occur in 50% of patients (levels can be lower with partial molar pregnancy)

--Intrauterine ‘ectopic’ (in the uterus but not in the endometrium)

Detection of EP/PUL:

Due to the urgency of early detection of EP, relying on risk factors (history) and clinical symptoms is insufficient. Although these provide suspicion, PELVIC ULTRASOUND is the most reliable diagnostic tool for confirming an intrauterine pregnancy (IUP) versus an EP/PUL . ACOG states that transvaginal ultrasound is the MINIMUM diagnostic evaluation step in confirming location of a pregnancy.²

Sensitivity of transvaginal ultrasound for diagnosing EP ranges from 73% to 93%, depending on gestational age and experience of sonographer.

It is considered to be within the scope of a POCUS to be able to use ultrasound to assess for this complication⁸ . Even if a POCUS provider is uncertain about locating the extrauterine pregnancy, he/she can at the very least confirm absence of an IUP, necessitating direct referral or further imaging.

Clinical importance

Detecting a PUL compels the provider to investigate with serial B-hCGs and repeat ultrasound until the location is found. If these measures are not available to the provider, then the woman should immediately be referred to a higher level of imaging and or care. For providers performing POCUS who also have credentials for managing ectopic pregnancy, outside referral may not be needed. Any time there is uncertainty about the location of the pregnancy, it is imperative to have a second opinion or more advanced assessment, since missing an ectopic pregnancy can be a life-and-death situation for the mother.

PUL versus Ectopic

Once the pregnancy has been identified, and is NOT in the uterus or endometrium, it can be termed “Ectopic”

The appropriate terms used to describe findings of early pregnancy of unknown location are:

Definite Extrauterine Pregnancy (EP) – this means that a pregnancy is confirmed songraphically to be outside the uterus or endometrial cavity

Probable EP – this means that the pregnancy is most likely to be outside the uterus or endometrial cavity. In other words, there is no evidence that the gestation is in the uterus, but presence outside the uterus has not yet been confirmed.

PUL: no signs of either EP or IUP – this means that it is perhaps too early to establish where the pregnancy is implanted

Probable IUP – this means that there are signs of an intrauterine implantation, such as a small gestational sac, but no real confirmation of a YS or embryo.

Definite IUP – this means that there is either a yolk sac or embryo seen within the uterus/endometrial cavity

The differences between these definitions seem subtle, but using these categories can help with clinical decision-making, such as next level imaging or immediate referral.

Ectopic pregnancy locations¹

Figure 1. Illustration of ectopic locations

.

This is a diagram of where ectopic pregnancies are commonly seen, and the incidence for each location.

Interstitial pregnancy is located in the fallopian tube at the junction of the uterus and fallopian tube. This can often be mistaken for a cornual pregnancy, described later in this chapter.

An isthmic pregnancy is located in the isthmus of the fallopian tube.

The most common place for an ectopic to implant is in the ampulla, or mid-section of the tube, with about 80% of ectopics landing there.

A fimbrial pregnancy occurs in about 5% of ectopics.

The rarer ectopic locations are ovarian, cervical and even abdominal pregnancy.

C/Section scar pregnancy will be discussed in more detail later in this chapter. The incidence of prior C/Section is variable in different regions – some as high as 30-40% of births. This creates increased potential for scar defects where pregnancies might implant.

Figure 2. Primary clues for EP or PUL suspicion

.

For establishing that a pregnancy has an unknown location, first note if a BhCG level was done. If the BhG level is where a YS or fetal pole should be seen in the uterus, but is NOT seen, it raises suspicion that the pregnancy might be elsewhere.

If you see a YS in the uterus or endometrial cavity, this virtually excludes the presence of an ectopic pregnancy. There is always a possibility for a heterotopic pregnancy (one gestation inside and one outside the uterus). Although this is rare, it validates the need to survey the entire pelvis, even when an IUP is seen in the uterus.

ULTRASOUND FINDINGS WITH EP/PUL

The first structure to visualize is the endometrium. In pregnancy it should be thickened, and if there is no GS noted, there may be a small amount of fluid in the endometrium without a decidual sign (pseudosac*). A definitive finding is seeing no evidence of a gestational sac or decidual sign at 6 weeks’ gestation by certain LMP in the endometrium.

The cervical canal may either appear normal or have slight amount of hypoechoic texture inside the os. It may appear closed.

In the posterior culdesac (Pouch of Douglas) there is typically fluid which may appear hypoechoic or have mixed echogenicity in the presence of blood.

Below is a table quantifying the descriptions commonly used for noting fluid in the culdesac.

Table 4. How to describe the amount of free fluid in the pelvis.⁹

The adnexa must be scanned completely to identify any complex mass with mixed echogenicty (sometimes cystic), having color flow encircling it (“Ring of Fire”). The mass needs to be seen as separate from the ovary.

ACOG states that seen a mass separate from the ovary has a predictive value for ectopic of 80%, which means 20% of the time there may be other adnexal structures labeled as an ectopic and misdiagnosed.² These structures could be: paratubal cyst, corpus luteum cyst, hydrosalpinx, endometrioma, or bowel. For this reason, a POCUS exam that suspects EP MUST be confirmed by a higher level of assessment such as imaging/sonography.

NOTE: A pseudosac used to be considered a reliable indicator of an ectopic gestation. However,

For confirming that a pregnancy is ectopic, the following ultrasound findings must be identified OUTSIDE of the endometrial cavity:

--Double decidual sign (usually within the mass)

-- GS with YS, or fetal pole (usually within the mass)

*A pseudo sac is a small collection of fluid within the endometrium which used to be considered an indicator of an ectopic. This is no longer considered a requisite finding for an ectopic. However, if you see a small hypoechoic area in the endometrium that has no decidual sign, this could represent what has been called a “pseudogestational sac”. Recent literature review indicates that most of the time this actually represents a very early pregnancy. The telltale sign can be if there is circulation detected within it; if not, then it is a pseudosac.

Phillips et all conducted a study to determine whether a small, empty gestational sac (without yolk sac or embryo) predicted a pregnancy of unknown location or ectopic.¹⁰ This study concluded that in a woman with positive BhCG and no adnexal mass, the finding of an intrauterine sac-like structure is virtually certain to be a gestational sac rather than a pseudosac. So the presence of a small “sac” in the uterus is more likely to be an early IUP, according to this study.

It is thought that when the term “pseudogestational sac” was coined, the imaging capability of the machines was more limited.

Gestational sac or pseudosac?

The image below is of a VERY early gestation. The sac is tiny, and it may represent either a GS or a pseudo sac. It is more likely to be a gestational sac since we see some evidence of a small decidual (hyperechoic) ring around it. However, if the pregnancy has otherwise been confirmed to be at 5-6 weeks menstrual age, a pregnancy of that size may be elsewhere. The other thing to note in this image is that there is a small amount of fluid in the cul-de-sac. This is always a tip to be looking for a cause, such as a ruptured cyst or ectopic pregnancy.

Image 1. Sagittal view of a uterus showing a very small hypoechoic circle in the upper endometrium, and free fluid in the culdesac.

Classic ectopic imaging findings

What does an extrauterine EP look like? ⁶

Figure 3. Images 2,3,4. Descriptions of how an ectopic would appear on ultrasound.

The most common appearance of an ectopic gestation is that its shape is less well-defined than an intrauterine gestation. It is a non-simple cystic adnexal mass separate from the ovary. It could be described as an irregular structure, or inhomogeneous adnexal mass. Because of its thickened walls, it can appear like a ‘bagel’ or ‘donut’; the EP walls are thicker than a normal intrauterine chorion, and thicker than the walls of a CL cyst.

Another classic sign of an ectopic is a circular ring of vascularity around the EP, known as the “ring of fire”. The drawback to this is that a ring of fire is also a hallmark feature of an ovarian corpus luteum cyst.

This is what a “ring of fire” looks like. Remember that a “ring of fire” indicates increased vascularity that encircles an active structure requiring additional circulation to grow. This image happens to be a corpus luteum (CL) cyst on an ovary since this is in a non-pregnant woman. However, if there was a confirmed pregnancy, with an empty endometrium, you should be suspicious if you saw this in the adnexa as separate from the ovary itself. This is how you would identify whether this is a “ring of fire” with an ectopic. You would likely also see other signs like free fluid in the cul-de-sac.

Image 5. Corpus luteum cyst with “ring of fire” seen with color flow

Ring of fire – ectopic

This image demonstrates an ectopic in a woman who has a positive pregnancy test and no evidence of an intrauterine gestation.

Image 6. Ectopic pregnancy with “ring of fire”

CL vs Ectopic ^1,11

To review, comparing an ectopic with normal corpus luteum cyst, the ectopic is:

1. Separate from the ovary – if the ovary is probed, the ectopic will not move with it

2. Thicker-walled and more echogenic (brighter) than the CL

3. Shape often has a “donut” or “bagel” appearance

4. More likely to have a heterogeneous texture, while the CL is more likely to have an anechoic texture

Images 7,8. Comparison between CL with “ring of fire” and ectopic with “ring of fire”.

NOTE: Identification of the CL can sometimes be helpful in locating the ectopic, since it is most likely implanted on the same side of the pelvis as the CL.

Rule outs

Because EP has such a high degree of inherent risk, the inclination is to assume that all suspicious pregnancies must be ectopoic, and fail to explore other conditions with similar presentations. The following represent some of the conditions to rule out when assessing for EP:

--Retention of products of conception post-ab

-- Trophoblastic disease. BhCG levels greater than 100,000 mIU/ml occur in 50% of patients with an early molar pregnancy (levels can be lower with partial molar pregnancy)

--Intrauterine ‘ectopic’ (in the uterus but not in the endometrium) – typically an intramural pregnancy (located in the uterine musculature)

Extrauterine ectopic

Image 9. is of a confirmed ectopic outside the uterus altogether. Using color doppler, definite blood flow to the embryo is noted. The uterus is identified toward the right of the image, and the right adnexa is identified in the far left of the image. The fetal pole and yolk sac are located in a space between the uterus and the right ovary.

Image 9. Ectopic pregnancy seen between the uterus and the left ovary. A fetal pole is identified in the GS.

Images 10-13 (below) demonstrate the progression of a suspected ectopic, to images that confirm the ectopic.

Images 10-13. Progression of suspected ectopic to confirmed ectopic.

Image 14. Confirmed extrauterine ectopic with fetal pole and color flow in the right adnexa between the uterus and right ovary.

Pitfalls in ultrasound diagnosis of EP ⁶

There are pitfalls in identifying an ectopic pregnancy.

Table 5. Pitfalls in ultrasound diagnosis of EP⁶

Structures that could mimic an ectopic pregnancy include a corpus luteum cyst, or other adnexal cysts. Color or spectral doppler can show vascularity with any of these – so it can be difficult to determine with just the use of color flow imaging.

For differentiating between an ectopic and a corpus luteum cyst, a transvaginal probe can be used to gently push the ovary to demonstrate sliding. A corpus luteum will move along with the ovary, since it is located on it. The echogenicity of the CL is also quite similar to the ovary itself, and one can see ovarian tissue surrounding the CL in most cases.

An ectopic, however, is in the adnexa separate from the ovary, and would not slide with the ovary (positive sliding sign) when probed. Probing of an ectopic typically elicits a marked pain response so scanning the region should be performed as gently as possible. Also, the tubal ring in a tubal ectopic is more echogenic than the stroma of an ovary.

As previously described, simple ovarian cysts do not have sonographic characteristics of an ectopic. Their walls are thin and smooth, and internally there are few or no echoes.

NON-tubal Ectopic pregnancies ⁶

Ectopic pregnancies NOT in the fallopian tubes include:

Cornual

C-section scar

Cervix

Intramural

Ovary

Table 6. Non-tubal ectopic pregnancies and descriptions.

Cornual

A pregnancy is sometimes located in a uterine cornual region. The cornual region describes the area in the upper corners of the uterus at the junction of the fallopian tube.

Some consider a true cornual pregnancy to only be found in a bicornuate or unicornate uterus, with the pregnancy located in one of the horns.¹² But many still use the term “cornual” to describe the general location, even in a normal uterus. The term is also used to describe the region of the tube adjacent to the uterus.

Sonographic criteria for cornual pregnancy are 1) empty uterine cavity, 2) GS located eccentrically (1 cm from lateral wall of the uterine cavity, with a thin myometrial layer (<5mm surrounding the GS). This measurement is the determining factor for labeling an ectopic as cornual – the amount of myometrium between the GS and the outer margin of the uterus.

Regardless of the precise definition, this implantation is abnormal, requiring an advanced sonographer to discriminate. A POCUS provider would simply identify a pregnancy in the upper/outer region of the junction of tube and uterus as abnormal and seek additional imaging.

In the image below (Image 15), a transabdominal ultrasound was used due to the size of the uterus (about 16 wks size). A pregnancy was located in the left upper uterus, bulging outward. Suspecting a cornual pregnancy, the myometrium was measured from the outer sac to the outer uterine margin and found to be 7 mm (greater than the 5 mm for diagnosing a true cornual pregnancy).

Image 15. Pregnancy at 7w 2d located in the upper left “cornual” area of the uterus, displaced by large uterine fibroid. Fetal pole was seen, but not in this view. Cornual pregnancy suspected.

Images 16,17 demonstrate the fetus in that GS, and how the distance was measured from GS to outer myometrial edge.

Images 16,17. Same pregnancy as in image 13, at 8w4d. Distance from the GS to the outer serosal edge of the uterus measured at 7 mm.

At first glance, Image 18 might appear to be a cornual pregnancy. This image shows a gestational sac with a tiny embryo in a transverse view of the uterus. Although it might appear that the gestation is off to the patient’s left side of the uterus, it is still within the endometrium – so it is NOT a cornual pregnancy.

Image 18. Transverse view of uterus with early GS. Not in cornua since it is within the endometrium.

Cervical, Lower Uterine Segment and Cesarean Scar pregnancy

Signs:

These may be mistaken for an abortion in progress.

Color doppler may reveal flow in ectopic implantation.

Cardiac activity confirms EP

Rounded shape causing bulging of uterus/cervix suggests ectopic

C-Section Scar (nonpreg uterus)

Globally, C/Section scar pregnancy rates have doubled since the year 2000, caused by an increase in the C/Section rates in some regions.¹³ Some have considered it to be an ectopic pregnancy, since it is not located in the usual endometrial space. However, It is now considered to be a type of ectopic and is known as a Cesarean Scar Pregnancy.

We discussed in the GYN course the importance of looking for a C-Section scar defect when scanning a non pregnant woman to determine whether a C/S scar with significant defect could potentially cause a problem. If a simple notch is seen, it is not as likely to be a problem if the pregnancy does implant low and anteriorly near the scar.

Figure 4. Illustration of C/Section scar pregnancy locations.

Non-pregnant C/S scar

In this image the endometrium appears to “bow upward” toward the anterior surface of the uterus. This could be a potentially dangerous place for a pregnancy to implant when this woman does achieve a pregnancy.

We also know that even if the pregnancy does not plant inside the scar, there is a much greater likelihood of the pregnancy advancing forward into the myometrium and perhaps beyond, potentially leading to placenta accreta syndrome (PAS), which includes placenta accreta, increta, and percreta.

This is described in more detail in the Second/Third Trimester Course describing the placenta.

Image 19 identifies the appearance of a C-Section scar notch seen in a nonpregnant woman.

Image 19. Non-pregnant uterus with C/Section scar notch indicated by arrow.

The images below compare a sagitall view of a uterus without a C-Section scar (left) and one with a small C-section scar “notch”. Note the shadow cast from this thickened area.,

Images 20,21. Comparison of C/Section scar notch on the right to uterus without a C/Section scar on the left.

The next image is one of a nonpregnant woman, but demonstrates an unusual configuration. The uterus is slight retroflexed, making the notch appear more prominent.

Image 22. Nonpregnant uterus slightly retroflexed, showing a C/Section scar notch. Note the thinning of the myometrium at the notch.

C-Section scar pregnancy

The image below shows an early gestation in the upper endometrium, appropriately located, and below it a well-defined C-Section scar defect. Fortunately this pregnancy is not at risk for ectopic implantation.

Image 23. Early IUP in uterus with a C/Section scar defect (area of defect is colorized with pale red)

The image below (Image 24) demonstrates what an early C-Section scar pregnancy looks like. As previously stated, this pregnancy has the potential to advance outward toward the anterior surface of the uterus, causing a possible rupture, or a placental invasion of the anterior myometrium (placenta accreta). This finding would necessitate a referral to an advanced provider for follow up or management.¹⁴

Image 24. Early GS located in the C/Section scar notch.

The image below (Image 25) is a C-Section scar pregnancy, despite appearing to be on the “back side” of the uterus. Keep in mind that this uterus is retroflexed/retroverted, so in essence, it is tilted backwards. This makes the anterior part of the uterus toward the back and the posterior part in front.

Image 25. GS with YS and fetal pole in C/Section scar defect. Note that the uterus is retroflexed, which makes the area at the arrow the ANTERIOR surface of the uterus rather than the posterior (since the uterus is bent backwards).

Cervical Ectopic

A cervical ectopic is very rare, but it presents a potential for massive hemorrhage if it ruptures. Treatment with methotrexate (to halt growth of the gestation) or aspiration are the recommended treatments. If hemorrhage cannot be stopped, emergency hysterectomy becomes necessary, associated with a high mortality rate. The sign of a cervical pregnancy is a heterogeneous mass in the cervical canal with a Ring of Fire. If the mass is probed with the transvaginal probe, there is a negative sliding sign; in other words, the mass does not slide or compress with pressure.

Image 26. Cervical pregnancy at 6 wks. This could also represent a C/Section scar ectopic.

Intramural Pregnancy

Intramural pregnancies are uncommon, but are thought to be due to tracts formed from the endometrium leading into the myometrium. The hallmark feature for this is that the GS lies OUTSIDE the endometrium.

The image below (Image 27) lies in the myometrium in the general cornual area of the uterus. But when to rule out a cornual pregnancy, the thickness of the myometrium lateral to the GS was greater than 5mm.

Image 27. Transverse view of a uterus demonstrating a GS in the outer left corner of the uterus in the cornual region. It is intramural since it is embedded in the myometrium. The distance to the outer uterine wall exceeded the criteria to label it a cornual ectopic.

Image 28 is another unusual finding of a pregnancy outside the endometrium.

Image 28. Intramural vs cornual ectopic. Uterus is viewed in sagittal plane and pregnancy appears to be at the outer edge of the fundus.

Ovarian Pregnancy

Tips:

An ovarian pregnancy is RARE and can easily appear like a corpus luteum or ovarian cyst. However, with an ovarian pregnancy, the sac rim is thicker and more echogenic.

And the VERY RARE abdominal pregnancy may occur anywhere on a peritoneal or visceral organ

TREATMENT

Treatment for ectopic pregnancy is covered only generally in this course. Some providers have the credentials to medically or surgically treat ectopic pregnancy. However, these options may be beyond the scope of other POCUS providers. There are a number of decision trees that delineate courses of action for the suspected ectopic pregnancy. Figures__ and __ outline the most basic steps for management.

The first algorithm (Diagram 1) differentiates potential ectopic pregnancy from women presenting with pelvic pain.

Diagram 1. Initial management algorithm for pelvic pain in ruling out ectopic.

The next algorithm (Diagram 2) is for differentiating treatment options based on POCUS ultrasound findings.

Diagram 2. Algorithm for EP/PUL management based on POCUS findings.

The options are to treat with methotrexate if the B-hCG is less than 5,000. (Hendricks)

The most important information is the list of indications for urgent surgical referral. These include:^2,14

1. Hemodynamic instability

2. Peritoneal signs

3. Ultrasound showing ectopic pregnancy with fetal cardiac activity

4. Ultrasound showing substantial fluid in the culdesac (significant or extensive)

Heterotopic

Heterotopic pregnancy is what we call a pregnancy where there is an intrauterine pregnancy AND an ectopic simultaneously. It used to be quite rare (1 in 4,000 to 1 in 30,000)² The incidence has increased in populations where artificial reproductive technology (ART) is used for infertile couples, now estimated to be up to 1 in 100.² So if you are seeing a woman who has had this performed, it is critical to observe the adnexa carefully, even if you see a definite intrauterine pregnancy.⁶

^{Figure 5. Heterotopic Pregnancy facts}

Heterotopic (image)

Image 29 presents an example of a true heterotopic – one gestation is in the uterus (appropriately) and the other is in the cervix (the ectopic).

Image 30 (below) presents an concurrent IUP and cervical pregnancy.Management of this pregnancy will be difficult to spare the intrauterine pregnancy, so expedited referral for advanced care is imperative.

Image 29. Heterotopic with IUP and left adnexal EP

Image 30. Heterotopic with IUP and Cervical or C/Section scar pregnancy.

Trophopoblastic disease: Hydatidiform mole

The next few paragraphs discuss trophoblastic disease, which is also referred to as a hydatidiform mole or “molar pregnancy”. This occurs when there is an abnormal combination of genetic material that forms within the uterus as a result of pregnancy implantation. The occurrence is about 1in 3000, although it is more common in Asian women (about 1 in 250). The cause is unknown, but one theory is that an early embryo succumbs, while the chorionic villi continue to proliferate as the maternal circulation continues. Another theory of causation is that duplicated chromosomes within the sperm (or fertilization of one egg by 2 sperm) causes genetic aberration of the ovum. This leads to a buildup of abnormal placental tissue and fluid, causing the cystic appearance seen on ultrasound.¹

As this placental tissue develops there is an accelerated production of BhCG levels above what is expected for the gestational age by LMP. This accelerated increase in BhCG levels often causes women to have hyperemesis.

Most often it is complete, in that there is only abnormal placental tissue, without embryonic tissue.

In some cases, a partial molar gestation is seen. In this situation, an embryo forms along with the molar tissue. The embryo is typically a product of a triploidy genetic abnormality and will not likely be viable.

Figure 6. Trophoblastic disease characteristics

A major concern about molar pregnancy is its ability to become an invasive mole which grows through the decidua and into the myometrium, becoming a malignancy known as choriocarcinoma. This is not always diagnosed until after the uterine contents are evacuated. If left untreated, it can cause hemorrhage. It can also metastasize to the lung, vagina, pelvis, brain, and liver. Because of this, women with a molar pregnancy must be referred for treatment and surveillance for this condition, even after the pregnancy is evacuated.

A reassuring note for counseling women is that the trophoblastic (molar) pregnancy is not likely to recur.¹

The images below (images 31,32) show 2 features of a trophoblastic or molar gestation. The image on the left is an example of what trophoblastic tissue would look like in early pregnancy. It appears cystic, and without borders. Enlarged ovarian theca lutein cysts are sometimes seen with a molar pregnancy. The image on the left demonstrates these.

Images 31,32. Sonographic appearance of trophoblastic disease: left image cystic endometrium, right image enlarged ovarian theca lutein cysts.

Trophoblastic disease

The sonographic appearance is fairly easy to see. In the absence of the usual landmarks there is amorphous, cystic like material in the uterus. The B-hCG levels will seem abnormally high, and the woman may have higher levels of pregnancy symptoms such as nausea and vomiting.

In review:

--The tissue in the endometrium will have poorly delineated borders,

--Molar tissue may have increased vascularity, with possible invasion of this tissue into the myometrium

--If a molar pregnancy is suspected, referral is indicated for confirmation. Thyroid testing should also be done. The reason for this is that high levels of B-hCG can mimic thyroid stimulating hormone (TSH) and subsequent hyperthyroidism. Excessive levels of B-hCG can cause thyroid toxicity and thyroid storm.

--Treatment is evacuation of the uterus as quickly as possible to avoid the potential for malignancy

Partial molar pregnancy

Image 33. demonstrates abnormal trophoblastic tissue in addition to a fetal pole. This is what is known as a partial molar pregnancy. It is typically the result of a triploidy conception, and the embryo/fetus is rarely viable. There are rare cases where the embryo is normal, but this presents a dilemma in following the pregnancy’s likely trophoblastic invasion. A Maternal-Fetal-Medicine or high risk pregnancy specialist should be consulted where available for management.

Image 33. Partial molar gestation with fetal pole and trophoblastic tissue.

SUMMARY

The following provide clues to search for Ectopic Pregnancy:

• Clinical history

• Clinical findings

• Ultrasound findings

The following are complications of early first trimester pregnancy:

• Pregnancy of Unknown Location

• Ectopic – known extra-endometrial location

• Trophoblastic Disease (molar pregnancy)

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Women's Point-of-Care Ultrasound: First Trimester

First TrimesteChapter 4. Pregnancy of Unknown Location/Ectopic and Trophoblastic Disease