Ultrasound of the Month: No Definitive Yolk Sac, No Definitive IUP!

THE CASE

A female in her early 20s, G4P2012, presents to the emergency department (ED) with a 5 day history of left lower quadrant abdominal pain which has been worsening since onset. She states her pain is similar to pain that she felt during a prior ectopic pregnancy. She reports that her previous ectopic pregnancy was treated medically. She has taken a home pregnancy test which was positive, and her last menstrual period was over one month ago. She denies any fevers, nausea, or vomiting. She denies dysuria, hematuria, vaginal bleeding, discharge, or leakage of fluids. 

On exam, she is in no acute distress and her vital signs are within normal limits. Cardiopulmonary exam is unremarkable, and her abdomen is soft and nondistended. She has tenderness to palpation of the left lower quadrant without rebound, guarding, or peritoneal signs. Pelvic exam reveals left adnexal tenderness without cervical motion tenderness, vaginal discharge, or bleeding. 

Laboratory evaluation reveals a hemoglobin and hematocrit of 12.6/37.1 and a beta-hCG (b-hCG) of 2400 IU/L. A bedside ultrasound is completed to assess the location of the pregnancy. Two representative clips of that study are included below.

As seen in the clips below, no definitive intrauterine pregnancy (IUP) is identified. A small amount of simple free fluid is seen in the posterior cul-de-sac.  In the fundus of the uterus, one can see heterogenous material within the endometrial cavity in a sac but no definite yolk sac is visualized. Given these findings along with her history, there is concern for ectopic pregnancy. A radiology performed ultrasound is ordered and has similar findings– Impression: no definitive IUP with a small amount of free fluid within physiologic limits. The findings do comment that the heterogenous material in the endometrial cavity could be a “questionable yolk sac and fetal pole”. Image 1 below demonstrates how the gestational sac is in the same plane as the stripe, so one could suspect the contents to be intrauterine. However, definitive findings of IUP are not present.  The patient continues to complain of worsening pain on exam, and with her b-hCG above the discriminatory zone and no definitive IUP, the obstetrics/gynecology team (OBGYN) is consulted for further management. 

Case 1 Clip 1 shows a long axis view of the uterus obtained with the use of an endoluminal probe.

CASE 1 CLIP 2 SHOWS EVIDENCE OF FREE FLUID IN THE ADNEXAL REGION

Case 1 Image 1 Depicts a questionable gestational sac (red arrow) in the same plane as the cervical stripe (purple arrow). there is also evident free fluid in the posterior cul-de-sac (yellow arrow)

The OBGYN team decides to admit the patient for monitoring. Ultimately the patient continues to have worsening left lower quadrant pain despite hydromorphone and her repeat hemoglobin is 11.2. At this point, the patient is taken to the operating room for a diagnostic laparoscopy. She is found to have 200 mL of blood in her pelvis with a ruptured left tubal ectopic pregnancy requiring a left salpingectomy. After a short period of recovery in the hospital, she is discharged home in stable condition with follow-up with OBGYN.


DIAGNOSING AN INTRAUTERINE PREGNANCY

Case 2 Image 1 depicts the gestational sac and its components in the same plane as the vaginal stripe

In order to diagnose an IUP, at minimum, a yolk sac +/- a fetal pole within a gestational sac must be visualized. It is important to emphasize that the sac itself must be within the endometrium. In order to ensure this is the case, one can follow the endometrial stripe to the cervix and find the gestational sac to be in the same plane (seen in the image to the right).

ECTOPIC PREGNANCY

An ectopic pregnancy is defined as the implantation of a fertilized ovum in any area outside of the uterine cavity. The most common locations for an ectopic pregnancy are tubal (95%), interstitial (1-6%), abdominal (1%), cervical (1%), ovarian (1-3%), or within a cesarean scar (1-3%) [1,6]. Patients with a history of damage to the fallopian tubes, either from ascending infection or surgery, smokers, and those with a prior history of ectopic pregnancy are all at greater risk for ectopic pregnancy [2]. 

The utilization of point of care ultrasound (POCUS) for rapid assessment and triage of patients with ectopic pregnancy directly impacts the time to appropriate intervention. In a study investigating the impact of POCUS on treatment time for ectopic pregnancy in the emergency department, inclusion of POCUS in the evaluation of patients with suspected ectopic pregnancy led to a significantly shorter time – approximately one and a half hours - to operative intervention than by radiology-performed ultrasound alone [5]. Multiple studies have shown similar findings, especially notable for a decrease in ED length of stay for patients ultimately diagnosed with an IUP [12-14].

ECTOPIC PREGNANCY AND POCUS

Findings on transvaginal and transabdominal ultrasound that may generally suggest ectopic pregnancy include lack of identifiable IUP, free fluid in the vesicouterine or rectouterine spaces, an extrauterine gestational sac, and solid hyperechoic masses [4,6]. Presence of free fluid in the pelvis or hemoperitoneum in the rectouterine space can be approximately 70% sensitive and 63% specific for ectopic pregnancy in the setting of a positive b-hCG [3,7].  One study showed that in a population of patients with clinical suspicion for ectopic pregnancy, POCUS findings of free fluid in the pelvis was close to 94% specific for ruptured ectopic pregnancy with a positive likelihood ratio of 9.5 [5]. In this same population, free fluid in the hepatorenal recess had a 99.5% specificity for a ruptured ectopic pregnancy with a positive likelihood ratio for operative management of 112, highlighting the importance of including a focused assessment with sonography for trauma (FAST) exam in the initial evaluation of suspected ectopic pregnancy [5]. Similar to the case discussed above, up to 42% of patients with ectopic pregnancies may present with isolated free fluid in the cul-de-sac as the only abnormality [5]. The clips below are representative of a case in which a patient was discovered to have a large amount of free fluid both in the pelvis and RUQ. They were ultimately diagnosed with a ruptured left adnexal ectopic pregnancy.

Case 2 Clip 1 represents a view of the pelvis obtained with a curvelinear probe. It demonstrates the presence of a large amount of complex free fluid, with no definitive IUP.

Case 2 Clip 2 demonstrates free fluid in the RUQ

Given that the most common location for an ectopic pregnancy is tubal, it is important to assess these structures during POCUS. One of the most common findings for tubal ectopic pregnancies on US is a discrete, non-cystic, heterogeneous adnexal mass separate from the ovaries with a sensitivity, specificity, positive and negative predictive value of 84.4, 98.9, 96.3 and 94.8%, respectively [3,6,7]. Another common finding is known as a tubal ring sign -  an echogenic ring surrounding an extrauterine gestational sac -  which has a 95% positive predictive value for ectopic pregnancy [4,7,9]. Simple adnexal cysts have 10% likelihood and complex extra-adnexal cysts have 95% likelihood of being an ectopic pregnancy, respectively [3]. The clips below is representative of a case in which a patient was found to have an adnexal mass with positive fetal heart tones, a large amount of complex fluid in the pelvis, and no definitive intrauterine pregnancy. They were ultimately diagnosed with a ruptured tubal ectopic pregnancy with some products of conception also adherent to the peritoneum.

Case 3 Clip 1 depicts a clip obtained using a curvelinear probe. The uterus is visualized and no definitive intrauterine pregnancy is seen. There is an abnormality detected by the adnexa

Case 3 Clip two depicts the trans view of the uterus. The abnormality in the left adnexa is again visualized along with a large amount of complex free fluid

Another important but less common location for ectopic pregnancy is embedded within the interstitial segment of the fallopian tube surrounded by a thin, continuous rim of myometrium. The clip below is from a patient ultimately diagnosed with a left sided interstitial ectopic pregnancy.

Case 4 Clip 1 was obtained using an endoluminal probe and depicts a gestational sac with a fetal pole that has cardiac activity. The location is unclear based on the image but not clearly within the endometrial cavity and thus concerning for ectopic pregnancy

Case 4 Image 1 depitcs an empty uterus (red arrwo) in the same plane as the stripe (yellow stripe) where one would anticipate an IUP to be

Case 4 image 2 depitcs the findings most consistent with a pregnancy, a sac with a fetal pole, with what appears to be thin myometrium and no stripe is seen

Due to their location high in the fundus near the uterine horn, these can be confused with intrauterine pregnancies, but are distinguished by the presence of a thinner endomyometrial mantle, often <5mm [6,9].  Discrimination between an IUP and an interstitial pregnancy is critical as interstitial pregnancies can have devastating outcomes. They carry a 7-fold increased risk of morbidity and mortality compared to tubal ectopic pregnancies due to risk of uterine rupture and the proximity to myometrial vasculature which increases the risk of severe hemorrhage [7, 11]. As such, it is important to measure the endomyometrial mantle which is the distance from the edge of the gestational sac to the outer wall of the myometrium. A measurement of 8mm is considered the lower limit of normal and any measurement less than 8mm should raise suspicion for an interstitial ectopic pregnancy [11].  An interstitial line sign - an echogenic line extending from the endometrium to the ectopic gestational sac - may be present and aids in the visualization of interstitial pregnancies [7,9].

Image depicts a measurement of the endomyometrial mantle

Rare locations for an ectopic pregnancy include cervical, cesarean scar, and ovarian [7]. A gestational sac in these locations is suggestive of ectopic pregnancy. Cervical ectopic pregnancies may present with an hourglass sign due to abnormal distension of the cervical canal in comparison to the uterus [9]. Cesarean scar ectopic pregnancies are located along the lower anterior segment of the uterus around the expected site of the scar [6]. Poorly healed cesarean scars have the potential for myometrial thinning, carrying a significant risk of uterine rupture in the case of ectopic pregnancy in this location [7,9]. Ovarian ectopic pregnancies are challenging to identify and may be mistaken for a corpus luteal or other ovarian cyst. While reports of ovarian ectopic ultrasound findings are limited, the presence of a cyst with a thick, echogenic wall directly attached to the ovary is more suggestive of ectopic pregnancy than the far more common thin-walled hypoechoic luteal cysts [6,9]. A pseudo-gestational sac - an apparent collection of intrauterine fluid without a discrete echogenic wall - may also be visible in some ectopic pregnancies but is in isolation non-diagnostic and will shift over time compared to a true fixed gestational sac [6,7]. The clip below is from a patient who presented with abdominal pain and had a positive pregnancy test. Her POCUS showed a large but empty gestational sac with no IUP and an abnormality in the right adnexa concerning for an ectopic pregnancy. She was taken to the operating room and found to have a right tubal ectopic pregnancy with a pseudogestational sac. While the differential for cysts and masses found on ultrasound is expansive, the index of suspicion for ectopic pregnancy should be increased for patients presenting with complex, non-homogenous masses and cysts in the setting of concerning clinical symptoms and history.

Case 5 Clip 1 shows an empty gestational sac with no yolk sac or fetal pole and an abnormality in the right adnexa

Case 5 image 1 shows the empty sac

Case 5 image 2 shows an abnormal extrauterine finding

SUMMARY

The case discussed above presented a patient with findings suggestive of a possible IUP but without definitive findings for such, and the patient was ultimately diagnosed with an ectopic pregnancy. Ectopic pregnancies can present in multiple different ways and the sonographic findings vary. It is important to take both the clinical presentation and ultrasound findings into consideration when considering management.


AUTHORED BY Michael Brooks

Michael Brooks is a fourth year medical student at the University of Cincinnati College of Medicine.

PEER REVIEW By Anita goel, MD

Dr. Goel is an Assistant Professor in Emergency Medicine at the University of Cincinnati.

PEER REVIEW By Meaghan K. Frederick, MD

Dr. Frederick is an Ultrasound Fellowship trained Assistant Professor in Emergency Medicine at the University of Cincinnati.

EDITING AND LAYOUT BY MARTINA DIAZ Mcdermott, MD

Dr. Diaz is a PGY-4 resident in Emergency Medicine at the University of Cincinnati and the current Resident Editor of Ultrasound of the Month.


REFERENCES

1- American College of Obstetricians and Gynecologists. Tubal Ectopic Pregnancy. ACOG Practice Bulletin No. 193. Obstet Gynecol 2018. Available from: https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/03/tubal-ectopic-pregnancy

2 - Cynthia M Farquhar. Ectopic pregnancy. The Lancet, Volume 366, Issue 9485, 2005, Pages 583-591, ISSN 0140-6736, https://doi.org/10.1016/S0140-6736(05)67103-6.

3 - Baker M, dela Cruz J. Ectopic Pregnancy, Ultrasound. [Updated 2023 Jan 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482192/

4 - https://radiopaedia.org/articles/ectopic-pregnancy?lang=us

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11 - Lewiss, R.E., Shaukat, N.M. and Saul, T. (2014), The Endomyometrial Thickness Measurement for Abnormal Implantation Evaluation by Pelvic Sonography. Journal of Ultrasound in Medicine, 33: 1143-1146. https://doi-org.uc.idm.oclc.org/10.7863/ultra.33.7.1143

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