Ectopic Pregnancy: Non-Tubal

Ectopic pregnancies, which occur in locations other than the fallopian tube, are characterized by delayed diagnosis and increased morbidity compared with tubal EPs. These pregnancies include interstitial pregnancy (implantation in the interstitial portion of the FT), cornual pregnancy (rudimentary horn of unicornuate uterus), cervical pregnancy (and cesarean scar pregnancy), and ovarian pregnancy.

Interstitial Pregnancy

An interstitial pregnancy (IP) is implanted near the uterine cavity in the interstitial portion of the fallopian tube (the portion of the FT which is within the uterine wall and connects the FT to the uterine cavity). An IP is difficult to distinguish from an IUP which is implanted high and laterally in the uterine cavity. Under these conditions, the coronal plane best demonstrates the gestational sac position, and 3-D ultrasound may be helpful.  On ultrasound, the gestational sac is surrounded by myometrium, which is capable of expanding and thus, delaying the interval from conception to rupture. The overall mortality is about 2% (1 in 50). 

Above. Probable interstitial pregnancy. Note gestational sac in the anatomic region where FT crosses the uterine fundus. Within the gestational sac is a small YS and fetal pole. A portion of the sac is surrounded by myometrium.

Above. Interstitial pregnancy. 3-D image.

The ultrasound findings in an interstitial pregnancy usually include a normal uterine shape and normal uterine cavity with a narrow communication between the gestational sac and uterine cavity, while a myometrial panel which is continuous with the uterus is present, and there is no sac mobility or vascular pedicle. 

Cornual Pregnancy

A cornual pregnancy is defined as a gestation that implants in the rudimentary horn of a unicornuate uterus. A unicornuate uterus is a developmental abnormality of the Mullerian duct, where 1 horn instead of 2 uterine horns develop. However, the ectopic pregnancy develops in the opposite horn that is small and fails to fully develop (the rudimentary horn). This anomaly represents < 1% of congenital uterine anomalies in the general (fertile) population. 

Above. Approximate location of the rudimentary horn of unicornuate uterus, which is the most likely location for a cornual pregnancy. (Image courtesy of RadsWiki, Creative Commons Attribution-Share Alike 3.0).

The following ultrasound criteria are necessary for the diagnosis of cornual pregnancy:

1. A single interstitial portion of the fallopian tube in the main uterine body is affected.
2. A gestational sac surrounded by myometrium is mobile and separate from the uterus.
3. A vascular pedicle joins the gestational sac to the unicornuate (developed horn) of the uterus.

Above. Possible cornual pregnancy. The location is near the cornual region of the cervix. Diagnosis or confirmation of rudimentary horn is not certain in this case. Interstitial pregnancy remains a possibility.

Above. Same patient as immediately above. Note connecting stalk or pedicle.

The diagnosis is based upon finding a single interstitial tube, which is near an empty uterus. In a normal intrauterine pregnancy, there is a wide communication between the uterine cavity and the gestational sac, which is not the case in ectopic pregnancies. Other distinguishing features in a cornual pregnancy include the mobility of the gestational sac and the presence of a vascular pedicle.

Sensitivity is 26% for the ultrasound diagnosis of rudimentary horn, while the sensitivity is 14% for the diagnosis before clinical symptoms. 

If the diagnosis is made before rupture, surgical management is recommended either by laparoscopy (usually first trimester) or in advanced cases, open surgery. 

Cervical Pregnancy

A cervical ectopic is one in which the implantation occurs below the internal cervical os. The prevalence is 1:10,000 deliveries, while previous curettage (50% of cases) and cesarean delivery (16.7% of cases) are historical antecedents.  Other historical factors include uterine manipulation from hysteroscopy and history of in vitro fertilization, while clinical symptoms include vaginal bleeding and abdominal discomfort. 

The following criteria are suggested for the diagnosis of cervical pregnancy:

1. Absence of gestational sac, fetal pole, or yolk sac within the endometrial cavity.
2. Hourglass uterine shape.
3. The presence of a gestational sac within the cervical canal.
4. Closed internal os.

Above. Cervical pregnancy. Longitudinal scan. Note uterine fundus and ES (endometrial stripe). The ICO (internal cervical os) is closed and demarcates the cervix and the gestational sac is seen within the substance of the cervix.

Above. Cervical pregnancy demonstrates the enlarged cervix and portions of the gestational sac.

Above. Cervical pregnancy. Post medical injection. Note the absence of a gestational sac within the EC (endometrial cavity). The general region of the IO is demonstrated. Trophoblastic tissue is noted within the endocervical canal and the cervix appears enlarged.

Above. Cervical pregnancy. Same patient as immediately above demonstrating trophoblastic tissue in the endocervical canal.

Above video. Cervical pregnancy. Note the decidual changes within the endometrium in the fundus of the uterus. The cervical ectopic demonstrates a small fetal pole.

Above. Cervical pregnancy. Same as above. Note endometrial changes, and cervix with ectopic pregnancy.

Incomplete abortion versus cervical pregnancy

Incomplete abortion may have tissue within the cervix, while the internal os may be open if there is a large cervical pregnancy. The level of the internal os can be determined on transvaginal ultrasound by noting the insertion of the uterine arteries with color Doppler, which are at the level of the internal os.  Color Doppler will also illustrate the vascular supply to the trophoblastic tissue, while in incomplete abortions, the trophoblastic blood supply is disrupted. Incomplete abortion may be distinguished from a cervical pregnancy by the “sliding sign” in which a gestational sac from a detached IUP slides towards the cervical canal with uterine pressure on the intravaginal probe.

Management of cervical pregnancy

In a review of the management of cervical pregnancies, the following is suggested:

1. Primary medical management of early cervical pregnancy is associated with less hemorrhage and fewer hysterectomies compared with surgical management.
2. Non-viable cervical pregnancies can be treated with systemic methotrexate.
3. Viable cervical pregnancies can be treated with local injections of methotrexate or potassium chloride.
4. Surgery should be reserved for failed medical management or patients presenting with catastrophic hemorrhage.
5. Surgical options include dilatation and curettage with cerclage or insertion of a Foley catheter to control hemorrhage.

Ovarian Pregnancy

Ovarian ectopic pregnancies are rare, comprising 2% of all EPs, while associated factors include assisted reproductive technology (ART) procedures (18.1%) and the presence of an intrauterine device (IUD) (19.4%).  The presenting symptoms are similar to tubal EP and include bleeding and pain with circulatory collapse reported in 21% of cases in some series. 

On transvaginal ultrasound, a gestational sac is surrounded by normal ovarian tissue, while gentle palpation during the exam does not separate the sac from the surrounding ovary. Color Doppler is important in the assessment. Two areas of vascularity may be seen within the ovary: the “ring of fire” surrounding the corpus luteum, and the increased vascularity due to the trophoblastic proliferation, which is typically thick and echogenic.

In a recent review, 52% of ovarian EPs were managed laparoscopically, while the success rate for medical management was 50% in a small number of cases.  Laparoscopy is used as a diagnostic and treatment method (wedge resection). 

Cesarean section scar ectopic pregnancy

Due to an increase in the number of Cesarean sections, the incidence of ectopic pregnancies within the scar is increasing. In a woman with a previous Cesarean section and evidence of early pregnancy, the onset of acute abdominal pain in the region of the previous uterine scar should be immediately investigated.

Above. Transvaginal ultrasound: midline sagittal image with gestation in the anatomical location of a prior cesarean scar. Image courtesy. With permission. radiology key.com-ultrasound-evaluation-of-ectopic-pregnancy/

Above. Transvaginal ultrasound: 3D rendering of cesarean scar ectopic pregnancy. Image courtesy. With permission. radiology key.com-ultrasound-evaluation-of-ectopic-pregnancy/

Workup of Pregnancy of Unknown Location

The classic triad for ectopic pregnancies is a pregnancy presenting with pain, bleeding, and the presence of a mass. Risk factors, which are reproductive failures, include the history of tubal disease and smoking, which may help to establish a diagnostic and management strategy.  Other risk factors include uterine anomalies, history of assisted reproduction, and pelvic infection.

The endometrium may help to define the presence of an ectopic pregnancy.

Above. Transvaginal ultrasound sagittal view. A thin endometrial lining in the presence of a positive pregnancy test and/or an increase in the levels of beta HCG suggest ectopic pregnancy. Image courtesy. With permission. radiologykey.com/ectopic-pregnancy-pregnancy-of-unknown-location

On transvaginal ultrasound (TVS), a tubal ectopic pregnancy may be present if no intrauterine pregnancy (IUP) is seen. A definitive gestational sac with a yolk sac excludes the diagnosis, but fluid within the endometrial cavity in the absence of a YS does not exclude the diagnosis. Rarely, a heterotopic gestation may be present with one gestational sac consistent with an IUP and another simultaneous pregnancy which is ectopic in location. To confirm the likelihood of a tubal EP, one of the following conditions should be met:

1. An inhomogeneous adnexal mass separate from the ovary.

Above. Tubal ectopic pregnancy. Note inhomogeneous mass surrounded by increased vascularity in the left adnexa.

2. An empty extra-uterine gestational sac with a hyperechoic ring in the adnexal region.

Above. An adnexal mass with a central anechoic area with a hyperechoic ring  (bagel sign) is suggestive of an ectopic pregnancy.
3. An extrauterine sac in the adnexal region with a yolk sac or fetal pole ± cardiac activity. Image courtesy. With permission. radiologykey.com/ectopic-pregnancy-pregnancy-of-unknown-location-pul

Above. An adnexal mass containing an embryo with cardiac activity. Image courtesy. With permission. radiologykey.com/ectopic-pregnancy-pregnancy-of-unknown-location-pul

Above. Tubal ectopic pregnancy. Note empty gestational sac surrounded by increased vascularity in the adnexa region.

Consensus Statement of Definitions and Outcomes for Pregnancy of Unknown Location (PUL)

A pregnancy diagnosis is sometimes made but the location of the pregnancy is not readily apparent. In 2011, a consensus statement of definitions and outcomes for pregnancy of unknown location (PUL) was published. 

The following categories for ultrasound diagnosis were suggested for diagnosis of pregnancy of unknown location (PUL):

1. Definite ectopic pregnancy: Extrauterine gestational sac with yolk sac and/or embryo (with or without cardiac activity).

Above. Adnexal mass with a yolk sac. Definitive diagnostic sign for ectopic pregnancy.
2. Probable EP: Inhomogeneous adnexal mass or extrauterine sac-like structure.

Above. Transvaginal gray-scale ultrasound image of the right adnexa shows a thickened heterogenous fallopian tube.  A round solid hyperechoic structure with a central cystic component (arrows) is located within the ampulla-infundibulum region of the right fallopian tube. No fetal pole, fetal heartbeat, or yolk sac is seen. The right ovary (RT OV) is intact and located more laterally to and separate from the ectopic pregnancy. Image used with permission. Revzin M V, Moshiri M, Katz D S, et al. Imaging Evaluation of Fallopian Tubes and Related Disease: A Primer for Radiologists. RadioGraphics 2020;40:1473–1501.

Above. Uncomplicated tubal ectopic pregnancy. Transvaginal ultrasound color Doppler ultrasound image shows a peripheral rim of flow (dashed arrows) around the fallopian ectopic pregnancy (solid arrow). The uterus and endometrium demonstrated no signs of intrauterine pregnancy. Image used with permission. Revzin M V, Moshiri M, Katz D S, et al. Imaging Evaluation of Fallopian Tubes and Related Disease: A Primer for Radiologists. RadioGraphics 2020;40:1473–1501.

3. Pregnancy of Unknown Location (PUL): No signs of either EP or IUP.
4. Probable IUP: Intrauterine echogenic sac-like structure.

Above. The intrauterine gestational sac is suggestive of probable intrauterine pregnancy.
5. Definite IUP: Intrauterine gestational sac with yolk sac and/or embryo (with or without cardiac activity).

Above. Definitive intrauterine pregnancy with embryo and fetal cardiac activity.

Treatment for tubal EP is either medical with methotrexate or surgical by laparoscopy. Many protocols suggest periodic hCG measurements and transvaginal ultrasound.

Some treatment protocols recommend medical management in patients with suspected ectopic pregnancy if the β-hCG level is <1 000 IU/l, the patient is asymptomatic, and the EP is not visualized. However, a single β-hCG level cannot exclude the possibility of an intrauterine pregnancy, and despite numerous studies and meta-analyses, no single protocol or method of management has been established. At least 6 diagnostic protocols have been defined using a combination of ultrasound, β-hCG, and serum progesterone.  Finally, serum β-hCG may not be useful in distinguishing IUPs from ETs in symptomatic pregnant women. 

The following observations relate to treatment and recurrence risk:

1. Irrespective of treatment mode, the chances of a subsequent successful IUP in EP patients are the same.
2. Generally, the size of the EP should not be a limiting factor for conservative laparoscopic surgery.
3. The risk of recurrent EP is about 10% after salpingectomy.

Among patients with a persisting pregnancy of unknown location, successful pregnancy resolution more frequently resulted when an initial active management strategy was employed. This active management involved either methotrexate alone or uterine evacuation with methotrexate as needed, compared with an expectant management strategy. (See reference number 27).