schematic representation of ectopic pregnancy

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Ectopic Pregnancy

(pregnancy of unknown location).

, MD, UCLA Health

• Pathophysiology
• Symptoms and Signs
• 3D Models (0)
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Ectopic pregnancy is the implantation of a pregnancy in a site other than the endometrial lining of the uterine cavity—ie, in the fallopian tube, uterine cornua, cervix, ovary, or abdominal or pelvic cavity. Ectopic pregnancy is a life-threatening condition for a pregnant woman; such pregnancies cannot be carried to term and eventually rupture or involute. Early symptoms and signs include pelvic pain and vaginal bleeding. Hemorrhagic shock can occur with rupture. Diagnosis is by measurement of the beta subunit of human chorionic gonadotropin and ultrasonography. Treatment is with laparoscopic or open surgical resection or with methotrexate .

Ectopic pregnancy can cause life-threatening hemorrhage, and if it is suspected, the patient should be evaluated and treated as soon as possible. Incidence of ectopic pregnancy is approximately 2/100 diagnosed pregnancies ( 1 General reference Ectopic pregnancy is the implantation of a pregnancy in a site other than the endometrial lining of the uterine cavity—ie, in the fallopian tube, uterine cornua, cervix, ovary, or abdominal... read more ). Patients with possible ectopic pregnancy or other cause of early pregnancy failure often present with symptoms early in pregnancy, when ultrasonography is not able to confirm the anatomic location or viability of the pregnancy. Therefore, these pregnancies are referred to as pregnancy of unknown location.

General reference

1. Van Den Eeden SK, Shan J, Bruce C, Glasser M : Ectopic pregnancy rate and treatment utilization in a large managed care organization. Obstet Gynecol 105 (5 Pt 1):1052–1057, 2015. doi: 10.1097/01.AOG.0000158860.26939.2d

Etiology of Ectopic Pregnancy

Most ectopic pregnancies are located in the fallopian tube, and any history of infection or surgery that increases the risk of tubal adhesions or other abnormalities increases risk of ectopic pregnancy.

Factors that particularly increase risk of ectopic pregnancy include

Prior ectopic pregnancy

Prior pelvic surgery, particularly tubal surgery, including tubal sterilization Tubal Sterilization In the United States, one third of couples attempting to prevent pregnancy, particularly if the woman is > 30 years old, choose permanent contraception with vasectomy or tubal sterilization... read more

Tubal abnormalities or damage (eg, due to ascending infection or surgery)

Other risk factors for ectopic pregnancy include

History of pelvic inflammatory disease Pelvic Inflammatory Disease (PID) Pelvic inflammatory disease (PID) is a polymicrobial infection of the upper female genital tract: the cervix, uterus, fallopian tubes, and ovaries; abscess may occur. PID may be caused by sexually... read more or sexually transmitted infections Overview of Sexually Transmitted Infections Sexually transmitted infection (STI) refers to infection with a pathogen that is transmitted through blood, semen, vaginal fluids, or other body fluids during oral, anal, or genital sex with... read more (particularly due to Chlamydia trachomatis )

Infertility Overview of Infertility Infertility is a disease defined by the inability to achieve a pregnancy and/or the need for medical intervention to achieve a successful pregnancy. In patients who have not achieved a pregnancy... read more

Cigarette smoking

Overall, becoming pregnant is much less likely in patients who have had tubal sterilization or have an intrauterine device (IUD) in place; however, when pregnancy does occur in these patients, risk of ectopic pregnancy is increased (eg, approximately 53% in pregnancies in current IUD users) ( 1 Etiology reference Ectopic pregnancy is the implantation of a pregnancy in a site other than the endometrial lining of the uterine cavity—ie, in the fallopian tube, uterine cornua, cervix, ovary, or abdominal... read more ).

Etiology reference

1. Backman T, Rauramo I, Huhtala S, Koskenvuo M : Pregnancy during the use of levonorgestrel intrauterine system. Am J Obstet Gynecol 190(1):50-54, 2004. doi:10.1016/j.ajog.2003.07.021

Pathophysiology of Ectopic Pregnancy

The most common site of ectopic implantation is a fallopian tube, followed by the uterine cornua (referred to as a cornual or an interstitial pregnancy). Pregnancies implanted in the cervix, a cesarean scar, an ovary, or the abdomen are rare.

The anatomic structure containing the fetus usually ruptures after about 6 to 16 weeks. Rupture results in bleeding that can be gradual or rapid enough to cause hemorrhagic shock Shock Shock is a state of organ hypoperfusion with resultant cellular dysfunction and death. Mechanisms may involve decreased circulating volume, decreased cardiac output, and vasodilation, sometimes... read more . The later in the pregnancy the rupture occurs, the more rapidly blood is lost and the higher the risk of death.

Pathophysiology reference

1. Perkins KM, Boulet SL, Kissin DM, et al : Risk of ectopic pregnancy associated with assisted reproductive technology in the United States, 2001-2011. Obstet Gynecol 125 (1):70–78, 2015. doi: 10.1097/AOG.0000000000000584

Symptoms and Signs of Ectopic Pregnancy

Symptoms of ectopic pregnancy vary and may be absent until rupture occurs.

Most patients have pelvic pain (which can be dull, sharp, or crampy), vaginal bleeding, or both. Patients who have irregular menses may not be aware that they are pregnant.

Rupture may be heralded by sudden, severe pain, followed by syncope or by symptoms and signs of hemorrhagic shock or peritonitis. Rapid hemorrhage is more likely in ruptured cornual pregnancies.

Cervical motion tenderness, unilateral or bilateral adnexal tenderness, or an adnexal mass may be present. Pelvic examination should be done carefully because excessive pressure may rupture the pregnancy . The uterus may be slightly enlarged (but often less than anticipated based on date of the last menstrual period).

Diagnosis of Ectopic Pregnancy

Quantitative serum beta– human chorionic gonadotropin (beta-hCG)

Pelvic ultrasonography

Sometimes laparoscopy

Ectopic pregnancy is suspected in any female patient of reproductive age with pelvic pain, vaginal bleeding, or unexplained syncope or hemorrhagic shock, regardless of menstrual, contraceptive, and sexual history. Findings of physical (including pelvic) examination are neither sensitive nor specific.

A ruptured ectopic pregnancy is a surgical emergency because it causes maternal hemorrhage and risk of death; prompt diagnosis is essential.

Pearls & Pitfalls

The first step in diagnosis is a urine pregnancy test, which is approximately 99% sensitive for pregnancy (ectopic and otherwise). If urine beta-hCG is negative and if clinical findings do not strongly suggest ectopic pregnancy, further evaluation is unnecessary unless symptoms recur or worsen. If urine beta-hCG is positive or if clinical findings strongly suggest ectopic pregnancy and pregnancy may be too early to detect based on urine beta-hCG, quantitative serum beta-hCG and pelvic ultrasonography should be done.

If ultrasonography detects an intrauterine pregnancy, a concurrent ectopic pregnancy (heterotopic pregnancy) is extremely unlikely except in women who have used assisted reproductive technologies (which increase risk of heterotopic pregnancy, although it is still rare in these patients). However, cornual and interstitial pregnancies may appear to be intrauterine pregnancies on ultrasound.

Ultrasonographic findings diagnostic of an intrauterine pregnancy are a gestational sac with a yolk sac or an embryo (with or without a heartbeat) within the uterine cavity. In addition to absence of an intrauterine pregnancy, ultrasonographic findings suggesting ectopic pregnancy include a complex (mixed solid and cystic) pelvic mass, particularly in the adnexa, and echogenic free fluid in the cul-de-sac.

If serum beta-hCG is above a certain level (called the discriminatory zone), ultrasonography should be able to detect a gestational sac with a yolk sac; the presence of a yolk sac confirms an intrauterine pregnancy. The appropriate hCG threshold for the discriminatory zone for women with suspected ectopic pregnancy has been reevaluated. To minimize overdiagnosis of ectopic pregnancy and preserve desired intrauterine pregnancies, the recommended threshold has been increased to 3500 mIU/mL) ( 1 Diagnosis reference Ectopic pregnancy is the implantation of a pregnancy in a site other than the endometrial lining of the uterine cavity—ie, in the fallopian tube, uterine cornua, cervix, ovary, or abdominal... read more ).

If the beta-hCG level is below the discriminatory zone and ultrasonography is unremarkable, patients may have an early intrauterine pregnancy or an ectopic pregnancy. If clinical evaluation suggests ectopic pregnancy with active bleeding or rupture (eg, signs of significant hemorrhage or peritoneal irritation), diagnostic laparoscopy may be necessary for diagnosis and treatment.

If ectopic pregnancy has not been confirmed and the patient is stable, serum levels of beta-hCG are measured serially on an outpatient basis (typically every 2 days). Normally, the level doubles every 1.4 to 2.1 days up to 41 days; in ectopic pregnancy (and in potential spontaneous abortions), levels may be lower than expected by dates and usually do not double as rapidly. If beta-hCG levels do not increase as expected or if they decrease, diagnosis of spontaneous abortion Spontaneous Abortion Spontaneous abortion is pregnancy loss before 20 weeks gestation. Diagnosis is by pelvic examination, measurement of beta subunit of human chorionic gonadotropin, and ultrasonography. Treatment... read more or ectopic pregnancy is likely.

Differential diagnosis

Bleeding Vaginal Bleeding During Early Pregnancy Vaginal bleeding occurs in approximately 20% of confirmed pregnancies during the first 20 weeks of gestation; about half of these cases end in spontaneous abortion ( 1). Vaginal bleeding is... read more is common in early pregnancy (see table for differential diagnosis).

Pelvic pain Pelvic Pain During Early Pregnancy Pelvic pain is common during early pregnancy and may accompany serious or minor disorders. Some conditions causing pelvic pain also cause vaginal bleeding. In some of these disorders (eg, ruptured... read more or pressure is also a common pregnancy symptom (see table for differential diagnosis).

Diagnosis reference

1. Doubilet PM, Benson CB, Bourne T, et al : Diagnostic criteria for nonviable pregnancy early in the first trimester. N Engl J Med 369(15):1443-1451, 2013. doi:10.1056/NEJMra1302417

Treatment of Ectopic Pregnancy

Usually, methotrexate for small, unruptured ectopic pregnancies

Surgical resection if rupture is suspected or criteria are not met for methotrexate treatment

Rho(D) immune globulin if the woman is Rh-negative

Methotrexate

The American College of Obstetricians and Gynecologists advises that patients with a tubal pregnancy may be treated with methotrexate if none of the following absolute contraindications is present:

Intrauterine pregnancy

Ruptured ectopic pregnancy

Hemodynamically unstable

Sensitivity to methotrexate

Evidence of immunodeficiency Overview of Immunodeficiency Disorders Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more

Clinically important hepatic or renal dysfunction

Breastfeeding

Unable to participate in follow-up surveillance

Additionally, the following relative contraindications should be considered:

Embryonic cardiac activity detected by transvaginal ultrasonography

High initial hCG concentration

Ectopic pregnancy > 4 cm in size (as imaged on transvaginal ultrasonography)

Refusal to accept blood donation

In a commonly used protocol, beta-hCG is measured on day 1, and the patient is given a single dose of methotrexate 50 mg/m2 IM. Beta-hCG measurement is repeated on days 4 and 7. If the beta-hCG level does not decrease by 15% from day 4 to 7, a 2nd dose of methotrexate or surgery is needed. Alternatively, other protocols can be used.

The beta-hCG level is then measured weekly until it is undetectable. Success rates with methotrexate are approximately 90%; 9% of women have complications that require hospitalization ( 1 Treatment reference Ectopic pregnancy is the implantation of a pregnancy in a site other than the endometrial lining of the uterine cavity—ie, in the fallopian tube, uterine cornua, cervix, ovary, or abdominal... read more ).

Usually, methotrexate can be used, but surgery is indicated when rupture is suspected, the patient is not able to comply with follow-up surveillance after methotrexate therapy, or methotrexate is ineffective.

Surgical resection

Hemodynamically unstable patients require immediate laparotomy and treatment of hemorrhagic shock Treatment of hemorrhagic shock Shock is a state of organ hypoperfusion with resultant cellular dysfunction and death. Mechanisms may involve decreased circulating volume, decreased cardiac output, and vasodilation, sometimes... read more .

For stable patients, surgical treatment is usually laparoscopic surgery; sometimes laparotomy is required. If possible, salpingotomy is done to conserve the tube, and the ectopic pregnancy is removed.

Salpingectomy is indicated in any of the following cases:

The ectopic pregnancy has ruptured.

Hemorrhage continues after salpingotomy.

The tube has been reconstructed.

The ectopic pregnancy represents a failure of a previous sterilization procedure, particularly if the pregnancy is in the blind-ending distal segment in women who have had a previous partial salpingectomy.

Only the irreversibly damaged portion of the tube is removed, maximizing the chance that tubal repair can restore fertility. The tube may or may not be repaired. After a cornual pregnancy, the tube and ovary involved can usually be salvaged, but occasionally repair is impossible, making hysterectomy necessary.

All patients who are Rh-negative, whether managed with methotrexate or surgery, are given Rho(D) immune globulin Prevention .

Treatment reference

1. Barnhart KT, Gosman G, Ashby R, Sammel M : The medical management of ectopic pregnancy: a meta-analysis comparing "single dose" and "multidose" regimens. Obstet Gynecol 101(4):778-784, 2003. doi:10.1016/s0029-7844(02)03158-7

Prognosis for Ectopic Pregnancy

Ectopic pregnancy is fatal to the fetus, but if treatment occurs before rupture, maternal death is rare. In the United States in 2018, the mortality rate due to ectopic pregnancies was 0.8 deaths per 100,0000 live births ( 1 Prognosis reference Ectopic pregnancy is the implantation of a pregnancy in a site other than the endometrial lining of the uterine cavity—ie, in the fallopian tube, uterine cornua, cervix, ovary, or abdominal... read more ).

Prognosis reference

1. Hoyert DL, Miniño AM : Maternal mortality in the United States. Changes in coding, publication, and data release, 2018. National Vital Statistics Reports; vol 69 no 2. Hyattsville, MD: National Center for Health Statistics. 2020.

Ectopic pregnancy is the implantation of a pregnancy in a site other than the endometrial lining of the uterine cavity; the most common site for ectopic pregnancies is a fallopian tube.

Symptoms can include pelvic pain and vaginal bleeding in a pregnant woman, but the woman may not be aware she is pregnant and symptoms may be absent until rupture occurs, sometimes with catastrophic results.

Suspect ectopic pregnancy in any female of reproductive age with pelvic pain, vaginal bleeding, or unexplained syncope or hemorrhagic shock.

If a urine pregnancy test is positive or clinical findings suggest ectopic pregnancy, determine quantitative serum beta-hCG and do pelvic ultrasonography.

Treatment usually involves methotrexate , but surgical resection is done if rupture is suspected or criteria are not met for methotrexate treatment.

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Terminology for describing normally sited and ectopic pregnancies on ultrasound: ESHRE recommendations for good practice

Affiliations.

• 1 Early Pregnancy and Emergency Gynaecology Unit, Royal Free Hospital London, London, UK.
• 2 Amsterdam Medical Centre, Amsterdam, the Netherlands.
• 3 Department of Obstetrics and Gynecology, University of Debrecen, Debrecen, Hungary.
• 4 European Society of Human Reproduction and Embryology, Belgium.
• 5 Department of Gynecology and Oncology, Jagiellonian University Medical College, Krakow, Poland.
• 6 Heart of England NHS Foundation Trust, Birmingham, UK.
• 7 Department of Gynecology, Oslo University Hospital, Ullevål, Oslo, Norway.
• 8 Fertinova Clinics, Helsinki, Finland.
• 9 Department of Obstetrics and Gynaecology, University Hospital Leuven, Belgium.
• 10 Laboratory for Tumor Immunology and Immunotherapy, Leuven, KU, Belgium.
• 11 Department of OB/GYN, University College Hospital, London, UK.
• PMID: 33354626
• PMCID: PMC7738750
• DOI: 10.1093/hropen/hoaa055

Study question: What recommendations can be provided to improve terminology for normal and ectopic pregnancy description on ultrasound?

Summary answer: The present ESHRE document provides 17 consensus recommendations on how to describe normally sited and different types of ectopic pregnancies on ultrasound.

What is known already: Current diagnostic criteria stipulate that each type of ectopic pregnancy can be defined by clear anatomical landmarks which facilitates reaching a correct diagnosis. However, a clear definition of normally sited pregnancies and a comprehensive classification of ectopic pregnancies are still lacking.

Study design size duration: A working group of members of the ESHRE Special Interest Group in Implantation and Early Pregnancy (SIG-IEP) and selected experts in ultrasound was formed in order to write recommendations on the classification of ectopic pregnancies.

Participants/materials setting methods: The working group included nine members of different nationalities with internationally recognised experience in ultrasound and diagnosis of ectopic pregnancies on ultrasound. This document is developed according to the manual for development of ESHRE recommendations for good practice. The recommendations were discussed until consensus by the working group, supported by a survey among the members of the ESHRE SIG-IEP.

Main results and the role of chance: A clear definition of normally sited pregnancy on ultrasound scan is important to avoid misdiagnosis of uterine ectopic pregnancies. A comprehensive classification of ectopic pregnancy must include definitions and descriptions of each type of ectopic pregnancy. Only a classification which provides descriptions and diagnostic criteria for all possible locations of ectopic pregnancy would be fit for use in routine clinical practice. The working group formulated 17 recommendations on the diagnosis of the different types of ectopic pregnancies on ultrasound. In addition, for each of the types of ectopic pregnancy, a schematic representation and examples on 2D and 3D ultrasound are provided.

Limitations reasons for caution: Owing to the limited evidence available, recommendations are mostly based on clinical and technical expertise.

Wider implications of the findings: This document is expected to have a significant impact on clinical practice in ultrasound for early pregnancy. The development of this terminology will help to reduce the risk of misdiagnosis and inappropriate treatment.

Study funding/competing interests: The meetings of the working group were funded by ESHRE. T.T. declares speakers' fees from GE Healthcare. The other authors declare that they have no conflict of interest.

Trial registration number: N/A.

Disclaimer: This Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation. ESHRE's GPRs should be used for informational and educational purposes. They should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. Furthermore, ESHRE's GPRs do not constitute or imply the endorsement, recommendation or favouring of any of the included technologies by ESHRE.

Keywords: ESHRE; early pregnancy; ectopic pregnancy; guideline; terminology; ultrasound.

© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.

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CHAPTER 12:  Ectopic Pregnancy

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Following fertilization and fallopian tube transit, the blastocyst normally implants in the endometrial lining of the uterine cavity. Implantation elsewhere is considered ectopic. In the United States, numbers from an insurance database and from Medicaid claims showed ectopic pregnancy rates of 1.54 percent and 1.38 percent, respectively, in 2013 ( Tao, 2017 ). Ectopic implantation accounts for 3 percent of all pregnancy-related deaths ( Creanga, 2017 ). Fortunately, beta-human chorionic gonadotropin (β-hCG) assays and transvaginal sonography (TVS) aid earlier diagnosis, maternal survival, and fertility conservation.

Classification

Of ectopic pregnancies, nearly 95 percent implant in the fallopian tube’s various segments ( Fig. 2-13 , p. 26). The ampulla (70 percent) is the most frequent site ( Fig. 12-1 ). The rate for isthmic implantation is 12 percent; fimbrial, 11 percent; and interstitial, 2 percent ( Bouyer, 2002 ). Nontubal ectopic pregnancies compose the remaining 5 percent and implant in the ovary, peritoneal cavity, cervix, or prior cesarean scar. Occasionally, a multifetal pregnancy contains one conceptus with normal uterine implantation and the other implanted ectopically. This is termed a heterotopic pregnancy (p. 231).

FIGURE 12-1

Ampullary tubal pregnancy ( arrow ) seen during laparoscopy. (Reproduced with permission from Dr. Lisa Chao.)

For all ectopic pregnancy sites, management is influenced by pregnancy viability, gestational age, maternal health, desires for the index pregnancy and for future fertility, physician skill, and available resources. Regardless of location, D-negative women with an ectopic pregnancy are given anti-D immunoglobulin. In first-trimester pregnancies, a single intramuscular 50- or 120-μg dose is appropriate. Later gestations are given 300 μg ( American College of Obstetricians and Gynecologists, 2019b ).

Abnormal fallopian tube anatomy underlies most cases of tubal ectopic pregnancy. Surgeries for a prior tubal pregnancy, for fertility restoration, or for sterilization confer the highest risk. After one prior ectopic pregnancy, the chance of another nears 10 percent ( de Bennetot, 2012 ). Previous tubal infection, which can distort normal tubal anatomy, is another risk. Specifically, one episode of salpingitis can be followed by a subsequent ectopic pregnancy in up to 9 percent of women ( Westrom, 1992 ). Peritubal adhesions that form from salpingitis, appendicitis, or endometriosis also raise chances.

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ERIN HENDRIKS, MD, RACHEL ROSENBERG, MD, AND LINDA PRINE, MD

Am Fam Physician. 2020;101(10):599-606

Author disclosure: No relevant financial affiliations.

Ectopic pregnancy occurs when a fertilized ovum implants outside of the uterine cavity. In the United States, the estimated prevalence of ectopic pregnancy is 1% to 2%, and ruptured ectopic pregnancy accounts for 2.7% of pregnancy-related deaths. Risk factors include a history of pelvic inflammatory disease, cigarette smoking, fallopian tube surgery, previous ectopic pregnancy, and infertility. Ectopic pregnancy should be considered in any patient presenting early in pregnancy with vaginal bleeding or lower abdominal pain in whom intrauterine pregnancy has not yet been established. The definitive diagnosis of ectopic pregnancy can be made with ultrasound visualization of a yolk sac and/or embryo in the adnexa. However, most ectopic pregnancies do not reach this stage. More often, patient symptoms combined with serial ultrasonography and trends in beta human chorionic gonadotropin levels are used to make the diagnosis. Pregnancy of unknown location refers to a transient state in which a pregnancy test is positive but ultrasonography shows neither intrauterine nor ectopic pregnancy. Serial beta human chorionic gonadotropin levels, serial ultrasonography, and, at times, uterine aspiration can be used to arrive at a definitive diagnosis. Treatment of diagnosed ectopic pregnancy includes medical management with intramuscular methotrexate, surgical management via salpingostomy or salpingectomy, and, in rare cases, expectant management. A patient with diagnosed ectopic pregnancy should be immediately transferred for surgery if she has peritoneal signs or hemodynamic instability, if the initial beta human chorionic gonadotropin level is high, if fetal cardiac activity is detected outside of the uterus on ultrasonography, or if there is a contraindication to medical management.

Ectopic pregnancy occurs when a fertilized ovum implants outside of the uterine cavity. The prevalence of ectopic pregnancy in the United States is estimated to be 1% to 2%, but this may be an underestimate because this condition is often treated in the office setting where it is not tracked. 1 , 2 The mortality rate for ruptured ectopic pregnancy has steadily declined over the past three decades, and from 2011 to 2013 accounted for 2.7% of pregnancy-related deaths. 1 , 3 Risk factors for ectopic pregnancy are listed in Table 1 4 , 5 ; however, one-half of women with diagnosed ectopic pregnancy have no identified risk factors. 4 – 6 The overall rate of pregnancy (including ectopic) is less than 1% when a patient has an intrauterine device (IUD). However, in the rare case that a woman does become pregnant while she has an IUD, the prevalence of ectopic pregnancy is as high as 53%. 7 , 8 There is no difference in ectopic pregnancy rates between copper or progestin-releasing IUDs. 9

Making the Diagnosis

Signs and symptoms.

Ectopic pregnancy should be considered in any pregnant patient with vaginal bleeding or lower abdominal pain when intrauterine pregnancy has not yet been established ( Table 2 ) . 10 Vaginal bleeding in women with ectopic pregnancy is due to the sloughing of decidual endometrium and can range from spotting to menstruation-equivalent levels. 10 This endometrial decidual reaction occurs even with ectopic implantation, and the passage of a decidual cast may mimic the passage of pregnancy tissue. Thus, a history of bleeding and passage of tissue cannot be relied on to differentiate ectopic pregnancy from early intrauterine pregnancy failure.

The nature, location, and severity of pain in ectopic pregnancy vary. It often begins as a colicky abdominal or pelvic pain that is localized to one side as the pregnancy distends the fallopian tube. The pain may become more generalized once the tube ruptures and hemoperitoneum develops. Other potential symptoms include presyncope, syncope, vomiting, diarrhea, shoulder pain, lower urinary tract symptoms, rectal pressure, or pain with defecation. 11

The physical examination can reveal signs of hemodynamic instability (e.g., hypotension, tachycardia) in women with ruptured ectopic pregnancy and hemoperitoneum. 12 Patients with unruptured ectopic pregnancy often have cervical motion or adnexal tenderness. 13 Sometimes the ectopic pregnancy itself can be palpated as a painful mass lateral to the uterus. There is no evidence that palpation during the pelvic examination leads to an increased risk of rupture. 10

BETA HUMAN CHORIONIC GONADOTROPIN

Beta human chorionic gonadotropin (β-hCG) can be detected in pregnancy as early as eight days after ovulation. 14 The rate of increase in β-hCG levels, typically measured every 48 hours, can aid in distinguishing normal from abnormal early pregnancy. In a viable intrauterine pregnancy with an initial β-hCG level less than 1,500 mIU per mL (1,500 IU per L), there is a 99% chance that the β-hCG level will increase by at least 49% over 48 hours. 15 As the initial β-hCG level increases, the rate of increase over 48 hours slows, with an increase of at least 40% expected for an initial β-hCG level of 1,500 to 3,000 mIU per mL (1,500 to 3,000 IU per L) and 33% for an initial β-hCG level greater than 3,000 mIU per mL. 15 A slower-than-expected rate of increase or a decrease in β-hCG levels suggests early pregnancy loss or ectopic pregnancy. The rate of increase slows as pregnancy progresses and typically plateaus around 100,000 mIU per mL (100,000 IU per L) at 10 weeks' gestation. 16 A decrease in β-hCG of at least 21% over 48 hours suggests a likely failed intrauterine pregnancy, whereas a smaller decrease should raise concern for ectopic pregnancy. 17

The discriminatory level is the β-hCG level above which an intrauterine pregnancy is expected to be seen on transvaginal ultrasonography; it varies with the type of ultrasound machine used, the sonographer, and the number of gestations. A combination of β-hCG level greater than the discriminatory level and ultrasonography that does not show an intrauterine pregnancy should raise concern for early pregnancy loss or an ectopic pregnancy. 5 The discriminatory zone was previously defined as a β-hCG level of 1,000 to 2,000 mIU per mL (1,000 to 2,000 IU per L); however, this cutoff can miss some intrauterine pregnancies that do not become apparent until a slightly higher β-hCG level is achieved. Therefore, in a desired pregnancy, it is recommended that a discriminatory level as high as 3,500 mIU per mL (3,500 IU per L) be used to avoid misdiagnosis and interruption of a viable pregnancy, although most pregnancies will be visualized by the time the β-hCG level reaches 1,500 mIU per mL. 18 , 19

TRANSVAGINAL ULTRASONOGRAPHY

Intrauterine pregnancy visualized on transvaginal ultrasonography essentially rules out ectopic pregnancy except in the exceedingly rare case of heterotopic pregnancy. 5 The definitive diagnosis of ectopic pregnancy can be made with ultrasonography when a yolk sac and/or embryo is seen in the adnexa; however, ultrasonography alone is rarely used to diagnose ectopic pregnancy because most do not progress to this stage. 5 More often, the patient history is combined with serial quantitative β-hCG levels, sequential ultrasonography, and, at times, uterine aspiration to arrive at a final diagnosis of ectopic pregnancy.

PREGNANCY OF UNKNOWN LOCATION

Ultrasonography showing neither intrauterine nor ectopic pregnancy in a patient with a positive pregnancy test is referred to as a pregnancy of unknown location. In a desired pregnancy, β-hCG levels and serial ultrasonography combined with patient reports of pain or bleeding guide management. 20 In an undesired pregnancy or when the possibility of a viable intrauterine pregnancy has been excluded, manual vacuum aspiration of the uterus can evaluate for chorionic villi that differentiate intrauterine pregnancy loss from ectopic pregnancy. If chorionic villi are seen, further workup is unnecessary, and exposure to methotrexate can be avoided  ( Figure 1 ) . 5 , 15 – 17 , 21 If chorionic villi are not seen after uterine aspiration, it is imperative to initiate treatment for ectopic pregnancy or repeat β-hCG measurement in 24 hours to ensure at least a 50% decrease. Ectopic precautions and serial β-hCG levels should be continued until the level is undetectable.

Management of Ectopic Pregnancy

It is appropriate for family physicians to treat hemodynamically stable patients in conjunction with their primary obstetrician. Patients with suspected or confirmed ectopic pregnancy who exhibit signs and symptoms of ruptured ectopic pregnancy should be emergently transferred for surgical intervention. If ectopic pregnancy has been diagnosed, the patient is deemed clinically stable, and the affected fallopian tube has not ruptured, treatment options include medical management with intramuscular methotrexate or surgical management with salpingostomy (removal of the ectopic pregnancy while leaving the fallopian tube in place) or salpingectomy (removal of part or all of the affected fallopian tube). The decision to manage the ectopic pregnancy medically or surgically should be informed by individual patient factors and preferences, clinical findings, ultrasound findings, and β-hCG levels. 12 Expectant management is rare but can be considered with close follow-up for patients with suspected ectopic pregnancy who are asymptomatic and have β-hCG levels that are very low and continue to decrease. 5

MEDICAL MANAGEMENT

Intramuscular methotrexate is the only medication appropriate for the management of ectopic pregnancy. A folate antagonist, it interrupts the rapidly dividing cells of the ectopic pregnancy, which are then resorbed by the body. 22 Its success rate decreases with higher initial β-hCG levels ( Table 3 ) . 23 Contraindications to methotrexate include renal insufficiency; moderate to severe anemia, leukopenia, or thrombocytopenia; liver disease or alcoholism; active peptic ulcer disease; and breastfeeding. 5 Therefore, a complete blood count and comprehensive metabolic panel should be obtained before it is administered.

Several methotrexate regimens have been studied, including a single-dose protocol, a two-dose protocol, and a multi-dose protocol ( Table 4 ) . 5 The single-dose protocol carries the lowest risk of adverse effects, whereas the two-dose protocol is more effective than the single-dose protocol in patients with higher initial β-hCG levels. 24 There is no consistent evidence or consensus regarding the cutoff above which a two-dose protocol should be used, so clinicians should choose a regimen based on the initial β-hCG level and ultrasound findings, as well as patient preference regarding effectiveness vs. the risk of adverse effects. In general, the single-dose protocol should be used in patients with β-hCG levels less than 3,600 mIU per mL (3,600 IU per L), and the two-dose protocol should be considered for patients with higher initial β-hCG levels, especially those with levels greater than 5,000 mIU per mL. Multidose protocols carry a higher risk of adverse effects and are not preferred. 25

Before administering methotrexate, β-hCG levels should be measured on days 1, 4, and 7 of treatment. The first measurement helps the clinician decide between the one- and two-dose protocols. Levels commonly increase between days 1 and 4, but should decrease by at least 15% between days 4 and 7. If this decrease does not occur, the clinician should discuss with the patient whether she prefers to repeat the course of methotrexate or pursue surgical treatment. If the β-hCG level does decrease by at least 15% between days 4 and 7, the patient should return for weekly β-hCG measurements until levels become undetectable, which can take up to eight weeks. 26

Close follow-up is critical for the safe use of methotrexate in women with ectopic pregnancies. Patients should be counseled that the risk of rupture persists until β-hCG levels are undetectable, and that they should seek emergency care if signs of ectopic pregnancy occur. It is common for patients to experience some abdominal pain two to three days after administration of methotrexate. This pain can be managed expectantly as long as there are no signs of rupture. 5 Gastrointestinal adverse effects (e.g., abdominal pain, vomiting, nausea) and vaginal spotting are common. Patients should be counseled to avoid taking folic acid supplements and nonsteroidal anti-inflammatory drugs, which can decrease the effectiveness of methotrexate, and to avoid anything that may mask the symptoms of ruptured ectopic pregnancy (e.g., narcotic analgesics, alcohol) and activities that increase the risk of rupture (e.g., vaginal intercourse, vigorous exercise). Sunlight exposure during treatment can cause methotrexate dermatitis and should be avoided. 5 Other adverse effects of methotrexate include alopecia and elevation of liver enzymes. Patients should be counseled to avoid repeat pregnancy until at least one ovulatory cycle after the serum β-hCG level becomes undetectable, although some experts recommend waiting three months so that the methotrexate can be cleared completely. 27 There is no evidence that methotrexate therapy affects future fertility. 28

SURGICAL MANAGEMENT

Overall, surgical management has a higher success rate for ectopic pregnancy than methotrexate. 5 The initial β-hCG level at which to transfer a patient for possible surgical treatment depends on local standards, although a level of 5,000 mIU per mL (5,000 IU per L) is commonly used. 5 , 11 Ultrasound visualization of an embryo with fetal cardiac activity outside of the uterus is an indication for urgent transfer for surgical management. 5 , 25 Additionally, social factors that preclude frequent laboratory testing (e.g., poor telephone access, work and family obligations, lack of transportation) can make surgical management the safer option 5 ( Table 5 5 , 11 ) . In cases where methotrexate is contraindicated or not preferred by the patient, surgical management can usually be performed laparoscopically if the patient is hemodynamically stable. Surgical options include salpingostomy or salpingectomy. Randomized trials have shown no difference in sequelae between methotrexate administration and fallopian tube–sparing laparoscopic surgery, including rates of future intrauterine pregnancy and risk of future ectopic pregnancy. 29 The decision whether to remove the fallopian tube or leave it in place depends on the extent of damage to the tube (evaluated intraoperatively) and the patient's desire for future fertility.

EXPECTANT MANAGEMENT

Expectant management can be considered for patients whose peak β-hCG level is below the discriminatory zone and is decreasing, but has plateaued or is decreasing more slowly than expected for a failed intrauterine pregnancy. 30 In cases where the initial β-hCG level is 200 mIU per mL (200 IU per L) or less, 88% of patients will have successful spontaneous resolution of the pregnancy; however, rates of spontaneous resolution decrease with higher β-hCG levels. 31 Patient counseling must include the risks of spontaneous rupture, hemorrhage, and need for emergency surgery. Patients who choose expectant management should have β-hCG levels monitored every 48 hours, and medical or surgical management should be recommended if β-hCG levels do not decrease sufficiently. 5

This article updates a previous article on this topic by Barash, et al. 12

Data Sources: An evidence summary from Essential Evidence Plus was reviewed and relevant studies referenced. Additionally, a PubMed search was completed in Clinical Queries using the key terms ectopic pregnancy, first trimester bleeding, and pregnancy of unknown location. The search included meta-analyses, guidelines, and reviews. Also searched were the Cochrane database, DynaMed, and the National Guideline Clearinghouse. Search dates: October 26, 2018, through January 14, 2020.

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The many faces of ectopic pregnancies: demystifying the common and less common entities

• Published: 05 September 2020
• Volume 46 , pages 1104–1114, ( 2021 )

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• F. Eymen Ucisik-Keser   ORCID: orcid.org/0000-0002-6083-7465 1 ,
• Eduardo J. Matta 1 ,
• Miguel G. Fabrega 1 ,
• Chitra Chandrasekhar 1 &
• Steven S. Chua 1  

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Ectopic pregnancy is a major cause of 1st trimester pregnancy deaths. It occurs in various locations in the abdominopelvic cavity. Ultrasonography is a first-line, rapid, and noninvasive modality for ectopic pregnancy evaluation. MRI can help clarify equivocal cases. When in doubt about the location, one should give an intrauterine pregnancy the benefit of the doubt with close ultrasound and hCG follow-up. Here, we will review the imaging findings and mimickers of ectopic pregnancies.

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Ucisik-Keser, F.E., Matta, E.J., Fabrega, M.G. et al. The many faces of ectopic pregnancies: demystifying the common and less common entities. Abdom Radiol 46 , 1104–1114 (2021). https://doi.org/10.1007/s00261-020-02681-6

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DOI : https://doi.org/10.1007/s00261-020-02681-6

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Ectopic Pregnancies

In an ectopic pregnancy, the embryo implants outside of the uterus, most typically in the fallopian tube. In rare cases, ectopic pregnancies in the abdomen or ovaries can proceed to term, 1 but in most cases, the embryo cannot continue to develop properly. Between 1% and 2% of all pregnancies are ectopic in the United States. 2 If a pregnancy is ectopic, the signs and symptoms begin between five and eight weeks gestation.

If the embryo grows too large inside the mother’s fallopian tube, the tube will rupture and bleed. Ectopic pregnancies are the leading cause of pregnancy-related death during the first twelve weeks of pregnancy because of the subsequent internal hemorrhage, accounting for 2.7% of these deaths. 3 The embryo cannot survive in the fallopian tube, and poses significant risk to the mother’s life, so the embryo is surgically removed or given drugs so that it stops growing. 4 Several studies have observed that only 5-7% of embryos in ectopic pregnancies are still alive when the ectopic implantation is first detected. 5 Even when the embryo has died, removing the remains is important for the health of the mother, because cells of the deceased embryo can continue to multiply, and cause the mother’s fallopian tubes to rupture. 6

Sometimes, the embryo is still alive after it has been removed. The first direct observations of fetal movements in response to a light touch came from embryos removed from ectopic pregnancies. Researchers stroked different body parts with a thin paintbrush to discover how the embryos moved in response. 7 As ultrasound technology improved, it confirmed the movement patterns seen in the ectopic embryos. 8

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• Tyler Mummert and David M. Gnugnoli, “Ectopic Pregnancy,” in StatPearls (Treasure Island (FL): StatPearls Publishing, 2021), http://www.ncbi.nlm.nih.gov/books/NBK539860/.
• Centers for Disease Control . 2012. “Ectopic Pregnancy Mortality—Florida, 2009–2010. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6106a2.htm?s_cid=mm6106a2_w; Bollig, K. J., Friedlander, H., & Schust, D. J. (2023). Ectopic Pregnancy and Lifesaving Care. JAMA . doi:10.1001/jama.2023.7292
• Condic, M. L., & Harrison, D. (2018). Treatment of an Ectopic Pregnancy: An Ethical Reanalysis. The Linacre Quarterly, 85(3), 241-251. https://doi.org/10.1177/0024363918782417.
• Frates, M. C., Doubilet, P. M., Peters, H. E., & Benson, C. B. (2014). Adnexal sonographic findings in ectopic pregnancy and their correlation with tubal rupture and human chorionic gonadotropin levels. Journal of Ultrasound in Medicine, 33(4), 697-703; Al Naimi, A., Moore, P., Brüggmann, D., Krysa, L., Louwen, F., & Bahlmann, F. (2021). Ectopic pregnancy: a single-center experience over ten years. Reproductive Biology and Endocrinology, 19(1), 1-6. https://doi.org/10.1186/s12958-021-00761-w.
• Tryphena Humphrey, “Some Correlations between the Appearance of Human Fetal Reflexes and the Development of the Nervous System,” in Progress in Brain Research , ed. Dominick P. Purpura and J. P. Schadé, vol. 4, Growth and Maturation of the Brain (Elsevier, 1964), 93–135, https://doi.org/10.1016/S0079-6123(08)61273-X.
• Hepper, P.G. “Unravelling Our Beginnings | The Psychologist,” 2005. https://thepsychologist.bps.org.uk/volume-18/edition-8/unravelling-our-beginnings.

All images and illustrations on The Voyage of Life were reviewed by credentialed scientists for accuracy.

Medical art animation was used to provide a schematic representation of fetal development, with some features, including timing, not to scale. The animation was chosen as an ethically uncompromised guide to fetal development. There are many real human images at each developmental age showing the most accurate fetal forms throughout development. A concerted effort was made to use images and material in which the human embryo or fetus did not undergo any known harm.

• Ectopic pregnancy

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When to see a doctor, risk factors, complications.

Pregnancy begins with a fertilized egg. Normally, the fertilized egg attaches to the lining of the uterus. An ectopic pregnancy occurs when a fertilized egg implants and grows outside the main cavity of the uterus.

An ectopic pregnancy most often occurs in a fallopian tube, which carries eggs from the ovaries to the uterus. This type of ectopic pregnancy is called a tubal pregnancy. Sometimes, an ectopic pregnancy occurs in other areas of the body, such as the ovary, abdominal cavity or the lower part of the uterus (cervix), which connects to the vagina.

An ectopic pregnancy can't proceed normally. The fertilized egg can't survive, and the growing tissue may cause life-threatening bleeding, if left untreated.

In a healthy pregnancy, the fertilized egg attaches itself to the lining of the uterus. In an ectopic pregnancy, the egg attaches itself somewhere outside the uterus usually to the inside of a fallopian tube.

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You may not notice any symptoms at first. However, some women who have an ectopic pregnancy have the usual early signs or symptoms of pregnancy — a missed period, breast tenderness and nausea.

If you take a pregnancy test, the result will be positive. Still, an ectopic pregnancy can't continue as normal.

As the fertilized egg grows in the improper place, signs and symptoms become more noticeable.

Early warning of ectopic pregnancy

Often, the first warning signs of an ectopic pregnancy are light vaginal bleeding and pelvic pain.

If blood leaks from the fallopian tube, you may feel shoulder pain or an urge to have a bowel movement. Your specific symptoms depend on where the blood collects and which nerves are irritated.

Emergency symptoms

If the fertilized egg continues to grow in the fallopian tube, it can cause the tube to rupture. Heavy bleeding inside the abdomen is likely. Symptoms of this life-threatening event include extreme lightheadedness, fainting and shock.

Seek emergency medical help if you have any signs or symptoms of an ectopic pregnancy, including:

• Severe abdominal or pelvic pain accompanied by vaginal bleeding
• Extreme lightheadedness or fainting
• Shoulder pain

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A tubal pregnancy — the most common type of ectopic pregnancy — happens when a fertilized egg gets stuck on its way to the uterus, often because the fallopian tube is damaged by inflammation or is misshapen. Hormonal imbalances or abnormal development of the fertilized egg also might play a role.

Some things that make you more likely to have an ectopic pregnancy are:

• Previous ectopic pregnancy. If you've had this type of pregnancy before, you're more likely to have another.
• Inflammation or infection. Sexually transmitted infections, such as gonorrhea or chlamydia, can cause inflammation in the tubes and other nearby organs, and increase your risk of an ectopic pregnancy.
• Fertility treatments. Some research suggests that women who have in vitro fertilization (IVF) or similar treatments are more likely to have an ectopic pregnancy. Infertility itself may also raise your risk.
• Tubal surgery. Surgery to correct a closed or damaged fallopian tube can increase the risk of an ectopic pregnancy.
• Choice of birth control. The chance of getting pregnant while using an intrauterine device (IUD) is rare. However, if you do get pregnant with an intrauterine device (IUD) in place, it's more likely to be ectopic. Tubal ligation, a permanent method of birth control commonly known as "having your tubes tied," also raises your risk, if you become pregnant after this procedure.
• Smoking. Cigarette smoking just before you get pregnant can increase the risk of an ectopic pregnancy. The more you smoke, the greater the risk.

An ectopic pregnancy can cause your fallopian tube to burst open. Without treatment, the ruptured tube can lead to life-threatening bleeding.

There's no way to prevent an ectopic pregnancy, but here are some ways to decrease your risk:

• Limiting the number of sexual partners and using a condom during sex helps to prevent sexually transmitted infections and may reduce the risk of pelvic inflammatory disease.
• Don't smoke. If you do, quit before you try to get pregnant.

Mar 12, 2022

• Cunningham FG, et al., eds. Implantation and placental development. In: Williams Obstetrics. 25th ed. McGraw-Hill Education; 2018. https://accessmedicine.mhmedical.com. Accessed Dec. 4, 2019.
• Tulandi T. Ectopic pregnancy: Epidemiology, risk factors, and anatomic sites. https://www.uptodate.com/contents/search. Accessed Dec. 4, 2019.
• Cunningham FG, et al., eds. Ectopic pregnancy. In: Williams Obstetrics. 25th ed. McGraw-Hill Education; 2018. https://accessmedicine.mhmedical.com. Accessed Dec. 4, 2019.
• Frequently asked questions. Pregnancy FAQ 155. Ectopic pregnancy. American College of Obstetricians and Gynecologists. https://www.acog.org/Patients/FAQs/Ectopic-Pregnancy. Accessed Dec. 4, 2019.
• Tulandi T. Ectopic pregnancy: Clinical manifestations and diagnosis. https://www.uptodate.com/contents/search. Accessed Dec. 29, 2017.
• Burnett TL (expert opinion). Mayo Clinic. Dec. 4, 2019.
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What Is an Ectopic Pregnancy? Here Are the Signs to Look For

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What is an ectopic pregnancy?

Read this next, what are the causes of an ectopic pregnancy, what are the symptoms of an ectopic pregnancy, what are the risk factors for an ectopic pregnancy, ectopic pregnancy tests and diagnosis, ectopic pregnancy treatment, laparoscopic surgery, ectopic pregnancy complications, preventing an ectopic pregnancy, coping with pregnancy loss, getting pregnant again after an ectopic pregnancy.

While it’s true that having an ectopic pregnancy does place you at a higher risk for another, you may be able to change several lifestyle factors (such as smoking) to lessen that chance. Talk to your doctor about the possible causes and discuss what you can do to reduce your future risk factors. And again, know that most women who have had an ectopic pregnancy later go on to have a healthy one. 

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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

StatPearls [Internet].

Ectopic pregnancy, ultrasound.

Mark Baker ; Jonathan dela Cruz .

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Last Update: January 16, 2023 .

• Continuing Education Activity

Ectopic pregnancy is a diagnosis that is quite challenging to make. It has been estimated that 40% of ectopic pregnancies go undiagnosed on initial presentation. Ectopic pregnancy is also a very difficult condition to identify based on history and physical, with both the history and physical examination features being neither sensitive nor specific for the diagnosis. Data suggests that even experienced gynecologists are unable to detect more than half of the masses created by ectopic pregnancy on physical exam. Due to these nature of the condition, laboratory data and diagnostic imaging are essential components of diagnosing ectopic pregnancy. Ultrasonography is the diagnostic imaging study of choice for ectopic pregnancy. Even if an ectopic pregnancy cannot be visualized on ultrasound, diagnosing an intrauterine pregnancy greatly reduces the risk of an ectopic pregnancy being present. This activity reviews ectopic pregnancy and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

• Identify the indications for an ultrasound in a patient with abdominal pain.
• Describe the equipment and technique involved in performing a transvaginal ultrasound.
• Summarize the steps involved in performing a transabdominal ultrasound to rule out an ectopic pregnancy.
• Outline interprofessional team strategies for improving care coordination and communication to advance the diagnosis and management of ectopic pregnancies to improve patient outcomes.
• Introduction

Ectopic pregnancy is a diagnosis that is quite challenging to make. It has been estimated that 40% of ectopic pregnancies go undiagnosed on initial presentation. [1] Ectopic pregnancy is also a very difficult condition to identify based on history and physical, with both the history and physical examination features being neither sensitive nor specific for the diagnosis. Data suggests that even experienced gynecologists are unable to detect more than half of the masses created by ectopic pregnancy on physical exam. [2] Due to these natures of the condition, laboratory data and diagnostic imaging are essential components of diagnosing ectopic pregnancy. Ultrasonography is the diagnostic imaging study of choice for ectopic pregnancy. Even if an ectopic pregnancy cannot be visualized on ultrasound, diagnosing an intrauterine pregnancy greatly reduces the risk of an ectopic pregnancy being present. Two ultrasonographical approaches exist for evaluation of ectopic pregnancy. The first is the less invasive transabdominal ultrasound, and the second is the more invasive but more diagnostic endovaginal ultrasonography. [3] [4]

• Anatomy and Physiology

As a basic anatomical review, the introitus is the vaginal canal, where the cervix of the uterus leads into the main body. Bilateral fallopian tubes and fimbria lead to the ovaries. An anatomical understanding is necessary when reviewing the ultrasound images and clips to understand what are normal and abnormal structures.

The common location of ectopic pregnancies differs between whether the patient had a natural conception or assisted reproductive technologies such as in vitro fertilization. In natural conception, 95% of the ectopic pregnancies will be tubal, 1.4% will be abdominal, and less than 1% will be cervical or ovarian. With assisted reproductive technologies, 82% of ectopic pregnancies will be tubal with a primary ampullary predominance. Approximately 11% of ectopic pregnancies after assisted reproductive technologies will be heterotopic, which is a vast difference from natural conception. Understanding these differences stresses the importance of obtaining a history of the method of conception.

• Indications

If the diagnosis of ectopic pregnancy is being considered, ultrasonography is an essential part of the diagnostic evaluation. Ectopic pregnancy must be considered as a potentially life-threatening diagnosis in any female of childbearing age presenting with abdominal pain, pelvic pain, or vaginal bleeding. If a beta human chorionic gonadotropin (beta hCG) is positive, an ectopic pregnancy must rise on a differential and be ruled out before a patient can be safely sent home. If the beta hCG is negative, an ectopic pregnancy is much less likely, but there have been rare case reports of ectopic pregnancies being identified in this state, notably when a qualitative urine beta hCG is ordered rather than a quantitative serum beta hCG level. [5]

• Contraindications

There is only one absolute contraindication to transvaginal ultrasonography, and there are no absolute contraindications to transabdominal imaging. The contraindication for transvaginal imaging is recent gynecologic surgery, which is an exceedingly rare situation for patients potentially in their first trimester.

Special considerations should be made when determining how the imaging should be completed. Obesity potentially limits the diagnostic ability of transabdominal imaging so that these patients may be better served with transvaginal imaging. Patients with vaginal trauma may have difficulties with the transvaginal approach due to pain. Another consideration is patient age. Younger patients may not have had pelvic examinations previously, and transvaginal ultrasonography may provoke anxiety in these patients. It may be reasonable to start with transabdominal imaging and use transvaginal imaging as a second line alternative. [3]

Transabdominal imaging is classically completed using a curvilinear probe in an obstetrical examination mode. A standard stretcher is appropriate for this examination mode as the patient will be lying supine.

Transvaginal imaging requires an endocavitary probe and a probe cover, usually a condom. The gel is needed inside the condom, and sterile water gel is needed for outside of the condom. This probe is usually higher frequency than the transabdominal probe, allowing for higher resolution at the shallow depths that are used from the transvaginal approach. An obstetrical stretcher with stirrups is the ideal stretcher for patient positioning. Alternatively, the patient may be placed on a pelvic pillow, allowing the pelvis to be elevated off the bed and for the probe handle to be angled below the level of the patient's buttocks.

The initial ultrasound images may be performed at the bedside when evaluating for intrauterine versus ectopic pregnancy. This is especially important in a hemodynamically unstable patient where obstetrical services for immediate consultation may not be available. Emergency physicians have been trained primarily and transabdominal ultrasonography, though there is a growing movement toward increasing training for transvaginal ultrasonography as well. The diagnosis may be made at this initial exam, but many times the examination is indeterminate. Out of these cases, the literature suggests that there are poor fetal and maternal outcomes, clearly indicating the need for formal diagnostic imaging by trained ultrasonography technicians in these patients.

• Preparation

The transabdominal examination is best performed with a curvilinear probe but may be performed using a phased array probe. To best evaluate the patient in the transabdominal views, the patient must be well hydrated and have a full bladder, creating an acoustic window. Intravenous fluids, oral hydration, or Foley catheter fluid insertion are appropriate methods for hydration, depending on the urgency of the workup.  Posterior enhancement, the artifact created when acoustic waves pass through a fluid-filled structure, may make it difficult to visualize the far field of the image.  It may be difficult to adjust the gain enough to correct this. The patient should be placed in a gown and sheets should be available to minimize exposure of the patient during evaluation.

In contrast to transabdominal preparation, transvaginal examination requires the patient to have an empty bladder. The patient is best able to be examined if she is positioned in stirrups on an obstetrical stretcher. A pelvic pillow is an alternative which allows the pelvis to be lifted off a standard stretcher. The probe should then be prepared for optimal acoustic transmission and maximal patient safety. This is done using a probe cover, typically a latex condom or synthetic alternative, with gel on the probe head beneath the condom. Any air bubbles need to be pressed off the probe head, as air will impede the ultrasound waves. Sterile, water-soluble lubricant should be used on the exterior of the condom as there is a theoretical risk of infection from ultrasound gel and some women find the gel irritating. The depth will likely require adjustment to optimize the visual field.

• Technique or Treatment

Obstetrical examination mode minimizes radiation exposure and should be used for all obstetric evaluation in accordance with the "As Low As (is) Reasonably Achievable" (ALARA) practice standard.

The base technique for both the transabdominal and transvaginal evaluation for ectopic pregnancy is the routine obstetric evaluation, as identifying a live intrauterine pregnancy greatly decreases the chances of an ectopic pregnancy being present as previously discussed.

Transabdominal Examination [3]

The transabdominal view is obtained with the patient in supine position on a stretcher with a full bladder. The probe is placed in the longitudinal plane (indicator towards the head of the patient) in the midline above the symphysis pubis. If the probe is placed too far cephalad, the bladder will not be able to be optimally used as an acoustic window and bowel gas may obstruct the view. The bladder and uterus should be identified.  Probe position and depth should be adjusted to center the uterus in the visual field. An adequate view of the uterus will have the length of the uterus on the screen with the cervix and part of the vagina being visualized. The endometrial stripe is a hyperechoic structure in the center of the uterus. Caution should be taken when identifying fluid surrounding the suspected pregnancy. If this is the focus of the examination instead of the endometrial stripe, an ectopic pregnancy may be mistaken as an intrauterine pregnancy. In the longitudinal view, the endometrial stripe and uterus will have elongated appearances. When switching to the transverse view, the uterus will be circular. While in the transverse view, the entire length of the uterus needs to be swept through, paying attention to the uterine tissue as well as the area around the uterus. This is the most difficult step as it is difficult to avoid bowel gas and follow the uterus through the entire length of the sweep. The bladder will be at the top of the screen and the uterus will be a round structure just far field to the bladder. The distal portion of the field the uterus to be centered in the screen so the entire area around the uterus can be visualized. A common mistake is incorrectly identified in the vagina as the uterus. To distinguish this, it is important to recognize that the endometrial stripe, while in the transverse view, will be a dot or oval while the vaginal stripe will appear to be a line going across the screen. If the uterus is anteverted, both the vagina and the uterus may be visualized in the same image. To ensure that uterine tissue is being visualized, use the bladder as a landmark, as this should be immediately adjacent to the uterus. This is one advantage of the abdominal approach, as the bladder is more easily visualized and any masses between the bladder and uterus should be clearer than with the transvaginal view. Free fluid between the bladder and uterus, a mass between the bladder and uterus, or free fluid anywhere around the uterus is a concerning finding for possible ectopic pregnancy in the transabdominal views. Masses posterior to the uterus may be more difficult to identify. If an intrauterine pregnancy is identified in the transabdominal view in a patient with a low index of suspicion for heterotopic pregnancy, the transvaginal views may not be necessary unless further diagnostic workup is desired for the pregnancy.

Transvaginal Examination

The initial approach is with the probe in the sagittal plane, with the indicator pointed towards the ceiling. There should be a tactile indicator on the handle of the probe to assist in orientation of the ultrasound. The probe should be inserted approximately 4 to 5 centimeters. The first step during the transvaginal examination is identified in the bladder, and subsequently of the juxtaposition between the bladder and the uterus. Confirming this juxtaposition is a critical step, as it makes it much less likely that the examination is being performed in the adnexa. To identify the bladder, the handle should be moved towards the stretcher thereby directing the probe head towards the ceiling. The opposing handle and probe head directions of movement make this a more difficult exam to maintain spatial awareness. The area of interest of the examination will be the uterine tissue in the endometrial stripe in the center. In the sagittal view, with the indicator towards the ceiling, the uterus will be oblong, and the endometrial stripe will be a line. Similar to the transabdominal view, the uterus needs to be centered on the screen, so the fundus and the surrounding tissue is not excluded from the field-of-view. When the uterus is centered, a side-to-side sweep is performed in the sagittal plane. This should be done slowly to visualize the entire uterus adequately. This needs to be done until the uterus completely disappears from the screen in each direction. After this, the probe will be rotated 90 degrees with the indicator pointing towards the patient's right in a coronal plane. The length of the uterus should be swept through again, this time with the probe handle moving up and down rather than right and left.  If there is no intrauterine pregnancy identified in a pregnant patient with a beta hCG greater than 2000, the patient should be considered to have an ectopic pregnancy until proven otherwise. Signs of free fluid around the uterus, masses between the uterus and the bladder, masses in the adnexa, or an identifiable pregnancy outside of the uterus are concerning or diagnostic of an ectopic pregnancy.

• Clinical Significance

The clinical impact of diagnosis timely diagnosis of ectopic pregnancy cannot be understated. There are significant morbidity and mortality associated with ectopic pregnancy, and early diagnosis can have a significant impact in reducing both of these. As previously mentioned, there is a role for bedside performance of these examinations, and this should be part of standard emergency physician and obstetrician training. After completing the ultrasounds, whether bedside or elective imaging, the images should be reviewed in detail as there are many signs of potential ectopic pregnancy to identify. The most reliable sign of ectopic pregnancy is the visualization of extrauterine gestation. However, this is found in the minority of ectopic pregnancies. A key concept to reiterate his the use of beta hCG levels when reviewing the ultrasonography images. The diagnosis ectopic pregnancy should be considered with elevated beta hCG levels with the absence of an intrauterine pregnancy on ultrasound. The discriminatory zone is the titer of hCG where an intrauterine sac should be seen with transvaginal ultrasonography and normal pregnancy.  There are varying standards for discriminatory zones, but 1500 to 2000 mIU/mL of hCG has been accepted in the past.  [6] [7]  If there is a practice standard for your institution, that should be taken into account. However, caution should also be exercised with using the discriminatory zone, as emergency department patients with hCG levels lower than 1500 mIU/mL have been shown to have a two-fold risk increase for ectopic pregnancy. The discriminatory zone also does not take into account the possibility of multiple gestations, where the intrauterine sac or sacs may still be too small to visualize despite higher levels of beta hCG. There are findings on ultrasound that are indicative of possible ectopic pregnancy. Positive findings include an empty uterine cavity, decidual cast, a thick echogenic endometrium, or a pseudo-gestational sac in the presence of beta hCG levels above the discriminatory zone. [6] In the peritoneal cavity, free pelvic fluid or hemoperitoneum in the pouch of Douglas in the presence of a positive beta hCG is 70% specific for ectopic pregnancy and 63% sensitive. A live pregnancy identified in the peritoneal cavity is 100% specific but is rarely identified. In the adnexal area, viewing the fallopian tubes and ovaries, there are multiple signs consistent with potential ectopic pregnancies. Simple adnexal cysts and the presence of positive beta hCG levels have approximately a 10% chance of being an ectopic pregnancy. A complex extra adnexal cyst or mass has a 95% chance of being a tubal ectopic if there is no intrauterine pregnancy identified. If this is within the adnexa, it is much more likely to be a corpus luteum ectopic pregnancy. Any solid mass in the adnexa may be ectopic but is not specific. A tubal ring sign is a sign of a tubal ectopic in which there is an echogenic ring surrounding a likely unruptured ectopic pregnancy, with a reported 95% positive predictive value.

• Enhancing Healthcare Team Outcomes

The diagnosis and management of an ectopic pregnancy is made by an interprofessional team that includes the emergency department physician, radiologist, obstetrician and the nurse practitioner. No patient should be discharged home if an ectopic is suspected.

Ectopic pregnancies are a common gynecologic emergency that typically are impacting otherwise healthy individuals and can have significant morbidity and mortality. Continued improvement in the ultrasonographic evaluation of these patients will aid in decreasing the mortality that continues to be associated with ruptured ectopic pregnancies. [8] [9] [10]

• Nursing, Allied Health, and Interprofessional Team Interventions

The initial action that is needed by the nurse at the time of patient presentation when there is a possibility of an ectopic pregnancy is to establish the patient safety net, consisting of obtaining a full set of vital signs, placing the patient on the monitor, and obtaining at least one large bore intravenous line.  If the local nursing scope of practice includes drawing blood for labs, that will be needed as well for these patients. 

If the patient is stable, the next nursing action will be to hydrate the patient. The transabdominal portion of the ultrasound assessment is best performed with a full bladder. Oral hydration is able to help with this, but intravenous fluid administration is another option, depending on if the patient is being allowed to take anything orally at that time.  It is important to coordinate the hydration status with the provider performing the ultrasound as it can be very uncomfortable for the patient if she is required to hold a full bladder for an extended time.

After the diagnosis of an ectopic pregnancy is established, it will be important for the nurse to be a patient advocate.  The patient should be given mental support and institutions may have support systems in place for mothers who have been diagnosed with a nonviable pregnancy.

• Nursing, Allied Health, and Interprofessional Team Monitoring

Any patient with a suspected ectopic pregnancy needs to have a full set of vital signs on initial presentation.  Frequent reassessments of the blood pressure and heart rate are important to clue the team towards the development of shock from a ruptured ectopic pregnancy.

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TA long image of a normal uterus Contributed by StatPearls

Ectopic pregnancy. Transabdominal probe showing a gestational sac and fetal pole, not within the uterus. Contributed by Ami Kurzweil, MD

This image demonstrates an ectopic pregnancy via ultrasound. Contributed by Kenn Ghaffarian, DO

Disclosure: Mark Baker declares no relevant financial relationships with ineligible companies.

Disclosure: Jonathan dela Cruz declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Baker M, dela Cruz J. Ectopic Pregnancy, Ultrasound. [Updated 2023 Jan 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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• Complicated first-trimester pregnancies: evaluation with endovaginal US versus transabdominal technique. [Radiology. 1987] Complicated first-trimester pregnancies: evaluation with endovaginal US versus transabdominal technique. Pennell RG, Baltarowich OH, Kurtz AB, Vilaro MM, Rifkin MD, Needleman L, Mitchell DG, Mervis SA, Goldberg BB. Radiology. 1987 Oct; 165(1):79-83.
• Diagnosis of ectopic pregnancy: endovaginal vs transabdominal sonography. [AJR Am J Roentgenol. 1990] Diagnosis of ectopic pregnancy: endovaginal vs transabdominal sonography. Thorsen MK, Lawson TL, Aiman EJ, Miller DP, McAsey ME, Erickson SJ, Quiroz F, Perret RS. AJR Am J Roentgenol. 1990 Aug; 155(2):307-10.
• Endovaginal sonographic evaluation of ectopic pregnancy: a prospective study. [AJR Am J Roentgenol. 1987] Endovaginal sonographic evaluation of ectopic pregnancy: a prospective study. Nyberg DA, Mack LA, Jeffrey RB Jr, Laing FC. AJR Am J Roentgenol. 1987 Dec; 149(6):1181-6.
• Review [Ultrasonography in acute pelvic pain]. [Acta Med Croatica. 2002] Review [Ultrasonography in acute pelvic pain]. Kupesić S, Aksamija A, Vucić N, Tripalo A, Kurjak A. Acta Med Croatica. 2002; 56(4-5):171-80.
• Review Clinical diagnosis of ectopic pregnancy. [Clin Obstet Gynecol. 1987] Review Clinical diagnosis of ectopic pregnancy. Weckstein LN. Clin Obstet Gynecol. 1987 Mar; 30(1):236-44.

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