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Ectopic Pregnancy

Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Affected patients may suffer from acute abdominal pain as the developing embryo increases in size and/or from vaginal bleeding; if the pregnancy ruptures, internal bleeding can be significant and lead to hemodynamic instability and hemorrhagic shock. Diagnosis involves measures of serum human chorionic gonadotropin (hCG) levels and transvaginal ultrasonography; often, serial assessments are required over several days to establish the correct diagnosis. Management can be expectant, medical, or surgical depending on the clinical situation. Severe cases involving rupture of the fallopian tube and hemorrhage are considered a medical emergency and require immediate surgery. 

Last updated: Feb 16, 2023

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Epidemiology and Etiology

Epidemiology

Etiology

Ectopic pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care (EP) can occur when the fertilized egg does not enter the uterine cavity by way of the fallopian tube Fallopian Tube A pair of highly specialized canals extending from the uterus to its corresponding ovary. They provide the means for ovum transport from the ovaries and they are the site of the ovum’s final maturation and fertilization. The fallopian tube consists of an interstitium, an isthmus, an ampulla, an infundibulum, and fimbriae. Its wall consists of three layers: serous, muscular, and an internal mucosal layer lined with both ciliated and secretory cells. Uterus, Cervix, and Fallopian Tubes: Anatomy by the 5th to 6th day of gestation. 

  • Caused by:
    • Abnormal passage of the embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week through the fallopian tube Fallopian Tube A pair of highly specialized canals extending from the uterus to its corresponding ovary. They provide the means for ovum transport from the ovaries and they are the site of the ovum’s final maturation and fertilization. The fallopian tube consists of an interstitium, an isthmus, an ampulla, an infundibulum, and fimbriae. Its wall consists of three layers: serous, muscular, and an internal mucosal layer lined with both ciliated and secretory cells. Uterus, Cervix, and Fallopian Tubes: Anatomy
    • Tubal passage may be affected by:
  • Risk factors:
    • Pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease (50% of cases, increases risk 3-fold) 
    • Adhesions after tubal surgery (25% of cases)
    • Assisted reproduction (e.g., in vitro fertilization In vitro fertilization An assisted reproductive technique that includes the direct handling and manipulation of oocytes and sperm to achieve fertilization in vitro. Infertility ( IVF IVF An assisted reproductive technique that includes the direct handling and manipulation of oocytes and sperm to achieve fertilization in vitro. Infertility))
    • Prior EP
    • Abnormal endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development (e.g., endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis or fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility)
    • Congenital Congenital Chorioretinitis malformation of the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy ( bicornuate uterus Bicornuate Uterus Congenital Malformations of the Female Reproductive System)
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
    • Advanced age (> 35 years old)
    • Intrauterine device/oral contraceptives (if pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care occurs despite their use)
  • Potential locations of implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week:
    • 90%‒95% within the fallopian tube Fallopian Tube A pair of highly specialized canals extending from the uterus to its corresponding ovary. They provide the means for ovum transport from the ovaries and they are the site of the ovum’s final maturation and fertilization. The fallopian tube consists of an interstitium, an isthmus, an ampulla, an infundibulum, and fimbriae. Its wall consists of three layers: serous, muscular, and an internal mucosal layer lined with both ciliated and secretory cells. Uterus, Cervix, and Fallopian Tubes: Anatomy 
    • 3% in the ovary
    • 1% in the peritoneal cavity Peritoneal Cavity The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of winslow, or epiploic foramen. Peritoneum: Anatomy (abdominal)
    • 1% in a cesarean scar Scar Dermatologic Examination
    • < 1% in the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy
Types of ectopic pregnancy

Different types of EP according to location

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Clinical Presentation

Ectopic pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care can present before, during, or after rupture. Early on (prior to rupturing), symptoms can be relatively mild, such as light bleeding or cramping. If the pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care does not spontaneously abort, it will eventually rupture, leading to a potentially massive internal hemorrhage.

  • Common presentation: vaginal bleeding and/or pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in the setting of a positive pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test (early in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care)
    • Bleeding is often light.
    • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways:
      • Typically menstrual-like cramping
      • May be unilateral or diffuse
  • Signs of a ruptured ectopic pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:
    • Acute abdomen Acute Abdomen Acute abdomen, which is in many cases a surgical emergency, is the sudden onset of abdominal pain that may be caused by inflammation, infection, perforation, ischemia, or obstruction. The location of the pain, its characteristics, and associated symptoms (e.g., jaundice) are important tools that help narrow the differential diagnosis. Acute Abdomen:
    • Hemodynamic instability: Rupture causes significant internal bleeding and may lead to hypovolemic shock Hypovolemic Shock Types of Shock.
  • General pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care symptoms:
  • Pelvic exam:
    • Cervical motion tenderness
    • Closed cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy
    • Adnexal tenderness
    • An adnexal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast may be felt in 10%–20% of cases.

Diagnosis

Labs

  • Very important: Perform a pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test on all women of reproductive age who present with abdominal pain Abdominal Pain Acute Abdomen
    • Typically start with a rapid urine hCG test.
    • If the rapid urine hCG test is positive and the individual has symptoms (e.g., bleeding, cramping), order a quantitative serum hCG
  • Type and screen: blood type and Rh factor Rh Factor Blood Group Systems (if negative, RhoGam is required)
  • Complete blood count (CBC): to look for anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types/evidence of hemorrhage
  • Liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests (LFTs), basic metabolic panel Basic Metabolic Panel Primary vs Secondary Headaches ( BMP BMP Primary vs Secondary Headaches), urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children (UA): to evaluate for other causes of acute abdomen Acute Abdomen Acute abdomen, which is in many cases a surgical emergency, is the sudden onset of abdominal pain that may be caused by inflammation, infection, perforation, ischemia, or obstruction. The location of the pain, its characteristics, and associated symptoms (e.g., jaundice) are important tools that help narrow the differential diagnosis. Acute Abdomen and look for contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to methotrexate Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy (a treatment for EP)

Date the pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care based on the last menstrual period Last menstrual period The 1st day of a woman’s last menstrual period. By convention, this date is usually used to date pregnancies. Pregnancy: Diagnosis, Physiology, and Care ( LMP LMP The 1st day of a woman’s LMP Pregnancy: Diagnosis, Physiology, and Care)

Diagnostic studies

Ultrasonography is the imaging method of choice and the gold standard for evaluating early pregnancies.

Ultrasonography:

  • Should be performed immediately in all individuals with a positive pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test and symptoms (e.g., bleeding, cramping) to determine the location and viability of the pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care.
  • Normal pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:
    • At 5–6 weeks’ gestation, a gestational sac and yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development are present within the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy.
    • Presence of a fetal pole with a heartbeat: seen around 5.5–6 weeks’ gestation age
  • EP findings:
    • An empty uterine cavity without an amniotic sac or with a pseudo-gestational sac (a collection of fluid within the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy that appears becaue of the hormonal milieu of an ectopic pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care; will never contain a yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development, which is an embryonic structure)
    • Adnexal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast, especially when it contains a hypoechoic Hypoechoic A structure that produces a low-amplitude echo (darker grays) Ultrasound (Sonography) area and is separate from the ovary (Note: Fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy are not normally visible on an ultrasound.)
    • Definitive diagnosis: visualization of a gestational sac with a yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development, embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week, or both outside the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy (most do not progress to this stage)
  • In the case of tubal rupture, free fluid (blood) is present in the pouch of Douglas Pouch of Douglas A sac or recess formed by a fold of the peritoneum. Ovaries: Anatomy.
  • Possible to determine if the embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week is alive by the detection of a fetal heartbeat

Management

An EP must be closely monitored. The management of an EP can be expectant, medical, or surgical depending on the patient’s condition, hCG trend, and additional maternal and fetal factors.

Emergency management

In cases where the individual is hemodynamically unstable owing to a ruptured ectopic pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:

  • Assess and stabilize ABCs ( airway Airway ABCDE Assessment, breathing, circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment). 
  • Give intravenous fluids Intravenous Fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids to compensate for blood loss.
  • Transfusion if blood loss is significant
  • If the patient has an Rh-negative blood type: Administer RhoGam to prevent Rh incompatibility Rh Incompatibility Hemolytic Disease of the Fetus and Newborn in future pregnancies.
  • Urgent surgical consultation

Medical management

  • Reserved for hemodynamically stable patients Hemodynamically Stable Patients Blunt Chest Trauma with an unruptured mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast and without any contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation
  • Methotrexate Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy (IM or, occasionally, injected directly into the EP) to induce a medical abortion Abortion Expulsion of the product of fertilization before completing the term of gestation and without deliberate interference. Spontaneous Abortion
  • Must monitor the patient’s hCG levels to 0
  • Adverse effects of methotrexate Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy:
    • Bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis suppression Suppression Defense Mechanisms
    • Pulmonary fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
    • Hepatic cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
    • Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
    • Gastric ulcers

Surgical management

  • Indications:
    • Hemodynamic instability
    • Symptoms of a ruptured ectopic pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to methotrexate Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy
    • Failure of methotrexate Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy
    • Patient preference for surgery over methotrexate Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy
    • Indications for concurrent surgical procedure (e.g., individual desires tubal sterilization Tubal sterilization Procedures that render the female sterile by interrupting the flow in the fallopian tube. These procedures generally are surgical, and may also use chemicals or physical means. Reproductive Ethical Issues)
  • Laparoscopic approach is preferred (over open).
  • Options include:
    • Salpingectomy:
      • Removal of the entire tube, including the EP
      • Definitive treatment
    • Salpingotomy:
      • Opening the tube and removing only the pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
      • Possible for trophoblastic tissue to persist → hCG should be followed to 0
  • Discuss pros/ cons CoNS Staphylococcus of salpingectomy vs salpingotomy with individual prior to surgery noting that it may be impossible to save the tube.

Expectant management

  • Only for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who meet the following criteria:
    • Asymptomatic
    • No evidence of extrauterine sac/ mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast on ultrasound
    • Low and decreasing serum hCG (evidence of spontaneous resolution)
    • Agreeable to close follow-up
  • Steps include:
    • Monitoring the pattern of serial hCG levels → follow levels all the way to 0
    • Giving strict return-for-followup instructions to ensure that hCG is monitored
    • Abandoning expectant management if significant abdominal pain Abdominal Pain Acute Abdomen develops or hCG increases or fails to decline

Differential Diagnosis

Since EPs typically present with bleeding and/or cramping in early pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care, it is critical to differentiate an EP from other types of abnormal pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care events, most notably threatened, missed, inevitable, incomplete, and complete spontaneous abortions. In addition, bleeding may be due to a molar pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care or non-obstetric causes. Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways can also be due to non-obstetric causes.

Obstetric and gynecologic causes of vaginal bleeding in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

The most notable causes of vaginal bleeding in early pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care include:

Table: Diagnosing vaginal bleeding in early pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
Diagnosis Typical bleeding pattern Cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy Cramping, pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways Products of conception (POC)
Threatened abortion Threatened abortion Uterine bleeding from a gestation of less than 20 weeks without any cervical dilatation. It is characterized by vaginal bleeding, lower back discomfort, or midline pelvic cramping and a risk factor for miscarriage. Spontaneous Abortion Light Closed Yes POC visible in uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy on ultrasound (depending on dates)
Missed abortion Missed abortion The retention in the uterus of a dead fetus two months or more after its death. Spontaneous Abortion None or light Closed Possible POC visible on ultrasound without a fetal heartbeat
Inevitable abortion Inevitable Abortion Spontaneous Abortion Heavy Dilated Yes POC visible in uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy or cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy on ultrasound (depending on dates)
Incomplete abortion Incomplete abortion Premature loss of pregnancy in which not all the products of conception have been expelled. Spontaneous Abortion Heavy Dilated Yes Partial expulsion of POC; POC may be visible at os
Complete abortion Complete Abortion Spontaneous Abortion Light Closed Yes
  • History of POC expulsion
  • No POC visible in the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy on ultrasound
Ectopic pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care Light Closed Yes
  • No intrauterine POC (though a pseudogestational sac may be present)
  • Tender adnexal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast, which may show a yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development and possibly a fetal pole with or without cardiac activity
Bleeding molar pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care Heavy Dilated Yes
  • Partial expulsion of POC which resembles grapes
  • No evidence of a fetus
Non-obstetric causes of vaginal bleeding Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables Closed Often no
  • Ultrasound findings show normal embryologic/fetal findings appropriate for gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care
  • Other cervical, vaginal, or uterine pathology may be identified (e.g., cervical polyps)

Note that threatened abortions will ultimately resolve or progress to another diagnosis:

  • May progress to spontaneous abortion Abortion Expulsion of the product of fertilization before completing the term of gestation and without deliberate interference. Spontaneous Abortion
  • A subchorionic hematoma Hematoma A collection of blood outside the blood vessels. Hematoma can be localized in an organ, space, or tissue. Intussusception may subsequently be identified on an ultrasound ( pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care may still continue normally).
  • Bleeding that resolves spontaneously with no other abnormal findings is typically attributed to bleeding from a physiologic cause, such as implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week bleeding.

Management of failed or failing intrauterine pregnancies (missed, inevitable, incomplete, or complete spontaneous abortions):

  • Expectant (i.e., await spontaneous passage of POC)
  • Medical management (e.g., misoprostol Misoprostol A synthetic analog of natural prostaglandin e1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties. Eicosanoids to induce passage of POC)
  • Surgical management, with uterine evacuation (e.g., suction dilatation and curettage Curettage A scraping, usually of the interior of a cavity or tract, for removal of new growth or other abnormal tissue, or to obtain material for tissue diagnosis. It is performed with a curet (curette), a spoon-shaped instrument designed for that purpose. Benign Bone Tumors)

Non-obstetric causes of pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways/cramping in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

  • Appendicitis Appendicitis Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. Appendicitis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy caused by obstruction (e.g., by fecaliths or infection). Produces symptoms such as abdominal pain Abdominal Pain Acute Abdomen, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, and malaise Malaise Tick-borne Encephalitis Virus. Diagnostic findings may include an elevated WBC count and a thickened appendiceal wall on CT scan. Surgery is the recommended treatment, although some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship respond to antibiotics. Unlike in EP, US may reveal an enlarged appendiceal diameter and hCG levels will rise appropriately.
  • Kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis: urine can become supersaturated with soluble substances (e.g., calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes oxalate), which crystallize and form stones that deposit throughout the urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may present with colicky flank or abdominal pain Abdominal Pain Acute Abdomen. Diagnostic studies reveal hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, urinary stones on CT scan, and/or hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis on US. Management consists of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control and varies depending on the chemical nature of the stones. hCG levels will rise appropriately and an early pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care should otherwise progress normally on ultrasound.

References

  1. Tulandi, T. (2022). Ectopic pregnancy: clinical manifestations and diagnosis. UpToDate. Retrieved July 13, 2022, from https://www.uptodate.com/contents/ectopic-pregnancy-clinical-manifestations-and-diagnosis
  2. Tulandi, T. (2022). Ectopic pregnancy: choosing a treatment. UpToDate. Retrieved July 13, 2022, from https://www.uptodate.com/contents/ectopic-pregnancy-choosing-a-treatment
  3. Tulandi, T. (2020). Ectopic pregnancy: Expectant management. UpToDate. Retrieved November 22, 2020, from Tulandi, T. (2020). Ectopic pregnancy: Expectant management. UpToDate. Retrieved November 22, 2020, from https://www.uptodate.com/contents/ectopic-pregnancy-expectant-management
  4. Sherwood, L. Human Physiology: From Cells to Systems. (9th ed., pp. 753, 756). Cengage Learning. 
  5. Marion, L. L., & Meeks, G. R. (2012). Ectopic pregnancy: History, incidence, epidemiology, and risk factors. Clinical obstetrics and gynecology, 55(2), 376–386. https://doi.org/10.1097/GRF.0b013e3182516d7b
  6. Farquhar C. M. (2005). Ectopic pregnancy. Lancet (London, England), 366(9485), 583–591. https://doi.org/10.1016/S0140-6736(05)67103-6
  7. Scibetta, E. W., & Han, C. S. (2019). Ultrasound in Early Pregnancy: Viability, Unknown Locations, and Ectopic Pregnancies. Obstetrics and gynecology clinics of North America, 46(4), 783–795. https://doi.org/10.1016/j.ogc.2019.07.013
  8. World Health Organization. (2017). Managing complications in pregnancy and childbirth: a guide for midwives and doctors (2nd ed.). Retrieved July 8, 2022, from https://www.who.int/publications/i/item/9789241565493

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