Ectopic Pregnancy (Clinical)

Epidemiology and Etiology

Epidemiology^[5]

• 3rd-leading cause of maternal mortality Mortality All deaths reported in a given population. Measures of Health Status 
• 1%–2% of all pregnancies
• Diagnosed in approximately 10% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship presenting with vaginal bleeding and abdominal pain Abdominal Pain Acute Abdomen 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

Etiology^[5,8,9,12]

Ectopic pregnancy 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. Ectopic Pregnancy ( EP EP 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. Ectopic Pregnancy) 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:
    • Congenital Congenital Chorioretinitis anomalies
    • Acquired tubal obstructions (e.g., adhesions)
    • Disruption of ciliary activity or tube motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility
• 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 Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week (IVF))
  • Prior EP EP 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. Ectopic Pregnancy
  • 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:^[8,9,12] 
  • 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 (anterior implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week at the visible or presumed site of a transverse incision in the lower uterine segment)
  • < 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 (defined as implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week below the level of the internal cervical os)

Clinical Presentation

Ectopic pregnancy 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. Ectopic Pregnancy can present before, during, or after rupture. Early on (prior to rupturing), symptoms can be relatively mild, such as light bleeding or cramping. As 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 enlarges (if it does not spontaneously abort), it will eventually rupture, leading to potentially massive internal hemorrhaging.^[1,10]

• A common presentation is 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 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. Ectopic Pregnancy
  • 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:
    • Severe lower abdominal or pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Abdominal rigidity Abdominal Rigidity Acute Abdomen
    • Rebound tenderness Rebound Tenderness Acute Abdomen and/or guarding
    • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways may be more diffuse if there is blood in the abdominal cavity.
    • 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:
  • Breast enlargement and tenderness
  • Secondary amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System 
  • Morning sickness
• 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

Ectopic pregnancy 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. Ectopic Pregnancy is diagnosed using a combination of the date of 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), the quantitative human chorionic gonadotropin (hCG) level, and ultrasound findings.^[1,8–10]

Labs^[6,8–10]

• 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 test is positive and the individual has symptoms (e.g., bleeding, cramping), order a quantitative serum hCG test.
• 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 EP 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. Ectopic Pregnancy)

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 LMP LMP The 1st day of a woman’s LMP Pregnancy: Diagnosis, Physiology, and Care^[6,8–10]

• After a positive urine 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, the 1st step is to determine the 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 based on the 1st day of 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).
  • The estimated due date Estimated Due Date Prenatal Care is the date that falls exactly 40 weeks (280 days) after the LMP LMP The 1st day of a woman’s LMP Pregnancy: Diagnosis, Physiology, and Care.
  • Frequently done using a digital obstetric calculator
• Knowing the approximate 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 is important when interpreting the ultrasound.

Ultrasonography^[6–10]

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

• 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) in order 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 gestational sac:
    • The 1st visible finding of 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 is seen around 4.5–5 weeks’ 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 (wga).
    • A hypoechoic Hypoechoic A structure that produces a low-amplitude echo (darker grays) Ultrasound (Sonography) circle within the uterine cavity, surrounded by hyperechoic Hyperechoic A structure that produces a high-amplitude echo (lighter grays and white) Ultrasound (Sonography) 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
    • Typically 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 if the quantitative serum β-hCG is > 2,000‒3,500 mIU/mL.
    • Note: In very 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 normal to not see anything 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.
  • Presence of 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 (definitively identifies a fluid collection as a gestational sac as opposed to a pseudogestational sac):
    • A thin hyperechoic Hyperechoic A structure that produces a high-amplitude echo (lighter grays and white) Ultrasound (Sonography) ring within the gestational sac
    • Approximately 3–5 mm in diameter
    • 1st seen at approximately 5.5 wga and disappears around 10 wga
  • Presence of a fetal pole with a heartbeat: seen around 5.5–6 wga
• EP EP 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. Ectopic Pregnancy findings:
  • An empty uterine cavity without an amniotic sac or with a pseudogestational 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 due to the hormonal milieu of an ectopic pregnancy 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. Ectopic Pregnancy; 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 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

Differentiating ectopic pregnancies from threatened or spontaneous abortions^[1,8–10]

When an individual presents with vaginal bleeding and/or cramping and has 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, it is critical 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. Intrauterine pregnancies (IUPs) may be viable or nonviable; ectopic pregnancies are never viable.

Initial assessment: Attempt to identify 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 location.

• If an IUP or ectopic pregnancy 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. Ectopic Pregnancy is obviously identified, proceed with appropriate management.
  • Findings diagnostic of an IUP: 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 and/or 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/fetus 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 (a gestational sac without 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 is not sufficient)
    • If an IUP is identified but viability is uncertain, additional criteria have been established to help determine viability. 
    • See table in the section on Differential Diagnosis below for details.
  • Findings diagnostic of an ectopic pregnancy 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. Ectopic Pregnancy: 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 and/or 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/fetus 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 (a gestational sac without 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 is not sufficient)
• If the location 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 cannot be definitively determined with the initial ultrasound:
  • The individual requires close follow-up with serial hCG and ultrasound assessments every 48 hours until the location is identified or 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 resolves (e.g., hCG levels fall to 0).
    • Make sure the individual has a serum quantitative hCG (and not just a urine 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) in order to track levels.
  • The higher the hCG, and the longer the time from the LMP LMP The 1st day of a woman’s LMP Pregnancy: Diagnosis, Physiology, and Care, the higher the likelihood that an IUP should be identified on ultrasonography (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 is in fact located 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).
  • The American College of Obstetricians and Gynecologists (ACOG) and the UK NICE Guidelines both recommend against using strict hCG cutoffs (known as the discriminatory zone) to diagnose ectopic pregnancy 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. Ectopic Pregnancy.
    • The concept of the discriminatory zone: above a particular hCG level, an IUP should be visible on ultrasonography 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 (if it is located there) → so an hCG level above the discriminatory zone but without a visible IUP is highly suspicious for ectopic pregnancy 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. Ectopic Pregnancy 
    • Traditionally, this cutoff was > 2,000 mIU/mL.
    • Owing to potential error Error Refers to any act of commission (doing something wrong) or omission (failing to do something right) that exposes patients to potentially hazardous situations. Disclosure of Information, ACOG recommends using a conservatively high cutoff such as 3,500 mIU/mL (if used at all) in order to avoid misdiagnosis.^[8]
    • NICE Guidelines do not recommend using discriminatory zones at all.^[10]
    • Note: Multiple gestations (e.g., twins) tend to have higher hCG levels than singleton gestations at any given 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.
  • Note: A heterogeneous adnexal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast in the setting of an hCG level > 2,000‒3,500 is highly suspicious for ectopic pregnancy 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. Ectopic Pregnancy and, in most clinical situations, is managed as an ectopic pregnancy 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. Ectopic Pregnancy.

2nd assessment (48 hours later):

• Look for an appropriate increase in the hCG level.
  • hCG levels increase in a curvilinear fashion until they plateau Plateau Cardiac Physiology at around 100,000 mIU/mL at about 10 wga.
  • Rate of rise = ( [hCG₂] ‒ [hCG₁] ) divided by [hCG₁]
  • Minimum expected rates of hCG rise over 48 hours for normal IUPs:^[1,8]
    • > 49% when the initial hCG level is < 1,500 mIU/mL
    • > 40% when the initial hCG level is 1,500‒3,000 mIU/mL
    • > 33% when the initial hCG is > 3,000 mIU/mL
  • Abnormal rates of rise (i.e., rates that do not meet these minimum thresholds) are likely to indicate abnormal pregnancies: either EPs or IUPs that are destined to fail.
  • Decreasing hCG levels suggest a failing 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.
• Repeat ultrasonography to look for progression 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.

Additional assessments:

• If there is still uncertainty, hCG testing and ultrasonography can be repeated again (in another 48 hours).
• If the possibility of a viable or progressing IUP has been excluded (e.g., plateaued or decreasing hCG levels over several repeat assessments), uterine aspiration can help determine the location 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 (which can guide follow-up):
  • Failed/failing intrauterine 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:
    • Chorionic villi Chorionic villi Threadlike vascular projections of the chorion. Chorionic villi may be free or embedded within the decidua forming the site for exchange of substances between fetal and maternal blood (placenta). Placenta, Umbilical Cord, and Amniotic Cavity present in aspirate
    • Large decreases in subsequent hCG levels (e.g., > 50% over 12‒24 hours)
  • Ectopic pregnancy 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. Ectopic Pregnancy:
    • Chorionic villi Chorionic villi Threadlike vascular projections of the chorion. Chorionic villi may be free or embedded within the decidua forming the site for exchange of substances between fetal and maternal blood (placenta). Placenta, Umbilical Cord, and Amniotic Cavity not identified in aspirate
    • Smaller decreases (or subsequent rise) in hCG levels
  • hCG levels should be followed weekly until they reach 0.

Diagnostic and treatment algorithm for women of reproductive age presenting with pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and/or vaginal bleeding

Management

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

Emergency management^[8,11]

In cases in which the individual is hemodynamically unstable owing to a ruptured ectopic pregnancy 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. Ectopic Pregnancy:

• 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^[6,8–10]

• 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 EP 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. Ectopic Pregnancy) to induce a medical abortion Abortion Expulsion of the product of fertilization before completing the term of gestation and without deliberate interference. Spontaneous Abortion
• Absolute 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:
  • Intrauterine or heterotopic Heterotopic Transplantation of tissue typical of one area to a different recipient site. The tissue may be autologous, heterologous, or homologous. Organ Transplantation 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
  • Ruptured ectopic pregnancy 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. Ectopic Pregnancy and/or hemodynamic instability
  • Active medical disease, including:
    • Pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis (not including asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma), renal, or hepatic disease
    • Peptic ulcer Peptic ulcer Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease disease
    • Immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome
    • Hematologic abnormalities, including: severe 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, leukopenia, or thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
  • Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
  • Sensitivity 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
  • Inability to follow up
• Relative 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:
  • Fetal cardiac activity (FCA) detected on ultrasound
  • Ectopic pregnancy 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. Ectopic Pregnancy > 3.5–4 cm in size on ultrasound
  • Initial hCG > 5,000 mIU/mL (best candidates have initial hCG < 1,500 mIU/mL)
  • Rapidly increasing hCG levels: > 50% in 48 hours
  • Refusal to accept a blood transfusion
• ACOG protocols (see table):
  • Single-dose regimen (most commonly used)
  • Fixed multiple dose regimen
• Monitor the patient’s hCG levels until they reach 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
• During 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 therapy, individuals should avoid alcohol and folate-containing vitamins (since 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 works through the folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 pathway).

Surgical management^[6,8–10]

• Indications:
  • Hemodynamic instability
  • Symptoms of a ruptured ectopic pregnancy 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. Ectopic Pregnancy
  • 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., patient 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)
• A laparoscopic approach is preferred (over open).
• Options include:
  • Salpingectomy:
    • Removal of the entire tube, including the EP EP 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. Ectopic Pregnancy
    • Potentially preferred in the presence of a healthy contralateral tube, when there is severe damage in the tube with the EP EP 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. Ectopic Pregnancy, or in cases of significant bleeding
    • 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
    • Associated with higher rates of subsequent IUP than with salpingectomy
    • Potentially preferred when other fertility-reducing factors are present (e.g., contralateral tubal damage, history of PID PID 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, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC).)
    • Possible for trophoblastic tissue to persist → hCG levels should be followed until they reach 0.
• Discuss pros and cons CoNS Staphylococcus of salpingectomy versus salpingotomy with individuals prior to surgery, noting that it may be impossible to save the tube.

Expectant management^[6–10]

• 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)
  • Agree 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 EP 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. Ectopic Pregnancy 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^[11,13]

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:

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 (see table below for features):
  • Ectopic pregnancy 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. Ectopic Pregnancy
  • Failed/failing pregnancies:
    • 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
    • Missed abortion Missed abortion The retention in the uterus of a dead fetus two months or more after its death. Spontaneous Abortion
    • Inevitable abortion Inevitable Abortion Spontaneous Abortion
    • Incomplete abortion Incomplete abortion Premature loss of pregnancy in which not all the products of conception have been expelled. Spontaneous Abortion
    • Complete spontaneous abortion Abortion Expulsion of the product of fertilization before completing the term of gestation and without deliberate interference. Spontaneous Abortion
  • 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
  • Non-obstetric causes of bleeding (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 ultrasonography ( 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.

Predicting 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 failure

If an IUP is identified but viability is uncertain, the US Society of Radiologists in Ultrasound have identified a set of criteria that are diagnostic of or suspicious for (but not diagnostic of) 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 failure:

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 dilation 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 EP 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. Ectopic Pregnancy, ultrasound (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 ultrasound. 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 in the US.
• Ovarian torsion Ovarian torsion Ovarian torsion is a clinical emergency in which the ovaries (with or without the fallopian tubes) twist along their axis, leading to partial or complete obstruction of their blood supply. Ovarian torsion is also called adnexal or tubo-ovarian torsion, especially if a fallopian tube is also involved. Ovarian Torsion: the complete or partial rotation Rotation Motion of an object in which either one or more points on a line are fixed. It is also the motion of a particle about a fixed point. X-rays of the ovary around its supporting ligaments. As a result, ischemic injury of the ovarian tissue occurs due to blood supply compromise. Associated with conditions that cause ovarian enlargement (e.g., cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change, tumors). May lead to acute abdominal pain Abdominal Pain Acute Abdomen and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia; US and 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 testing can be used to distinguish this condition from EP EP 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. Ectopic Pregnancy, though it is important to note that torsion can also occur with normal intrauterine pregnancies. Urgent surgical detorsion is indicated to preserve the ovary.