Background

• Ectopic pregnancy is a potentially dangerous syndrome in which a fertilized egg implant is outside the uterus, usually in the fallopian tube. It occurs in approximately 1-2% of all pregnancies, most cases occurring in the fallopian tube. Other possible implantation sites include the cervix, ovary, and abdominal cavity. 
• A history of pelvic inflammatory disease, a previous ectopic pregnancy, tubal surgery, infertility treatment, and certain contraceptives, such as  progestin-only tablets or an intrauterine device (IUD), are risk factors for ectopic pregnancy. 

Epidemiology

• The incidence of ectopic pregnancy varies depending on several factors, including geography, age, and risk factors. 
• In the United States, ectopic pregnancy occurs in approximately 1-2% of all pregnancies, estimated to be approximately 70,000 yearly. Ectopic pregnancies have been more common over the past several decades. This may be partially due to the greater use of assisted reproductive technologies (ART) and better ways to detect early pregnancies. 
• Ectopic pregnancy is more common in women older than 35 and those with a previous ectopic pregnancy, pelvic inflammatory disease (PID), tubal surgery, or infertility treatment. Women who smoke or use an intrauterine device (IUD) for contraception may also have an increased risk of ectopic pregnancy. 
• The incidence of ectopic pregnancy varies worldwide, with higher rates reported in developing countries. In some regions, such as sub-Saharan Africa, ectopic pregnancy is a leading cause of maternal mortality. 

Anatomy

Pathophysiology

• An ectopic pregnancy develops when a fertilised egg implants abnormally, most frequently in one of the fallopian tubes. This occurs when the fertilized egg fails to move correctly through the fallopian tube and instead implants in the tube itself or other locations outside the uterus. 
• Ectopic pregnancy can arise due to a number of circumstances. An increased chance of ectopic pregnancy might result from, for instance, scarring or damage to the fallopian tubes as a result of infections, surgery, or other diseases. 
• Ectopic pregnancy 
•  can also arise as a result of hormonal abnormalities. For example, certain medical conditions or medications that affect the production of hormones, such as progesterone and estrogen, can interfere with the normal development of the fertilized egg and increase the risk of ectopic pregnancy. 
• Once the fertilized egg implants outside, the uterus begins to grow and develop, but it cannot receive the nutrients and support it needs to develop normally. Over time, the growing embryo can cause damage to the surrounding tissues, including the fallopian tube or other structures where it has implanted. This can lead to symptoms such as vaginal bleeding, abdominal pain, and, in severe cases, rupture of the fallopian tube and internal bleeding. 
• Ectopic pregnancy treatment typically involves removing the affected tissue through surgery or medication to prevent further complications and protect the mother’s health. Early diagnosis and treatment are essential to minimize the risk of severe complications and improve outcomes for women with ectopic pregnancy. 

Etiology

• Fallopian tube abnormalities: Most ectopic pregnancies occur in the fallopian tubes, and anything that interferes with the standard structure or function of the fallopian tubes can increase the risk of ectopic pregnancy. This includes scarring or damage from infections (such as pelvic inflammatory disease), previous surgeries, or congenital abnormalities. 
• Hormonal imbalances: Abnormal Progesterone and estrogen levels may interfere with the ability of the fertilized egg to implant in the uterus, increasing the risk of an ectopic pregnancy. 
• In vitro fertilization (IVF): Women who undergo IVF treatment have a higher risk of ectopic pregnancy, possibly due to the manipulation of the fertilized egg or damage to the fallopian tubes during the procedure. 
• Contraceptive methods: Certain contraceptive methods, such as intrauterine devices (IUDs) and progestin-only pills, have been associated with an increased risk of ectopic pregnancy. 
• Smoking: Smoking has been linked to an increased risk of ectopic pregnancy, possibly due to the adverse effects of smoking on the fallopian tubes and hormonal balance. 
• Previous ectopic pregnancy: Women who have had a previous ectopic pregnancy have a higher risk of having another ectopic pregnancy. 
• Age: Ectopic pregnancy is more common in women over 35. 

Genetics

Prognostic Factors

• Site of implantation: Ectopic pregnancies in the fallopian tubes are more likely to result in serious complications, such as tubal rupture and internal bleeding, than those in other locations outside of the uterus. 
• Size and development of the embryo: Ectopic pregnancies diagnosed early, when the embryo is tiny and has not yet caused significant damage to surrounding tissue, are generally associated with better outcomes than those diagnosed later. Ectopic pregnancies that have progressed further in development, with a larger embryo or more advanced gestational age, are more likely to result in complications and require more extensive treatment. 
• Time to diagnosis and treatment: Early diagnosis and treatment of ectopic pregnancy are critical for improving outcomes and minimizing the risk of serious complications. Delayed diagnosis and treatment can increase the risk of tubal rupture and internal bleeding, which can be life-threatening. 
• Patient factors: Certain patient factors, such as age, overall health, and previous medical history, can also influence the prognosis of ectopic pregnancy. For example, women with underlying medical conditions or previous ectopic pregnancies may be at higher risk of complications. 

Clinical History

Some of the standard clinical presentations of ectopic pregnancy: 

• Abdominal pain: This is the most common symptom of ectopic pregnancy, and it may be localized to one side of the abdomen or generalized. The discomfort or cramping may come with the pain, which may be slight or severe. 
• Vaginal bleeding: Vaginal bleeding from an ectopic pregnancy may not resemble regular menstrual blood. There may be tissue or clots present, as well as light or moderate bleeding. 
• Shoulder pain: In rare cases, ectopic pregnancy can cause referred pain to the shoulder due to irritation of the diaphragm by blood or other fluids. 
• Gastrointestinal symptoms: Some women with ectopic pregnancy may experience nausea, vomiting, diarrhea, or constipation. 

The clinical presentation of ectopic pregnancy can vary based on several factors, including age group, associated comorbidities or activities, and acuity of presentation. 

• Age group: Women of any age can become pregnant ectopically. However, this is most likely in those between 20 and 35. Ectopic pregnancies may be more common in older women because of lower fertility and a higher risk of tubal injury. 

Physical Examination

The critical physical examination findings that may be observed in women with ectopic pregnancy: 

• Abdominal tenderness: On physical examination, the abdomen may be tender to palpation, particularly in the lower quadrants. 
• Abdominal distension: In cases of ruptured ectopic pregnancy, there may be evidence of abdominal distension or swelling due to the accumulation of blood or other fluids in the abdominal cavity. 
• Vaginal bleeding: Vaginal or spotting should be noted during the pelvic examination. 
• Adnexal tenderness or mass: In many cases of ectopic pregnancy, there may be tenderness or a palpable mass in the area of the affected fallopian tube or ovary. 
• Cervical motion tenderness: This is tenderness or pain upon movement of the cervix and may indicate pelvic inflammatory disease or other inflammatory conditions that can increase the risk of ectopic pregnancy. 
• Referred pain: In rare cases, referred pain to the shoulder may be observed due to diaphragm irritation by blood or other fluids. 

Age group

Associated comorbidity

• Certain medical conditions or activities can increase the risk of ectopic pregnancy, such as pelvic inflammatory disease, previous tubal surgery, or in vitro fertilization (IVF). Women who smoke or use certain contraceptives may also be at higher risk. 

Associated activity

Acuity of presentation

• Ectopic pregnancy can be acute or chronic. Acute presentations, such as sudden onset of severe abdominal pain and vaginal bleeding, may indicate a ruptured ectopic pregnancy and require emergency treatment. Chronic presentations, such as mild or intermittent symptoms, may be more challenging to diagnose and may require further testing to confirm. 

Differential Diagnoses

Spontaneous abortion occurs when a pregnancy is lost before 20 weeks of gestation. Symptoms of spontaneous abortion may include vaginal bleeding, cramping, and pelvic pain. 

• Ovarian cysts: Fluid-filled sacs called cysts can develop in the ovaries. Pelvic or abdominal discomfort, missed periods, and other symptoms may result. 
• Pelvic inflammatory disease (PID): PID is an infection of the female reproductive system that can cause abdominal pain, fever, vaginal discharge, and other symptoms. 
• Appendicitis: It is an inflammation of the appendix that can cause abdominal pain, fever, nausea, and vomiting. 
• Urinary tract infection (UTI): UTI is a bacterial infection of the urinary tract that can cause pelvic pain, frequent urination, and other symptoms. 
• Endometriosis: Endometriosis is a disorder in which uterine lining-like tissue develops outside the uterus. Other symptoms include excessive menstrual bleeding, pelvic discomfort, and others. 
• Ruptured corpus luteum cyst: The corpus luteum is a temporary structure that forms after ovulation. A ruptured corpus luteum cyst can cause abdominal pain and bleeding, which can be mistaken for ectopic pregnancy. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

• In the context of ectopic pregnancy, Modification of the environment refers to the surgical removal of the ectopic pregnancy from the fallopian tube or other location where it has been implanted.
• Minimally invasive laparoscopy is used for this procedure, in which a camera and surgical equipment are introduced through tiny incisions in the belly to perform the necessary procedures. In some cases, a more invasive laparotomy may be required. 

• The administration of a pharmaceutical agent with drugs can be used to treat ectopic pregnancy in some instances.
• Methotrexate is a medication used to stop the growth of the developing embryo and cause it to be absorbed by the body. This medication is typically only used in cases where the ectopic pregnancy is small, and the woman’s condition is stable. 

• Intervention with a procedure refers to any surgical or medical procedure used to treat ectopic pregnancy.
• In addition to surgical removal of the ectopic pregnancy, other procedures that may be used include salpingostomy (opening the fallopian tube and removing the pregnancy), salpingectomy (removal of the affected fallopian tube), or hysterectomy (removal of the uterus). 

• The management of ectopic pregnancy typically involves three phases: diagnosis, treatment, and follow-up. The condition is identified and confirmed during the diagnosis phase through physical examination, ultrasound, and blood tests.
• In the treatment phase, the appropriate intervention is selected based on the woman’s health, the size and location of the ectopic pregnancy, and other factors. Finally, during the follow-up phase, the woman is monitored closely to ensure that the ectopic pregnancy has been successfully treated and that there are no complications. 

Medication

Future Trends

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References

• https://www.ncbi.nlm.nih.gov/books/NBK539860/ 
• https://emedicine.medscape.com/article/2041923-treatment