ectopic pregnancy presentation

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Coping and support, preparing for your appointment.

A pelvic exam can help your doctor identify areas of pain, tenderness, or a mass in the fallopian tube or ovary. However, your doctor can't diagnose an ectopic pregnancy by examining you. You'll need blood tests and an ultrasound.

Pregnancy test

Your doctor will order the human chorionic gonadotropin (HCG) blood test to confirm that you're pregnant. Levels of this hormone increase during pregnancy. This blood test may be repeated every few days until ultrasound testing can confirm or rule out an ectopic pregnancy — usually about five to six weeks after conception.

A transvaginal ultrasound allows your doctor to see the exact location of your pregnancy. For this test, a wandlike device is placed into your vagina. It uses sound waves to create images of your uterus, ovaries and fallopian tubes, and sends the pictures to a nearby monitor.

Abdominal ultrasound, in which an ultrasound wand is moved over your belly, may be used to confirm your pregnancy or evaluate for internal bleeding.

Transvaginal ultrasound

During a transvaginal ultrasound, you lie on an exam table while a health care provider or a medical technician puts a wandlike device, known as a transducer, into the vagina. Sound waves from the transducer create images of the uterus, ovaries and fallopian tubes.

Other blood tests

A complete blood count will be done to check for anemia or other signs of blood loss. If you're diagnosed with an ectopic pregnancy, your doctor may also order tests to check your blood type in case you need a transfusion.

More Information

A fertilized egg can't develop normally outside the uterus. To prevent life-threatening complications, the ectopic tissue needs to be removed. Depending on your symptoms and when the ectopic pregnancy is discovered, this may be done using medication, laparoscopic surgery or abdominal surgery.

An early ectopic pregnancy without unstable bleeding is most often treated with a medication called methotrexate, which stops cell growth and dissolves existing cells. The medication is given by injection. It's very important that the diagnosis of ectopic pregnancy is certain before receiving this treatment.

After the injection, your doctor will order another human chorionic gonadotropin (HCG) test to determine how well treatment is working, and if you need more medication.

Laparoscopic procedures

Salpingostomy and salpingectomy are two laparoscopic surgeries used to treat some ectopic pregnancies. In these procedure, a small incision is made in the abdomen, near or in the navel. Next, your doctor uses a thin tube equipped with a camera lens and light (laparoscope) to view the tubal area.

In a salpingostomy, the ectopic pregnancy is removed and the tube left to heal on its own. In a salpingectomy, the ectopic pregnancy and the tube are both removed.

Which procedure you have depends on the amount of bleeding and damage and whether the tube has ruptured. Also a factor is whether your other fallopian tube is normal or shows signs of prior damage.

Emergency surgery

If the ectopic pregnancy is causing heavy bleeding, you might need emergency surgery. This can be done laparoscopically or through an abdominal incision (laparotomy). In some cases, the fallopian tube can be saved. Typically, however, a ruptured tube must be removed.

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Losing a pregnancy is devastating, even if you've only known about it for a short time. Recognize the loss, and give yourself time to grieve. Talk about your feelings and allow yourself to experience them fully.

Rely on your partner, loved ones and friends for support. You might also seek the help of a support group, grief counselor or other mental health provider.

Many women who have an ectopic pregnancy go on to have a future, healthy pregnancy. The female body normally has two fallopian tubes. If one is damaged or removed, an egg may join with a sperm in the other tube and then travel to the uterus.

If both fallopian tubes have been injured or removed, in vitro fertilization (IVF) might still be an option. With this procedure, mature eggs are fertilized in a lab and then implanted into the uterus.

If you've had an ectopic pregnancy, your risk of having another one is increased. If you wish to try to get pregnant again, it's very important to see your doctor regularly. Early blood tests are recommended for all women who've had an ectopic pregnancy. Blood tests and ultrasound testing can alert your doctor if another ectopic pregnancy is developing.

Call your doctor's office if you have light vaginal bleeding or slight abdominal pain. The doctor might recommend an office visit or immediate medical care.

However, emergency medical help is needed if you develop these warning signs or symptoms of an ectopic pregnancy:

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

Call 911 (or your local emergency number) or go to the hospital if you have the above symptoms.

What you can do

It can be helpful to jot down your questions for the doctor before your visit. Here are some questions you might want to ask your doctor:

• What kinds of tests do I need?
• What are the treatment options?
• What are my chances of having a healthy pregnancy in the future?
• How long should I wait before trying to become pregnant again?
• Will I need to follow any special precautions if I become pregnant again?

In addition to your prepared questions, don't hesitate to ask questions anytime you don't understand something. Ask a loved one or friend to come with you, if possible. Sometimes it can be difficult to remember all of the information provided, especially in an emergency situation.

What to expect from your doctor

If you don't require emergency treatment and haven't yet been diagnosed with an ectopic pregnancy, your doctor will talk to you about medical history and symptoms. You'll be asked many questions about your menstrual cycle, fertility and overall health.

Menstruation

• When was your last period?
• Did you notice anything unusual about it?
• Could you be pregnant?
• Have you taken a pregnancy test? If so, was the test positive?
• Have you been pregnant before? If so, what was the outcome of each pregnancy?
• Have you ever had fertility treatments?
• Do you plan to become pregnant in the future?
• Are you in pain? If so, where does it hurt?
• Do you have vaginal bleeding? If so, is it more or less than your typical period?
• Are you lightheaded or dizzy?

Health history

• Have you ever had reproductive surgery, including getting your tubes tied (or a reversal)?
• Have you had a sexually transmitted infection?
• Are you being treated for any other medical conditions?
• What medications do you take?

Mar 12, 2022

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

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Frequently Asked Questions Expand All

An ectopic pregnancy occurs when a fertilized egg grows outside of the uterus . Almost all ectopic pregnancies—more than 90%—occur in a fallopian tube . As the pregnancy grows, it can cause the tube to burst (rupture). A rupture can cause major internal bleeding. This can be a life-threatening emergency that needs immediate surgery.

The risk factors for ectopic pregnancy include the following:

Previous ectopic pregnancy

Prior fallopian tube surgery

Previous pelvic or abdominal surgery

Certain sexually transmitted infections (STIs)

Pelvic inflammatory disease

Endometriosis

Other factors that may increase a woman’s risk of ectopic pregnancy include:

Cigarette smoking

Age older than 35 years

History of infertility

Use of assisted reproductive technology , such as in vitro fertilization (IVF)

About one half of all women who have an ectopic pregnancy do not have known risk factors. Sexually active women should be alert to changes in their bodies, especially if they experience symptoms of an ectopic pregnancy.

At first, an ectopic pregnancy may feel like a typical pregnancy with some of the same signs, such as a missed menstrual period, tender breasts, or an upset stomach. Other signs may include:

Abnormal vaginal bleeding

Low back pain

Mild pain in the abdomen or pelvis

Mild cramping on one side of the pelvis

At this stage, it may be hard to know if you are experiencing a typical pregnancy or an ectopic pregnancy. Abnormal bleeding and pelvic pain should be reported to your obstetrician–gynecologist (ob-gyn) or other health care professional.

As an ectopic pregnancy grows, more serious symptoms may develop, especially if a fallopian tube ruptures. Symptoms may include the following:

Sudden, severe pain in the abdomen or pelvis

Shoulder pain

Weakness, dizziness, or fainting

A ruptured fallopian tube can cause life-threatening internal bleeding. If you have sudden, severe pain; shoulder pain; or weakness, you should go to an emergency room.

If you do not have the symptoms of a fallopian tube rupture but your ob-gyn or other health care professional suspects you may have ectopic pregnancy, he or she may:

Perform a pelvic exam

Perform an ultrasound exam to see where the pregnancy is developing

Test your blood for a pregnancy hormone called human chorionic gonadotropin (hCG)

An ectopic pregnancy cannot move or be moved to the uterus, so it always requires treatment. There are two methods used to treat an ectopic pregnancy: 1) medication and 2) surgery. Several weeks of follow-up are required with each treatment.

The most common drug used to treat ectopic pregnancy is methotrexate. This drug stops cells from growing, which ends the pregnancy. The pregnancy then is absorbed by the body over 4–6 weeks. This does not require the removal of the fallopian tube.

Methotrexate may be used if the pregnancy has not ruptured a fallopian tube. Several factors go into the decision to use methotrexate. One of the most important factors is your ability to follow up with blood tests that check your blood levels of hCG. You will not be able to use methotrexate if you are breastfeeding or have certain health problems.

Methotrexate often is given by injection in one dose. Before you take methotrexate, blood tests will be done to measure the level of hCG and the functions of certain organs. If hCG levels have not decreased enough after the first dose, another dose of methotrexate may be recommended. You will have careful follow-up over time until hCG is no longer found in your blood.

Taking methotrexate can have some side effects. Most women have some abdominal pain. Vaginal bleeding or spotting also may occur. Other side effects may include:

It is important to follow up with your ob-gyn or other health care professional until your treatment with methotrexate is complete. The risk of a fallopian tube rupture does not go away until your treatment is over. Seek care right away if you have symptoms of a rupture, including sudden abdominal pain, shoulder pain, or weakness.

Yes, during treatment with methotrexate you should avoid the following:

Heavy exercise

Sexual intercourse

Vitamins and foods that contain folic acid, including fortified cereal, enriched bread and pasta, peanuts, dark green leafy vegetables, orange juice, and beans

Prescription pain medication and nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen. These medications can affect the way methotrexate works in the body.

Foods that produce gas, which can cause discomfort and mask the pain of a possible rupture of a fallopian tube

Prolonged exposure to sunlight. Methotrexate can cause sun sensitivity.

If the ectopic pregnancy has ruptured a tube, emergency surgery is needed. Sometimes surgery is needed even if the fallopian tube has not ruptured. In these cases, the ectopic pregnancy can be removed from the tube, or the entire tube with the pregnancy can be removed.

Surgery typically is done with laparoscopy . This procedure uses a slender, lighted camera that is inserted through small cuts in the abdomen. It is done in a hospital with general anesthesia .

Your ob-gyn or other health care professional will talk with you about the possible side effects and risks of surgery for ectopic pregnancy. These may include pain, fatigue, bleeding, and infection.

Whether you were treated with methotrexate or surgery, you may feel tired for several weeks while you recover. You may feel abdominal discomfort or pain. If you have pain that does not respond to over-the-counter medication, talk with your ob-gyn or other health care professional.

It can take time for the level of hCG in your body to drop after treatment for an ectopic pregnancy. You may continue to feel pregnant for a while. It may take a few cycles for your periods to return to normal.

For some women, ectopic pregnancy can be traumatic. You may be dealing with many emotions after an ectopic pregnancy, even if you were not planning to become pregnant. Take time to work through your feelings. Counseling may be helpful. Ask your ob-gyn or other health care professional to recommend a counselor. Online forums also can be a place to get support from other women who have had ectopic pregnancies.

Once you have had an ectopic pregnancy, you are at higher risk of having another one. During future pregnancies, be alert for signs and symptoms of ectopic pregnancy until your ob-gyn or other health care professional confirms the next pregnancy is growing in the right place.

Assisted Reproductive Technology: A group of infertility treatments in which an egg is fertilized with a sperm outside the body; the fertilized egg then is transferred to the uterus.

Endometriosis: A condition in which tissue that lines the uterus is found outside of the uterus, usually on the ovaries, fallopian tubes, and other pelvic structures.

Fallopian Tube: Tube through which an egg travels from the ovary to the uterus.

General Anesthesia: The use of drugs that produce a sleep-like state to prevent pain during surgery.

Hormone: A substance made in the body by cells or organs that controls the function of cells or organs.

In Vitro Fertilization (IVF): A procedure in which an egg is removed from a woman’s ovary, fertilized in a laboratory with the man’s sperm, and then transferred to the woman’s uterus to achieve a pregnancy.

Laparoscopy: A surgical procedure in which an instrument called a laparoscope is inserted into the pelvic cavity through a small incision. The laparoscope is used to view the pelvic organs. Other instruments can be used with it to perform surgery.

Obstetrician–Gynecologist (Ob-Gyn): A physician with special skills, training, and education in women’s health.

Pelvic Inflammatory Disease: An infection of the uterus, fallopian tubes, and nearby pelvic structures.

Sexually Transmitted Infections (STIs): Infections that are spread by sexual contact, including chlamydia, gonorrhea, human papillomavirus (HPV), herpes, syphilis, and human immunodeficiency virus (HIV, the cause of acquired immunodeficiency syndrome [AIDS]).

Ultrasound Exam: A test in which sound waves are used to examine internal structures. During pregnancy, it can be used to examine the fetus.

Uterus: A muscular organ located in the female pelvis that contains and nourishes the developing fetus during pregnancy.

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Published: April 2020

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Ectopic Pregnancy

• Author: Vicken P Sepilian, MD, MSc; Chief Editor: Michel E Rivlin, MD  more...
• Sections Ectopic Pregnancy
• Practice Essentials
• Epidemiology
• Patient Education
• Physical Examination
• Approach Considerations
• Beta–Human Chorionic Gonadotropin Levels
• Progesterone Levels
• Other Markers
• Ultrasonography
• Dilatation and Curettage
• Culdocentesis
• Laparoscopy
• Expectant Management
• Methotrexate Therapy
• Methotrexate Treatment Protocols
• Investigational Medical Treatments
• Salpingostomy and Salpingectomy
• Medication Summary
• Antineoplastics, Antimetabolite
• Vasopressors
• Media Gallery

Ectopic pregnancy is the result of a flaw in human reproductive physiology that allows the conceptus to implant and mature outside the endometrial cavity (see the image below), which ultimately ends in the death of the fetus. Without timely diagnosis and treatment, ectopic pregnancy can become a life-threatening situation. [ 1 ]

Signs and symptoms

The classic clinical triad of ectopic pregnancy is as follows:

Abdominal pain

Vaginal bleeding

Unfortunately, only about 50% of patients present with all 3 symptoms.

Patients may present with other symptoms common to early pregnancy (eg, nausea, breast fullness). The following symptoms have also been reported:

Painful fetal movements (in the case of advanced abdominal pregnancy)

Dizziness or weakness

Flulike symptoms

Cardiac arrest

The presence of the following signs suggests a surgical emergency:

Abdominal rigidity

Involuntary guarding

Severe tenderness

Evidence of hypovolemic shock (eg, orthostatic blood pressure changes, tachycardia)

Findings on pelvic examination may include the following:

The uterus may be slightly enlarged and soft

Uterine or cervical motion tenderness may suggest peritoneal inflammation

An adnexal mass may be palpated but is usually difficult to differentiate from the ipsilateral ovary

Uterine contents may be present in the vagina, due to shedding of endometrial lining stimulated by an ectopic pregnancy

See Clinical Presentation for more detail.

Serum β-HCG levels

In a normal pregnancy, the β-HCG level doubles every 48-72 hours until it reaches 10,000-20,000mIU/mL. In ectopic pregnancies, β-HCG levels usually increase less. Mean serum β-HCG levels are lower in ectopic pregnancies than in healthy pregnancies.

No single serum β-HCG level is diagnostic of an ectopic pregnancy. Serial serum β-HCG levels are necessary to differentiate between normal and abnormal pregnancies and to monitor resolution of ectopic pregnancy once therapy has been initiated.

The discriminatory zone of β-HCG (ie, the level above which an imaging scan should reliably visualize a gestational sac within the uterus in a normal intrauterine pregnancy) is as follows:

1500-1800 mIU/mL with transvaginal ultrasonography, but up to 2300 mIU/mL with multiple gestates [ 2 ]

6000-6500 mIU/mL with abdominal ultrasonography

Absence of an intrauterine pregnancy on a scan when the β-HCG level is above the discriminatory zone represents an ectopic pregnancy or a recent abortion.

Ultrasonography is probably the most important tool for diagnosing an extrauterine pregnancy.

Visualization of an intrauterine sac, with or without fetal cardiac activity, is often adequate to exclude ectopic pregnancy. [ 3 ]

Transvaginal ultrasonography, or endovaginal ultrasonography, can be used to visualize an intrauterine pregnancy by 24 days post ovulation or 38 days after the last menstrual period (about 1 week earlier than transabdominal ultrasonography). An empty uterus on endovaginal ultrasonographic images in patients with a serum β-HCG level greater than the discriminatory cut-off value is an ectopic pregnancy until proved otherwise.

Color-flow Doppler ultrasonography improves the diagnostic sensitivity and specificity of transvaginal ultrasonography, especially in cases in which a gestational sac is questionable or absent.

Laparoscopy remains the criterion standard for diagnosis; however, its routine use on all patients suspected of ectopic pregnancy may lead to unnecessary risks, morbidity, and costs. Moreover, laparoscopy can miss up to 4% of early ectopic pregnancies.

Laparoscopy is indicated for patients who are in pain or hemodynamically unstable.

See Workup for more detail.

Therapeutic options in ectopic pregnancy are as follows:

Expectant management

Methotrexate

Candidates for successful expectant management should be asymptomatic and have no evidence of rupture or hemodynamic instability. Candidates should demonstrate objective evidence of resolution (eg, declining β-HCG levels).

Close follow-up and patient compliance are of paramount importance, as tubal rupture may occur despite low and declining serum levels of β-HCG.

Methotrexate is the standard medical treatment for unruptured ectopic pregnancy. A single-dose IM injection is the more popular regimen. The ideal candidate should have the following:

Hemodynamic stability

No severe or persisting abdominal pain

The ability to follow up multiple times

Normal baseline liver and renal function test results

Absolute contraindications to methotrexate therapy include the following:

Existence of an intrauterine pregnancy

Immunodeficiency

Moderate to severe anemia, leukopenia, or thrombocytopenia

Sensitivity to methotrexate

Active pulmonary or peptic ulcer disease

Clinically important hepatic or renal dysfunction

Breastfeeding

Evidence of tubal rupture

Surgical treatment

Laparoscopy has become the recommended surgical approach in most cases. Laparotomy is usually reserved for patients who are hemodynamically unstable or for patients with cornual ectopic pregnancies; it also is a preferred method for surgeons inexperienced in laparoscopy and in patients in whom a laparoscopic approach is difficult.

See Treatment and Medication for more detail.

Ectopic pregnancy refers to the implantation of a fertilized egg in a location outside of the uterine cavity, including the fallopian tubes (approximately 97.7%), cervix, ovary, cornual region of the uterus, and abdominal cavity. Of tubal pregnancies, the ampulla is the most common site of implantation (80%), followed by the isthmus (12%), fimbria (5%), cornua (2%), and interstitia (2-3%). (See the image below.)

In ectopic pregnancy (the term ectopic is derived from the Greek word ektopos , meaning out of place), the gestation grows and draws its blood supply from the site of abnormal implantation. As the gestation enlarges, it creates the potential for organ rupture, because only the uterine cavity is designed to expand and accommodate fetal development. Ectopic pregnancy can lead to massive hemorrhage, infertility, or death (see the images below). (See Etiology and Prognosis.)

In 1970, the Centers for Disease Control and Prevention (CDC) began to record statistics regarding ectopic pregnancy, reporting 17,800 cases. By 1992, the number of ectopic pregnancies had increased to 108,800. Concurrently, however, the case-fatality rate decreased from 35.5 deaths per 10,000 cases in 1970 to 2.6 per 10,000 cases in 1992. (See Epidemiology.)

The increased incidence of ectopic pregnancy has been partially attributed to improved ability in making an earlier diagnosis. Ectopic pregnancies that previously would have resulted in tubal abortion or complete, spontaneous reabsorption and remained clinically undiagnosed are now detected. (See Presentation, DDx, and Workup.)

In the 1980s and 1990s, medical therapy for ectopic pregnancy was implemented; it has now replaced surgical therapy in many cases. [ 4 , 5 , 6 ] As the ability to diagnose ectopic pregnancy improves, physicians will be able to intervene sooner, preventing life-threatening sequelae and extensive tubal damage, as well as, it is hoped, preserving future fertility. (See Treatment and Medication.)

Implantation sites

The faulty implantation that occurs in ectopic pregnancy occurs because of a defect in the anatomy or normal function of either the fallopian tube (as can result from surgical or infectious scarring), the ovary (as can occur in women undergoing fertility treatments), or the uterus (as in cases of bicornuate uterus or cesarean delivery scar). Reflecting this, most ectopic pregnancies are located in the fallopian tube; the most common site is the ampullary portion of the tube, where over 80% of ectopic pregnancies occur. (See Etiology.)

Nontubal ectopic pregnancies are a rare occurrence, with abdominal pregnancies accounting for 1.4% of ectopic pregnancies and ovarian and cervical sites accounting for 0.2% each. Some ectopic pregnancies implant in the cervix (< 1%), in previous cesarean delivery scars, [ 7 , 8 ] or in a rudimentary uterine horn; although these may be technically in the uterus, they are not considered normal intrauterine pregnancies. [ 9 ]

About 80% of ectopic pregnancies are found on the same side as the corpus luteum (the old, ruptured follicle), when present. [ 10 ] In the absence of modern prenatal care, abdominal pregnancies can present at an advanced stage (>28 wk) and have the potential for catastrophic rupture and bleeding. [ 11 ]

An ectopic pregnancy requires the occurrence of 2 events: fertilization of the ovum and abnormal implantation. Many risk factors affect both events; for example, a history of major tubal infection decreases fertility and increases abnormal implantation.

Multiple factors contribute to the relative risk of ectopic pregnancy. In theory, anything that hampers or delays the migration of the fertilized ovum (blastocyst) to the endometrial cavity can predispose a woman to ectopic gestation. The following risk factors have been linked to ectopic pregnancy:

Tubal damage - Which can be the result of infections such as pelvic inflammatory disease (PID) or salpingitis (whether documented or not) or can result from abdominal surgery or tubal ligation or from maternal in utero diethylstilbestrol (DES) exposure [ 12 ]

History of previous ectopic pregnancy [ 12 ]

Smoking - A risk factor in about one third of ectopic pregnancies; smoking may contribute to decreased tubal motility by damage to the ciliated cells in the fallopian tubes [ 12 ]

Altered tubal motility - As mentioned, this can result from smoking, but it can also occur as the result of hormonal contraception; progesterone-only contraception and progesterone intrauterine devices (IUDs) have been associated with an increased risk of ectopic pregnancy

History of 2 or more years of infertility (whether treated or not) [ 13 ] - Women using assisted reproduction seem to have a doubled risk of ectopic pregnancy (to 4%), although this is mostly due to the underlying infertility [ 14 ]

History of multiple sexual partners [ 13 ]

Maternal age - Although this is not an independent risk factor [ 13 ]

The most logical explanation for the increasing frequency of ectopic pregnancy is previous pelvic infection; however, most patients presenting with an ectopic pregnancy have no identifiable risk factor. [ 15 ]

A literature review found 56 reported cases of ectopic pregnancy (by definition), dating back to 1937, after hysterectomy. [ 16 ]

Pelvic inflammatory disease

The most common cause of PID is an antecedent infection caused by Chlamydia trachomatis. Patients with chlamydial infection have a range of clinical presentations, from asymptomatic cervicitis to salpingitis and florid PID. More than 50% of women who have been infected are unaware of the exposure.

Other organisms that cause PID, such as Neisseria gonorrhoeae , also increase the risk of ectopic pregnancy, and a history of salpingitis increases the risk of ectopic pregnancy 4-fold. The incidence of tubal damage increases after successive episodes of PID (ie, 13% after 1 episode, 35% after 2 episodes, 75% after 3 episodes).

Effective vaccination against Chlamydia trachomatis is under investigation. Once clinically available, it should have a dramatic impact on the frequency of ectopic pregnancy, as well as on the overall health of the female reproductive system.

History of previous ectopic pregnancy

After 1 ectopic pregnancy, a patient incurs a 7- to 13-fold increase in the likelihood of another ectopic pregnancy. Overall, a patient with a previous ectopic pregnancy has a 50-80% chance of having a subsequent intrauterine gestation and a 10-25% chance of a future tubal pregnancy.

History of tubal surgery and conception after tubal ligation

Previous tubal surgery has been demonstrated to increase the risk of developing ectopic pregnancy. The increase depends on the degree of damage and the extent of anatomic alteration. Surgeries carrying higher risk of subsequent ectopic pregnancy include salpingostomy , neosalpingostomy, fimbrioplasty, tubal reanastomosis, and lysis of peritubal or periovarian adhesions.

Conception after previous tubal ligation also increases a women's risk of having an ectopic pregnancy; 35-50% of patients who conceive after a tubal ligation are reported to experience an ectopic pregnancy. Failure after bipolar tubal cautery is more likely to result in ectopic pregnancy than is occlusion using suture, rings, or clips. This failure is attributed to fistula formation that allows sperm passage. In one study, 33% of pregnancies occurring after tubal ligation were ectopic; those who underwent electrocautery and women younger than 35 years were at higher risk. [ 17 ]

Ectopic pregnancies following tubal sterilizations usually occur 2 or more years after sterilization rather than immediately after. In the first year, only about 6% of sterilization failures result in ectopic pregnancy.

Cigarette smoking has been shown to be a risk factor for ectopic pregnancy development. Studies have demonstrated an elevated risk ranging from 1.6 to 3.5 times that of nonsmokers. A dose-response effect has also been suggested.

Based on laboratory studies in humans and animals, researchers have postulated several mechanisms by which cigarette smoking might play a role in ectopic pregnancies. These mechanisms include one or more of the following: delayed ovulation, altered tubal and uterine motility, and altered immunity. To date, however, no study has supported a specific mechanism by which cigarette smoking affects the occurrence of ectopic pregnancy.

Use of oral contraceptives or an intrauterine device

All contraceptive methods lead to an overall lower risk of pregnancy and therefore to an overall lower risk of ectopic pregnancy. However, among cases of contraceptive failure, women at increased risk of ectopic pregnancy compared with pregnant controls included those using progestin-only oral contraceptives, progestin-only implants, or IUDs and those with a history of tubal ligation. [ 18 ]

The presence of an inert, copper-containing or progesterone IUD traditionally has been thought to be a risk factor for ectopic pregnancy. Data from the Contraceptive CHOICE Project demonstrated a relative risk of 3.16 for ectopic pregnancy in women not using any form of contraception as compared with women using the progesterone IUD. [ 19 ] Nevertheless, if a woman ultimately conceives with an IUD in place, it is more likely to be an ectopic pregnancy. [ 20 ] The incidence of ectopic pregnancy in IUD users is 1 in 1000 over a 5-year period. [ 19 ]

Emergency contraception (levonorgestrel, or Plan B) does not appear to lead to a higher-than-expected rate of ectopic pregnancy. [ 21 ]

Use of fertility drugs or assisted reproductive technology

Ovulation induction with clomiphene citrate or injectable gonadotropin therapy has been linked to a 4-fold increase in the risk of ectopic pregnancy in a case-control study. This finding suggests that multiple eggs and high hormone levels may be significant factors.

One study demonstrated that infertility patients with luteal phase defects have a statistically higher ectopic pregnancy rate than do patients whose infertility is caused by anovulation. In addition, the risk of ectopic pregnancy and heterotopic pregnancy (ie, pregnancies occurring simultaneously in different body sites) dramatically increases when a patient has used assisted reproductive techniques—such as  in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT)—to conceive. [ 22 ]

In a study of 3000 clinical pregnancies achieved through in vitro fertilization, the ectopic pregnancy rate was 4.5%, which is more than double the background incidence. Furthermore, studies have demonstrated that up to 1% of pregnancies achieved through IVF or GIFT can result in a heterotopic gestation, compared with an incidence of 1 in 30,000 pregnancies for spontaneous conceptions. [ 23 ]

In a retrospective (2006-2014) cohort study of 8120 assisted reproduction technology cycles, Rombauts et al found that endometrial combined thickness (ECT) measured prior to embryo transfer was associated with ectopic pregnancy. [ 24 ] The investigators reported that, following IVF, there was a 4-fold increased risk of ectopic pregnancy in women with an ECT of up to 9 mm compared with women with an ECT of  at least 12 mm. They noted that increased ECT is a marker for increased fundus-to-cervix uterine peristalsis, which may be a reason for the increased risk for placenta praevia but a decreased risk for ectopic pregnancy. [ 24 ]

Increasing age

The highest rate of ectopic pregnancy occurs in women aged 35-44 years. A 3- to 4-fold increase in the risk of developing an ectopic pregnancy exists compared with women aged 15-24 years. One proposed explanation suggests that aging may result in a progressive loss of myoelectrical activity in the fallopian tube; myoelectrical activity is responsible for tubal motility.

Salpingitis isthmica nodosum

Salpingitis isthmica nodosum is defined as the microscopic presence of tubal epithelium in the myosalpinx or beneath the tubal serosa. These pockets of epithelium protrude through the tube, similar to small diverticula. Studies of serial histopathologic sections of the fallopian tube have revealed that approximately 50% of patients treated with salpingectomy for ectopic pregnancy have evidence of salpingitis isthmica nodosum. The etiology of salpingitis isthmica nodosum is unclear, but proposed mechanisms include postinflammatory and congenital changes, as well as acquired tubal changes, such as those observed with endometriosis. [ 25 ]

DES exposure

Before 1971, several million women were exposed in utero to DES, which was given to their mothers to prevent pregnancy complications. In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes, including infertility, spontaneous abortion, and ectopic pregnancy. [ 26 ]

Other risk factors associated with increased incidence of ectopic pregnancy include anatomic abnormalities of the uterus such as a T-shaped or bicornuate uterus, fibroids or other uterine tumors, previous abdominal surgery, failure with progestin-only contraception, and ruptured appendix. [ 15 ]

United States statistics

The incidence of ectopic pregnancy is reported most commonly as the number of ectopic pregnancies per 1000 conceptions. Since 1970, when the reported rate in the United States was 4.5 cases per 1000 pregnancies, the frequency of ectopic pregnancy has increased 6-fold, with ectopic pregnancies now accounting for approximately 1-2% of all pregnancies. Consequently, the prevalence is estimated at 1 in 40 pregnancies, or approximately 25 cases per 1000 pregnancies. These statistics are based on data from the US Centers for Disease Control and Prevention (CDC), which used hospitalizations for ectopic pregnancy to determine the total number of ectopic pregnancies.

Looking at raw data, 17,800 hospitalizations for ectopic pregnancies were reported in 1970. This number rose to 88,000 in 1989 [ 27 ] but fell to 30,000 in 1998. An estimated 108,800 ectopic pregnancies in 1992 resulted in 58,200 hospitalizations, with an estimated cost of $1.1 billion.

Changes in the management of ectopic pregnancy, however, have made it difficult to reliably monitor incidence (and therefore mortality rates). [ 28 ] A review of hospital discharges in California found a rate of 15 cases per 1000 in 1991, declining to a rate of 9.3 cases per 1,000 in 2000, [ 29 ] but a review of electronic medical records (inpatient and outpatient) from a large health maintenance organization (HMO) in northern California found a stable rate of 20.7 cases per 1,000 reported pregnancies from 1997-2000. [ 30 ] This suggests that the incidence of ectopic pregnancy in the United States remained steady at about 2% in the 1990s, despite the shift to outpatient treatment.

The above data raise the question of whether the number of ectopic pregnancies is declining or whether many ectopic pregnancies are now being treated in ambulatory surgical centers or are even being addressed with medical therapy, without admission. Some authors believe the latter is true, but truly accurate statistics are lacking.

Diagnoses of ectopic pregnancy in US emergency departments (ED) may be on the rise. From 2006 to 2013, the overall ratio of ED visits with an ectopic pregnancy diagnosis increased from 11.0 per 1000 live births to 13.7 per 1000 live births. [ 31 ]

Approximately 85-90% of ectopic pregnancies occur in multigravid women. In the United States, rates are nearly twice as high for women of other races compared with White women.

International statistics

The increase in incidence of ectopic pregnancy in the 1970s in the United States was also mirrored in Africa, although data there tend to be hospital based rather than derived from nationwide surveys, with estimates in the range of 1.1-4.6%. [ 32 ]

The United Kingdom estimated the incidence of ectopic pregnancy at about 11.1 per 1,000 reported pregnancies from 1997 to 2005, compared with 9.6 per 1,000 from 1991 to 1993. [ 33 ]

Racial- and age-related demographics

In the United States from 1991 to 1999, ectopic pregnancy was the cause of 8% of all pregnancy-related deaths among Black women, compared with 4% among White women. [ 34 ]

Any woman with functioning ovaries can potentially have an ectopic pregnancy, which includes women from the age of menarche until menopause. Women older than 40 years were found to have an adjusted odds ratio of 2.9 for ectopic pregnancy. [ 15 ]

Ectopic pregnancy presents a major health problem for women of childbearing age. It is the result of a flaw in human reproductive physiology that allows the conceptus to implant and mature outside the endometrial cavity, which ultimately ends in the death of the fetus. Without timely diagnosis and treatment, ectopic pregnancy can become a life-threatening situation. [ 1 ]

The evidence in the literature reporting on the treatment of ectopic pregnancy with subsequent reproductive outcome is limited mostly to observational data and a few randomized trials comparing treatment options.

Assessment of successful treatment and future reproductive outcome with various treatment options is often skewed by selection bias. For example, comparing a patient who was managed expectantly with a patient who received methotrexate or with a patient who had a laparoscopic salpingectomy is difficult.

A patient with spotting, no abdominal pain, and a low initial beta–human chorionic gonadotropin (β-HCG) level that is falling may be managed expectantly, whereas a patient who presents with hemodynamic instability, an acute abdomen, and high initial β-HCG levels must be managed surgically. These 2 patients probably represent different degrees of tubal damage; thus, comparing the future reproductive outcomes of the 2 cases would be flawed.

Salpingostomy, salpingectomy, and tubal surgery

Data in the literature have failed to demonstrate substantial and consistent benefit from either salpingostomy or salpingectomy with regard to improving future reproductive outcome. However, despite the risk of persistent ectopic pregnancy, some studies have shown salpingostomy to improve reproductive outcome in patients with contralateral tubal damage. Yao and Tulandi concluded from a literature review that laparoscopic salpingostomy had a reproductive performance that was equal to or slightly better than salpingectomy; however, slightly higher recurrent ectopic pregnancy rates were noted in the salpingostomy group. [ 35 ]

In reporting on 10 years of surgical experience in Paris, Dubuisson et al concluded that, for selected patients who desire future fertility, using salpingectomy, which is simpler and avoids the risk of persistent ectopic pregnancy, is possible and can result in a comparable fertility rate to tubal conservation surgery. [ 36 ] Future fertility rates were no different with either surgical approach when the contralateral tube was either normal or scarred but patent.

Clausen reviewed literature from the previous 40 years and concluded that only a small number of investigators have suggested, indirectly, that conservative tubal surgery increases the rate of subsequent intrauterine pregnancy. He also concluded that the more recent studies may reflect an improvement in surgical technique. [ 37 ]

In an earlier study, Maymon et al, after reviewing 20 years of ectopic pregnancy treatment, concluded that conservative tubal surgery provided no greater risk of recurrent ectopic pregnancy than the more radical salpingectomy. [ 38 ]

The modern pelvic surgeon has been led to believe that the treatment of choice for unruptured ectopic pregnancy is salpingostomy, sparing the affected fallopian tube and thereby improving future reproductive outcome.

However, if the treating surgeon has neither the laparoscopic skill nor the instrumentation necessary to atraumatically remove the trophoblastic tissue via linear salpingostomy, then salpingectomy by laparoscopy or laparotomy is not the wrong surgical choice. Leaving a scarred, charred fallopian tube behind after removing the ectopic pregnancy but requiring extensive cautery to control bleeding does not preserve reproductive outcome.

Fertility following surgery

Previous history of infertility has been found to be the most significant factor affecting postsurgical fertility.

Parker and Bistis concluded that when the contralateral fallopian tube is normal, the subsequent fertility rate is independent of the type of surgery. [ 39 ] Similarly, a prospective study of 88 patients by Ory et al indicated that the surgical method had no effect on subsequent fertility in women with an intact contralateral tube. [ 40 ]

Several other studies reported that the status of the contralateral tube, the presence of adhesions, and the presence of other risk factors, such as endometriosis, have a more significant impact on future fertility than does the choice of surgical procedure.

According to Rulin, salpingectomy should be the treatment of choice in women with intact contralateral tubes, because conservative treatment provides no additional benefit and incurs the additional costs and morbidity associated with persistent ectopic pregnancy and recurrent ectopic pregnancy in the already damaged tube. [ 41 ]

Future fertility rates have been found to be similar in patients who are treated surgically by laparoscopy or laparotomy. Salpingectomy by laparotomy carries a subsequent intrauterine pregnancy rate of 25-70%, compared with laparoscopic salpingectomy rates of 50-60%. Very similar rates exist for laparoscopic salpingostomy versus laparotomy. The rate of persistent ectopic pregnancy between the 2 groups is also similar, ranging from 5-20%.

A slightly higher recurrent ectopic pregnancy rate exists in patients treated by laparotomy (7-28%), regardless of conservative or radical approach, when compared with laparoscopy (6-16%). This surprising finding is believed to be secondary to increased adhesion formation in the group treated by laparotomy.

Comparison of medical and surgical treatment of small, intact extrauterine pregnancies also revealed similar success and subsequent spontaneous pregnancy rates in a prospective, randomized trial. [ 42 ]

A study by Xu et al found that in women undergoing 51,268 fresh in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) cycles, previous ectopic pregnancy has no effect on IVF-ICSI outcomes. The study also found that women with a prior history of ectopic pregnancy have a higher recurrence risk of ectopic pregnancy after IVF in comparison with women with no history of ectopic pregnancy. [ 43 ]

Methotrexate versus surgery

The success rates after methotrexate are comparable with laparoscopic salpingostomy, assuming that the previously mentioned selection criteria are observed. The average success rates using the multiple-dosage regimen are in the range of 91-95%, as demonstrated by multiple investigators. One study of 77 patients desiring subsequent pregnancy showed intrauterine pregnancies in 64% of these patients and recurrent ectopic pregnancy in 11% of them. Other studies have demonstrated similar results, with intrauterine pregnancy rates ranging from 20-80%.

The average success rates for the single-dosage methotrexate regimen are reported to be from 88-94%. In a study by Stovall and Ling, 113 patients (94%) were treated successfully, 4 (3.3%) of whom needed a second dose. [ 42 ] No adverse effects were encountered. Furthermore, 87.2% of these patients achieved a subsequent intrauterine pregnancy, whereas 12.8% experienced a subsequent ectopic pregnancy. [ 42 ] Other studies have reported similar results, with some mild adverse effects and lower reproductive outcomes.

A meta-analysis that included data from 26 trials demonstrated a success rate of 88.1% with the single-dose methotrexate regimen and a success rate of 92.7% with the multiple-dose regimen. [ 44 ] A small, randomized clinical trial also demonstrated the single-dose regimen to have a slightly higher failure rate. [ 45 ] A hybrid protocol, involving 2 equal doses of methotrexate (50 mg/m 2 ) given on days 1 and 4 without the use of leucovorin, has been shown to be an effective and convenient alternative to the existing regimens. [ 46 ]

Complications

Complications of ectopic pregnancy can be secondary to misdiagnosis, late diagnosis, or treatment approach. Failure to make the prompt and correct diagnosis of ectopic pregnancy can result in tubal or uterine rupture (depending on the location of the pregnancy), which in turn can lead to massive hemorrhage, shock, disseminated intravascular coagulopathy (DIC), and death. Ectopic pregnancy is the leading cause of maternal death in the first trimester, accounting for 9-13% of all pregnancy-related deaths. In the United States, an estimated 30-40 women die each year from ectopic pregnancy.

Any time a surgical approach is chosen as the treatment of choice, consider the complications attributable to the surgery, whether it is laparotomy or laparoscopy. These include bleeding, infection, and damage to surrounding organs, such as the bowel, bladder, and ureters, and to the major vessels nearby. Infertility may also result secondary to loss of reproductive organs after surgery. Also consider the risks and complications secondary to anesthesia. Make the patient aware of these complications, and obtain the appropriate written consents.

In the United States, ectopic pregnancy is estimated to occur in 1-2% of all pregnancies and accounts for 3-4% of all pregnancy-related deaths. [ 47 ] It is the leading cause of pregnancy-related mortality during the first trimester in the United States. In a review of deaths from ectopic pregnancy in Michigan, 44% of the women who died were either found dead at home or were dead on arrival at the emergency department. [ 48 ]

Virtually all ectopic pregnancies are considered nonviable and are at risk of eventual rupture and resulting hemorrhage. In addition to the immediate morbidity caused by ectopic pregnancy, the woman's future ability to reproduce may be adversely affected as well. However, patients who are diagnosed with ectopic pregnancy before rupture have a low mortality rate and also have a chance at preserved fertility.

From 1970 to 1989, the US mortality rate for ectopic pregnancies dropped from 35.5 deaths to 3.8 deaths per 10,000 ectopic pregnancies. [ 27 ] If the overall incidence of ectopic pregnancy remained stable in the 1990s, then the mortality rate dropped to 3.19 deaths per 10,000 ectopic pregnancies by 1999. [ 49 ]

Surveillance data for pregnancy-related deaths in the United States from 1991-1999 showed that ectopic pregnancy was the cause of 5.6% of 4200 maternal deaths. Of these deaths, 93% occurred via hemorrhage. [ 34 ]

Surveillance data from 2012-2019 indicated that ruptured ectopic pregnancy was the most common cause of hemorrhage-related maternal mortality (22.9%) in the United States. It accounted for 32.6% of hemorrhage-related deaths among non-Hispanic Black women. [ 50 ]

During 1999–2008, the ectopic pregnancy mortality rate in the United States was 0.6 deaths per 100,000 live births. The CDC reported a higher rate in Florida, 2.5 deaths per 100,000 live births during 2009-2010. The 11 ectopic pregnancy deaths in Florida during 2009-2010 contrasted with the total number of deaths (14) identified in national statistics for 2007. There was a high prevalence of illicit drug use among the women who died in Florida. [ 47 ]

The mortality rate reported in African hospital-based studies varied from 50-860 deaths per 10,000 ectopic pregnancies; these were almost certainly underestimates resulting from underreporting of maternal deaths and misclassification of ectopic pregnancies as induced abortions. [ 32 ]

Using data from 1997 to 2002, the World Health Organization (WHO) estimated that ectopic pregnancy was the cause of 4.9% of pregnancy-related deaths in the industrialized world. [ 51 ] Ectopic pregnancy caused 26% of maternal deaths in early pregnancy in the United Kingdom from 2003-2005, second only to venous thromboembolism, despite a relatively low mortality rate of 0.035 per 10,000 estimated ectopic pregnancies. [ 33 ]

Advise patients receiving methotrexate therapy to avoid alcoholic beverages, vitamins containing folic acid, nonsteroidal anti-inflammatory drugs (NSAIDs), and sexual intercourse, until advised otherwise. A signed written consent demonstrating the patient's comprehension of the course of treatment must be obtained.

Provide an information pamphlet to all patients receiving methotrexate; the pamphlet should include a list of adverse effects, a schedule of follow-up visits, and a method of contacting the physician or the hospital in case of emergency, as well as the need to return to the emergency department for concerning symptoms.

Patients with risk factors for ectopic pregnancy should be educated regarding their risk of having an ectopic pregnancy. Women who are being discharged with a pregnancy of unknown location should be educated regarding the possibility of ectopic pregnancy and their need for urgent follow-up.

Patients undergoing assisted reproduction technology should be educated regarding their risk of heterotopic pregnancy.

For patient education information, see the Pregnancy Center and the Women's Health Center , as well as Ectopic Pregnancy , Bleeding During Pregnancy , Vaginal Bleeding , Birth Control Overview , and Birth Control Methods .

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• Sites and frequencies of ectopic pregnancy. By Donna M. Peretin, RN. (A) Ampullary, 80%; (B) Isthmic, 12%; (C) Fimbrial, 5%; (D) Cornual/Interstitial, 2%; (E) Abdominal, 1.4%; (F) Ovarian, 0.2%; and (G) Cervical, 0.2%.
• Laparoscopic picture of an unruptured right ampullary tubal pregnancy; bleeding out of the fimbriated end has resulted in hemoperitoneum.
• A 12-week interstitial gestation, which eventually resulted in a hysterectomy. Courtesy of Deidra Gundy, MD, Department of Obstetrics and Gynecology at Medical College of Pennsylvania and Hahnemann University (MCPHU).
• An endovaginal sonogram reveals an intrauterine pregnancy at approximately 6 weeks. A yolk sac (ys), gestational sac (gs), and fetal pole (fp) are depicted.
• Linear incision being made at the antimesenteric side of the ampullary portion of the fallopian tube.
• Laparoscopic picture of an ampullary ectopic pregnancy protruding out after a linear salpingostomy was performed.
• Schematic of a tubal gestation being teased out after linear salpingostomy.

Contributor Information and Disclosures

Vicken P Sepilian, MD, MSc Medical Director, Reproductive Endocrinology and Infertility, CHA Fertility Center Vicken P Sepilian, MD, MSc is a member of the following medical societies: American College of Obstetricians and Gynecologists , American Society for Reproductive Medicine Disclosure: Nothing to disclose.

Ellen Wood, DO, FACOG Voluntary Assistant Professor, University of Miami, Leonard M Miller School of Medicine Ellen Wood, DO, FACOG is a member of the following medical societies: American Society for Reproductive Medicine Disclosure: Nothing to disclose.

Frances E Casey, MD, MPH Associate Professor, Director of Family Planning Services, Department of Obstetrics and Gynecology, VCU Medical Center Frances E Casey, MD, MPH is a member of the following medical societies: American College of Obstetricians and Gynecologists , Association of Reproductive Health Professionals , National Abortion Federation , Physicians for Reproductive Health , Society of Family Planning Disclosure: Nothing to disclose.

Michel E Rivlin, MD Former Professor, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine Michel E Rivlin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists , American Medical Association , Mississippi State Medical Association , Royal College of Surgeons of Edinburgh , Royal College of Obstetricians and Gynaecologists Disclosure: Nothing to disclose.

A David Barnes, MD, PhD, MPH, FACOG Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, California), Pioneer Valley Hospital (Salt Lake City, Utah), Warren General Hospital (Warren, Pennsylvania), and Mountain West Hospital (Tooele, Utah)

A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners , American College of Obstetricians and Gynecologists , American Medical Association , Association of Military Surgeons of the US , and Utah Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Robert K Zurawin, MD Associate Professor, Director of Baylor College of Medicine Program for Minimally Invasive Gynecology, Director of Fellowship Program, Minimally Invasive Surgery, Department of Obstetrics and Gynecology, Baylor College of Medicine

Robert K Zurawin, MD is a member of the following medical societies: American Association of Gynecologic Laparoscopists , American College of Obstetricians and Gynecologists , American Society for Reproductive Medicine , Association of Professors of Gynecology and Obstetrics , Central Association of Obstetricians and Gynecologists , Harris County Medical Society , North American Society for Pediatric and Adolescent Gynecology , and Texas Medical Association

Disclosure: Johnson and Johnson Honoraria Speaking and teaching; Conceptus Honoraria Speaking and teaching; ConMed Consulting fee Consulting

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Ectopic pregnancy

• Overview  
• Theory  
• Diagnosis  
• Management  
• Follow up  
• Resources  

Ectopic pregnancy typically presents 6 to 8 weeks after the last normal menstrual period, but can present earlier or later.

Risk of ectopic pregnancy increases with prior ectopic pregnancy, tubal surgery, history of sexually transmitted infections, smoking, in vitro fertilisation, or if the woman is pregnant despite IUD usage.

Classical symptoms and signs of ectopic pregnancy are pain, vaginal bleeding, and amenorrhoea. Haemodynamic instability and cervical motion tenderness may indicate rupture or imminent rupture of an ectopic pregnancy.

If the woman is haemodynamically stable, transvaginal ultrasound is the initial test of choice.

Treatment approaches for ectopic pregnancy include expectant, medical (methotrexate), or surgical (salpingectomy, salpingostomy).

If an ectopic pregnancy ruptures, the woman may present in shock from blood loss and with unusual patterns of referred pain from intraperitoneal blood.

An ectopic pregnancy occurs when a fertilised ovum implants and matures outside the uterine endometrial cavity, with the most common site being the fallopian tube (97%), followed by the ovary (3.2%) and the abdomen (1.3%). [1] Bouyer J, Coste J, Fernandez H, et al. Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases. Hum Reprod. 2002 Dec;17(12):3224-30. https://academic.oup.com/humrep/article/17/12/3224/569616 http://www.ncbi.nlm.nih.gov/pubmed/12456628?tool=bestpractice.com If undiagnosed or untreated, it may lead to maternal death due to rupture of the implantation site and intraperitoneal haemorrhage. [2] Ankum WM, Mol BW, Van Der Veen F, et al. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril. 1996 Jun;65(6):1093-9. http://www.ncbi.nlm.nih.gov/pubmed/8641479?tool=bestpractice.com

History and exam

Key diagnostic factors.

• abdominal pain
• amenorrhoea
• vaginal bleeding
• abdominal tenderness
• adnexal tenderness or mass
• blood in vaginal vault
• haemodynamic instability, orthostatic hypotension
• cervical motion tenderness

Other diagnostic factors

• urge to defecate
• referred shoulder pain

Risk factors

• previous ectopic pregnancy
• previous tubal sterilisation surgery
• in utero diethylstilbestrol exposure of the mother
• intrauterine device (IUD) use
• previous genital infections
• chronic salpingitis
• salpingitis isthmica nodosa
• infertility
• multiple sexual partners
• race/ethnicity
• assisted reproductive technology (ART)
• first sexual encounter <18 years
• maternal age >35 years
• tubal reconstruction surgery

Diagnostic investigations

1st investigations to order.

• urine or serum pregnancy test
• high resolution transvaginal ultrasound (TVUS)
• transabdominal ultrasound

Investigations to consider

• serial serum human chorionic gonadotrophin (hCG)
• uterine aspiration

Treatment algorithm

Tubal ectopic pregnancy: ruptured ectopic pregnancy or failed medical management, tubal ectopic pregnancy: moderate risk or failed expectant management, tubal ectopic pregnancy: low risk, contributors, kurt t. barnhart, md, msce.

William Shippen Jr. Professor of Obstetrics and Gynecology and Epidemiology

Vice Chair for Clinical Research

Director, Women's Health Clinic Research Center

The Perelman School of Medicine

University of Pennsylvania

Associate Chief, Penn Fertility Care

Philadelphia

Disclosures

KTB is a co-author on several papers cited in this topic.

Acknowledgements

Dr Kurt T. Barnhart would like to gratefully acknowledge Dr Ingrid Granne, Dr Veronica Gomez-Lobo, Dr Sina Haeri, and Dr Mohammad Ezzati, previous contributors to this topic.

IG, VGL, SH, and ME declare that they have no competing interests.

Peer reviewers

Alan decherney, md.

Reproductive Biology Medicine and Biology

AD declares that he has no competing interests.

Joanna C. Girling, MA, MRCP, FRCOG

Consultant in Obstetrics and Gynaecology

West Middlesex University Hospital

JCG declares that she has no competing interests.

Differentials

• Miscarriage
• Acute appendicitis
• Ovarian torsion
• Ectopic pregnancy and miscarriage: diagnosis and initial management
• ACR appropriateness criteria: acute pelvic pain in the reproductive age group

Patient information

Ectopic pregnancy: what is it?

Ectopic pregnancy: what treatments work?

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ANNE-MARIE LOZEAU, M.D., M.S., AND BETH POTTER, M.D.

This is a corrected version of the article that appeared in print.

Am Fam Physician. 2005;72(9):1707-1714

Patient information: See related handout on ectopic pregnancy , written by the authors of this article.

Author disclosure: nothing to disclose.

Ectopic pregnancy is a high-risk condition that occurs in 1.9 percent of reported pregnancies. The condition is the leading cause of pregnancy-related death in the first trimester. If a woman of reproductive age presents with abdominal pain, vaginal bleeding, syncope, or hypotension, the physician should perform a pregnancy test. If the patient is pregnant, the physician should perform a work-up to detect possible ectopic or ruptured ectopic pregnancy. Prompt ultrasound evaluation is key in diagnosing ectopic pregnancy. Equivocal ultrasound results should be combined with quantitative beta subunit of human chorionic gonadotropin levels. If a patient has a beta subunit of human chorionic gonadotropin level of 1,500 mIU per mL or greater, but the transvaginal ultrasonography does not show an intrauterine gestational sac, ectopic pregnancy should be suspected. Diagnostic uterine curettage may be appropriate in patients who are hemodynamically stable and whose beta subunit of human chorionic gonadotropin levels are not increasing as expected. Appropriate treatment for patients with nonruptured ectopic pregnancy may include expectant management, medical management with methotrexate, or surgery. Expectant management is appropriate only when beta subunit of human chorionic gonadotropin levels are low and declining. Initial levels determine the success of medical treatment. Surgical treatment is appropriate if ruptured ectopic pregnancy is suspected and if the patient is hemodynamically unstable.

Ectopic pregnancy is any pregnancy that occurs outside the uterine cavity. Pregnancies in the fallopian tube account for 97 percent of ectopic pregnancies: 55 percent in the ampulla; 25 percent in the isthmus; 17 percent in the fimbria; and 3 percent in the abdominal cavity, ovary, and cervix. 1

The rate of ectopic pregnancies in North America climbed from less than 0.5 percent of all pregnancies in 1970 to 2 percent in 1992. 1 – 3 Ruptured ectopic pregnancy accounts for 10 to 15 percent of all maternal deaths. 1 , 2 Fortunately, after the advent of transvaginal ultrasonography and beta subunit of human chorionic gonadotropin (beta-hCG) tests, the incidence of rupture and case-fatality rates declined from 35.5 deaths per 10,000 ectopic pregnancies in 1970 to 3.8 per 10,000 in 1989. 2 Management options for ectopic pregnancy include expectant management, medical treatment, and surgery.

Risk Factors

Risk factors most strongly associated with ectopic pregnancy include previous ectopic pregnancy, tubal surgery, and in utero diethylstilbestrol (DES) exposure. A history of genital infections or infertility and current smoking increase risk. 3 , 4 Contraceptive use reduces the annual risk for intrauterine and ectopic pregnancy 5 , 6 ; however, previous intrauterine device use may increase risk. Table 1 lists common risk factors for ectopic pregnancy. 4 , 5 [ corrected ]

Ectopic pregnancy is most common in women of reproductive age who present with abdominal pain and vaginal bleeding approximately seven weeks after amenorrhea. 1 , 2 , 7 These findings are nonspecific and are common in patients who may miscarry. 1 Table 2 lists the common differential diagnosis of ectopic pregnancy.

CLINICAL EXAMINATION

A normal or slightly enlarged uterus, vaginal bleeding, pelvic pain with manipulation of the cervix, and a palpable adnexal mass significantly increase the likelihood of an ectopic pregnancy. Significant abdominal tenderness suggests ruptured ectopic pregnancy, especially in a patient with hypotension who presents with guarding and rebound tenderness.

Physicians can categorize hemodynamically stable patients as high, intermediate, or low risk for ectopic pregnancy ( Table 3 7 , 8 ) based on clinical examination findings. 7 Clinical examinations are not diagnostic because up to 30 percent of patients with ectopic pregnancies have no vaginal bleeding, 10 percent have a palpable adnexal mass, and up to 10 percent have negative pelvic examinations. 1 , 7 The overall likelihood of ectopic pregnancy is 39 percent in a patient with abdominal pain and vaginal bleeding but no other risk factors. 9 The probability of ectopic pregnancy increases to 54 percent if the patient has other risk factors (e.g., history of tubal surgery, ectopic pregnancy, or pelvic inflammatory disease; in utero DES exposure; or an intrauterine device in situ at the time of conception). 9 Physicians should remember that no combination of physical examination findings can reliably exclude ectopic pregnancy. 1 , 10 – 13

DIAGNOSTIC TESTS

Diagnostic tests for ectopic pregnancy include a urine pregnancy test; ultrasonography; beta-hCG measurement; and, occasionally, diagnostic curettage. In the past, some physicians have used serum progesterone levels as well. 2 , 14 Table 4 summarizes the accuracy rates of diagnostic tests for ectopic pregnancy. 1 , 14 – 17

Ultrasonography is the diagnostic test of choice, with limitations largely based on availability and the gestational age of the pregnancy. 3 , 14 , 18 Ectopic pregnancy is suspected if transabdominal ultrasonography does not show an intrauterine gestational sac and the patient’s beta-hCG level is greater than 6,500 mIU per mL (6,500 IU per L) or if transvaginal ultrasonography does not show an intrauterine gestational sac and the patient’s beta-hCG level is 1,500 mIU per mL (1,500 IU per L) or greater. 2 , 19 Ultrasound findings that suggest ectopic pregnancy are listed in Table 5 . 9 [ corrected ] More than one half of women with ectopic pregnancy have beta-hCG levels less than 2,000 mIU per mL (2,000 IU per L) at presentation. Therefore, it may be difficult to determine by ultrasonography alone whether an empty uterus indicates early pregnancy or ectopic pregnancy. 2 , 7

Beta-hCG levels may assist in interpreting ultrasound findings. In a normal intrauterine pregnancy, these levels would increase by at least 53 percent every two days, peaking at a level greater than 100,000 mIU per mL (100,000 IU per L). 1 , 20 Beta-hCG levels alone cannot differentiate between ectopic and intrauterine pregnancy, and serial beta-hCG levels that do not increase appropriately in a woman with suspected ectopic pregnancy are only 36 percent sensitive and approximately 65 percent specific for detection of ectopic pregnancy. 14 , 15 It also is important to note that ruptured and unruptured ectopic pregnancies have been identified at beta-hCG levels less than 100 mIU per mL (100 IU per L) and greater than 50,000 mIU per mL (50,000 IU per L). 1

Serum progesterone levels can detect pregnancy failure and identify patients at risk for ectopic pregnancy, but they are not diagnostic of ectopic pregnancy. Sensitivity for diagnosis of ectopic pregnancy is very low (15 percent); therefore, 85 percent of patients with ectopic pregnancy will have normal serum progesterone levels. 9 Algorithms for diagnosing ectopic pregnancy that include progesterone levels miss more ectopic pregnancies and require more surgeries than do algorithms without progesterone. 9 , 10 , 14 , 16 , 17

Diagnostic uterine curettage may detect chorionic villi. If chorionic villi are not detected, ectopic pregnancy should be suspected. Curettage should only be considered when beta-hCG levels are falling or when levels are elevated and ultrasonography does not show intrauterine pregnancy. 2 , 14 Diagnostic uterine curettage could terminate a desired pregnancy.

RECOMMENDED DIAGNOSTIC STRATEGY

The American College of Emergency Physicians and the American College of Obstetricians and Gynecologists have issued guidelines for using ultrasonography and beta-hCG levels to evaluate patients with suspected ectopic pregnancy. 14 , 15 Figures 1 and 2 are algorithms based on these guidelines. 1 , 14 , 15 , 17 , 20

When evaluating patients for suspected ectopic pregnancy, physicians should take a history and perform a physical examination; then they should determine the patient’s risk stratification ( Table 3 7 , 8 ) and order transvaginal ultrasonography. 10 , 18 If a low-risk patient’s ultrasonography is negative for intrauterine pregnancy, and she is hemodynamically stable and has a beta-hCG level less than 1,500 mIU per mL, the physician should take another beta-hCG measurement after 48 hours. Patients with a nondiagnostic transvaginal ultrasonography result and a beta-hCG level of 1,500 mIU per mL or greater are at an increased risk for ectopic pregnancy and may need a surgical consultation or uterine evacuation procedure. If a patient’s condition is unstable, immediate surgical consultation is needed, and a uterine evacuation procedure may be considered. If chorionic villi are absent, ectopic pregnancy is likely.

Combined transvaginal ultrasonography and serial quantitative beta-hCG measurements are approximately 96 percent sensitive and 97 percent specific for diagnosing ectopic pregnancy. Therefore, transvaginal ultrasonography followed by quantitative beta-hCG testing is the optimal and most cost-effective strategy for diagnosing ectopic pregnancy. 9 , 10 , 21

EXPECTANT MANAGEMENT

Expectant management is between 47 and 82 percent effective in managing ectopic pregnancy. 22 , 23 A good candidate for expectant management has a beta-hCG level less than 1,000 mIU per mL (1,000 IU per L) and declining, an ectopic mass less than 3 cm, no fetal heartbeat, and has agreed to comply with follow-up requirements.

MEDICAL TREATMENT

Methotrexate, a folic acid antagonist, is a well-studied medical therapy. Methotrexate deactivates dihydrofolate reductase, which reduces tetrahydrofolate levels (a cofactor for deoxyribonucleic acid and ribonucleic acid synthesis), thereby disrupting rapidly-dividing trophoblastic cells. 24 Other therapeutic agents include hyperosmolar glucose, prostaglandins, and mifepristone (Mifeprex). 24

Protocols for methotrexate therapy include single-dose and multiple-dose regimens ( Table 6 24 ). Although no studies have compared the protocols, the single-dose regimen is easier to administer and is used more often. In a 2003 meta-analysis 24 of methotrexate therapies, 20 studies examined the single-dose regimen, and six examined the multiple-dose regimen. The single-dose regimen created fewer side effects but was slightly less effective, with a crude overall success rate of 88 percent compared with the multiple-dose regimen’s 93 percent success rate. Methotrexate, regardless of the protocol, had an overall 89 percent crude success rate. 24 Side effects of methotrexate include bone marrow suppression, elevated liver enzymes, rash, alopecia, stomatitis, nausea, and diarrhea. The time to resolution of the ectopic pregnancy is three to seven weeks after methotrexate therapy.

Patient selection is important in the medical management of ectopic pregnancy. The lower the beta-hCG levels at initiation of treatment, the higher the success rate of methotrexate therapy ( Table 7 ). 26 In addition to having a beta-hCG level less than 15,000 mIU per mL (15,000 IU per L), a candidate for medical treatment must be reliable and able to follow-up daily if necessary. 15 Surgical management may be considered if a patient does not meet these criteria. Women with certain medical conditions (e.g., liver disease with a transaminase level two times greater than normal, renal disease with a creatinine level greater than 1.5 mg per dL [133 μmol per L], immune compromise with a white blood cell count less than 1,500 per mm 3 [1.5 3 10 9 per L] and platelets less than 100,000 3 10 3 per mm 3 [100 3 10 9 per L], significant pulmonary disease) are not candidates for methotrexate. 27

Patients treated with methotrexate have been shown to have the same quality of life after methotrexate treatment compared with patients who had surgical treatment. Women experienced more pain, had less energy, and had worse health perception during the first few weeks after treatment with methotrexate, but they had the same quality of life after 16 weeks. 28

SURGICAL TREATMENT

Before the advent of laparoscopy, laparotomy with salpingectomy (removal of the fallopian tube through an abdominal incision) was the standard therapy for managing ectopic pregnancy. Laparoscopy with salpingostomy, without fallopian tube removal, has become the preferred method of surgical treatment. Laparoscopy has similar tubal patency and future fertility rates as medical treatment. 25 Salpingostomy has an estimated 8 to 9 percent failure rate, which can be managed with methotrexate.

Follow-Up and Prognosis

During treatment, physicians should examine patients at least weekly and sometimes daily. Serial beta-hCG measurements should be taken after treatment until the level is undetectable. If the levels fail to decline, the patient can be treated with a second course of methotrexate or with methotrexate post-surgery. Surgical intervention is necessary if beta-hCG levels increase.

The prognosis is good for patients who receive appropriate treatment. With proper patient selection, success rates approach 82 percent for expectant management, 90 percent for medical management, and 92 percent for surgical management. 22 , 23 , 26

FUTURE FERTILITY AND RISK OF RECURRENCE

Approximately 30 percent of women treated for ectopic pregnancy later have difficulty conceiving. The overall conception rate is approximately 77 percent regardless of treatment. 3 Rates of recurrent ectopic pregnancy are between 5 and 20 percent, but the risk increases to 32 percent in women who have had two consecutive ectopic pregnancies. 2 , 3

Della-Giustina D, Denny M. Ectopic pregnancy. Emerg Med Clin North Am. 2003;21:565-84.

Tenore JL. Ectopic pregnancy. Am Fam Physician. 2000;61:1080-8.

Tay JI, Moore J, Walker JJ. Clinical review: Ectopic pregnancy [published correction appears in BMJ 2000;321:424]. BMJ. 2000;320:916-9.

Ankum WM, Mol BW, Van der Veen F, Bossuyt PM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril. 1996;65:1093-9.

Mol BW, Ankum WM, Bossuyt PM, Van der Veen F. Contraception and the risk of ectopic pregnancy: a meta-analysis. Contraception. 1995;52:337-41.

Sivin I. Dose- and age-dependent ectopic pregnancy risks with intrauterine contraception. Obstet Gynecol. 1991;78:291-8.

Buckley RG, King KJ, Disney JD, Gorman JD, Klausen JH. History and physical examination to estimate the risk of ectopic pregnancy: validation of a clinical prediction model. Ann Emerg Med. 1999;34:589-94.

Gallagher EJ. Application of likelihood ratios to clinical decision rules: defining the limits of clinical expertise. Ann Emerg Med. 1999;34:664-7.

Mol BW, Van der Veen F, Bossuyt PM. Implementation of probabilistic decision rules improves the predictive values of algorithms in the diagnostic management of ectopic pregnancy. Hum Reprod. 1999;14:2855-62.

Gracia CR, Barnhart KT. Diagnosing ectopic pregnancy: decision analysis comparing six strategies. Obstet Gynecol. 2001;97:464-70.

Dart RG, Kaplan B, Varaklis K. Predictive value of history and physical examination in patients with suspected ectopic pregnancy. Ann Emerg Med. 1999;33:283-90.

Yip SK, Sahota D, Cheung LP, Lam P, Haines CJ, Chung TK. Accuracy of clinical diagnostic methods of threatened abortion. Gynecol Obstet Invest. 2003;56:38-42.

Mol BW, Hajenius PJ, Engelsbel S, Ankum WM, Van der Veen F, Hemrika DJ, et al. Should patients who are suspected of having an ectopic pregnancy undergo physical examination?. Fertil Steril. 1999;71:155-7.

American College of Obstetricians and Gynecologists. Medical management of tubal pregnancy. Number 3, December 1998. Clinical management guidelines for obstetricians-gynecologists. Int J Gynaecol Obstet. 1999;65:97-103.

American College of Emergency Physicians.. Clinical policy: critical issues in the initial evaluation and management of patients presenting to the emergency department in early pregnancy. Ann Emerg Med. 2003;41:123-33.

Mol BW, Lijmer JG, Ankum WM, Van der Veen F, Bossuyt PM. The accuracy of single serum progesterone measurement in the diagnosis of ectopic pregnancy: a meta-analysis. Hum Reprod. 1998;13:3220-7.

Barnhart K, Mennuti MT, Benjamin I, Jacobson S, Goodman D, Coutifaris C. Prompt diagnosis of ectopic pregnancy in an emergency department setting. Obstet Gynecol. 1994;84:1010-5.

Durston WE, Carl ML, Guerra W, Eaton A, Ackerson LM. Ultrasound availability in the evaluation of ectopic pregnancy in the ED: comparison of quality and cost-effectiveness with different approaches. Am J Emerg Med. 2000;18:408-17.

Borrelli PT, Butler SA, Docherty SM, Staite EM, Borrelli AL, Iles RK. Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy. Clin Chem. 2003;49:2045-9.

Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, Hummel AC, Guo W. Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined. Obstet Gynecol. 2004;104:50-5.

Buckley RG, King KJ, Disney JD, Ambroz PK, Gorman JD, Klausen JH. Derivation of a clinical prediction model for the emergency department diagnosis of ectopic pregnancy. Acad Emerg Med. 1998;5:951-60.

Trio D, Strobelt N, Picciolo C, Lapinski RH, Ghidini A. Prognostic factors for successful expectant management of ectopic pregnancy. Fertil Steril. 1995;63:469-72.

Shalev E, Peleg D, Tsabari A, Romano S, Bustan M. Spontaneous resolution of ectopic tubal pregnancy: natural history. Fertil Steril. 1995;63:15-9.

Barnhart KT, Gosman G, Ashby R, Sammel M. The medical management of ectopic pregnancy: a meta-analysis comparing “single dose” and “multidose” regimens. Obstet Gynecol. 2003;101:778-84.

Hajenius PJ, Mol BW, Bossuyt PM, Ankum WM, Van der Veen F. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev. 2000;1:CD00324.

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Ectopic Pregnancy

What is an ectopic pregnancy.

A pregnancy that develops outside the uterus is called an ectopic pregnancy. This nearly always happens in a fallopian tube. So it’s often called a tubal pregnancy. In rare cases, an ectopic pregnancy will happen in an ovary, in the cervix, or the belly (abdomen).

What causes an ectopic pregnancy?

A fertilized egg normally moves down a fallopian tube and into the uterus. But the egg can get stuck in the tube if the tube is blocked. This might be from an infection or scar tissue. If the fertilized egg can't reach the uterus, it begins to develop in the tube.

Who is at risk for an ectopic pregnancy?

Ectopic pregnancy is more common in women who:

• Have had trouble getting pregnant (infertility)
• Have endometriosis. This is when uterine tissue grows in other areas of the pelvis.
• Have a sexually transmitted disease. This can cause infection and scarring in the pelvis.
• Have had tubal surgery
• Had an ectopic pregnancy in the past
• Have multiple sex partners

What are the symptoms of an ectopic pregnancy?

Women with an ectopic pregnancy may have irregular bleeding and pelvic or belly (abdominal) pain. The pain is often just on one side. Symptoms often appear 6 to 8 weeks after the last normal menstrual period. If the ectopic pregnancy is not in the fallopian tube, symptoms may happen later. The classic symptoms of an ectopic pregnancy are:

• Belly (abdominal) pain
• No recent period
• Vaginal bleeding not related to a period

How is an ectopic pregnancy diagnosed?

Your healthcare provider will measure the level of the hormone hCG (human chorionic gonadotropin) in your blood. He or she will use ultrasound to check the uterus for a fetus or other pregnancy tissue. In some cases, your healthcare provider will use laparoscopy to diagnose and treat an ectopic pregnancy. This is surgery that uses a lighted tube inserted into your abdomen to check inside the pelvis. It often gives the most accurate diagnosis.

How is an ectopic pregnancy treated?

Ectopic pregnancy may be treated in several ways. This depends on whether the fallopian tube has broken open (ruptured), how far along the pregnancy is, and your hormone levels. Treatments may include:

• Letting the ectopic pregnancy heal and the body absorb it on its own. This is only for certain cases.
• Using the medicine methotrexate to stop the pregnancy from growing further
• Using surgery (usually laparoscopy) to make a small opening in the fallopian tube. The surgeon removes the pregnancy and sometimes the tube.

In rare cases, healthcare providers must make a larger incision in the abdomen to remove the ectopic pregnancy or damaged fallopian tube.

What are the complications of an ectopic pregnancy?

The tube may start to let out some of the tissues or bleed. Some embryos do keep growing and may become large enough to burst the fallopian tube. This can cause severe bleeding and shock.

Ectopic pregnancy is the leading cause of pregnancy-related deaths during the first 3 months of pregnancy in the U.S.

When should I call the healthcare provider?

• Don’t ignore symptoms of ectopic pregnancy. Call your healthcare provider if you have any bleeding or pain in pregnancy.

Key points about ectopic pregnancy

• Pregnancy that develops outside the uterus is called ectopic pregnancy.
• Women with an ectopic pregnancy may have irregular bleeding and pelvic or abdominal pain, often on one side.
• Symptoms most often appear 6 to 8 weeks after the last normal menstrual period.
• Ectopic pregnancy may be treated in several ways, depending on whether the fallopian tube has burst.

Tips to help you get the most from a visit to your healthcare provider:

• Know the reason for your visit and what you want to happen.
• Before your visit, write down questions you want answered.
• Bring someone with you to help you ask questions and remember what your provider tells you.
• At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you.
• Know why a new medicine or treatment is prescribed, and how it will help you. Also know what the side effects are.
• Ask if your condition can be treated in other ways.
• Know why a test or procedure is recommended and what the results could mean.
• Know what to expect if you do not take the medicine or have the test or procedure.
• If you have a follow-up appointment, write down the date, time, and purpose for that visit.
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Diagnosis and treatment of ectopic pregnancy

ABSTRACT: Ectopic pregnancy refers to implantation of an embryo outside the endometrium. It is a medical emergency, but associated maternal mortality has significantly declined over the decades due to earlier diagnosis and treatment. Timely detection of ectopic pregnancy is contingent on having a high index of suspicion in all women of reproductive age, identifying patient risk factors, and then performing appropriate laboratory testing and imaging. Expectant management is less commonly used than medical management, which is preferred for asymptomatic, vitally stable women who wish to avoid surgery. Minimally invasive surgery is the gold standard for management of unstable or ruptured ectopic pregnancy. Recent data favor salpingectomy for women with a healthy contralateral tube because it has higher treatment success and does not appear to reduce future fertility compared to salpingotomy. However, salpingotomy is suggested for women with a dysfunctional or absent contralateral tube, or those who elect to preserve both tubes and accept the increased risk of treatment failure. Knowledge of the risks and benefits of each treatment option is critical for delivering patient-centred care.

Early diagnosis of ectopic pregnancy is critical to reducing maternal mortality and improving treatment success rates, especially since many women have no identifiable risk factors.

Ectopic pregnancy occurs when a developing embryo implants at a site other than the endometrium of the uterine cavity, most commonly within the fallopian tube. Although the incidence of ectopic pregnancy is estimated to be approximately 2% of all pregnancies, it is one of the most common gynecologic emergencies encountered by community physicians.[ 1 ] Ruptured ectopic pregnancy can lead to severe hemorrhage and is a significant cause of pregnancy-related maternal mortality in the first trimester.[ 2 ] Thus, timely diagnosis of ectopic pregnancy is essential to prevent maternal mortality and improve treatment outcomes.

Maternal mortality related to ectopic pregnancy has plummeted over the last two decades due to the availability of quantitative beta-human chorionic gonadotropin (b-hCG) testing, transvaginal ultrasound, and laparoscopy, which allow for early diagnosis and intervention.[ 1 ] Despite this, ectopic pregnancy and its treatments remain a prevalent cause of morbidity among women and can affect long-term reproductive success. With a comprehensive understanding of ectopic pregnancy, community physicians can help women make informed decisions and thus provide personalized health care. This review outlines the current practices, recent advances, and unresolved topics related to diagnosis, management, and prognosis of ectopic pregnancy.

Risk factors

Only half of the women who are diagnosed with ectopic pregnancy have identifiable risk factors.[ 2 ] Thus, it is critical to maintain a high index of suspicion in all women of reproductive age who present with amenorrhea, abdominal pain, irregular vaginal bleeding, or a history of ectopic pregnancy.[ 3 ] The pretest probability of ectopic pregnancy is increased if multiple risk factors are elicited when taking a history, which can aid in making a prompt diagnosis.

The most well-documented risk factor for an ectopic pregnancy is a previous ectopic pregnancy.[ 4 , 5 ] Women with a prior ectopic pregnancy have a 10-times higher risk of recurrence than the general population.[ 6 ] After one ectopic pregnancy, there is a 10% to 15% chance of recurrence, which increases to 25% in women who have had two or more ectopic pregnancies.[ 6 ] Recurrence can be attributed to congenital tubal dysfunction, acquired tubal damage from pelvic inflammatory disease, or previous tubal surgery—all of which may impede embryonic passage through the fallopian tube.[ 4 , 7 ] Women with perihepatic adhesions (commonly known as Fitz-Hugh-Curtis syndrome), a complication of pelvic inflammatory disease, carry twice the risk of ectopic pregnancy recurrence compared to unaffected women.[ 7 ]

Smoking, even “light” consumption of one to nine cigarettes per day, increases the risk of ectopic pregnancy by up to twofold.[ 8 ] Some other well-recognized risk factors for ectopic pregnancy are age over 35 years, history of infertility, prior tubal surgery, and laboratory/laparoscopy confirmed pelvic inflammatory disease.[ 2 ] Additionally, genital surgery, endometriosis, and dysmenorrhea have been recognized as significant risk factors.[ 4 ] Jacob and colleagues also described a 1.8-fold (95% CI 1.54-2.09) increase in the risk of ectopic pregnancy in women with a diagnosis of mental health disorders, including depression, anxiety, adjustment disorder, and somatoform disorder.[ 4 ] This finding might be limited to an association, confounded by increased rates of psychiatric disorders in women with a history of infertility, chronic pelvic pain, endometriosis, recurrent miscarriages, and so on. It is also possible that the medications used for treating such disorders disrupt embryo transport through the fallopian tube.[ 4 ] More studies are needed to understand the association between mental health and ectopic pregnancy before drawing definitive conclusions.

Older data associated intrauterine contraceptive devices (IUDs) with ectopic pregnancy.[ 9 ] And while it remains true that if pregnancy occurs with an IUD in situ the risk of ectopic pregnancy is high, all forms of contraception reduce the risk of pregnancy and ectopic pregnancy.[ 6 ] In vitro fertilization (IVF) was previously thought to be associated with increased risk of ectopic pregnancy due to possible underlying fallopian tube dysfunction in the infertile population and procedure-related factors.[ 2 ] The latter may not be relevant today because the IVF practices associated with increased rates of ectopic pregnancy, such as transfer of multiple embryos and day-3 embryo transfer, are less common in modern clinical practice. As a result, the incidence of ectopic pregnancy after IVF has decreased significantly, and many physicians now suggest that IVF pregnancies may be at little or no increased risk of ectopic pregnancy compared to natural conceptions.[ 6 ]

History and presentation

Ectopic pregnancies almost always occur in the fallopian tube (> 95%), particularly in the ampulla (distal portion) (70%).[ 7 ] Fewer tubal pregnancies occur in the isthmus (middle portion) (12%) and fimbria (11%).[ 10 ] Rarely, pregnancies may grow in the cervix (< 1%) or abdomen (1%), or on the ovary (3%).[ 10 , 11 ] It is important to obtain a full history, including menstrual and obstetrical history, to determine gestational age and evaluate for risk factors in all women of reproductive age. Women with an ectopic pregnancy most commonly present with abdominal pain, vaginal bleeding, or both.[ 2 ] However, these are also symptoms of miscarriage, which is, by far, the most common cause of failing pregnancy and/or abnormally rising b-hCG levels. An ectopic pregnancy may be intact or ruptured at presentation; the latter might present with hemodynamic instability and an acute abdomen that requires urgent surgical management to address ongoing hemorrhage.[ 10 ] Initial workup includes confirmation of pregnancy (through urine or serum b-hCG testing) and a transvaginal ultrasound to determine the location of the pregnancy.[ 2 ]

Laboratory investigations

Serial quantitative serum b-hCG testing can be helpful in determining if the current pregnancy is likely to be in an ectopic location. In a normal pregnancy, the b-hCG level rises steeply for the first 4 weeks, followed by a slower rise until 10 weeks gestational age, with an eventual plateauing.[ 12 ] In most normal intrauterine pregnancies, the b-hCG level will rise 65% to 100% every 48 hours, although even a short plateau in b-hCG can be normal in rare cases.[ 2 ] When performing serial b-hCG measurements, it is recommended that the same laboratory be used to minimize the risk of interassay variability, which can be 5% to 10%.[ 10 ]

Decreasing b-hCG levels strongly suggest a failing pregnancy, but they do not indicate its location. If no intrauterine pregnancy has been confirmed, the woman should be closely monitored because it is possible for an ectopic pregnancy to rupture, even with very low b-hCG levels. The use of discriminatory b-hCG levels to determine when an intrauterine pregnancy should be visible on ultrasound is discouraged. Evidence from the 1980s suggested that b-hCG of 1000 to 2000 IU/L without a visible pregnancy could be assumed to be ectopic.[ 13 ] It is now widely acknowledged that b-hCG can be nonspecific, as many ectopic pregnancies will never reach a level of 2000 IU/L or might rupture before that threshold. Conversely, women who have had multiple gestations have higher b-hCG levels than women who have had a single gestation, and using 2000 IU/L as a discriminatory value might not be accurate for such pregnancies.[ 2 ] Historical use of a “threshold” has resulted in the treatment of intrauterine pregnancies with methotrexate, a chemotherapeutic agent; hence, newer studies have urged caution and patience when evaluating early pregnancies of uncertain viability.[ 13 ]

Transvaginal ultrasound is the optimal method for imaging pregnancies in the early first trimester. In a normal pregnancy, a gestational sac is visualized at 5 weeks gestation (3 weeks after conception), when it is 2 to 5 mm in diameter.[ 13 ] Following that, the yolk sac is the earliest structure to develop inside the gestational sac and is normally seen by 5 weeks and 5 days of pregnancy.[ 10 ] Presence of an intrauterine pregnancy (gestational sac plus a yolk sac or embryo) on transvaginal ultrasound effectively eliminates the diagnosis of an ectopic pregnancy other than the rare scenario of a heterotopic pregnancy (one embryo within the uterus and another extra-uterine).[ 10 ] However, even with modern high-resolution ultrasound, it is rare that ultrasound alone is sufficient to be definitive. Without a yolk sac, an intrauterine pregnancy cannot be confirmed, and clinicians should be wary because it might represent a pseudosac—a fluid collection in the endometrial cavity caused by sloughing of the decidua.[ 10 ] To differentiate between a pseudosac and an early gestational sac, a follow-up ultrasound in 7 to 14 days should be arranged.

Transvaginal ultrasound can definitively diagnose an ectopic pregnancy if an extra-uterine gestational sac with yolk sac/embryo is visible[ 2 ] [ Figure ]. However, most ectopic pregnancies lack these definitive features on imaging and are often described as an inhomogeneous adnexal mass separate from the ovaries.[ 10 ] An adnexal mass might also represent a cyst, corpus luteum, or bowel.[ 2 ] The presence of hemoperitoneum (echogenic intraperitoneal fluid) and placental blood flow within the periphery of this mass (“ring of fire”) on color doppler can aid in diagnosis.[ 10 ]

Expectant management

Expectant management of ectopic pregnancy involves allowing the pregnancy to take its natural course with close physician follow-up until there is clinical resolution of symptoms, a negative urine pregnancy test, or negative serum b-hCG.[ 14 ] There is evidence that expectant management of ectopic pregnancy can be a safe option in a select population of women who are hemodynamically stable, asymptomatic, have a b-hCG value less than 1000 IU/L, with decreasing levels, and can reliably access regular physician follow-up.[ 15 ] These women can avoid the use of methotrexate and its possible side effects. It is worth noting, however, that a 5-year follow-up cohort study of 217 women who underwent expectant, medical, or surgical management of a first ectopic pregnancy suggested there was a 2.68 times higher risk of recurrent ectopic pregnancy in women who were managed expectantly.[ 5 ] A randomized study called ACTorNOT (ClinicalTrials.gov NCT02152696) has completed recruitment to compare expectant management versus uterine evacuation plus methotrexate versus methotrexate alone in women with ectopic pregnancy.

Medical treatment

Methotrexate, the most common option for treating ectopic pregnancy, was first used for this purpose in 1982.[ 16 ] It is a folate antagonist that prevents DNA replication and affects rapidly proliferating cells like that of a developing embryo.[ 17 ] A single dose of methotrexate is administered intramuscularly based on body surface area (50 mg/m 2 ). Its effectiveness is assessed by serial b-hCG measurements on days 4 and 7 post-treatment, then weekly until resolution.[ 2 ] A reduction of less than 15% in b-hCG level between days 4 and 7 posttreatment may indicate that treatment is inadequate; therefore, a second dose of methotrexate might be required.[ 2 ] Close observation is required to ensure patient stability, declining b-hCG levels, and normal liver function tests because methotrexate can affect liver function.[ 2 , 17 ]

The b-hCG level at presentation is strongly associated with treatment success of a single dose methotrexate injection. A systematic review that analyzed five observational studies determined that women with a baseline b-hCG level of more than 5000 IU/L were 4 times more likely to have treatment failure with single-dose methotrexate than those with a presenting baseline between 2000 and 4999 IU/L.[ 18 ] Thus, most guidelines suggest using methotrexate to treat ectopic pregnancy in women with a presenting b-hCG level less than 5000 IU/L. Other factors such as ectopic mass > 3.5 cm and presence of fetal heartbeat on transvaginal ultrasound are considered relative contraindications to the use of medical therapy because they might indicate a more developed embryo, which implies increased risk of ectopic rupture.[ 2 , 10 ] However, few data are available to support these recommendations.[ 10 ]

One in three women may experience mild, self-limited side effects of methotrexate, including nausea, diarrhea, stomatitis, and conjunctivitis.[ 2 ] Serious complications, including anaphylaxis, pulmonary damage, and myelosuppression, have also been reported.[ 10 ] Since methotrexate can cause temporary hepatic dysfunction, it is important to obtain a CBC and baseline liver and renal function laboratory results, and to monitor liver function if indicated. Patients should also be advised to stop their folate-containing supplements because they inhibit methotrexate function.[ 10 ] Nonsteroidal anti-inflammatory medications should also be avoided because they may reduce renal clearance of the drug by reducing renal blood flow.[ 10 ] Alcohol should be avoided during methotrexate treatment to prevent the combined effect of hepatotoxic drugs. Methotrexate should not be administered to patients with liver or renal dysfunction, lung disease, hematologic dysfunction, immunodeficiency, or peptic ulcer disease, or to those who are breastfeeding. Given that this is an outpatient treatment, and an ectopic pregnancy may rupture during therapy, it is important to alert patients to the symptoms of a ruptured ectopic pregnancy and to seek immediate medical attention if they occur.

Advances in medical treatment of ectopic pregnancy may be on the horizon. Researchers from the University of British Columbia have demonstrated that gonadotropin-releasing hormone (GnRH) and its receptor are expressed in trophoblast cells and fallopian tube epithelium at ectopic pregnancy implantation sites.[ 19 ] This presents the potential to use a targeted and less toxic agent for conservative treatment of ectopic pregnancies. A randomized controlled trial comparing GnRH agonist versus methotrexate was registered in March 2020.[ 20 ] The trial is also planning to investigate the use of letrozole, an aromatase inhibitor that blocks the final step in estrogen synthesis, versus methotrexate to treat ectopic pregnancy, and is stated to conclude in 2022.

Surgical management

With improved laparoscopic instruments and techniques, minimally invasive surgery has become the gold standard for treating ectopic pregnancy and has mostly replaced laparotomy. Laparoscopic surgery offers a safer, faster, cheaper, and more esthetic option.[ 10 , 21 ] With improved operator experience, even stable but symptomatic ectopic pregnancies can be managed with laparoscopy, which can result in quicker hemostasis and better patient outcomes.[ 21 ] However, laparotomy is sometimes used for hemodynamically unstable cases because it might offer better field visualization when managing a large bleed.[ 10 ]

Two laparoscopic techniques are available for treating tubal pregnancies: salpingectomy, where the fallopian tube containing the ectopic pregnancy is removed, and salpingotomy, where after removal of the ectopic mass, the affected fallopian tube is preserved. There is ongoing debate about treatment success, future fertility, and risk of repeat ectopic pregnancy after treatment with salpingotomy versus salpingectomy.

Salpingectomy versus salpingotomy

Treatment success and future fertility.

Given that salpingotomy requires the surgeon to meticulously extract a small trophoblastic mass while preserving the fallopian tube, the method might be prone to trophoblastic tissue retention, which can necessitate a salpingectomy. Multiple retrospective studies report trophoblast persistence rates between 9.0% and 12.0% for salpingotomy and 1.8% for salpingectomy.[ 22 ] In an open-label, randomized control trial named European Surgery in Ectopic Pregnancy, women with ultrasound-confirmed ectopic pregnancy who were eligible for surgical management were randomly assigned to either salpingotomy or salpingectomy. The trial reported significantly higher postsurgical trophoblast persistence in the salpingotomy group (n = 215) than in the salpingectomy group (n = 231) (RR 15.0, p = 0.01).[ 23 ] The trial also found no significant difference in rates of naturally conceived pregnancies 36 months postsurgery (fecundity ratio 1.06, p = 0.687).[ 23 ] Thus, for women with tubal pregnancy and a healthy contralateral tube, salpingectomy is a reasonable treatment option because it minimizes risk of ectopic mass persistence and does not seem to reduce future fertility. However, for women with contralateral tubal pathology or no contralateral tube, conservative treatment with salpingotomy should be considered if they wish to maintain the potential for natural conception.

Risk of recurrent ectopic pregnancy

Multiple studies have evaluated the risk of ectopic recurrence following salpingotomy versus salpingectomy, but no consensus has been reached. A 12-year retrospective study found a recurrent ectopic pregnancy rate of 13% in the ipsilateral tube following salpingotomy, while in the salpingectomy group, there were no recorded recurrences.[ 22 ] These data might be confounded by the fact that women who choose to undergo salpingotomy are more likely intending to conceive and have higher pregnancy rates compared to those who choose to undergo salpingectomy. Multiple retrospective studies that have included only women who are actively wanting to conceive post-salpingotomy or post-salpingectomy have reported no difference in rates of ectopic pregnancy recurrence between the two groups.[ 24 , 25 ] Thus, data on the rates of ectopic pregnancy recurrence after different surgical procedures are still conflicting.

Medical versus surgical management

Patients who are asymptomatic and hemodynamically stable can be managed with either intramuscular methotrexate or laparoscopic surgery. The decision should be guided by patient characteristics, laboratory and radiological findings, and patient preference after discussion of the risks and benefits. When a patient has any contraindications to methotrexate use, surgical management is often necessary. Surgical management of a stable, asymptomatic patient might also be prudent if the patient wishes to concurrently undergo tubal sterilization or requests removal of a tube with recurrent ectopics.

It is important to clarify that no long-term effects on future fertility have been identified after methotrexate use or surgical treatment. It is common to suggest a 3-month waiting period post-methotrexate treatment before attempting to conceive again. This time frame appears to be somewhat arbitrary because studies have suggested that conception before the 3-month mark is no more likely to result in birth defects.[ 26 ] Among women intending to conceive, no significant difference in spontaneous intrauterine pregnancy rates have been found when comparing women previously treated with single dose methotrexate versus those who underwent surgical treatment for ectopic pregnancy.[ 17 ] One study reviewed 594 patients who achieved pregnancy using IVF after one or more ectopic pregnancies. Comparing women who were managed with unilateral salpingectomy to those managed with methotrexate indicated that the rates of ectopic pregnancy were equivalent (3.6% versus 2.8%; adjusted OR 1.4, 95% CI 0.5-3.8).[ 27 ] The rate of recurrence was most strongly associated with the number of previous ectopic pregnancies rather than the treatment modality used during those pregnancies.[ 27 ] Thus, risk of recurrence of ectopic pregnancies should not play a major role in decisions about treatment when comparing medical versus surgical options in eligible women.

Clinicians should be aware of the possibility of ectopic pregnancy for all women of reproductive age because early diagnosis is critical to reducing maternal mortality and improving treatment success rates. An understanding of the treatments, eligibility criteria, necessary follow-up, and pros and cons of each treatment option can help clinicians ensure patient safety and autonomy. Medical or expectant management is a safe and effective option for a carefully selected population of stable, asymptomatic women. Laparoscopy is the gold standard for surgical management of ectopic pregnancy, with salpingectomy having higher success rates than salpingotomy and comparable future fertility rates. Clinical presentation, ectopic size, b-hCG level, and patient preference are all important to consider when recommending treatment options for ectopic pregnancy because these factors may influence treatment success, risk of recurrent ectopic pregnancy, and short-term fertility.

Acknowledgments

The authors would like to acknowledge the College of Physicians and Surgeons’ librarians and library technicians for their assistance in conducting the literature search, which was critical to the production of this article.

Competing interests

Dr Dunne is a member of the BCMJ Editorial Board but did not participate in the review or decision making regarding this article. No competing interests declared.

Ectopic pregnancy—clinical pearls

• In most normal pregnancies, the b-hCG level rises 65% to 100% every 48 hours for the first 4 weeks.
• The yolk sac is the earliest structure to develop inside the gestational sac and is normally seen by 5 weeks and 5 days of pregnancy.
• An intrauterine gestational sac without a yolk sac or embryo is not sufficient to rule out ectopic pregnancy and might represent a pseudosac.
• Hemodynamically stable, asymptomatic women with a decreasing presenting b-hCG level < 1000 IU/L might be eligible for expectant management of ectopic pregnancy.
• Methotrexate is administered intramuscularly at a dose of 50 mg/m 2 of body surface area.
• A reduction of < 15% in the b-hCG level between days 4 and 7 post-methotrexate may indicate that treatment is inadequate, and a second dose of methotrexate might be required.

This article has been peer reviewed.

1.    Creanga AA, Shapiro-Mendoza CK, Bish CL, et al. Trends in ectopic pregnancy mortality in the United States: 1980-2007. Obstet Gynecol 2011;117:837-843.

2.    Barnhart KT, Franasiak J. ACOG Practice Bulletin No. 193: Tubal ectopic pregnancy. Obstet Gynecol 2018;131:e91-e103.

3.    Ramakrishnan K, Scheid DC. Ectopic pregnancy: Forget the “classical presentation” if you want to catch it sooner. J Fam Pract 2006;55:388-395.

4.    Jacob L, Kalder M, Kostev K. Risk factors for ectopic pregnancy in Germany: A retrospective study of 100,197 patients. Ger Med Sci 2017;15:Doc19.

5.    Ellaithy M, Asiri M, Rateb A, et al. Prediction of recurrent ectopic pregnancy: A five-year follow-up cohort study. Eur J Obstet Gynecol Reprod Biol 2018;225:70-78.

6.    Ectopic pregnancy. In: Taylor HS, Pal L, Seli E. Speroff’s clinical gynecologic endocrinology and infertility. 9th ed. Philadelphia, PA: Wolters Kluwer; 2020. p.1260-1288.

7.    Mullins E, Agarwal N, Oliver R, Odejinmi JF. Implications of perihepatic adhesions in women undergoing laparoscopic surgery for ectopic pregnancy. Int J Gynecol Obstet 2015;130:247-249.

8.    Saraiya M, Berg CJ, Kendrick JS, et al. Cigarette smoking as a risk factor for ectopic pregnancy. Am J Obstet Gynecol 1998;178:493-498.

9.    Franks AL, Beral V, Cates Jr W, Hogue CJ. Contraception and ectopic pregnancy risk. Am J Obstet Gynecol 1990;163(4 Pt 1):1120-1123.

10.    Ectopic pregnancy. In: Hoffman BL, Schorge JO, Bradshaw KD, et al., editors. Williams gynecology. 3rd ed. New York: McGraw-Hill; 2016.

11.    Dunne C, Havelock JC. Ovarian ectopic pregnancy after in vitro fertilization. J Obstet Gynaecol Can 2012;34:409.

12.    Morin L, Cargill YM, Glanc P. Ultrasound evaluation of first trimester complications of pregnancy. J Obstet Gynaecol Can 2016;38:982-988.

13.    Doubilet PM, Benson CB. Further evidence against the reliability of the human chorionic gonadotropin discriminatory level. J Ultrasound Med 2011;30:1637-1642.

14.    Jurkovic D, Memtsa M, Sawyer E, et al. Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: A placebo–controlled randomized trial. Ultrasound Obstet Gynecol 2017;49:171-176.

15.    Odejinmi F, Huff KO, Oliver R. Individualisation of intervention for tubal ectopic pregnancy: Historical perspectives and the modern evidence based management of ectopic pregnancy. Eur J Obstet Gynecol Reprod Biol 2017;210:69-75.

16.    Tanaka T, Hayashi H, Kutsuzawa T, et al. Treatment of interstitial ectopic pregnancy with methotrexate: Report of a successful case. Fertil Steril 1982;37:851-852.

17.    Olofsson JI, Poromaa IS, Ottander U, et al. Clinical and pregnancy outcome following ectopic pregnancy; a prospective study comparing expectancy, surgery and systemic methotrexate treatment. Acta Obstet Gynecol Scand 2001;80:744-749.

18.    Menon S, Colins J, Barnhart KT. Establishing a human chorionic gonadotropin cutoff to guide methotrexate treatment of ectopic pregnancy: A systematic review. Fertil Steril 2007;87:481-484.

19.    Peng B, Klausen C, Campbell L, Leung PCK. Gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor are expressed at tubal ectopic pregnancy implantation sites. Fertil Steril 2016;105:1620-1627.e3.

20.    Ali SA. The aromatase inhibitor and Gnrh antagonist versus methotrexate for management of undisturbed ectopic pregnancy. NIH: U.S. National Library of Medicine 2020. Accessed 23 June 2020. https://clinicaltrials.gov/ct2/show/NCT04308343 .

21.    Cohen A, Almog B, Satel A, et al. Laparoscopy versus laparotomy in the management of ectopic pregnancy with massive hemoperitoneum. Int J Gynecol Obstet 2013;123:139-141.

22.    Lagana AS, Vitale SG, De Dominici R, et al. Fertility outcome after laparoscopic salpingostomy or salpingectomy for tubal ectopic pregnancy A 12-years retrospective cohort study. Ann Ital Chir 2016;87:461-465.

23.    Mol F, van Mello NM, Strandell A, et al. Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): An open-label, multicentre, randomised controlled trial. Lancet 2014;383(9927):1483-1489.

24.    Bangsgaard N, Lund CO, Ottesen B, Nilas L. Improved fertility following conservative surgical treatment of ectopic pregnancy. BJOG 2003;110:765-770.

25.    Chen L, Zhu D, Wu Q, Yu Y. Fertility outcomes after laparoscopic salpingectomy or salpingotomy for tubal ectopic pregnancy: A retrospective cohort study of 95 patients. Int J Surg 2017;48:59-63.

26.    Hackmon R, Sakaguchi S, Koren G. Effect of methotrexate treatment of ectopic pregnancy on subsequent pregnancy. Can Fam Physician 2011;57:37-39.

27.    Irani M, Robles A, Gunnala V, Spandorfer SD. Unilateral salpingectomy and methotrexate are associated with a similar recurrence rate of ectopic pregnancy in patients undergoing in vitro fertilization. J Minim Invasive Gynecol 2017;24:777-782.

Ms Ranchal is a fourth-year medical student at the University of British Columbia. Dr Dunne is a clinical assistant professor at the University of British Columbia and a co-director at the Pacific Centre for Reproductive Medicine in Vancouver. She also serves on the BCMJ Editorial Board.

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Overview - Ectopic pregnancy

An ectopic pregnancy is when a fertilised egg implants itself outside of the womb, usually in one of the fallopian tubes.

The fallopian tubes are the tubes connecting the ovaries to the womb. If an egg gets stuck in them, it won't develop into a baby and your health may be at risk if the pregnancy continues.

Unfortunately, it's not possible to save the pregnancy. It usually has to be removed using medicine or an operation.

In the UK, around 1 in every 90 pregnancies is ectopic. This is around 11,000 pregnancies a year.

Symptoms of an ectopic pregnancy

An ectopic pregnancy doesn't always cause symptoms and may only be detected during a routine pregnancy scan.

If you do have symptoms, they tend to develop between the 4th and 12th week of pregnancy.

Symptoms can include a combination of:

• a missed period and other  signs of pregnancy
• tummy pain  low down on one side
• vaginal bleeding  or a brown watery discharge
• pain in the tip of your shoulder
• discomfort when peeing or pooing

But these symptoms aren't necessarily a sign of a serious problem. They can sometimes be caused by other problems, such as a  stomach bug .

Read more about the symptoms of an ectopic pregnancy .

When to get medical advice

Contact your GP or call  NHS 111 if you have a combination of any of the above symptoms and you might be pregnant – even if you haven't had a positive pregnancy test .

An ectopic pregnancy can be serious, so it's important to get advice right away.

Your GP will ask about your symptoms and you'll usually need to do a pregnancy test to determine if you could have an ectopic pregnancy.

You may be referred to a specialist early pregnancy clinic for further assessment, where an  ultrasound scan and  blood tests may be carried out to confirm the diagnosis.

Read more about ectopic pregnancy tests .

When to get emergency help

Call 999 for an ambulance or go to  your nearest accident and emergency (A&E) department immediately if you experience a combination of:

• a sharp, sudden and intense pain in your tummy
• feeling very dizzy or fainting
• feeling sick
• looking very pale

These symptoms could mean that your fallopian tube has split open (ruptured). This is very serious and surgery to repair the fallopian tube needs to be carried out as soon as possible.

A rupture can be life threatening, but fortunately they're uncommon and treatable, if dealt with quickly. Deaths from ruptures are extremely rare in the UK.

How an ectopic pregnancy is treated

There are 3 main treatments for an ectopic pregnancy:

• expectant management – you're carefully monitored and 1 of the treatments below is used if the fertilised egg doesn't dissolve by itself
• medicine – an injection of a powerful medicine called methotrexate is used to stop the pregnancy growing
• surgery –  keyhole surgery (laparoscopy) is performed under  general anaesthetic to remove the fertilised egg, usually along with the affected fallopian tube

You'll be told about the benefits and risks of each option. In many cases, a particular treatment will be recommended based on your symptoms and the results of the tests you have.

Some treatments may reduce your chances of being able to conceive naturally in the future, although most women will still be able to get pregnant. Talk to your doctor about this.

Read more about treating an ectopic pregnancy .

Help and support after an ectopic pregnancy

Losing a pregnancy can be devastating, and many women feel the same sense of grief as if they had lost a family member or partner.

It's not uncommon for these feelings to last several months, although they usually improve with time. Make sure you give yourself and your partner time to grieve.

If you or your partner are struggling to come to terms with your loss, you may benefit from professional support or counselling . Speak to your GP about this.

Support groups for people who have been affected by loss of a pregnancy can also help.

These include:

• The Ectopic Pregnancy Trust
• Ectopic Pregnancy Foundation
• Miscarriage Association
• Cruse Bereavement Care

Read more about  dealing with loss and find bereavement support services in your area .

Trying for another baby

You may want to try for another baby when you and your partner feel physically and emotionally ready.

You'll probably be advised to wait until you've had at least 2 periods after treatment before trying again to allow yourself to recover.

If you were treated with methotrexate, it's usually recommended that you wait at least 3 months because the medicine could harm your baby if you become pregnant during this time.

Most women who have had an ectopic pregnancy will be able to get pregnant again, even if they've had a fallopian tube removed. Occasionally, it may be necessary to use fertility treatment such as  IVF .

The chances of having another ectopic pregnancy are higher if you've had one before, but the risk is still small.

If you do become pregnant again, it's a good idea to let your GP know as soon as possible so early scans can be carried out to check everything is OK.

What can cause an ectopic pregnancy?

In many cases, it's not clear why a woman has an ectopic pregnancy. Sometimes it happens when there's a problem with the fallopian tubes, such as them being narrow or blocked.

The following are all associated with an increased risk of ectopic pregnancy:

• pelvic inflammatory disease (PID) – inflammation of the female reproductive system, usually caused by a  sexually transmitted infection (STI)
• previous ectopic pregnancy – the risk of having another ectopic pregnancy is around 10%
• previous surgery on your fallopian tubes – such as an unsuccessful  female sterilisation procedure
• fertility treatment, such as IVF – taking medicine to stimulate ovulation (the release of an egg) can increase the risk of ectopic pregnancy
• becoming pregnant while using an intrauterine device (IUD) or intrauterine system (IUS) for contraception – it's rare to get pregnant while using these, but if you do you're more likely to have an ectopic pregnancy
• increasing age – the risk is highest for pregnant women aged over 35

You can't always prevent an ectopic pregnancy, but you can reduce your risk by using a  condom when not trying for a baby to protect yourself against STIs, and by stopping smoking if you smoke.

Page last reviewed: 23 August 2022 Next review due: 23 August 2025

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Diagnosis and management of ectopic pregnancy

Vanitha n sivalingam.

1 Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA

W Colin Duncan

2 MRC Centre for Reproductive Health, University of Edinburgh, Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

3 North Middlesex University Hospital, Sterling Way, London, N18 1QX

Lucy A Shephard

Andrew w horne.

An ectopic pregnancy occurs when a fertilised ovum implants outside the normal uterine cavity. 1 - 3 It is a common cause of morbidity and occasionally of mortality in women of reproductive age. The aetiology of ectopic pregnancy remains uncertain although a number of risk factors have been identified. 4 Its diagnosis can be difficult. In current practice, in developed countries, diagnosis relies on a combination of ultrasound scanning and serial serum beta-human chorionic gonadotrophin (β-hCG) measurements. 5 Ectopic pregnancy is one of the few medical conditions that can be managed expectantly, medically or surgically. 1 , 3 , 6

In the developed world, between 1% and 2% of all reported pregnancies are ectopic pregnancies (comparable to the incidence of spontaneous twin pregnancy). 7 The incidence is thought to be higher in developing countries, but specific numbers are unknown. Although the incidence in the developed world has remained relatively static in recent years, between 1972 and 1992 there was an estimated six-fold rise in the incidence of ectopic pregnancy. 8 This increase was attributed to three factors: an increase in risk factors such as pelvic inflammatory disease and smoking in women of reproductive age, the increased use of assisted reproductive technology (ART) and increased awareness of the condition, facilitated by the development of specialised early pregnancy units (EPUs).

Morbidity and mortality

In the UK, ectopic pregnancy remains the leading cause of pregnancy-related first trimester death (0.35/1000 ectopic pregnancies). 3 , 6 , 9 However, in the developing world it has been estimated that 10% of women admitted to hospital with a diagnosis of ectopic pregnancy ultimately die from the condition. 10 Ectopic pregnancy is a considerable cause of maternal morbidity, causing acute symptoms such as pelvic pain and vaginal bleeding and long-term problems such as infertility. 3 Short- and long-term consequences of ectopic pregnancy on health-related quality of life and on bereavement issues are likely to be significant but have not been formally quantified.

Risk factors

Although women with ectopic pregnancy frequently have no identifiable risk factors, a prospective case-controlled study has shown that increased awareness of ectopic pregnancy and a knowledge of the associated risk factors helps identify women at higher risk in order to facilitate early and more accurate diagnosis. 11 Most risk factors are associated with risks of prior damage to the Fallopian tube ( Box 1 ). These factors include any previous pelvic or abdominal surgery, and pelvic infection. 11 Chlamydia trachomatis has been linked to 30-50% of all ectopic pregnancies. 12 The exact mechanism of this association is not known but it has been proposed that in addition to distortion of tubal architecture, it may to be due to an effect on the tubal microenvironment. 13

Risk factors for ectopic pregnancy

Previous tubal surgery (including female sterilisation) and pelvic surgery including Caesarean section and ovarian cystectomy

Previous abdominal surgery including appendicectomy and bowel surgery

Confirmed genital infection and pelvic inflammatory disease, commonly caused by chlamydial infection

Documented tubal disease

Assisted reproductive technology

Endometriosis

Unexplained infertility

Progestogen-only contraception

Intrauterine contraceptive device

• □ Cigarette smoking – including past exposure.
• □ Age >35 years
• □ Previous ectopic pregnancy
• □ Previous spontaneous abortion or induced abortion

Ectopic pregnancy is more common in women attending infertility clinics 14 even in the absence of tubal disease. In addition, the use of ART increases the rate of ectopic pregnancies. In vitro fertilisation (IVF) is associated with an ectopic pregnancy risk of 2-5% and it may be higher than this where there is tubal disease. Indeed the first IVF pregnancy, before the first IVF live birth, was a tubal ectopic pregnancy. 15

Some types of contraception, such as progestogen-only contraception and the intrauterine contraceptive device, are associated with an increased incidence of ectopic pregnancy when there is contraceptive failure, without necessarily increasing the absolute risk of ectopic pregnancy. 16

One third of all cases of ectopic pregnancy are thought to be associated with smoking. 17 There is a dose–effect relationship, with the highest adjusted odds ratio (OR) (3.9) when more than 20 cigarettes are smoked a day. 18 Several mechanisms for this association have been suggested, including one or more of the following: delayed ovulation, altered tubal and uterine motility and microenvironment, or altered immunity. 19 , 20

The risk of ectopic pregnancy increases with advancing maternal age, with age over 35 years being a significant risk factor. 6 Hypotheses for this association include the higher probability of exposure to most other risk factors with advancing age, increase in chromosomal abnormalities in trophoblastic tissue and age-related changes in tubal function delaying ovum transport, resulting in tubal implantation. 18

Women with a previous history of ectopic pregnancy also have an increased risk, which increases further in proportion to the number of previous ectopic pregnancies. In one study the OR for having an ectopic pregnancy was 12.5 after one previous ectopic pregnancy and 76.6 after two. 18

The exact aetiology of ectopic pregnancy is unknown. It is notable that it is unique to humans, and perhaps the higher apes, so that there are no good animal models that could be used to further our understanding. 21 However, it is thought that tubal implantation occurs as a result of a combination of arrest of the embryo in the Fallopian tube and changes in the tubal microenvironment that allow early implantation to occur. 4 Inflammation within the tube, resulting from infection or smoking, may affect embryo-tubal transport by disrupting smooth muscle contractility and ciliary beat activity and may also provide pro-implantation signals. Molecular research generally involves studying Fallopian tube biopsies taken from women with ectopic pregnancies. Interpretation is limited as comparable Fallopian tube samples are not available from women with an intrauterine pregnancy (IUP) or in advance of an ectopic pregnancy occurring. Thus, it is difficult to ascertain whether any molecular changes observed are a cause or a consequence of ectopic implantation. Novel studies focusing on the functional consequences of smoking and infection on Fallopian tube physiology and pathobiology are required.

Clinical presentation

Patients with an ectopic pregnancy commonly present with pain and vaginal bleeding between 6 and 10 weeks’ gestation. 1 However, these are common symptoms in early pregnancy, with one third of women experiencing some pain and/or bleeding. 22 - 24 The pain can be persistent and severe and is often unilateral. However unilateral pain is not always indicative of ectopic pregnancy as, in early pregnancy, a prominent painful ovarian corpus luteum cyst is common. Shoulder tip pain, syncope and shock occur in up to 20% of women and abdominal tenderness in more than 75%. Bimanual examination, if performed at all, should be done cautiously and gently. Cervical motion tenderness has been reported in up to 67% of cases, and a palpable adnexal mass in about 50%. 23 - 25 More recently, it has been reported that one third of women with ectopic pregnancy have no clinical signs and 9% have no symptoms. 26 , 27

A ruptured ectopic pregnancy should be strongly suspected if a woman has a positive pregnancy test and presents with syncope and signs of shock including tachycardia, pallor and collapse. There may be abdominal distension and marked tenderness. While a bimanual examination may reveal tenderness, cervical excitation and an adnexal mass, great caution is required as this may exacerbate bleeding. As ectopic pregnancy affects young, fit women they are often able to mount remarkable haemodynamic compensation. Tachycardia is a particularly important sign, but decompensation with shock is a sign of significant intraperitoneal bleeding. In an emergency, where the patient has collapsed and there is high clinical suspicion of tubal rupture, extensive clinical examination is inappropriate and immediate surgical intervention is indicated.

Unfortunately, atypical presentation is also relatively common. Ectopic pregnancy may mimic other gynaecological disorders and gastrointestinal or urinary tract disease, including appendicitis, salpingitis, ruptured corpus luteum or follicular cysts, threatened or inevitable spontaneous abortion, ovarian torsion and urinary tract infection. The 1997-1999 and 2003-2005 Confidential Enquiries into Maternal Deaths reports highlighted that most of the women who died from ectopic pregnancy were misdiagnosed in the primary care or accident and emergency settings. 28 , 29 It was therefore recommended that all clinicians should be made aware of the atypical clinical presentations of ectopic pregnancy. While there has been a welcome decline in the case death rate in women with ectopic pregnancies, a key lesson emphasised in these reports does not appear to have been learnt. In the 2006-2008 Centre for Maternal and Child Enquiries (CMACE) report, four of the six women who died from early ectopic pregnancy complained of diarrhoea, dizziness or vomiting as early symptoms, without triggering any consideration of extrauterine pregnancy by their medical attendants. 30

However, it remains difficult to diagnose an ectopic pregnancy from risk factors, history and examination alone. Clinicians should be suspicious of pregnancy in any such woman who presents with abdominal or pelvic symptoms and should always bear in mind the possibility of ectopic pregnancy in any woman of reproductive age who presents with any of the symptoms mentioned above.

Diagnosis of ectopic pregnancy has improved significantly due to advances in ultrasound technology, rapid and sensitive serum hormone assays, the development of EPUs and an increased awareness and understanding of the associated risk factors. Despite this, around half of the women with an eventual diagnosis of ectopic pregnancy are not diagnosed at their first presentation. 31 , 32 Early diagnosis reduces the risk of tubal rupture and allows more conservative medical treatments to be employed. 1 , 33

Currently, diagnosis in unruptured ectopic pregnancy is achieved using a combination of transvaginal ultrasonography and measurement of serum β-hCG concentrations. One of the key elements in the diagnosis is the exclusion of a viable or non-viable IUP. Diagnosis can be straightforward when a transvaginal ultrasound scan (TVS) positively identifies an IUP or ectopic pregnancy 34 ( Figure 1 ). However, TVS fails to identify the location of a pregnancy in a significant number of women and such women are currently diagnosed as having a ‘pregnancy of unknown location’ (PUL). 35 , 36

Transvaginal ultrasound images of an intrauterine pregnancy (IUP) and ectopic pregnancy. (A) An IUP at 6 weeks. The central dark area is the intrauterine gestational sac and within the sac is a circular ringed structure that is the yolk sac. The small oval structure below the yolk sac is the fetus. (B) An ectopic pregnancy. To the right of the image is the normal uterus and to the left of the uterus is the doughnut-shaped ectopic pregnancy.

The 2006–2008 CMACE report drew attention to a maternal death secondary to ruptured ectopic pregnancy where a diagnosis of PUL had been made. 30 Although most patients with a PUL will subsequently be diagnosed with either a failed IUP (a spontaneous abortion) or viable IUP, the report highlights that 7-20% will be diagnosed with an ectopic pregnancy. It is therefore very important that a diagnosis of PUL should trigger further diagnostic pathways and follow-up until the final outcome of the pregnancy is known.

The concept of a ‘discriminatory β-hCG level’ was introduced in 1985 to highlight the serum concentration of β-hCG when a pregnancy should be visible on an ultrasound scan. Using transabdominal ultrasound examination, it was reported then that the absence of an intrauterine gestational sac at a β-hCG concentration over 6500 IU/l had a sensitivity of 100%, specificity of 96%, positive predictive value of 87% and negative predictive value of 100% for the prediction of ectopic pregnancy. In the context of a 19.4% prevalence of ectopic pregnancies in the study group, this diagnostic paradigm was 98% efficient. 37 With the introduction of high-resolution TVS, the discriminatory β-hCG level of 6500 IU/l is now less helpful. 35 , 38 An ectopic pregnancy can be detected at β-hCG concentrations well below this level and an ultrasound scan should not be delayed because of low β-hCG concentrations.

Transvaginal ultrasonography

High-definition ultrasonography, particularly using the transvaginal route, has revolutionised the assessment of patients with early pregnancy problems, allowing for clearer visualisation of both normal and abnormal gestations. 39 In a healthy IUP, a TVS should identify the intrauterine gestation sac with almost 100% accuracy at a gestational age of 5.5 weeks. 40 , 41 Even so, it is recognised radiographic practice that an IUP is only definitively diagnosed by ultrasound visualisation of a yolk sac or embryo in addition to a gestation sac. 42 - 44 This is because an ectopic pregnancy can be accompanied by a ‘pseudosac’, a collection of fluid within the endometrial cavity that may be the result of localised breakdown of the decidualised endometrium. However, its central location within the endometrial cavity distinguishes it from the very early gestation sac that is typically eccentrically placed. 45 In addition, pseudosacs are transient rather than consistent and they do not have a hyperechoic decidual reaction around them. Additional embryonic features including the yolk sac and cardiac activity should be clearly visible after 6 weeks’ gestation. A sonographer with experience in early pregnancy scanning should generally be able to tell the difference between a pseudosac and an empty early intrauterine sac.

The identification of an IUP can rule out ectopic pregnancy in most settings unless a heterotopic pregnancy is suspected, where an ectopic pregnancy coexists with an IUP. 46 They are rare (1 in 40 000), although more common after assisted conception, and difficult to diagnose.

In the absence of an intrauterine gestation sac, an ectopic pregnancy can be diagnosed by the presence of an adnexal mass, often visible within the Fallopian tube. The positive identification of a non-cystic adnexal mass with an empty uterus has a sensitivity of 84-90% and a specificity of 94-99% for the diagnosis of an ectopic gestation. 47 In one large prospective study of 6621 patients, ectopic pregnancy was correctly diagnosed by TVS with a sensitivity of 90.9% and specificity of 99.9%. 24 False positives can, however, occur if other structures such as the corpus luteum, bowel, a paratubal cyst, a hydrosalpinx or an endometrioma are mistaken for an ectopic pregnancy. False negatives can occur if the ectopic is small or if it is concealed by bowel or uterine anomalies such as fibroids. It is therefore possible for an ectopic pregnancy to go unnoticed on an ultrasound scan, especially if the patient is asymptomatic.

Around 80% of ectopic pregnancies will be on the same side as the ovarian corpus luteum, the identification of which can help in the search for an adnexal mass. The mass may appear as an inhomogenous echogenic area adjacent to the ovary that moves separately from it on gentle pressure; a gestation sac enclosed by a hyperechoic ring (the so-called ‘bagel’ appearance); or a gestation sac with a fetal pole, with or without cardiac activity.

Suspicion of an ectopic pregnancy increases if free fluid (representing blood) is visualised, either surrounding the uterus or in the Pouch of Douglas, 48 although a small amount of free fluid in the Pouch of Douglas, a transudate due to increased vascular permeability, is common in early pregnancy.

Box 2 summarises ultrasonographic findings that are useful in diagnosing an ectopic pregnancy.

Useful ultrasonographic findings in the diagnosis of ectopic pregnancy

• □ Absence of intrauterine pregnancy (IUP)
• □ Positive identification of an ectopic pregnancy mass: inhomogenous mass, empty adnexal gestation sac or adnexal sac containing yolk sac or fetal pole
• □ Free fluid (i.e. blood): suggestive of ectopic pregnancy in the absence of IUP, but not diagnostic (small amount may be physiological)

Serum β-hCG concentrations

The changes in serum β-hCG concentrations over time have been used to predict the outcome of PULs. 49 Kadar and Romero 50 were the first to describe these serial changes on the basis of a small sample of 20 women using an 85% confidence interval (CI). They showed that in a normal ongoing pregnancy, the minimal rate of increase in β-hCG is 66% in 2 days. In a recent study of 287 patients with pain or bleeding, the minimum rise in β-hCG for a viable IUP was 24% at 24 hours and 53% at 48 hours. 51 In addition, Seeber et al. 52 produced data with a 99% CI that suggested a more conservative minimum rise of 35% over 2 days. In current practice most units use a minimum value of between 50% and 66% for the acceptable 48-hour increase in β-hCG in a normal pregnancy. 53 Some non-viable IUPs will also demonstrate an exponential increase in serum β-hCG, so normal β-hCG changes do not necessarily confirm viability. However, absence of this expected rise suggests early pregnancy failure.

A rapid decline in β-hCG concentrations over 2 days, commonly by 21-35% or more, is indicative of a spontaneous abortion 52 or a resolving ectopic pregnancy. In an ectopic pregnancy, β-hCG concentrations are just as likely to fall as to rise, with no single pattern able to characterise the condition. 54 However, 71% have serial serum β-hCG values that increase more slowly than would be expected with a viable IUP and decrease more slowly than would be expected with a spontaneous abortion. 9

If the history is not compatible with a spontaneous abortion, or the β-hCG concentrations continue to rise and the scan location of the pregnancy is still unknown, an ectopic pregnancy is likely and a clear management strategy should be put in place.

Serum progesterone

Although there are no definitive values that demarcate an ectopic pregnancy from an IUP, the measurement of serum progesterone levels is a potentially useful adjunct in the assessment of PULs. 55 Serum progesterone concentrations in a viable IUP are >50 ng/ml. Although progesterone assessment cannot easily discriminate between an ectopic pregnancy and a failing IUP 56 some EPUs use a low progesterone (<5 ng/ml) to differentiate between ‘low-risk’ patients, when a PUL may be suitable for conservative management, and ‘at-risk’ patients who require definitive treatment. 57

Other serum biomarkers

Although other potential serum biomarkers have been proposed, 58 none of these are used in common clinical practice. New biomarkers with clinical utility would be helpful in improving the diagnosis of ectopic pregnancy, with the potential benefits of greater safety and reduced diagnostic costs. 5 , 32

Diagnostic laparoscopy

In cases where an ectopic pregnancy is suspected and ultrasound is inconclusive, a diagnostic laparoscopy may be required. This is believed by many to be the ‘gold standard’ investigation in ectopic pregnancy. Indeed reluctance or delay in performing a diagnostic laparoscopy has been highlighted as a factor in fatal cases. 30 However, some small ectopic pregnancies may be missed at the time of laparoscopy or laparotomy. In one study, 2 of 44 (4.5%) women reported to have no evidence of an ectopic pregnancy at the time of laparoscopy were subsequently diagnosed with one. 55 An alternative to diagnostic laparoscopy may involve a repeat ultrasound examination, particularly when β-hCG concentrations are close to 1500 IU/l. Other strategies include alternative diagnostic tests, such as serum progesterone or an endometrial biopsy, or empirical medical treatment as the patient may well have an ectopic pregnancy. If β-hCG concentrations are falling but an ectopic has not been excluded, consideration should be given to performing serial β-hCG measurements until levels become undetectable, as rupture can still occur. 40

Endometrial biopsy

In selected cases of PUL, an endometrial biopsy may be taken and analysed for the presence or absence of chorionic villi. Their absence in the presence of a static β-hCG is suggestive of an ectopic pregnancy. A dilatation and curettage may be useful when performed in association with a ‘negative’ diagnostic laparoscopy for a suspected ectopic pregnancy. The clinician should be certain that the pregnancy, if intrauterine, is non-viable and appropriate consent obtained, as this procedure could potentially interrupt a continuing pregnancy.

Ectopic pregnancy may be managed surgically, medically or expectantly. In these days of increasing outpatient diagnosis and management it is important to remember the risks of ruptured ectopic pregnancy. Clear documentation of diagnostic and management strategies – with clinical, sonographic and biochemical assessment of the patient – is therefore important. Which management is most appropriate depends on ongoing assessment and on numerous clinical factors. Management is tailored to individual patients, based on their presentation and on the severity of their condition, suitability of treatment options and patient preference. Figure 2 demonstrates a suggested diagnosis and management pathway.

Recommended diagnostic and management approach for suspected ectopic pregnancy. It is important to highlight that the figure of 66% is used as a practical guide only and that all cases of pregnancy of unknown location should be considered as a potential ectopic pregnancy until assessment proves otherwise or management is complete. β-hCG, beta-human chorionic gonadotrophin.

Surgical management is imperative in the clinical scenario of a ruptured ectopic pregnancy. A laparoscopic approach is preferable to an open approach in a patient who is haemodynamically stable. Laparoscopic procedures are associated with shorter operative times, less intraoperative blood loss, shorter hospital stays and lower analgesia requirements. 59 - 61 Laparotomy should be reserved for patients who present with rupture and are in a state of hypovolaemic shock and compromise. If the contralateral tube is healthy, the preferred option is salpingectomy, where the entire Fallopian tube, or the affected segment containing the ectopic gestation, is removed ( Figure 3 ). A salpingostomy is the removal of the ectopic pregnancy, by dissecting it out of the tube, leaving the Fallopian tube in situ in an attempt to preserve fertility on that side.

(A) Left tubal ectopic pregnancy at laparoscopy. (B) Tubal ectopic pregnancy has been removed by salpingectomy.

A number of systematic reviews have examined reproductive outcomes following the two procedures in patients with a healthy contralateral tube. Studies in this area can be criticised with regard to patient selection, surgical techniques and follow-up times 62 - 64 and some studies report conflicting results. 65 , 66 However, it is generally accepted that the chance of subsequent IUP is not increased after salpingostomy compared with salpingectomy. In addition, the use of conservative surgical techniques exposes women to a small risk of tubal bleeding in the immediate postoperative period and the potential need for further treatment of persistent trophoblast. 9 This supports current guidelines stating that the operation of choice, where there is a healthy contralateral tube, is laparoscopic salpingectomy. 67

In the presence of contralateral tubal disease, a laparoscopic salpingostomy should be considered if future fertility is desired. Persistent trophoblast is the main concern after a salpingostomy. This is usually detected by a failure of serum β-hCG levels to fall and is more common following active tubal bleeding, where the ectopic pregnancy size was >2 cm or if serum β-hCG concentrations are >3000 IU/l or rising prior to surgery. 68 Women should be followed up with serial β-hCG measurements and systemic methotrexate treatment may be required if the levels fail to fall as expected. While the short-term costs of postoperative follow-up and treatment of persistent trophoblast are greater following a salpingostomy, 69 the potential avoidance of the subsequent need for assisted conception will make it more cost effective compared with salpingectomy. 66

Medical treatment with methotrexate

Medical treatment is useful for patients with an unruptured tubal ectopic pregnancy who are haemodynamically stable and have minimal symptoms and a low volume of free intraperitoneal fluid on ultrasound scan. 70 Intramuscular methotrexate is the most widely used and successful medical therapy for ectopic pregnancy and is generally administered in a single-dose protocol. 34 , 69 Methotrexate is a folic acid antagonist that targets rapidly dividing cells and arrests mitosis. 9 , 71 In ectopic pregnancy, the drug prevents the proliferation of cytotrophoblast cells, reducing cell viability and β-hCG secretion and thus progesterone support for the pregnancy. This facilitates the resolution of the ectopic pregnancy and tissue remodelling.

After assessing patient suitability for medical management ( Box 3 ), body surface area is calculated using height and weight measurements. In addition, a baseline full blood count and renal and liver function tests are obtained. In general, apart from some abdominal discomfort 1-3 days after treatment and abdominal bloating, side effects are not common and return to normal activities is quicker than after surgery. Potential serious side effects such as significant hepatotoxicity, bone marrow toxicity or alopecia are extremely rare with ectopic pregnancy treatment regimens. Patients require careful monitoring to ensure complete resolution of the ectopic gestation using serial assessment of β-hCG levels every 4-7 days (protocols vary between units) until the β-hCG level is <5 IU/l. 72

Inclusion criteria for medical management of ectopic pregnancy with methotrexate

Would prefer medical option

Willing to attend follow-up for up to 6 weeks

Willing to abstain from alcohol for 7 days following the treatment

Not breastfeeding or willing to stop

Haemodynamically stable

Minimal abdominal pain

No fetal heart activity or clear yolk sac in adnexal mass

Small amount of free fluid

Unlikely to be early intrauterine pregnancy failure

Usually <3000 IU/l (Although limits of <5000 IU/l are used in some units and earlier studies, treatment success rates are higher when this more commonly used lower limit applies.)

No active peptic ulcer disease

No severe medical conditions including renal disease, hepatic disease, severe anaemia, leucopenia or thrombocytopenia

Non-steroidal anti-inflammatory agents (NSAIDs), aspirin, penicillins, sulphonamides, trimethoprim, tetracyclines, diuretics, phenytoin, antimalarials, ciclosporin, retinoids, probenecid, folic acid, hypoglycaemics, live vaccines, nephrotoxic or hepatotoxic drugs

The commonly used single-dose methotrexate treatment regimen involves a deep intramuscular injection at a dose of 50 mg/m 2 of the calculated body surface area. Approximately 14-20% of patients receiving single-dose treatment will require a repeat dose, 73 , 74 usually decided on following a fall of the β-hCG concentration of less than 15% from Day 4 to 7 after treatment. This timescale is used as methotrexate can cause a transient rise in serum β-hCG after initial treatment. Approximately 10% of women will require surgical intervention, 75 although most of these are for slowly falling β-hCG levels rather than for acute tubal rupture. However, rupture still remains a possibility during treatment. Close treatment surveillance, and staff and patient awareness of potential treatment failure, are vital.

Two much less common uses of methotrexate for the treatment of ectopic gestation are the multi-dose protocol and direct injection of methotrexate into the ectopic pregnancy. The multi-dose regimen consists of methotrexate treatment on Days 1, 3, 5 and 7 to a maximum of four doses and leucovorine ‘rescue-therapy’ at a dose of 0.1 mg/kg on alternate Days 2, 4, 6 and 8. This treatment may be more appropriate for patients who present with a larger adnexal masses and greater initial β-hCG levels (>5000 IU/l). Direct injection of methotrexate into the ectopic sac, either laparoscopically or with ultrasound guidance, limits systemic toxicity and maintains a higher therapeutic level. However, local injection has no significant advantage in most patients and is accompanied by a risk of provoking tubal rupture.

Methotrexate treatment is very successful for small stable ectopic pregnancies. A meta-analysis of non-randomised studies showed success rates of 93% (95% CI 89-96%) for multi-dose protocols and 88% (95% CI 86-90%) for single dose therapy. 76 Failure of single-dose medical management is associated with initial serum β-hCG concentrations >5000 IU/l, a moderate or large amount of free fluid on ultrasound, the presence of fetal cardiac activity and a pretreatment increase in serum β-hCG of >50% over a 48-hour period. It is not known whether methotrexate treatment has better fertility outcomes than surgery but this is likely to be the case when the ectopic gestation occurs in the only functioning tube.

Expectant management

Some ectopic pregnancies resolve spontaneously through either regression or tubal abortion, without causing harm to the patient. Expectant management is a conservative strategy consisting of observation and assessment of whether the ectopic pregnancy is continuing to resolve spontaneously and successfully without intervention. 34 A suitable candidate for expectant management must have an ectopic pregnancy with no evidence of rupture, be clinically stable and asymptomatic, and have consistently declining β-hCG concentrations. A low serum progesterone is also a possible marker of suitability for the expectant approach. Follow-up should be between one and three times weekly with β-hCG measurement and ultrasonography as required. Expectant management is reported to be most useful when the initial β-hCG is <1000 IU/l. 58 A rapidly declining β-hCG level also appears to predict a favourable outcome. 77 Success rates between 47% and 82% are reported, depending on the patient’s initial status. 78

The importance of compliance with follow-up and ease of access to the hospital should be emphasised. If β-hCG levels remain static or decline suboptimally, consideration should be given to reverting to surgical or medical management.

Unusual sites of implantation

Over 98% of ectopic pregnancies implant in the Fallopian tube, in its ampullary region (70%), isthmus (12%) or fimbria (11.1%). Interstitial or cornual ectopics, where the pregnancy implants in the intramyometrial portion of the Fallopian tube, are less common (2.4%) but have a mortality twice that of any other type of Fallopian tube ectopic pregnancy. 77 Rarely, an ectopic pregnancy implants at an extratubal location, such as the cervix, ovary, abdomen, liver, spleen or Caesarean section scar. 1 This produces a diagnostic challenge and colour Doppler visualisation aids in the identification of the ectopic pregnancy by creating awareness of vasculature supplying the implanted gestation. 77 Surgical treatment is difficult and systemic methotrexate is considered first-line treatment, with an early recourse to more than one dose, for the majority of extratubal ectopic pregnancies. 78 A more detailed description of the management of these unusual cases is beyond the scope of this review.

Subsequent pregnancies

Studies suggest that around 60% of women affected by an ectopic pregnancy go on to have a viable IUP. 79 This figure includes those who do not plan to have another pregnancy and so the proportion will be higher if further pregnancy is planned. There is thought to be a 5-20% risk of a recurrence of ectopic pregnancy with one previous ectopic pregnancy and a risk of 32% or more following more than one previous ectopic. 79 However, the risk is reduced after each subsequent IUP. 80 Even when there has been a bilateral salpingectomy there is still a risk of ectopic pregnancy in the interstitial tube or in tubal remnants following IVF. Women should receive an early scan in their next pregnancy to exclude a recurrent ectopic pregnancy.

There have been major advances in the diagnosis and management of ectopic pregnancies during the last 20 years. However, even now a significant proportion of ectopic pregnancies are not diagnosed at presentation and there are wide variations in management strategies between different units. Current screening methods have a high false-positive rate, and are not cost effective. Consequently, there are a number of ongoing studies developing biomarkers that allow definitive diagnosis. 53 , 58 81 In addition, there is a lack of randomised trials investigating the optimal management of ectopic pregnancy, particularly focusing on recurrence rates and impact on future fertility. Results are awaited from a large randomised trial comparing laparoscopic salpingectomy with salpingostomy. 82

Key message points

• □ Clinicians should be suspicious of ectopic pregnancy in any woman of reproductive age presenting with abdominal or pelvic symptoms.
• □ The diagnosis of ectopic pregnancy can be difficult and protracted.
• □ A diagnosis of ‘pregnancy of unknown location’ should trigger further diagnostic pathways and follow-up until the final outcome of the pregnancy is known.
• □ Medical management with methotrexate is successful for small, stable ectopic pregnancies.

ACKNOWLEDGEMENTS

The authors thank Ronnie Grant for graphics support and Dr Graeme Walker for images.

FINANCIAL SUPPORT:

AWH receives grant support from UK Medical Research Council (2009-13) (G0802808), IKTF (2009-2011) and an Albert McKern Bequest (2010-11). WCD holds a Scottish Senior Clinical Fellowship and has grant support from The Cunningham Trust.

Andrew Horne receives grant support from the UK Medical Research Council (2009-2013), IKTF (2009-2011) and an Albert McKern Bequest (2010-2011). Colin Duncan holds a Scottish Senior Clinical Fellowship and has grant support from The Cunningham Trust.

COMPETING INTEREST:

Andrew Horne holds a UK patent for a diagnostic biomarker for ectopic pregnancy (# 0712801.0).

• Mammary Glands
• Fallopian Tubes
• Supporting Ligaments
• Reproductive System
• Gametogenesis
• Placental Development
• Maternal Adaptations
• Menstrual Cycle
• Antenatal Care
• Small for Gestational Age
• Large for Gestational Age
• RBC Isoimmunisation
• Prematurity
• Prolonged Pregnancy
• Multiple Pregnancy
• Miscarriage
• Recurrent Miscarriage

Ectopic Pregnancy

• Hyperemesis Gravidarum
• Gestational Trophoblastic Disease
• Breech Presentation
• Abnormal lie, Malpresentation and Malposition
• Oligohydramnios
• Polyhydramnios
• Placenta Praevia
• Placental Abruption
• Pre-Eclampsia
• Gestational Diabetes
• Headaches in Pregnancy
• Haematological
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Original Author(s): Nandhaa Pazhaniappan Last updated: 20th December 2022 Revisions: 11

• 1 Risk Factors
• 2 Clinical Features
• 3 Differential Diagnosis
• 4 Investigations
• 5.1 Medical
• 5.2 Surgical
• 5.3 Conservative
• 6 Complications

An ectopic pregnancy is any pregnancy which is implanted at a site outside of the uterine cavity. In the UK, 1 in 80-90 pregnancies are ectopic. [ NHS UK ]

The most common sites include the ampulla and isthmus of the fallopian tube. Less commonly, the ovaries, cervix or peritoneal cavity can be involved.

In this article, we shall look at the risk factors, clinical features and management of an ectopic pregnancy.

Fig 1 – An ectopic pregnancy is one that is implanted outside the uterine cavity.

Risk Factors

The risk factors for an ectopic pregnancy are shown in Table 1.

Note: The use of contraception actually reduces the rate of pregnancy. However, if there is failure of the contraception types below, the pregnancy is more likely to be ectopic.

Clinical Features

The leading symptom of ectopic pregnancy is pain . Patients commonly present with lower abdominal/pelvic pain, with or without vaginal bleeding. There also can be a history of amenorrhoea.

Note: Vaginal bleeding in ectopic pregnancy is the result of decidual breakdown in the uterine cavity due to suboptimal β-HCG levels. Bleeding from a ruptured ectopic pregnancy is usually intra-abdominal, not vaginal.

Other symptoms include:

• Shoulder tip pain – the irritation of the diaphragm by blood in the peritoneal cavity leads to referred shoulder tip pain. This is because the diaphragm and the supraclavicular nerves (which innervate the shoulder tip) share the C3-C5 dermatomes.
• Vaginal discharge – brown in colour, classically described as being akin to prune juice. This is the result of the decidua breaking down.

On examination, the patient may have localised abdominal tenderness , with vaginal examination revealing cervical excitation and/or adnexal tenderness.

If the ectopic pregnancy has ruptured, the patient may also be haemodynamically unstable (pallor, increased capillary refill time, tachycardia, hypotension), with signs of peritonitis (abdominal rebound tenderness and guarding). Vaginal examination may reveal fullness in the pouch of Douglas.

Differential Diagnosis

An ectopic pregnancy should always be considered in cases of abdominal pain in a woman of reproductive age.

However, its clinical features are largely non-specific , and can be seen in other conditions:

• Ovarian cyst accident (this refers to cyst haemorrhage, torsion or rupture)
• Acute pelvic inflammatory disease
• Urinary tract infection
• Appendicitis
• Diverticulitis

Fig 2 – Differential diagnoses for pain in each region of the abdomen.

Investigations

A pregnancy test (urine β-HCG) is the most important initial investigation for an ectopic pregnancy.

If positive, a pelvic USS should be performed – this can determine the presence or absence of an intrauterine (‘normal’) pregnancy. If an intrauterine pregnancy is not seen on transabdominal USS, a transvaginal scan should be offered.

If a pregnancy cannot be identified on ultrasound scan (but β-HCG is positive), this is termed a pregnancy of unknown location . It has three main differential diagnoses; (i) very early intrauterine pregnancy; (ii) miscarriage; and (iii) ectopic pregnancy. In this situation, a serum β-HCG   should be taken:

• If the initial β-HCG level is >1500 iU (discriminatory level), and there is no intrauterine pregnancy on transvaginal ultrasound, then this should be considered an ectopic pregnancy until proven otherwise, and a diagnostic laparoscopy should be offered.
• In a viable pregnancy, HCG level would be expected to double every 48 hours.
• In a miscarriage, HCG level would be expected to halve every 48 hours
• Where the increase or drop in the rate of change is outside these limits, an ectopic pregnancy cannot be excluded and the patient should be managed accordingly.

Other investigations should be used as appropriate to rule in/out the other differential diagnoses – e.g. urinalysis for urinary tract infection.

Fig 3 – Ectopic pregnancy identified by transvaginal ultrasound, in a woman with an intrauterine contraceptive device (IUD).

Any patient with a suspected ectopic pregnancy should be admitted to hospital. If unstable, an A-E approach  should be used to resuscitate the patient. This may include the use of blood products if there are signs of haemodynamic instability.

The definitive management of ectopic pregnancy can be medical, surgical, or conservative.

Medical management of an ectopic pregnancy is with  IM methotrexate . It is an anti-folate cytotoxic agent that disrupts the folate dependent cell division of the developing fetus. The pregnancy will then gradually resolve.

The serum β-HCG  level is monitored regularly to ensure the level is declining (by >15% in day 4-5). If there isn’t such a decline, a repeat dose is administered.

Medical management is offered to patients who are stable, with well controlled pain and β-HCG levels <1500 iU/ml. The ectopic should be  unruptured , and without a visible heartbeat. The patient should have access to 24-hour gynaecology services and be informed of the symptoms of rupture.

• Advantages : Avoids the complications of surgical management and the patient can be at home after the injection.
• Disadvantages : Potential side effects of methotrexate – abdominal pain, myelosuppression, renal dysfunction, hepatitis, teratogenesis (patients must be advised to use contraception for 3-6 months after methotrexate use). The treatment can fail, which would necessitate surgical intervention.

Surgical management involves the surgical removal of the ectopic pregnancy.

In cases of tubal ectopics (most common), a laparoscopic salpingectomy is usually performed – removing the ectopic and the tube that it is implanted in.

However, if there is damage to the contralateral tube from infection, disease or surgery, a salpingotomy (a cut in the fallopian tube) can be performed to remove the ectopic and salvage the tube to preserve future fertility.

Note: In a salpingotomy, HCG follow up is required until the level reaches <5iU (negative), to ensure there is no residual trophoblast. The risk of recurrent ectopic pregnancy in the salvaged tube will be increased.

Surgical management is typically offered to patients with severe pain, serum β-HCG >5000 mIU/ml, adnexal mass >34 mm and/or fetal heartbeat visible on scan.

• Advantages : Reassurance about when the definitive treatment can be provided, high success rate.
• Disadvantages : General anaesthetic risk, risk of damage to neighbouring structures like the bladder, bowel, ureters, DVT/PE, haemorrhage, infection. With salpingotomy, there is also a risk of treatment failure – as some of the pregnancy may remain within the tube.

All rhesus negative women who receive surgical management of an ectopic pregnancy should be offered Anti-D prophylaxis .

Fig 4 – Laparoscopic view of ectopic pregnancy within the left fallopian tube (red arrows). Uterus marked by blue arrows.

Conservative

Conservative management involves watchful waiting of the stable patient, while allowing the ectopic to resolve naturally. This is suitable in a small number of selected patients only, and is not the first line management. This approach needs to be discussed at senior level.

The serum B-hCG should be monitored every 48 hrs to ensure it is falling by equal to or greater 50% of the level until it falls to approximately <5mIU/ml.

This method is offered for patients in whom a rupture is unlikely; these are  stable patients , with well controlled pain, with a low baseline β-HCG, small unruptured ectopic on USS.

The patient should have access to 24-hour gynaecology services and informed of the symptoms of rupture.

• Advantages : Avoid the risks of medical and surgical management, can be done at home.
• Disadvantages : Failure or complications necessitating medical or surgical management (25% of patients), rupture of ectopic.

Complications

Complications of individual treatments are detailed above.

An untreated ectopic pregnancy can lead to fallopian tube rupture . The resulting blood loss can cause hypovolaemic shock, resulting in organ failure and death.

If positive, a pelvic USS should be performed - this can determine the presence or absence of an intrauterine ('normal') pregnancy. If an intrauterine pregnancy is not seen on transabdominal USS, a transvaginal scan should be offered.

In cases of tubal ectopics (most common), a laparoscopic salpingectomy is usually performed - removing the ectopic and the tube that it is implanted in.

• Disadvantages : General anaesthetic risk, risk of damage to neighbouring structures like the bladder, bowel, ureters, DVT/PE, haemorrhage, infection. With salpingotomy, there is also a risk of treatment failure - as some of the pregnancy may remain within the tube.

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What Is an Ectopic Pregnancy? Here Are the Signs to Look For

Copy changes throughout, plus fact-checked and medically reviewed for accuracy.

What is an ectopic pregnancy?

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

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

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Dozens of pregnant women, some bleeding or in labor, are turned away from ers despite federal law.

Amanda Seitz

Associated Press

WASHINGTON – Bleeding and in pain, Kyleigh Thurman didn’t know her doomed pregnancy could kill her.

Emergency room doctors at Ascension Seton Williamson in Texas handed her a pamphlet on miscarriage and told her to “let nature take its course" before discharging her without treatment for her ectopic pregnancy.

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When she returned three days later, still bleeding, doctors finally agreed to give her an injection to end the pregnancy. It was too late. The fertilized egg growing on Thurman’s fallopian tube ruptured it, destroying part of her reproductive system.

That’s according to a complaint Thurman and the Center for Reproductive Rights filed last week asking the government to investigate whether the hospital violated federal law when staff failed to treat her initially in February 2023.

“I was left to flail," said Thurman, 35. “It was nothing short of being misled.”

The Biden administration says hospitals must offer abortions when needed to save a woman's life, despite state bans enacted after the Supreme Court overturned the constitutional right to an abortion more than two years ago. Texas is challenging that guidance and, earlier this summer, the Supreme Court declined to resolve the issue.

More than 100 pregnant women in medical distress who sought help from emergency rooms were turned away or negligently treated since 2022, an Associated Press analysis of federal hospital investigations found.

Two women — one in Florida and one in Texas — were left to miscarry in public restrooms. In Arkansas, a woman went into septic shock and her fetus died after an emergency room sent her home. At least four other women with ectopic pregnancies had trouble getting treatment, including one in California who needed a blood transfusion after she sat for nine hours in an emergency waiting room.

Abortion bans complicate risky pregnancy care

In Texas, where doctors face up to 99 years of prison if convicted of performing an illegal abortion, medical and legal experts say the law is complicating decision-making around emergency pregnancy care.

Although the state law says termination of ectopic pregnancies isn't considered abortion, the draconian penalties scare Texas doctors from treating those patients, the Center for Reproductive Rights argues.

“As fearful as hospitals and doctors are of running afoul of these state abortion bans, they also need to be concerned about running afoul of federal law,” said Marc Hearron, a center attorney. Hospitals face a federal investigation, hefty penalties and threats to their Medicare funding if they violate the federal law.

The organization filed complaints last week with the Centers for Medicare and Medicaid Service alleging that different Texas emergency rooms failed to treat two patients, including Thurman, with ectopic pregnancies.

One complaint says Kelsie Norris-De La Cruz, 25, lost a fallopian tube and most of an ovary after an Arlington, Texas, hospital sent her home without treating her ectopic pregnancy, even after a doctor said discharge was “not in her best interest.”

“The doctors knew I needed an abortion, but these bans are making it nearly impossible to get basic emergency healthcare,” she said in a statement. “I’m filing this complaint because women like me deserve justice and accountability from those that hurt us.”

Conclusively diagnosing an ectopic pregnancy can be difficult. Doctors cannot always find the pregnancy’s location on an ultrasound, three doctors consulted for this article explained. Hormone levels, bleeding, a positive pregnancy test and an ultrasound of an empty uterus all indicate an ectopic pregnancy.

“You can't be 100% — that's the tricky part," said Kate Arnold, an OB-GYN in Washington. “They're literally time bombs. It's a pregnancy growing in this thing that can only grow so much."

Texas Right to Life Director John Seago said state law protects doctors from prosecution for terminating ectopic pregnancies, even if a doctor “makes a mistake” in diagnosing it.

“Sending a woman back home is completely unnecessary, completely dangerous," Seago said.

But the state law has “absolutely” made doctors afraid of treating pregnant patients, said Hannah Gordon, an emergency medicine physician who worked in a Dallas hospital until last year.

She recalled a patient with signs of an ectopic pregnancy at her Dallas emergency room. Because OB-GYNs said they couldn't definitively diagnose the problem, they waited to end the pregnancy until she came back the next day.

“It left a bad taste in my mouth," said Gordon, who left Texas hoping to become pregnant and worried about the care she'd receive there.

“Oh my God, I’m dying”

When Thurman returned to Ascension Seton Williamson a third time, her OB-GYN told her she'd need surgery to remove the fallopian tube, which had ruptured. Thurman, still heavily bleeding, balked. Losing the tube would jeopardize her fertility.

Her doctor told her she risked death if she waited any longer.

“She came in and she’s like, you're either going to have to have a blood transfusion, or you’re going to have to have surgery or you’re going to bleed out,” Thurman said, through tears. “That’s when I just kind of was like, ‘Oh my God, I’m, I’m dying.’”

The hospital declined to comment on Thurman’s case, but said in a statement it “is committed to providing high-quality care to all who seek our services.”

In Florida, a 15-week pregnant woman leaked amniotic fluid for an hour in Broward Health Coral Springs' emergency wait room, according to federal documents. An ultrasound revealed the patient had no amniotic fluid surrounding the fetus, a dangerous situation that can cause serious infection.

The woman miscarried in a public bathroom that day, after the emergency room doctor listed her condition as “improved” and discharged her, without consulting the hospital's OB-GYN.

Emergency crews rushed her to another hospital, where she was placed on a ventilator and discharged after six days.

Abortions after 15 weeks were banned in Florida at the time. Broward Health Coral Springs’ obstetrics medical director told an investigator that inducing labor for anyone who presents with pre-viable premature rupture of membranes is "the standard of care, has been a while, regardless of heartbeat, due to the risk to the mother.”

The hospital declined comment.

In another Florida case, a doctor admitted state law had complicated emergency pregnancy care.

“Because of the new laws ... staff cannot intervene unless there is a danger to the patient's health," a doctor at Memorial Regional Hospital in Hollywood, Florida, told an investigator who was probing the hospital's failure to offer an abortion to a woman whose water broke at 15 weeks, well before the fetus could survive.

Troubles extend beyond abortion ban states

Serious violations that jeopardized a mother or her fetus’ health occurred in states with and without abortion bans, the AP’s review found.

Two short-staffed hospitals — in Idaho and Washington — admitted to investigators they routinely directed pregnant patients to other hospitals.

A pregnant patient at a Bakersfield, California, emergency room was quickly triaged, but staff failed to realize the urgency of her condition, a uterine rupture. The delay, an investigator concluded, may have contributed to the baby's death.

Doctors at emergency rooms in California, Nebraska, Arkansas and South Carolina failed to check for fetal heartbeats or discharged patients who were in active labor, leaving them to deliver at home or in ambulances, according to the documents.

Nursing and doctor shortages, trouble staffing ultrasounds around-the-clock and new abortion laws are making the emergency room a dangerous place for pregnant women, warned Dara Kass, an emergency medicine doctor and former U.S. Health and Human Services official.

“It is increasingly less safe to be pregnant and seeking emergency care in an emergency department,” she said.

This story was first published on Aug. 12, 2024. It was updated on Aug. 14, 2024, to correct that Kyleigh Thurman is 35, not 25.

Copyright 2024 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed without permission.

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Risk factors and prediction of ectopic pregnancy rupture following methotrexate treatment: A retrospective cohort study

Affiliations.

• 1 Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Israel; Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel. Electronic address: [email protected].
• 2 Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Israel.
• 3 Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Israel; Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
• PMID: 37146508
• DOI: 10.1016/j.ejogrb.2023.04.030

Objective: Ectopic pregnancy (EP) rupture after methotrexate (MTX) treatment can have severe consequences. We examined clinical characteristics and beta-hCG trends that may predict EP rupture after MTX treatment.

Study design: In this 10-year retrospective study of 277 women with an EP, we compared clinical, sonographic and beta-hCG trends, before and after MTX treatment, between those who did and did not have an EP rupture after MTX treatment.

Results: EP rupture was diagnosed in 41 women (15.1%) within 25 days of MTX treatment, and was correlated with higher parity and advanced pregnancy age: 2(0-5) vs. 1(0-6), P = 0.027 and 6.6(4.2-9.8) vs. 6.1(4-9.5), P = 0.045. EP rupture was also correlated with higher beta-hCG levels on days 0, 4 and 7 of MTX treatment: (2063 vs. 920 mIU/ml), (3221 vs. 921 mIU/ml) and (2368 vs. 703 mIU/ml), respectively, P < 0.001, for all. An increase of beta-hCG by>14% during days 0-4 showed a sensitivity of 71.4% CI 95% [55.4%-84.3%] and a specificity of 67.5% CI 95% [61.1%-73.6%] for predicting EP rupture after MTX treatment. Beta-hCG > 910 mIU/ml on day 0 showed a sensitivity of 80.9% CI 95% [66.7%-90.8%] and a specificity of 70.4% CI 95% [64.1%-76.3%] for predicting EP rupture after MTX treatment. A beta-hCG increase by>14% during days 0-4, and a beta-hCG value > 910 mUI/mL on day 0 were associated with increased risks of EP rupture after MTX treatment; the odds ratios were 6.4 and 10.5, respectively. Odds ratios were 8.06 [CI 95% (3.70-17.56)], P < 0.001 for every percent rise in beta-hCG during days 0-4; 1.37 [CI 95% (1.06-1.86)], P = 0.046 for every week change in gestational age; and 1.001 [CI 95% (1.000-1.001)], P < 0.001 for every unit rise in beta-hCG at day 0.

Conclusion: Beta-hCG > 910 mIU/ml at day 0, a rise in beta-hCG by>14% during days 0-4, and more advanced gestational age were associated with EP rupture after MTX treatment.

Keywords: Extrauterine pregnancy; Hemoperitoneum; Laparoscopy; Methotrexate; Tubal pregnancy.

Copyright © 2023 Elsevier B.V. All rights reserved.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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