Ectopic Pregnancy: Diagnosis and Treatment

by Scott J. Roseff, MD, FACOG

An ectopic pregnancy is a pregnancy that grows outside of the normal location, namely the uterus. Often called a "tubal pregnancy," the majority (about 97%) of ectopic pregnancies occur in the fallopian tube. Ectopic pregnancies can also occur in the ovary, cervix, or abdominal cavity, but this is rare. For the purpose of this article, the terms "ectopic pregnancy" and "tubal pregnancy" will be used interchangeably.

The danger of ectopic pregnacy lies in the fact that a fallopian tube is not large enough or sufficiently elastic to accommodate a growing embryo, and thus may rupture as the ectopic pregnancy grows. An ectopic pregnancy is considered to be a medical emergency because tubal rupture can cause severe internal bleeding that may lead to shock and even the death of the mother.

The incidence of ectopic pregnancy is rising; about 7 per 1,000 reported pregnancies in the United States are ectopic. However, since the 11th century when the condition was first described the death rate from ectopic pregnancy has declined significantly. This is due to the advent of modern techniques permitting early diagnosis and treatment. The current maternal mortality rate due to ectopic pregnancy is less than 1 per 2,500 cases. This low death rate may be attributed to several important modern developments, including:

  1. Early pregnancy detection -- The availability of sensitive pregnancy tests that can detect all pregancies much earlier than before means that ectopic pregnacies are detected at a time prior to advanced tubal damage and rupture.
  2. Ultrasound monitoring -- Modern and improved ultrasound equipment permits detailed evaluation of early pregnancies, including the location of the pregnancy and the actual flow of blood to the uterus/tube (which helps assess the risk of blood loss from ectopic rupture).
  3. Improved surgical techniques -- Laparoscopy (see below for definition) and other surgical techniques have been refined over the years, allowing for the safer removal of tubal pregnancies and improved tubal healing.
  4. Improvements in anesthesia and blood products -- Refinements in anesthesia, as well as safer and more widely available blood for transfusion, have dramatically improved surgical outcomes.

Risk Factors and Causes

Risk factors for the development of an ectopic pregnancy generally relate to processes that damage or narrow the fallopian tubes, resulting in a situation whereby the fertilized egg can not travel the length of the tube. Well-recognized risk factors for ectopic pregnancy include:

  1. Pelvic inflammatory disease (PID) -- An infection of the female reproductive tract, PID can cause damage to and scarring of the fallopian tubes. PID is the single greatest risk factor for an ectopic pregnancy.
  2. Endometriosis -- A disease whereby tissue similar to the uterine lining grows outside of the uterine cavity, endometriosis can cause pelvic scar tissue to form, increasing the possibility of tubal damage and dysfunction.
  3. Prior pelvic surgery -- Surgery within the pelvis increases the odds of scar formation around the fallopian tubes, again increasing the possibility of tubal damage and dysfunction.
  4. Previous ectopic pregnancy -- A history of a prior ectopic pregnancy increases the chances of a subsequent ectopic pregnancy (to an average of 15%).
  5. Abnormalities of the fallopian tubes present since birth.
  6. Cigarette smoking -- Nicotine can damage the hair-like cells within the fallopian tube, making entrapment of the fertilized egg within the tube more likely.
  7. Usage of certain types of intrauterine devices (known commonly as IUDs) for birth control.
  8. Use of certain hormonal preparations, including progestin-only oral contraceptive pills and possibly fertility drugs and treatments.

Many times, however, there are no obvious predisposing factors for ectopic gestation. Therefore, many physicians agree with the philosophy that any woman of reproductive age who is pregnant should be considered to have an ectopic pregnancy until proven otherwise.

Signs and Symptoms

Most women with an ectopic pregnancy exhibit the following signs and symptoms:

  • Lower abdominal/pelvic pain or cramping (either constant or intermittent)
  • Irregular vaginal bleeding or spotting

Occasionally, and especially late in the course of this disorder, a patient with an ectopic pregnancy may display additional symptoms like shoulder pain (due to blood in the abdomen irritating the nerves which go to the shoulder region), dizziness, fainting, and shock. Of course, a woman should never wait to see if she develops these late signs and symptoms and should call an ambulance for transportation to the nearest emergency room if she suspects she might have an impending ruptured ectopic pregnancy.

Diagnosis

The early and rapid diagnosis of ectopic pregnancy is critical for saving the reproductive health and possibly the life of the patient. Diagnostic tests used to uncover ectopic pregnancy are:

  1. Quantitative beta-hCG: This test measures the level of beta-hCG -- a hormone present during pregnancy -- in the blood. The hCG levels rise in a fairly predictable manner early in a normal pregnancy (60-100% rise every 2-3 days). An abnormally rising hCG level may be an important clue in signaling an ectopic pregnancy.
  2. Ultrasound imaging: Modern ultrasound equipment, which is frequently found in the doctor's office, assists in visualization of the early pregnancy. Through ultrasound, a doctor can confirm that the pregnancy sac and the fetus are within the uterus, essentially ruling out an ectopic pregnancy. Rarely, a patient may have a pregnancy sac within the uterus yet still have an ectopic pregnancy. This possibility (called a heterotopic pregnancy) is increased in patients undergoing assisted reproductive technologies (such as in vitro fertilization).
  3. Laparoscopy: A thin telescope (laparoscope) is introduced through the navel (belly button) under general anesthesia. This allows the surgeon to see the pelvis directly and examine the fallopian tubes without having to make a big incision into your abdomen. In the case of a confirmed ectopic pregnancy, the abnormal gestation can usually be treated/removed at the time of laparoscopy
  4. Culdocentesis: Rarely, a doctor may need to insert a long, thin needle through the back of the vagina and into the pelvis, to determine if blood is found. This test, known as culdocentesis, is seldom done today due to the widespread availability of the less invasive tests described above
  5. Dilation and curettage: "D & C" is a procedure where the cervix is dilated by inserting a number of increasingly wide rubber dilators, after which a curette, or spoon-like instrument, is inserted into the uterus to scrape the inside lining. This may assist in determining the location of an abnormal pregnancy.

Treatment

The treatment options for ectopic pregnancy depend upon several factors. The most important determining factors are:

  • How far along the pregnancy has developed
  • Whether the fallopian tube is rupturing or has ruptured
  • The clinical status of the patient (stable without symptoms vs. unstable)
  • The woman's overall general state of health

Treatment types are classified into medical and surgical categories.

Medical therapy
Medical therapy is reserved for women diagnosed early in the course of their ectopic pregnancy. This treatment usually involves a drug called methotrexate. Methotrexate was originally developed as a chemotherapy drug, as it kills rapidly dividing cells (such as is seen in cancer). Injections of methotrexate in much lower doses than those given for chemotherapy have been shown to effectively treat ectopic pregnancy in at least 90% of cases.

There are several potential advantages of methotrexate therapy over surgical intervention. These include:

  • Less invasive - By definition, surgery is invasive (it involves the cutting of tissue and the opening of body cavities), and can cause further damage to the fallopian tube, resulting in lower subsequent pregnancy rates or higher repeat ectopic pregnancy rates
  • Lower cost - The total cost of treating and monitoring an ectopic pregnancy with medication is significantly lower than that of general anesthesia and surgery.

One disadvantage of methotrexate over surgery is the longer time period needed to resolve the condition, compared to the immediate surgical termination of the ectopic pregnancy. Side effects of methotrexate may occur (such as mild nausea), but they are generally not severe and are time limited.

For methotrexate treatment to be effective, the patient must fit several strict criteria. Below is a partial list of these criteria.

  1. The patient must have an early ectopic pregnancy in which the tubes have not been ruptured
  2. Patient must have few or no symptoms (little to no pain) and must have good heart function and blood pressure
  3. The patient must be reliable, must agree to call if problems occur, and must be willing to return for testing and clinical follow-up
  4. Good general health -- blood counts as well as kidney and liver function must be normal prior to receiving methotrexate

Usually, methotrexate is given as a single injection into a muscle. The dosage is based upon the patient's height and weight. A blood test for the hormone hCG is analyzed four days after the injection and is measured again seven days after the shot. The hCG level must decline at least 15% between the fourth and seventh day in order for the single injection to be considered successful. If the hormonal decline was not adequate, the patient is reassessed to determine whether a second methotrexate injection is appropriate. If the hormonal decline is adequate, weekly hCG levels are followed along with the woman's clinical status until it is determined that the ectopic pregnancy has been resolved. If the patient becomes unstable at any point in time, she is rushed to the hospital for surgical intervention.

Surgical therapy
Surgical therapy is generally chosen for women who are not candidates for medical treatment. These women may be in shock (hemodynamically unstable), have an advanced ectopic pregnancy (determined by high hCG blood levels or an ultrasound measurement of a large pregnancy sac), and be in moderate to severe pain.

"Conservative" surgery involves creating a small incision in the fallopian tube at the site of the tubal pregnancy. Depending on the individual circumstance, the surgeon may use laparoscopy (see above) or a larger, major abdominal incision to get to the fallopian tube. Once the incision into the tube is made, the ectopic pregnancy tissue is removed from the tube and the tube is allowed to heal naturally. This procedure preserves the fallopian tube. Occasionally, some of the pregnancy tissue is inadvertently left behind, necessitating the postoperative use of methotrexate or possibly another surgical procedure. If the tube heals well, it may function adequately in the future, allowing the patient to potentially conceive normally. However, if the tube heals poorly or was previously damaged, leaving it in place may make a future ectopic pregnancy more likely.

"Radical" surgery involves removing all or part of the fallopian tube via a procedure called salpingectomy. Again, performed by either laparoscopy or a larger abdominal incision, the potential advantage of removing the affected tube is a lower likelihood of accidentally leaving some of the ectopic pregnancy tissue behind (and therefore a lower probability of needing further treatment after the surgery). The disadvantage of removing the tube is the decrease in fertility that is generally experienced with an absent fallopian tube.

Regardless of the method chosen to treat an ectopic pregnancy, the woman's blood hCG levels must be followed until they are undetectable. Once the levels are negative, she should wait three months for tubal healing to occur (unless the tube was removed) before trying to conceive again. Since her fertility potential may be diminished and since her odds of a subsequent ectopic pregnancy are increased following an ectopic pregnancy, a patient should not try too long to conceive without success (generally 3-6 months) before seeking the assistance of a fertility specialist. It may be necessary to "bypass" the fallopian tube(s) and undergo in vitro fertilization (IVF).

Even if she conceives via IVF, a woman with a history of tubal pregnancy has at least a 5% chance of a repeat ectopic pregnancy. Therefore, early pregnancy monitoring (via blood testing and ultrasound) is critically important for all women with this history. Finally, should a woman conceive naturally, she should seek early medical attention to decrease her risk of disaster and increase her odds of present and future reproductive success.

Conclusion

The advent of modern diagnostic and therapeutic modalities has changed the clinical scenario of ectopic pregnancy from one of possible disaster (and even death) to one of potential success. It is important to remember that every woman of reproductive age is at a potential risk for having a tubal pregnancy. Women who heighten their awareness of the signs and symptoms of an ectopic pregnancy will help their doctors to make the diagnosis earlier, treat the problem with less invasive methods, preserve the fallopian tubes, and greatly increase the odds of achieving a healthy and fruitful outcome.

Dr. Scott Roseff is the Director of the West Essex Center for Advanced Reproductive Endocrinology (W.E. C.A.R.E.) in West Orange, New Jersey. Following his graduation from the UAG School of Medicine, he completed a one year rotating "Internship" in Internal Medicine, General Surgery, Pediatrics, Psychiatry, and Obstetrics/Gynecology at St. Barnabas Medical Center in Livingston, New Jersey. His Residency training in Obstetrics and Gynecology was performed at The Stamford Hospital in Stamford, Connecticut. He then went on to complete his Postgraduate Fellowship in Reproductive Endocrinology and Infertility at The UCSD School of Medicine, San Diego, California, after which he achieved Board Certification in the specialty of Obstetrics and Gynecology, as well as in the subspecialty of Reproductive Endocrinology and Infertility.

Dr. Roseff's research and special areas of interest include the mechanisms of action of clomiphene citrate (Clomid/Serophene), the hormonal dynamics of the menstrual cycle, laser laparoscopy, endometriosis, abnormal sperm function, polycystic ovarian syndrome (PCOS), and menopause (to name just a few). Dr. Roseff maintains active staff privileges in the Ob/Gyn Departments at St. Barnabas Medical Center (Livingston, NJ) and at Morristown Memorial Hospital (Morristown, NJ).

Copyright © Scott Roseff. Permission to republish granted to Pregnancy.org, LLC.