Ectopic Pregnancy

Vol.2 No.3  

by Steven J. Fleischman, M.D.
Resident, Department of Obstetrics and Gynecology
Yale University School of Medicine
Yale New Haven Hospital
 
Introduction:

Ovulation typically occurs two weeks into the menstrual cycle. The oocyte is released from the ovary and enters the end of the fallopian tube furthest from the uterus known as the fimbriated end. Fertilization takes place in the fallopian tube close to the ovary. As the embryo develops within the first week, it traverses the fallopian tube where it will eventually implant into the wall of the uterus. This process occurs in greater than ninety-eight percent of pregnancies. An ectopic pregnancy, or tubal pregnancy, occurs when implantation of the embryo occurs anywhere outside of the uterus. The majority of ectopic pregnancies are located along the length of the fallopian tube (>97%). A remaining percentage will occur in the portion of the uterus where the fallopian tube enters (known as the cornua), in the ovary or cervix, or even within the abdominal cavity outside the uterus. Another type of ectopic pregnancy which may occur is known as a heterotopic ectopic pregnancy and this refers to an ectopic which coexists with an intrauterine pregnancy.  

How common is an ectopic pregnancy and what is the significance?


The past two decades in the United States has seen a marked increase in the number of ectopic pregnancies. In 1992 almost 2% of all pregnancies were ectopic, and ectopic pregnancy related deaths accounted for 10% of all pregnancy related deaths. The heterotopic ectopic pregnancy is rare and occurs at a rate of 1 in 7000 pregnancies. Ectopic pregnancy remains the second leading cause of maternal mortality in the US, and is the leading cause of maternal mortality in the first trimester.  

Why do people get ectopic pregnancies?
There are many underlying problems which predispose women to having an ectopic pregnancy. In general there is a problem with the tube which fails to permit the passage of the fertilized ovum to enter the uterus. Some specific risk factors include:


1. History of infection of the tube. This may include pelvic inflammatory disease as well as other sexually transmitted diseases. The inflammation associated with the infection causes damage to the internal walls of the fallopian tube, narrowing the lumen. 2. Adhesions around the tube. Adhesions are band-like pieces of tissue which can form after surgery within the abdomen, infections, or endometriosis. These bands can cause a kinking of the fallopian tube and make passage of the embryo difficult. 3. Previous ectopic pregnancy. After having one ectopic pregnancy there is between a 7% and 15% risk of having another one. 4. Developmental abnormalities of the tube. While rare, it is possible to have abnormalities of the fallopian tube. Women who were exposed to diethylstilbestrol while in utero have an increased risk of anomalies of the genital tract. 5. Cigarette smoking at the time of conception has been shown to increase the risk of ectopic pregnancy. 6. Assisted reproduction. There have been several studies showing that several forms of assisted reproduction have been associated with increased risk of ectopic pregnancies. However, further studies seem to indicate that this risk is associated with concurrent tubal disease. 7. Hormonal imbalance. Excessive levels of estrogens or progesterones may interfere with the normal contractility of the fallopian tube. 8. Previous tubal sterilization. In women who become pregnant after a tubal ligation procedure there is a 16% to 50% rate of ectopic pregnancy.  

How do women with ectopic pregnancy present? 

Typically women who have ectopic pregnancies present with complaints of lower abdominal pain. In addition, they may notice absence of menses, irregular bleeding or spotting. Most importantly these symptoms are present in the setting of a positive pregnancy test. The most common misdiagnoses for ectopic pregnancy include gastrointestinal disorders, normal pregnancy withan ovarian cyst, and pelvic inflammatory disease. 

The greatest risk related to an ectopic pregnancy is rupture. As the pregnancy grows outside of the uterus the embryo begins to enlarge beyond the size of the tube. In combination with the increased blood flow to a growing embryo, the risk of rupturing through the tube also means that women can lose a significant amount of blood in a very short period of time. Women who have a ruptured ectopic pregnancy classically present with sudden onset of severe lower abdominal pain, possible fainting episode, lightheadedness or dizziness, and a history of irregular bleeding.

How is it diagnosed? 

Initially when a woman presents to their doctor with the complaints described above, a urine pregnancy test is performed. At the same time a blood sample is drawn and sent for the beta human chorionic gonadotropin level (B-hCG). The B-hCG is the blood test sent to determine whether a woman is pregnant or not. While a urine pregnancy test can tell whether a woman is pregnant or not, the blood test will give a numeric value which correlates with how far along in the pregnancy a woman is. In normal pregnancies the B-hCG level doubles about every two days. However, in an ectopic pregnancy the rise is less than normal. In addition, the B-hCG level will correlate with certain ultrasound findings.
After the initial urine pregnancy test is positive and the blood B-hCG is sent to the lab, an ultrasound is performed. Based on the last menstrual period an approximate gestational age is determined. A transvaginal ultrasound can see evidence of an intrauterine pregnancy as early as 5 weeks. The majority of ectopic pregnancies cannot be seen on ultrasound, therefore we use the presence of an intrauterine pregnancy on ultrasound to rule out an ectopic pregnancy. In addition, if the B-hCG level returns >1500 we should be able to see evidence of an intrauterine pregnancy on transvaginal ultrasound. If the blood B-hCG level does not correlate with the ultrasound findings, our suspicion for an ectopic is raised.
If the B-hCG level is too low to see an intrauterine pregnancy we are faced with a dilemma. At this point we assess the severity of the patients current symptoms. If the patient is stable (meaning normal blood pressure and heart rate, able to sit up without getting lightheaded, and having only a mild amount of pain,) then we may send the patient home to follow-up with another blood B-hCG level. If this second level is double the initial level, then we suspect a normal pregnancy and repeat the ultrasound. If the level is less than double then our suspicion for an ectopic pregnancy is high.
If the B-hCG rise is abnormal (less than double) then either an ectopic pregnancy or an abnormal intrauterine pregnancy exists. A dilatation and curettage performed now can document whether there was evidence of abnormal embryonic tissue within the uterus. If present t,hen there was an abnormal intrauterine pregnancy. However, if there is no evidence of embryonic tissue then an ectopic pregnancy is suspect.
Laparoscopy (the visualization of the pelvic organs using a telescope-like instrument inserted through the belly button) or laparotomy (making an incision and looking directly at the internal organs) are the procedures of choice for the definitive diagnosis of an ectopic pregnancy. In any patients that are felt to be unstable one of these procedures should be undertaken immediately. 
Other procedures and tests have been used for the diagnosis of ectopic pregnancy by various physicians. A serum progesterone level has been shown to be low in abnormal pregnancies, however, the level cannot differentiate between an ectopic and an abnormal pregnancy. Culdocentesis is a procedure where fluid is removed from the abdominal cavity by inserting a needle through the vaginal wall next to the cervix. The fluid removed can help diagnose a ruptured ectopic. 
What is the treatment?
Once an ectopic pregnancy has been diagnosed there are two major treatment options based on the severity of the case in question as well as expectant management . 
The majority of cases, including those ruptured, are managed surgically. Laparoscopy or laparotomy is performed and the ectopic pregnancy is removed This is done by either opening the tube with a small incision and allowing the embryo to be removed, or in the event that there is significant bleeding or the embryo cannot be fully removed a portion of the tube is removed.
In a small proportion of the cases it is possible to treat ectopic pregnancies medically with a drug called Methotrexate. This drug interferes with DNA synthesis (the building blocks of chromosomes which tell cells what to do.)The criteria for medical management with Methotrexate is that the patient is stable, the tubal pregnancy is unruptured, the size is smaller than <3.5cm, and the peak B-hCG is <15,000.
Expectant management is undertaken in those women who present early, with decreasing B-hCG levels, and are stable. These women must follow-up closely to assure that the levels continue to decline and that they do not develop evidence of rupture. There have been cases of patients whose levels have returned to almost normal and then ruptured, indicating the importance of close monitoring.

What is the prognosis for future pregnancy? 

Overall the subsequent conception rate leading to a live birth is about 35%. This number is significantly higher in those women who have a history of an unruptured ectopic pregnancy. So early diagnosis is extremely important. Women who have had an ectopic pregnancy in the past should make their physician aware and be followed closely early on to assure proper implantation of the embryo.