Ectopic pregnancy is defined as a pregnancy that occurs outside of the uterus. The most common site is in the fallopian tube, but sometimes it can occur in the ovary, the cervix or anywhere in the abdominal cavity. The incidence of ectopic pregnancy is 1% of all pregnancies and for in vitro fertilization (IVF) cases it is estimated to be 1-3%. Ectopic pregnancy is one of the most dangerous complications of pregnancy and the number one cause of death in the first trimester. If undetected, the ectopic pregnancy will continue to grow inside the tube and eventually tear the tube and result in excessive intra-abdominal bleeding, which can result in death.
It is possible to detect an ectopic pregnancy at an early stage with a vaginal pelvic ultrasound and beta hCG hormone measurements. Ectopic pregnancy historically has been treated with laparotomy (open abdominal surgery) and removal of the fallopian tube. But more recently, laparoscopic removal of the ectopic mass and conservation of the fallopian tube is the most common type of surgery performed. Medical treatment of ectopic pregnancy has largely replaced surgical treatment in clinically stable patients, using the drug called Methotrexate (MTX).
The fertilization of the egg takes place in the fallopian tube and the fertilized egg (embryo) then travels into the uterus by the peristaltic movements of the healthy fallopian tube, where it implants into the endometrial cavity 6-7 days after ovulation. The delay of the transfer of the embryo from the fallopian tube into the uterus can result in the embryo hatching and implanting into the wall of the fallopian tube. One of the most common predisposing factors is pelvic inflammatory disease (PID) caused by chlamydia or gonorrhea, resulting in damage of the inner lining of the tube. If tubes are surgically opened (neosalpingostomy) or repaired (tuboplasty) because of prior tubal damage, the risk of an ectopic pregnancy is increased. The risk of ectopic pregnancy also increases with each additional ectopic pregnancy. The risk of having a second ectopic is approximately 15% and 25-30% for the third ectopic. Smoking and a history of prior abortions (controversial) may also increase the risk of an ectopic pregnancy. The risk may be increased further based on each individual case and exposure to sexually transmitted diseases or when additional variables are present.
The risk of an ectopic pregnancy is reduced with all methods of contraception. If the tubes are tied for contraception and a pregnancy is diagnosed (failed tubal ligation) there is a 35% chance that the pregnancy is in the tube and a 65% chance that it is in the uterus. If there is an intrauterine device (IUD) and pregnancy occurs, there is a 50% chance that the pregnancy may be ectopic. In such cases of failed contraception, it is important to know that the risk of having an ectopic pregnancy is high. It should also be noted that some of the failed contraception related pregnancies can be intrauterine and totally normal.
If a patient misses her period, the first test to be done is a pregnancy test. If the test is positive and there is abdominal pain or vaginal spotting/bleeding, ectopic pregnancy should be ruled out. Pain is relatively common in ectopic pregnancy and can be in the form of cramping (similar to menstrual cramps) or lower abdominal/pelvic pain. Bleeding can be in the form of heavy bleeding (similar to a period or an early miscarriage) or very light (similar to the last few days of a regular period). Bleeding is due to the hormonal stimulation of the uterine (endometrial) cells that continue to grow even though the pregnancy is not in the uterus, but in the fallopian tube. Such hormone stimulation of the uterus can result in a circular structure called the pseudosac. This structure is similar to a normal 5 week intrauterine pregnancy and in some cases can be mistaken for an early normal intrauterine pregnancy. The presence of a yolk sac (ring type of structure) inside “the sac” or a fetal pole rules out an ectopic pregnancy.
In some cases, shoulder pain can be the main complaint which is due to bleeding from the end of the tube (not necessarily ruptured tube) that travels to the upper part of the abdomen. Blood can irritate the phrenic nerve in this area and cause shoulder or back pain. Other symptoms include dizziness and fainting, which suggest profound intraabdominal bleeding. In such cases, emergency surgery needs to be done to save the patient’s life.
It’s important to suspect the presence of an ectopic pregnancy in high risk patients such as women with a history of ectopic pregnancy, prior tubal surgery, pelvic adhesions, infertility, sexually transmitted or pelvic inflammatory diseases. In some cases, there is no prior history or risk factors involved but ectopic pregnancy is still observed.
Ectopic pregnancy is generally diagnosed by serial measurements of the pregnancy hormone called beta hCG and a pelvic vaginal ultrasound. Beta hCG hormone levels double every 2-3 days in the first 6-8 weeks of a normal pregnancy. In 10% of normal pregnancies beta hCG levels may not double every 2-3 days, making the diagnosis of a normal pregnancy difficult. Conversely, in 10% of ectopic pregnancies beta hCG levels may double appropriately, mimicking a normal pregnancy.
A vaginal pelvic ultrasound is very helpful in differentiating a normal pregnancy from an ectopic pregnancy in most cases. In very early pregnancies, it can be difficult to visualize the pregnancy in the uterus. If the beta hCG level is above 1500, an intrauterine pregnancy can be seen with vaginal ultrasound. Especially if a yolk sac or a fetal pole is observed, ectopic pregnancy is ruled out. If there is no gestational sac or there is a gestational sac or pseudosac (may look like a normal pregnancy), but there are no other structures (yolk sac or fetal pole) suggesting a pregnancy in the uterus, ectopic pregnancy is highly suspected or diagnosed.
On ultrasound, presence of blood in the pelvic cavity can be visualized and depending on the amount, it can be diagnostic of bleeding from the end of the tube (without rupture) or a full blown ruptured ectopic pregnancy. In some cases, the diagnosis can be difficult because there can be blood in the pelvis but the tube may still be intact. In others, small amounts of blood may be due to a torn tube from the ectopic. For this reason, a historic intervention called culdocentesis (withdrawal of blood with a syringe from the pelvic cavity through vaginal approach) is no longer performed because the presence of blood does not confirm or rule out a ruptured ectopic pregnancy. In some cases of early miscarriage, similar symptoms can be observed and complicate the diagnosis and clinical treatment approach. In such cases, beta hCG levels and ultrasound finings are very helpful in following patients to make sure that they don’t have an ectopic pregnancy.
Ectopic pregnancy can be managed expectantly, medically by the use of Methotrexate or surgically through laparoscopy or open abdominal surgery called laparotomy.
Expectant management includes careful monitoring of symptoms, measurement of beta hCG levels and ultrasound examinations. If there is no change in the clinical status and beta hCG levels are steadily decreasing, expectant management is appropriate. Approximately, 10-15% of all ectopic pregnancies can be managed expectantly and the long term outcome for pregnancy (risk of ectopic or intrauterine) is similar to medical and surgical interventions.
Medical management of ectopic pregnancy includes the administration of a chemotherapeutic agent called Methotrexate (MTX) intramuscularly in clinically stable patients. MTX destroys rapidly dividing cells, such as those present in an early pregnancy and side effects are limited because of the low dose of medication used.
In some cases, multiple injections of MTX may be necessary if the beta hCG levels do not decrease over time. However, in most cases a single injection is adequate enough for complete resolution of symptoms. The chances of success depend on many variables but mostly the initial beta hCG level with higher success rates observed with lower beta hCG levels. Blood work is done prior to administration of the drug, and beta hCG levels are checked 4 and 7 days following MTX injection. If the beta hCG levels do not drop at least 15% from day 4 to 7, a second injection is given and hormone levels are checked again in a similar schedule to make sure that the levels are decreasing.
Following administration of the drug, patients need to be monitored for signs of rupture. In some cases, ectopic pregnancy can tear/rupture the tube despite medical intervention. Some pain and bleeding following MTX treatment is relatively common, but if it’s excessive, patients need to go to the nearest emergency room for immediate evaluation and treatment.
In IVF cases, embryos are injected into the uterine cavity and one or more embryos can be sucked back into the fallopian tubes (due to the negative pressure in the abdomen). In such cases, treatment is the same as a naturally occurring ectopic pregnancy.
Medical management is not suitable for all ectopic pregnancies. The following include contraindications to medical management and require surgical intervention:
Clinically unstable patient
Non-compliant patient with possible poor follow up
Alcoholism, liver disease, kidney disease, active lung disease
Anemia or other blood disorders
Allergy or sensitivity to Methotrexate
Stomach or intestinal ulcers
Surgical management of ectopic pregnancy is a less common initial approach, due to the advent of medical treatment using MTX. If medical or expectant management are not options, surgical treatment using the minimally invasive surgical approach called laparoscopy becomes the best option. Most commonly, ectopic pregnancy is removed without the removal of the entire tube with a procedure called linear salpingostomy. Laparoscopically, an incision is made on the tube, ectopic pregnancy tissue is removed and then tube is irrigated and bleeding is controlled. The fallopian tube then heals on its own over time and in most cases remains functional. In some cases, the tubes may be severely damaged or the bleeding is excessive during surgery and removal of the tube along with the ectopic mass may be more appropriate. This type of a surgical intervention is called laparoscopic salpingectomy. If the other tube is normal, patients can become pregnant regardless of the ovulation site (right or left ovary).
In cases of an emergency with suspected excessive blood loss, in clinically unstable patients or non-responsive patients, blood transfusion and immediate open abdominal surgery (laparotomy) can be life-saving measures. In most cases, laparoscopy instead of laparotomy can be performed safely even in ruptured ectopic cases, although the clinical decision is made by the surgeon at that time based on each individual case.
Heterotopic pregnancy is the co-existence of a normal intrauterine and an ectopic pregnancy with an incidence of 1 in 15,000 pregnancies. It is more common following IVF treatment because one of the embryos may implant into the tube and the other into the uterus. Expectant and medical treatments are not management options for heterotopic pregnancies. Surgical removal of the ectopic tissue or removal of the entire tube laparoscopically or through laparotomy is the appropriate treatment.
The outcome of pregnancy following treatment of an ectopic pregnancy is similar with all treatment options. The tube remains open in 80% of cases with 50-75% intrauterine and 15% ectopic pregnancy rates. Any patient with a history of a prior ectopic pregnancy should have a pregnancy test with missed periods and immediately seek medical attention to document the pregnancy in the uterus. Until the pregnancy is documented to be in the uterus, an ectopic pregnancy should be suspected and beta hCG levels measured along with a pelvic ultrasound.