An ectopic pregnancy is one in which the fertilized ovum (egg) is implanted in any tissue other than the uterine wall. Most ectopic pregnancies occur in the Fallopian tube (so-called tubal pregnancies), but implantation also can occur in the cervix, ovaries, and abdomen.
In a normal pregnancy, the fertilized egg enters the uterus and settles into the uterine lining where it has plenty of room to divide and grow. About 1% of pregnancies are in an ectopic location with implantation not occurring inside of the womb; of these, 98% occur in the Fallopian tubes.
In a typical ectopic pregnancy, the embryo does not reach the uterus, but instead adheres to the lining of the Fallopian tube. The implanted embryo burrows actively into the tubal lining. Most commonly this invades vessels and will cause bleeding. This bleeding expels the implantation out of the tubal end as a tubal abortion. Some women who suspect that they are having a miscarriage are actually having a tubal abortion. There is no inflammation of the tube in ectopic pregnancy. The pain is caused by prostaglandins released at the implantation site, and by free blood in the peritoneal cavity, which is locally an irritant. Sometimes the bleeding might be heavy enough to threaten the health or life of the woman. Usually this degree of bleeding is due to a delay in diagnosis, but sometimes, especially if the implantation is in the proximal tube (just before it enters the uterus), it may invade into the Sampson artery, causing heavy bleeding earlier than usual.
If left untreated, about half of ectopic pregnancies will resolve without treatment. These are the tubal abortions. The advent of methotrexate treatment for ectopic pregnancy has reduced the need for surgery, yet surgical intervention is still required in cases where the Fallopian tube has ruptured or is in danger of doing so. This intervention may be laparoscopic or through a larger incision, known as a laparotomy.
The causes of ectopic pregnancy are unknown. After fertilization of the oocyte in the peritoneal cavity, the egg takes about 9 days to migrate down the tube to the uterine cavity, at which time it implants. Wherever the embryo finds itself at that time, it will begin to implant.
There are some speculative specific causes or associations. Smoking, advanced maternal age, and prior tubal damage of any origin are known risk factors for ectopic pregnancy.
Cilial Damage and Tube Occlusion
Hair-like cilia located on the internal surface of the Fallopian tubes carry the fertilized egg to the uterus. Damage to the cilia or blockage of the Fallopian tubes is likely to lead to an ectopic pregnancy. Women with pelvic inflammatory disease (PID) have a high occurrence of ectopic pregnancy. This results from the build-up of scar tissue in the Fallopian tubes, causing damage to cilia. If, however, both tubes were occluded by PID, pregnancy would not occur and this would be protective against ectopic pregnancy. Tubal surgery for damaged tubes might remove this protection and increase the risk of ectopic pregnancy. Tubal ligation can predispose a woman to ectopic pregnancy. Seventy percent of pregnancies after tubal cautery are ectopic, while 70% of pregnancies after tubal clips are intrauterine. Reversal of tubal sterilization (tubal reversal) carries a risk for ectopic pregnancy. This is higher if more destructive methods of tubal ligation (tubal cautery, partial removal of the tubes) have been used than less destructive methods (tubal clipping). A history of ectopic pregnancy increases the risk of future occurrences to about 10%. This risk is not reduced by removing the affected tube, even if the other tube appears normal.
Excessive Estrogen and Progesterone
There has been speculation about the role of hormones in the genesis of ectopic pregnancy. No proven association has been established. High levels of estrogen and progesterone are thought possibly to increase the risk of ectopic pregnancy, because these hormones slow the movement of the fertilized egg through the Fallopian tube. Advancing age is a risk factor for ectopic pregnancy, however, even though this is a period of declining hormone levels.
Role of Intrauterine Devices (IUD)
The use of IUDs was thought at one time to increase the risk of ectopic pregnancy. Yet the older model, copper-based IUDs were only effective in preventing intrauterine pregnancies, not tubal pregnancies. As the IUD is effective in reducing pregnancy overall, the relative risk only of ectopic is increased. The old copper-based IUDs reduced the overall pregnancy rate so effectively that even the gross ectopic rates were reduced. Nonetheless any pregnancy conceived with an IUD in situ must be investigated to exclude possible ectopic pregnancy.
The newer hormone-based (levonorgestrel) intrauterine system (IUS) creates such a profound suppression of the endometrium that the overall pregnancy rate is lower even than that of male or female sterilization. There are some data available for ectopic pregnancy with the IUS, but the relative risk is extremely low, approximately 0.01%.
Association with Infertility
Infertility treatments are highly variable and specific to individual patients. In vitro fertilization (IVF) is used for patients with damaged tubes, which are an inherent risk factor for ectopic pregnancy. Ectopic pregnancies have been seen with IVF, but this is uncommon and quickly diagnosed by the early ultrasounds that these intensively surveyed patients undergo.
Patients are at higher risk for ectopic pregnancy with advancing age. Also, it has been noted that smoking is associated with ectopic risk. Vaginal douching is thought by some to increase ectopic pregnancies. Women exposed to diethylstilbestrol (DES) in utero (aka "DES daughters") also have an elevated risk of ectopic pregnancy, up to three times the risk of unexposed women.
Early symptoms are either absent or subtle. Clinical presentation of ectopic pregnancy occurs at a mean of 7.2 weeks after the last normal menstrual period, with a range of 5 to 8 weeks. Later presentations are more common in communities deprived of modern diagnostics.
The early signs are:
Pain and discomfort, usually mild. A corpus luteum on the ovary in a normal pregnancy may give very similar symptoms
Vaginal bleeding, usually mild. An ectopic pregnancy is usually a failing pregnancy, and falling levels of progesterone from the corpus luteum on the ovary cause withdrawal bleeding. This can be indistinguishable from an early miscarriage or the “implantation bleed” of a normal early pregnancy.
Patients with a late ectopic pregnancy typically have pain and bleeding. This bleeding will be both vaginal and internal and has two discrete pathophysiologic mechanisms.
External bleeding is due to the falling progesterone levels.
Internal bleeding is due to hemorrhage from the affected tube.
The differential diagnosis at this point is between miscarriage, ectopic pregnancy, and early normal pregnancy. The presence of a positive pregnancy test virtually rules out pelvic infection, as it is rare to find pregnancy with an active pelvic inflammatory disease (PID). The most common misdiagnosis assigned to early ectopic pregnancy is PID.
More severe internal bleeding may cause:
Lower back, abdominal, or pelvic pain
Shoulder pain, caused by free blood tracking up the abdominal cavity, an ominous sign
Cramping or tenderness on one side of the pelvis
The pain is of recent onset, meaning it must be differentiated from cyclical pelvic pain, and is often getting worse
Ectopic pregnancy can mimic symptoms of other diseases such as appendicitis, gastrointestinal disorders, problems of the urinary system, as well as pelvic inflammatory disease and other gynecologic problems.
An ectopic pregnancy has to be suspected in any woman with lower abdominal pain and/or unusual bleeding who is or might be sexually active and whose pregnancy test is positive. An abnormal rise in blood human chorionic gonadotropin (HCG) levels also may indicate an ectopic pregnancy. The threshold of discrimination of intrauterine pregnancy today is around 3000 IU/mL of HCG. A high resolution, vaginal ultrasound scan showing no intrauterine pregnancy is presumptive evidence that an ectopic pregnancy is present if the threshold of discrimination for HCG has been reached. An empty uterus with levels lower than 3000IU/mL may be evidence of an ectopic pregnancy but may also be consistent with an intrauterine pregnancy that is too small to be seen on ultrasound. If there is uncertainty, it might be necessary to wait a few days and repeat the bloodwork and ultrasound.
An ultrasound showing a gestational sac with fetal heart is clear evidence of ectopic pregnancy.
Free fluid that is non-echogenic is a normal finding in the late menstrual cycle and early normal pregnancy. This is a transudate and is not presumptive evidence of bleeding. Echogenic free fluid suggests the presence of blood clot and is suggestive of free blood in the peritoneum.
A laparoscopy or laparotomy also can be performed to visually confirm an ectopic pregnancy. If a tubal abortion or a tubal rupture has occurred, it often is difficult to locate the pregnancy tissue. In rare cases, with laparoscopy that is performed very early in an ectopic pregnancy, the Fallopian tube may appear normal.
Nontubal Ectopic Pregnancy
Two percent of ectopic pregnancies occur in the ovary, cervix, or are intra-abdominal. In most cases, transvaginal ultrasound examination can detect a cervical pregnancy. An ovarian pregnancy is differentiated from a tubal pregnancy by the Spiegelberg criteria.
While a fetus from an ectopic pregnancy is typically not viable, very rarely, an abdominal pregnancy has been salvaged. In such cases, the placenta sits on the intra-abdominal organs or the peritoneum and has obtained a sufficient blood supply. In this author's experience, this is invariably bowel or mesentery, but other sites such as the renal artery, the hepatic artery, or even the aorta have been described. Support to near viability has occasionally been described, but even in third-world countries, the diagnosis is most commonly made at 16 to 20 weeks gestation. Such a fetus would have to be delivered by laparotomy. Maternal morbidity and mortality from extrauterine pregnancy are high, as attempts to remove the placenta from the organs to which it is attached usually lead to uncontrollable bleeding from the attachment site. If the organ to which the placenta is attached is removable, such as a section of bowel, then the placenta should be removed together with that organ. This is such a rare occurrence that true data are unavailable and there has been a reliance on anecdotal reports. The vast majority of abdominal pregnancies require intervention well before fetal viability, however, because of the risk of hemorrhage.
Early treatment of an ectopic pregnancy with the drug methotrexate has proven to be a viable alternative to surgical treatment. If administered early in the pregnancy, methotrexate can disrupt the growth of the developing embryo, causing the cessation of pregnancy.
If hemorrhaging has occurred and there is evidence of continuing blood loss, surgical intervention may be necessary. As already stated, however, about half of ectopic pregnancies result in tubal abortion and are self-limiting. The option to proceed with surgery is thus often a difficult decision to make in the case of an obviously stable patient for whom an ultrasound revealed minimal evidence of a blood clot.
Surgeons use laparoscopy or laparotomy to gain access to the pelvis and can either incise the affected Fallopian and remove only the pregnancy (salpingostomy) or remove the affected tube with the pregnancy (salpingectomy). The first successful surgery for an ectopic pregnancy was performed by Robert Lawson Tait in 1883.
Chances of future pregnancy
The likelihood of future pregnancy is decreased, though it depends on the status of the tube(s) that remain. The chance of recurrent ectopic pregnancy is about 10% and is independent of whether the affected tube was repaired (salpingostomy) or removed (salpingectomy). Successful pregnancy rates vary widely between different centers, and appear to be operator-dependent. Pregnancy rates with successful methotrexate treatment compare favorably with the highest reported pregnancy rates. Often, patients may have to resort to IVF to achieve a successful pregnancy. The use of IVF does not preclude further ectopic pregnancies, but the likelihood is reduced.
The most common complication is rupture with internal bleeding that leads to shock. Death from rupture is rare. Infertility occurs in 10% to 15% of women who have had an ectopic pregnancy.