An ectopic pregnancy is one in which the fertilized ovum is implanted in any tissue other than the uterine wall. Most ectopic pregnancies occur in the Fallopian tube (so-called tubal pregnancies), but implantation can also occur in the cervix, ovaries, and abdomen.
An Overview of ectopic pregnancy
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, and 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 thinking 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 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 delay in diagnosis, but sometimes, especially if the implantation is in the proximal tube (just before it enters the uterus), it may invade into Sampson's 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; however, 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.
What causes an ectopic pregnancy
The cause of ectopic pregnancy is unknown. After fertilization of the oocyte in the peritoneal cavity, the egg takes about nine 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 well shown 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 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 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 oestrogen 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 oestrogen 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. However, advancing age is a risk factor for ectopic pregnancy, although this is a period of declining hormone levels.
Role of intrauterine devices (IUD)
The use of intrauterine devices (IUDs) was thought at one time to increase the risk of ectopic pregnancy. However the older model copper based IUDs were only effective in preventing intrauterine pregnancies, not tubal pregnancies. As the IUD is effective in reducing pregnacy 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) IUS creates such a profound suppression of the endometrium that 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, around 0.01%.
Association with infertility
Infertility treatments are highly variable and specific to individual patients. IVF is used for patients with damaged tubes which are an inherent risk factor for ectopic. Ectopic pregnancies have been seen with In Vitro Fertilization, but is uncommon and quickly diagnosed by the early ultrasounds that these intensively surveyed patients undergo.
Other
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 3 times the risk of unexposed women.
What are the symptoms of an ectopic pregnancy
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 diagnostic ability.
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 miscarraige 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 indeed 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. This is caused by free blood tracking up the abdominal cavity, and is an ominous sign.
- There may be cramping or even 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 is noted that it can mimic symptoms of other diseases such as appendicitis, other gastrointestinal disorder, problems of the urinary system, as well as pelvic inflammatory disease and other gynaecologic problems.
How is an ectopic pregnancy diagnosed ?
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. And abnormal rise in blood hCG levels may also indicate an ectopic pregnancy. The threshold of discrimination of intrauterine pregnancy today is around 3000 IU/ml of Human Chorionic Gonadotropin (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 which is simply 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 foetal heart is clear evidence of ectopic pregnancy.
Free fluid which is non echogenic is a normal finding in the late menstrual cycle and early normal pregnacy. 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 can also be performed to visually confirm an ectopic pregnancy. Often if a tubal abortion has occurred, or a tubal rupture has occurred, it is hard actually to find the pregnancy tissue. Laparoscopy in very early ectopic pregnancy may rarely show a normal looking Fallopian tube.
Nontubal ectopic pregnancy
2% of ectopic pregnancies occur in the ovary, cervix, or are intraabdominal. Transvaginal ultrasound examination is usually able to detect a cervical pregnancy. An ovarian pregnancy is differentiated from a tubal pregnancy by the Spiegelberg criteria.
While a foetus of ectopic pregnancy is typically not viable, very rarely, an abdominal pregnancy has been salvaged. In such a situation the placenta sits on the intraabdominal organs or the peritoneum and has found sufficient blood supply. In this author's experience this is invariably bowel or mesentery, but other sites, such as the renal (kidney), liver or hepatic (liver) artery or even 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 foetus would have to be delivered by laparotomy. Maternal morbidity and mortality from extrauterine pregnancy is 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 reliance must be made on anecdotal reports. However, the vast majority of abdominal pregnancies require intervention well before fetal viability because the risk of hemorrhage.
Treatment of ectopic pregnancy
Nonsurgical treatment
Early treatment of an ectopic pregnancy with the drug methotrexate has proven to be a viable alternative to surgical treatment since 1993. If administered early in the pregnancy, methotrexate can disrupt the growth of the developing embryo causing the cessation of pregnancy.
Surgical treatment
If haemorrhaging has already occurred, surgical intervention may be necessary if there is evidence of ongoing blood loss. However, as already stated, about half of ectopics result in tubal abortion and are self limiting. The option to go to surgery is thus often a difficult decision to make in an obviously stable patient with minimal evidence of blood clot on ultrasound.
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).
Chances of future pregnancy after an ectopic pregnancy
The chance of future pregnancy depends on the status of the tube(s) that are left behind, but is decreased. 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 centres, and appear to be operator dependent. Pregnancy rates with successful methotrexate treatment compare favourably 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.
Complications with ectopic pregnancy
The most common complication is rupture with internal bleeding that leads to shock. Death from rupture is rare. Infertility occurs in 10 - 15% of women who have had an ectopic pregnancy.
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