Ectopic pregnancy

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An ectopic pregnancy is a complication of pregnancy 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. The fetus produces enzymes that allow it to implant in varied types of tissues, and thus an embryo implanted elsewhere than the uterus can cause great tissue damage in its efforts to reach a sufficient supply of blood.

Overview

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. [cite web | author=Serdar Ural | title=Ectopic pregnancy | url=http://www.kidshealth.org/parent/pregnancy_newborn/pregnancy/ectopic.html | month=May | year=2004 | publisher=KidsHealth | accessdate=2006-11-26]

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 intratubal bleeding (hematosalpinx) 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 a local 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 the nearby 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; 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.

Causes

The causes of ectopic pregnancy are unknown. After fertilization of the oocyte in the peritoneal cavity, the egg takes about 6 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 known risk factors for ectopic pregnancyFact|date=August 2007.

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 (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. The best method for diagnosing this is to do an early ultrasound.

Hysterectomy

Ectopic pregnancy occasionally occurs in women who have had a hysterectomy. Rather than implanting in the absent uterus, the embryo implants in the abdomen, and must be removed via caesarean section. [http://www.dailyprincetonian.com/archives/2002/05/08/opinion/5154.shtml] [ [http://content.nejm.org/cgi/content/full/329/16/1174 SA Carson, JE Buster, Ectopic Pregnancy. New Engl J Med 329:1174-1181] ]

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; this is speculative. 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.

Symptoms

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 in the lower abdomen, and inflammation (Pain may be confused with a strong stomach pain, it may also feel like a strong cramp)
* Pain while urinating
* 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.
* Pain while having a bowel movement

Patients with a late ectopic pregnancy typically experience 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 (hematoperitoneum) 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 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.

Diagnosis

An ectopic pregnancy has to be suspected in any woman with lower abdominal pain or unusual bleeding who is or might be sexually active and whose pregnancy test is positive. An abnormal rise in blood βhCG levels may also indicate an ectopic pregnancy. The threshold of discrimination of intrauterine pregnancy today is around 1500 IU/ml of β-human chorionic gonadotropin (βhCG). 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 βhCG has been reached. An empty uterus with levels lower than 1500 IU/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 the diagnosis is uncertain, it may be necessary to wait a few days and repeat the blood work and ultrasound. If the βhCG falls on repeat examination, this strongly suggests an abortion or rupture.

An ultrasound showing a gestational sac with fetal heart in the fallopian tube is clear evidence of ectopic pregnancy.

Free fluid which 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 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 difficult to find the pregnancy tissue. A laparoscopy in very early ectopic pregnancy rarely shows a normal looking fallopian tube.

A less commonly performed test, a culdocentesis, may be used to look for internal bleeding. In this test, a needle is inserted into the space at the very top of the vagina, behind the uterus and in front of the rectum. Any blood or fluid found there likely comes from a ruptured ectopic pregnancy.

Cullen's sign can indicate a ruptured ectopic pregnancy.

Nontubal ectopic pregnancy

Two percent 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. [WhoNamedIt|synd|2274|Spiegelberg's criteria]

While a fetus of ectopic pregnancy is typically not viable, very rarely, a live baby has been salvaged from an abdominal pregnancy. In such a situation the placenta sits on the intraabdominal organs or the peritoneum and has found sufficient blood supply. This is generally 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 fetus 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. [cite news | title='Special' baby grew outside womb | url=http://news.bbc.co.uk/1/hi/england/beds/bucks/herts/4197194.stm | date=2005-08-30 | publisher=BBC news | accessdate=2006-07-14] [cite news | title="Bowel baby born safely
url=http://news.bbc.co.uk/2/hi/health/671390.stm | date=2005-03-09 |publisher=BBC news | accessdate=2006-11-10] However, the vast majority of abdominal pregnancies require intervention well before fetal viability because of the risk of hemorrhage.

On 19 April 2008 an English woman, Jayne Jones (age 37) who had an ectopic pregnancy attached to the omentum, the fatty covering of her large bowel, gave birth. The baby was delivered by a laparotomy at 28 weeks gestation. The surgery, the first of its kind to be performed in the UK, was successful, and both mother and baby survived. [cite news | first= | last= | coauthors= | title=Miracle baby Billy grew outside his mother's womb | date=2008-08-31| publisher=Daily Mail | url =http://www.dailymail.co.uk/femail/article-1050942/Miracle-baby-Billy-grew-outside-mothers-womb.html| work = | pages = | accessdate = 2008-09-03 | language = ]

On May 29, 2008 an Australian woman, Meera Thangarajah (age 34), who had an ectopic pregnancy in the ovary, gave birth to a healthy full term 6 pound 3 ounce (2.8 kg) baby girl, Durga, via Caesarean section. She had no problems or complications during the 38 week pregnancy. [cite news | first= | last= | coauthors= | title=Baby Born After Rare Ovarian Pregnancy | date=2008-05-30| publisher=Associated Press | url =http://ap.google.com/article/ALeqM5h7An_4HQLG6rSVO-h1eBIntgYOyAD90VRLKO1 | work = | pages = | accessdate = 2008-05-30 | language = ] [cite news | first=Rebekah | last=Cavanagh | coauthors= | title=Miracle baby may be a world first | date=2008-05-30 | publisher= | url =http://www.news.com.au/story/0,23599,23782145-2,00.html | work = | pages = | accessdate = 2008-05-30 | language = ]

Heterotopic Pregnancy

In rare cases of ectopic pregnancy, there may actually be two fertilized eggs, one outside the uterus and the other inside. This is called a heterotopic pregnancy. Often the intrauterine pregnancy is discovered later than the ectopic, mainly because of the painful, emergency nature of ectopic pregnancies. Since ectopic pregnancies are normally discovered and removed very early in the pregnancy, an ultrasound may not find the additional pregnancy inside the uterus. When hCG levels continue to rise after the removal of the ectopic pregnancy, there is the chance that a pregnancy inside the uterus is still viable. This is normally discovered through an ultrasound.

Although rare, with the continual increase of IVFs, heterotopic pregnancies are becoming more and more common. However, these pregnancies are still considered moderate to high risk. The survival rate of the uterine fetus of an ectopic pregnancy is around 70%. [http://answers.google.com/answers/threadview?id=568935]

[http://news.bbc.co.uk/1/hi/health/443373.stm This link] describes a case of a burst tubal pregnancy continuing by the placenta implanting on the outside of the uterus, plus intra-uterine twins; laparotomy rescued three live babies. The intra-uterine twins were removed first.

Treatment

Nonsurgical treatment

Early treatment of an ectopic pregnancy with the antimetabolite methotrexate has proven to be a viable alternative to surgical treatmentcite journal |author=Mahboob U, Mazhar SB |title=Management of ectopic pregnancy: a two-year study |journal=Journal of Ayub Medical College, Abbottabad : JAMC |volume=18 |issue=4 |pages=34–7 |year=2006 |pmid=17591007 |doi=] since 1993Fact|date=September 2007 (though the literature dates back to at least 1989).cite journal |author=Clark L, Raymond S, Stanger J, Jackel G |title=Treatment of ectopic pregnancy with intraamniotic methotrexate--a case report |journal=The Australian & New Zealand journal of obstetrics & gynaecology |volume=29 |issue=1 |pages=84–5 |year=1989 |pmid=2562613 |doi=] If administered early in the pregnancy, methotrexate can disrupt the growth of the developing embryo causing the cessation of pregnancy.

Surgical treatment

If hemorrhaging 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). The first successful surgery for an ectopic pregnancy was performed by Robert Lawson Tait in 1883. [cite web |url=http://www.emedicine.com/med/byname/Surgical-Management-of-Ectopic-Pregnancy.htm |title=eMedicine - Surgical Management of Ectopic Pregnancy : Article Excerpt by R Daniel Braun |accessdate=2007-09-17 |format= |work=]

Chances of future pregnancy

The chance of future pregnancy depends on the status of the adnexa left behind. The chance of recurrent ectopic pregnancy is about 10% and depends on whether the affected tube was repaired (salpingostomy) or removed (salpingectomy). Successful pregnancy rates vary widely between different centries, 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 in vitro fertilisation to achieve a successful pregnancy. The use of in vitro fertilisation does not preclude further ectopic pregnancies, but the likelihood is reduced.

Complications

The most common complication is rupture with internal bleeding that leads to shock. Death from rupture is rare in women who have access to modern medical facilities. Infertility occurs in 10 - 15% of women who have had an ectopic pregnancy.

References

External links

* [http://www.ectopic.org.uk The Ectopic Pregnancy Trust] - Information and support for those who have suffered the condition by a medically overseen and moderated, UK based charity, recognised by the National Health Service (UK) Department of Health (UK) and [http://www.rcog.org.uk/ The Royal College of Obstetricians and Gynaecologists]