Ectopic pregnancy

Ectopic pregnancy
Classification and external resources

Ectopic by Reinier de Graaf
ICD-10 O00.
ICD-9 633
DiseasesDB 4089
MedlinePlus 000895
eMedicine med/3212 emerg/478 radio/231
MeSH D011271

An ectopic pregnancy, or eccyesis, is a complication of pregnancy in which the pregnancy implants outside the uterine cavity.[1] With rare exceptions, ectopic pregnancies are not viable. Furthermore, they are dangerous for the mother, internal bleeding being a common complication. Most ectopic pregnancies occur in the Fallopian tube (so-called tubal pregnancies), but implantation can also occur in the cervix, ovaries, and abdomen. An ectopic pregnancy is a potential medical emergency, and, if not treated properly, can lead to death.

Contents

Overview

Ruptured tubal pregnancy with approx 6-weeks-embryonic-age or 8-weeks-gestational-age embryo, with intact amniotic sac
Oviduct with an ectopic pregnancy (tubal pregnancy) showing an embryo of approx. 6-7 menstrual weeks
Tubal pregnancy necessitating removal of fallopian tube (fetus is 8 weeks gestational age, 6 weeks from conception)

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.[2]

In other words it can be said that in an ectopic pregnancy the embryonic implantation occurs outside the uterus, most commonly in the fallopian tubes but at times also in the extra tubal locations. It poses serious threat to the general and reproductive health of the mother.

Ectopic pregnancy comprises 2% of all pregnancies reported to the Center for Disease Control and Prevention (CDC).

It has been noted that ectopic pregnancy is steadily and persistently rising since 1970; between 1970 and 1992, the rate of ectopic pregnancy increased from 4.5 to 19.7 per 1000 reported pregnacies (including live birth, legal abortions and ectopic pregnancies).[3][4]

Detection of ectopic pregnancy in early gestation has been achieved mainly due to enhanced diagnostic capability.

Despite all these notable successes in diagnostics and detection techniques ectopic pregnancy remains a source of serious maternal morbidity and mortality all over the world.

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.

Classification

Tubal pregnancy

The vast majority of ectopic pregnancies implant in the Fallopian tube. Pregnancies can grow in the fimbrial end (5% of all ectopics), the ampullary section (80%), the isthmus (12%), and the cornual and interstitial part of the tube (2%).[5] Mortality of a tubal pregnancy at the isthmus or within the uterus (interstitial pregnancy) is higher as there is increased vascularity that may result more likely in sudden major internal hemorrhage. A review published in 2010 supports the hypothesis that tubal ectopic pregnancy is caused by a combination of retention of the embryo within the fallopian tube due to impaired embryo-tubal transport and alterations in the tubal environment allowing early implantation to occur. [6]

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.[7]

While a fetus of ectopic pregnancy is typically not viable, very rarely, a live baby has been delivered 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.[8][9][10] However, the vast majority of abdominal pregnancies require intervention well before fetal viability because of the risk of hemorrhage.

Heterotopic pregnancy

In rare cases of ectopic pregnancy, there may 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, heterotopic pregnancies are becoming more common. The survival rate of the uterine fetus of an ectopic pregnancy is around 70%.[11]

Successful pregnancies have been reported from ruptured tubal pregnancy continuing by the placenta implanting on abdominal organs or on the outside of the uterus.

Persistent ectopic pregnancy

A persistent ectopic pregnancy refers to the continuation of trophoplastic growth after a surgical intervention to remove an ectopic pregnancy. After a conservative procedure that attempts to preserve the affected fallopian tube such as a salpingotomy, in about 15-20% the major portion of the ectopic may have been removed, but some trophoblastic tissue perhaps deeply embedded has escaped removal and continues to growth, generating a new rise in hCG levels.[12] After weeks this may lead to new clinical symptoms including bleeding. For this reason hCG levels may have to be monitored after removal of an ectopic to assure their decline, also methotrexate can be given at the time of surgery prophyllactically.

Signs and 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.

Early signs include:

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:

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:

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.

Causes

There are a number of risk factors for ectopic pregnancies. However, in as many as one third[13] to one half[14] of ectopic pregnancies, no risk factors can be identified. Risk factors include: pelvic inflammatory disease, infertility, use of an intrauterine device (IUD), endometriosis, those who have been exposed to DES, tubal surgery, intrauterine surgery (e.g. D&C), smoking, previous ectopic pregnancy, and tubal ligation.[15]

Cilial damage and tube occlusion

Hair-like cilia located on the internal surface of the Fallopian tubes carry the fertilized egg to the uterus. Fallopian cilia are sometimes seen in reduced numbers subsequent to an ectopic pregnancy, leading to a hypothesis that cilia damage in the Fallopian tubes is likely to lead to an ectopic pregnancy.[16] Women with pelvic inflammatory disease (PID) have a high occurrence of ectopic pregnancy.[17] This results from the build-up of scar tissue in the Fallopian tubes, causing damage to cilia.[5] If however both tubes were completely blocked, so that sperm and egg were physically unable to meet, then fertilization of the egg would naturally be impossible, and neither normal pregnancy nor ectopic pregnancy could occur. Tubal surgery for damaged tubes might remove this protection and increase the risk of ectopic pregnancy. Intrauterine adhesions (IUA) present in Asherman's syndrome can cause ectopic cervical pregnancy or, if adhesions partially block access to the tubes via the ostia, ectopic tubal pregnancy.[18] [19] [20] Asherman's syndrome usually occurs from intrauterine surgery, most commonly after D&C.[18] Endometrial/pelvic/genital tuberculosis, another cause of Asherman's syndrome, can also lead to ectopic pregnancy as infection may lead to tubal adhesions in addition to intrauterine adhesions.[21]

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 a tubal pregnancy increases the risk of future occurrences to about 10%.[5] 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.

Other

Although some investigations have shown that patients may be at higher risk for ectopic pregnancy with advancing age, it is believed that age is a variable which could act as a surrogate for other risk factors. Also, it has been noted that smoking is associated with ectopic risk. Vaginal douching is thought by some to increase ectopic pregnancies.[5] 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. It has also been suggested that pathologic generation of nitric oxide through increased iNOS production may decrease tubal ciliary beats and smooth muscle contractions and thus affect embryo transport, which may consequently result in ectopic pregnancy.[22]

Diagnosis

An ectopic pregnancy should be considered in any woman with abdominal pain or vaginal bleeding who has a positive pregnancy test. An ultrasound showing a gestational sac with fetal heart in the fallopian tube is clear evidence of ectopic pregnancy.

An abnormal rise in blood β-human chorionic gonadotropin (β-hCG) levels may indicate an ectopic pregnancy. The threshold of discrimination of intrauterine pregnancy is around 1500 IU/ml of β-hCG. A high resolution, transvaginal ultrasound showing no intrauterine pregnancy is presumptive evidence that an ectopic pregnancy is present if the threshold of discrimination for β-hCG has been reached. An empty uterus with levels higher 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. This can be done by measuring the β-hCG level approximately 48hrs later and repeating the ultrasound. If the β-hCG falls on repeat examination, this strongly suggests a spontaneous abortion or rupture.

A laparoscopy or laparotomy can also be performed to visually confirm an ectopic pregnancy. Often if a tubal abortion or 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.

Culdocentesis, in which fluid is retrieved from the space separating the vagina and rectum, is a less commonly performed test that 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 may have been derived from a ruptured ectopic pregnancy.

Cullen's sign can indicate a ruptured ectopic pregnancy.

Treatment

Medical

Early treatment of an ectopic pregnancy with methotrexate is a viable alternative to surgical treatment[23] since at least 1993.[24] If administered early in the pregnancy, methotrexate terminates the growth of the developing embryo; this may cause an abortion, or the tissue may then be either resorbed by the woman's body or pass with a menstrual period.

Surgical

If hemorrhage has already occurred, surgical intervention may be necessary. However, whether to pursue surgical intervention is an often difficult decision in a 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.[25]

Complications

The most common complication is rupture with internal haemorrhage which may lead to hypovolaemic 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.

Prognosis

Future fertility

Fertility following ectopic pregnancy depends upon several factors, the most important of which is a prior history of infertility.[26] The treatment choice, whether surgical or nonsurgical, also plays a role. For example, the rate of intrauterine pregnancy may be higher following methotrexate compared to surgical treatment.[27] Rate of fertility may be better following salpingostomy than salpingectomy.[27]

Cases with live birth

There have been cases where ectopic pregnancy lasted many months and ended in a live baby delivered by laparotomy.

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.[28]

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.[29][30]

The case of Olivia, Mary and Ronan had an extrauterine fetus (Ronan) and intrauterine twins. All three survived. The intrauterine twins were taken out first.[31]

In other animals

Ectopic gestation exists in other mammals.

In sheep, it can go to term, with mammary preparation to parturition, and expulsion efforts.

The foetus can be removed by caesarian section.

Pictures of caesarian section of a ewe, 5 days after parturition signs.

Leg of fetal lamb appearing out of the uterus during cesarian section.

External view of fetal sac, necrotic distal part.

Internal view of fetal sac, before resection of distal necrotic part.

Internal view of fetal sac, the necrotic distal part is to the left.

External side of fetal sac, proximal end, with ovary and uterine horn.

Resected distal part of fetal sac, with attached placenta.

References

  1. ↑ Page EW, Villee CA, Villee DB. Human Reproduction, 2nd Edition. W. B. Saunders, Philadelphia, 1976. p. 211. ISBN 0-7216-7042-3. 
  2. ↑ Serdar Ural (May 2004). "Ectopic pregnancy". KidsHealth. http://www.kidshealth.org/parent/pregnancy_newborn/pregnancy/ectopic.html. Retrieved 2006-11-26. 
  3. ↑ Riviere L, Culpeper N, Cole A, Rowland W. On Barrenness.In The Practice of Physick, Book 15.London:Peter Code,1658;131, p.916.
  4. ↑ Gream GT. Dilatation or division of the cervix uteri. Lancet 1865;1:381
  5. ↑ 5.0 5.1 5.2 5.3 Speroff L, Glass RH, Kase NG. Clinical Gynecological Endocrinology and Infertility, 6th Ed.. Lippincott Williams & Wilkins (1999). p. 1149ff. ISBN 0-683-30379-1. 
  6. ↑ Shaw JL, Dey SK, Critchley HO, Horne AW (January 2010). "Current knowledge of the aetiology of human tubal ectopic pregnancy". Hum Reprod Update 16 (4): 432–44. doi:10.1093/humupd/dmp057. PMID 20071358. 
  7. ↑ Spiegelberg's criteria at Who Named It?
  8. ↑ "'Special' baby grew outside womb". BBC news. 2005-08-30. http://news.bbc.co.uk/1/hi/england/beds/bucks/herts/4197194.stm. Retrieved 2006-07-14. 
  9. ↑ ""Bowel baby born safely". BBC news. 2005-03-09. http://news.bbc.co.uk/2/hi/health/671390.stm. Retrieved 2006-11-10. 
  10. ↑ Zhang J, Li F, Sheng Q (2008). "Full-term abdominal pregnancy: a case report and review of the literature". Gynecol. Obstet. Invest. 65 (2): 139–41. doi:10.1159/000110015. PMID 17957101. 
  11. ↑ http://answers.google.com/answers/threadview?id=568935
  12. ↑ Kemmann E, Trout S, Garcia A (February 1994). "Can we predict patients at risk for persistent ectopic pregnancy after laparoscopic salpingotomy?". The Journal of the American Association of Gynecologic Laparoscopists 1 (2): 122–126. doi:10.1016/S1074-3804(05)80774-1. PMID 9050473. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7W6G-4KFTB5B-6&_user=10&_coverDate=02%2F28%2F1994&_rdoc=1&_fmt=high&_orig=article&_cdi=28550&_sort=v&_docanchor=&view=c&_ct=432&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ebbee42acb01b64a9d7df19cba0ab1c0. Retrieved January 22, 2010. 
  13. ↑ C.M. Farquhar, Ectopic Pregnancy, Lancet 366 (2005), p. 583
  14. ↑ J Indian Med Assoc. 2007 Jun;105(6):308, 310, 312 passim
  15. ↑ "BestBets: Risk Factors for Ectopic Pregnancy". http://www.bestbets.org/bets/bet.php?id=921. 
  16. ↑ Lyons RA, Saridogan E, Djahanbakhch O (2006). "The reproductive significance of human Fallopian tube cilia". Hum Reprod Update. 12 (4): 363–72. doi:10.1093/humupd/dml012. PMID 16565155. 
  17. ↑ Tay JI, Moore J, Walker JJ (2000). "Ectopic pregnancy". West J Med. 173 (2): 131–4. doi:10.1136/ewjm.173.2.131. PMID 10924442. 
  18. ↑ 18.0 18.1 Schenker JG, Margalioth EJ. (1982). "Intra-uterine adhesions: an updated appraisal". Fertility and Sterility 37 (5): 593–610.. PMID 6281085. 
  19. ↑ Klyszejko C, Bogucki J, Klyszejko D, Ilnicki W, Donotek S, Kozma J. (1987). "Cervical pregnancy in Asherman’s syndrome [article in Polish].". Ginekol Pol 58: 46-8.. PMID 3583040. 
  20. ↑ Dicker, D. Feldberg, D. Samuel, N. and Goldman, JA. (1985). "Etiology of cervical pregnancy. Association with abortion, pelvic pathology, IUDs and Asherman's syndrome.". J Reprod Med 30 (1): 25-7. PMID 4038744. 
  21. ↑ Bukulmez O., Yarali H., Gurgan T. (1999). "Total corporal synechiae due to tuberculosis carry a very poor prognosis following hysteroscopic synechialysis". Human Reproduction 14 (8): 1960-1.. PMID 10438408. 
  22. ↑ Al-Azemi M, Refaat B, Amer S, Ola B, Chapman N, Ledger W (May 2009). "The expression of inducible nitric oxide synthase in the human fallopian tube during the menstrual cycle and in ectopic pregnancy". Fertil. Steril. 94 (3): 833–840. doi:10.1016/j.fertnstert.2009.04.020. PMID 19482272. 
  23. ↑ Mahboob U, Mazhar SB (2006). "Management of ectopic pregnancy: a two-year study". Journal of Ayub Medical College, Abbottabad: JAMC 18 (4): 34–7. PMID 17591007. 
  24. ↑ Clark L, Raymond S, Stanger J, Jackel G (1989). "Treatment of ectopic pregnancy with intraamniotic methotrexate—a case report". The Australian & New Zealand journal of obstetrics & gynaecology 29 (1): 84–5. doi:10.1111/j.1479-828X.1989.tb02888.x. PMID 2562613. 
  25. ↑ "eMedicine - Surgical Management of Ectopic Pregnancy: Article Excerpt by R Daniel Braun". http://www.emedicine.com/med/byname/Surgical-Management-of-Ectopic-Pregnancy.htm. Retrieved 2007-09-17. 
  26. ↑ Togas Tulandi; Tan, S. L; Tan, Seang Lin; Tulandi, T. (2002). Advances in Reproductive Endocrinology and Infertility: Current Trends and Developments. Informa Healthcare. pp. 240. ISBN 0-8247-0844-X. 
  27. ↑ 27.0 27.1 Hurd, William W.; Falcone, Tommaso (2007). Clinical reproductive medicine and surgery. St. Louis, Mo: Mosby/Elsevier. pp. 724. ISBN 0-323-03309-1. 
  28. ↑ "Miracle baby Billy grew outside his mother's womb". Daily Mail. 2008-08-31. http://www.dailymail.co.uk/femail/article-1050942/Miracle-baby-Billy-grew-outside-mothers-womb.html. Retrieved 2008-09-03. 
  29. ↑ "Baby Born After Rare Ovarian Pregnancy". Associated Press. 2008-05-30. http://ap.google.com/article/ALeqM5h7An_4HQLG6rSVO-h1eBIntgYOyAD90VRLKO1. Retrieved 2008-05-30. 
  30. ↑ Cavanagh, Rebekah (2008-05-30). "Miracle baby may be a world first". http://www.news.com.au/story/0,23599,23782145-2,00.html. Retrieved 2008-05-30. 
  31. ↑ "Doctors hail 'miracle' baby". BBC News. 2009-09-10. http://news.bbc.co.uk/1/hi/health/443373.stm. 

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