Ectopic pregnancy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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.^[1] 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 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.

Ectopic pregnancy (EP) remains one of the few life threatening diseases where the incidence is increasing (19.7/1000 pregnancies in 1992) but the mortality is decreasing.

There are a number of risk factors for ectopic pregnancies. They include: pelvic inflammatory disease, infertility, those who have been exposed to DES, tubal surgery, smoking, previous ectopic pregnancy, multiple sexual partners, current IUD use, tubal ligation, and previous abortion.^[2]

Diagnosis can be made by the 7th week of pregnancy (~ 4.5 weeks after conception).

There has only been one randomized controlled trail comparing medical to surgical therapy, and there was no difference as far as elimination of the EP or tubal preservation, however the methotrexate (MTX) group had a higher incidence of side effects.

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.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo M.D.

The normal site of implatation for a pregnancy is always the uterus, most of them occuring the upper third and posterior walls of the uterine body (corpus uteri). hCH levels in an ectopic pregnancy are usually lower than in uterine pregnancies. No visible intruterine transvaginal utrasonography with a serum hCG higher than 2000 mIU/ml is indicateive of an ectopic pregnancy. The most common site of ectopic pregnancies is in the Fallopian tubes (80% ampullar). An ectopic pregnancy may be seen in gross pathology as a distension of the Fallopian tube. Histopathological findings of ectopic pregnancies are intraluminal chorionic villi and extravillous trophoblast (may be degenerated) with variable fetal parts.

• The normal site of implatation for a pregnancy is always the uterus, most of them occuring the upper third and posterior walls of the uterine body (corpus uteri); lower implantations may cause a placenta previa.
• Hair-like cilia located on the internal surface of the Fallopian tubes carry the fertilized egg to the uterus.
• Normaly, after fecundation, the blastocyst begins to implant in the endometrium at day 7 after fecundation (8-10 days after ovulation in most successful cases) and is completed by day 9.^[1][2] By this time the level of hCG is usually higher than 5000mIU/mL.
• The discriminatory level of hCG for a pregnancy is around 1000 mIU/mL.^[3][4]
• In most normal pregnancies at an hCG level below 1,200 mIU/ml, the hCG usually doubles every 48-72 hours. At levels below 6,000 mIU/ml, the hCG levels normally increase by at least 60% every 2-3 days.

• The most common site of ectopic pregnancies is in the Fallopian tubes (80% ampullar).
• hCH levels in an ectopic pregnancy are usually lower than in uterine pregnancies.
• No visible intruterine transvaginal utrasonography with a serum hCG higher than 2000 mIU/ml is indicateive of an ectopic pregnancy.

• Damage to the cilia or blockage of the Fallopian tubes is likely to lead to an ectopic pregnancy.
• A common cause of Fallopian tubes occlusion and damage to cilia is by scaring of tissues after pelvic inflammatory disease (PID).
• Tubal ligation can predispose to ectopic pregnancy, variably increasing the risk depending on the method used. Seventy percent of pregnancies after tubal cautery are ectopic, while seventy percent of pregnancies after tubal clips are intrauterine. Reversal of tubal sterilization (Tubal reversal) still carries an additional risk for ectopic pregnancy when comparing with normal women.^[5]
• Normal pregnancy may still be possible if only one Fallopian tube is occluded.
• A history of ectopic pregnancy increases the risk of future occurrences in about 10%.^[6]

• Infertility management is highly variable and specific to individual patients.
• In vitro fertilization is used for patients with damaged tubes, which are an inherent risk factor for ectopic pregnancy.
• Ectopic pregnancies have been seen with in vitro fertilization, but this is an uncommon complication and quickly diagnosed by the early ultrasounds that these intensively surveyed patients undergo.

• In rare occasions, ectopic pregnancies may occur in women who underwent an hysterectomy. Blastocysts, rather than implanting in the absent uterus, the fetus implants in the abdomen.
• In most of these cases, a laparotomy is indicated.^[7]

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.

• The most important conditions/diseases associated with ectopic pregnancy include:
  • Pelvic inflammatory disease (PID)
  • Previous ectopic pregnancy
  • Previous surgery on your fallopian tubes
  • Fertility treatment, such as in-vitro fertilization (IVF)
  • Becoming pregnant while using an intrauterine device (IUD) or intrauterine system (IUS) for contraception
  • Smoking
  • Increasing age after 40 years old

Ectopic pregnancy may reveal in gross pathology a distension of the Fallopian tube with thin or ruptured wall, dusky red serosa and hematosalpinx, possibly with fetal parts identified.

Histopathological findings in an ectopic pregnancy may be the following:

• Intraluminal chorionic villi and extravillous trophoblast (may be degenerated); variable fetal parts.
• Decidual change in lamina propria in 1/3; mesothelial reactive proliferation with papillary formation and psammoma bodies.
• Uterus: gestational hyperplasia with Arias-Stella reaction, no enlarged, hyalinized spiral arteries, no fibrinoid matrix.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo, M.D.

Ectopic pregnancy may be caused by . The most common cause of ectopic pregnancy is a history of tubal surgery. Among the most common causes of ectopic pregnancies, the less common cause is a history of 1st intercourse before 18 years old.

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• All causes of ectopic pregnancy can potentially cause death or permanent disability within 24 hours if left untreated.
  

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2], Moises Romo, M.D

• Ectopic pregnancy must be differentiated from other diseases that cause abdominal pain, pelvic pain, vaginal bleeding, and/ or ammenorrhea, such as:
• Threatened or incomplete abortion
• Adnexal torsion
• Appendicitis
• Ruptured corpus luteum cyst
• Pancreatitis
• Pelvic inflammatory disease (PID)
• Pyelonephritis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Moises Romo, M.D.

Ectopic pregnancy remains an important cause of death among all pregnancies. Drug abuse, unmarried status, no insurance, and had less than a high school education are factors associated with higher incidence of death. Ectopic pregnancies compose 1-2% of all pregnancies worldwide. In The United States, the incidence of ectopic pregnancy is 197 new cases per 100,000 persons. White females are more commonly affected, although, mortality rate is higher in those of black race.

• Ectopic pregnancy is a disease of short duration, immediately approached, hence difficult to calculate its prevalence.
• Around 1 in every 50 pregnancies in The United States are ectopic pregnancies.^[1]

• Worldwide, ectopic pregnancies occur in 1-2% of all pregnancies.
• In developing countries, the incidence of ectopic pregnancies range between 0.4% of all pregnancies in places such as Middle East and India, and over 4% reported in certain African countries, such as Ghana.
• In developed countries, such as The United States, the incidence of ectopic pregnancy is 197 new cases per 100,000 persons.
• Ectopic pregnancies are though to be as high as 4% in pregnancies involving assisted reproductive technology.^[2]

• Ectopic pregnancies account for 3-4% of all pregnancy-related deaths in The United States.^[3]
• Case-fatality rate has greatly decreased in The United States in the last decades, from 1.2 per 100,000 live births in 1980 to 0.5 per 100,000 live births in 2007.^[4]
• Among the deaths from ectopic pregnancies in hospitalized women between 1998 and 2007, 70.5% were tubal pregnancies.^[5]
• In lately years (2008-2010), from the women who died from ectopic pregnancies, 1.8 deaths per 100,000 live births died from hypovolemic shock from hemorrhage as compared with 0.3 deaths per 100,000 live births in 1999-2008.^[6]

• The rate of ectopic pregnancies is higher in women aged between 35-44.^[7]
• Ectopic pregnancy mortality ratio was 3.5 times higher for women older than 35 years than those younger than 25 years during 2003-2007 in The United States.^[5]

• Ectopic pregnancies, are unique to female gender.

• Ectopic pregnancies usually affects women of black race more than others.^[8] Asian women are less likely to develop ectopic pregnancies.^[9]
• Ectopic pregnancy mortality ratio was 6.8 times higher in African Americans than their whites counterparts during 2003-2007 in The United States.^[5]

• Drug abuse, unmarried status, no insurance, and had less than a high school education were factors associated with higher incidence of death in patients with ectopic pregnancies.^[6]
• A previous ectopic pregnancy, increases the risk of a second ectopic pregnancy by 15%.

• In most of European countries and North America, the incidence of ectopic pregnancy has tripled over the past 30 years.^[10]
• In developed countries, tubal damage resulting from infection or surgery, previous ectopic pregnancy, history of secondary infertility and treatment for in-vitro fertilization are rising risk factors for ectopic pregnancy.^[11]

• The diagnosis of ectopic pregnancy is especially challenging in developing countries before 7 weeks of amenorrhea, due to the poor access to ultrasound scans. It is often confused with miscarriage or induced abortion, an ovary problem, or with a PID.^[12]
• In developing countries, surgery remains the mainstay of treatment, mostly performed by laparotomy rather than by laparoscopy.^[12]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Moises Romo M.D.

Ectopic pregnancy usually occurs in women with fallopian tube dysfunction. There are a number of risk factors for ectopic pregnancies, among them pelvic inflammatory disease, infertility, DES exposure, tubal surgery, smoking, previous ectopic pregnancy, multiple sexual partners, current IUD use, tubal ligation, and previous abortion. The most potent risk factor in the development of ectopic pregnancy is tubal surgery.

• Risk factors in the development of ectopic pregnancies may be occupational, environmental, genetic, and viral. The following table summarizes these risks and its odds ratio:

• Tubal surgery. It is known as the major risk factor for ectopic pregnancy developemnt.^[1][2]
• Tubal ligation. Although tubal ligation is highly effective in preventing pregnancies, if a pregnancy does occur, it is more likely to be ectopic.^[3]
• Previous ectopic pregnancy. Same as having a previous ectopic pregnancy increases the risk for further ectopic pregnancies, having a intrauterine pregnancy decreases this risk.[4][./Ectopic_pregnancy_risk_factors#cite_note-pmid8641479-1 [4]]^[5][6]
• In-utero DES exposure. The usage causes a loss of fimbriae and stenosis of fallopian tubes, which may increase up to 3 times the risk of ectopic pregnancy as compared to unexposed women.^[7]
• IUD. It is thought that IUD-induced inflammation may result in deciliation of the endosalpinx and then delays ovum transport, altough, the exact mechanism is not fully understood.^[4]
• Documented tubal pathology. Ectopic tubal pregnancy may occur in a blocked tube with contralateral tubal patency, although, this association was found to be weaker for those with two blocked tubes.^[8][9]

• Infertility. Treatment of infertility, such as in vitro fertilization is associated with a 2 – 3 % increased risk compared with the general population.^[10][11][12]
• Previous STD. This possibly due to tubal scarring from gonococcal and chlamydial infections, which produce changes in tubal function leading to delay in ovum transport and tubal implantation.^[4][7]
• Multiple sexual partners. There has been an association between multiple sexual partners and ectopic pregnancies, especially when 1st intercourse < 18 years old.^[7]
• Prior pelvic / abdominal surgery. Women with histories of laparotomy and appendectomy have higher risk of developing an ectopic pregnancy, although this risks increases even higher when it involves tubal involvement.^[13]
• Cigarette smoking. Inhalation of cigarette smoke may impair fallopian tube function by affecting on ciliary beat frequency and smooth muscle contraction.^[14][15]
• Pior abortions. There is conflict between studies in revealing an association; the cause of this relationship is most likely due to infection, hormonal imbalance, or immunologic factors.^[16][17]
• Advanced age. There is a 9 times-fold increased risk of developing an ectopic pregnancy in women ≥39 as compared with those ≤26 years.^[18][4]
• Vaginal douching. It is thought by some to increase ectopic pregnancies.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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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.

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