eMedicine Specialties > Obstetrics and Gynecology > General Gynecology
Ectopic Pregnancy
Updated: Aug 2, 2009
Introduction
Ectopic pregnancy presents a major health problem for women of childbearing age. It is the result of a flaw in human reproductive physiology that allows the conceptus to implant and mature outside the endometrial cavity, which ultimately ends in death of the fetus. Without timely diagnosis and treatment, ectopic pregnancy can become a life-threatening situation.
Ectopic pregnancy currently is the leading cause of pregnancy-related death during the first trimester in the United States, accounting for 9% of all pregnancy-related deaths. In addition to the immediate morbidity caused by ectopic pregnancy, the woman's future ability to reproduce may be adversely affected as well.
Ectopic pregnancy. Laparoscopic picture of an unruptured right ampullary tubal pregnancy with bleeding out of the fimbriated end resulting in hemoperitoneum.
History of the Procedure
Ectopic pregnancy was first described in the 11th century, and, until the middle of the 18th century, it was usually fatal. John Bard reported the first successful surgical intervention to treat an ectopic pregnancy in New York City in 1759.
The survival rate in the early 19th century was dismal. One report demonstrated only 5 patients of 30 surviving the abdominal operation. Interestingly, the survival rate in patients who were left untreated was 1 of 3.
In the beginning of the 20th century, great improvements in anesthesia, antibiotics, and blood transfusion contributed to the decrease in the maternal mortality rate. In the early half of the 20th century, 200-400 deaths per 10,000 cases were attributed to ectopic pregnancy. In 1970, the Centers for Disease Control and Prevention (CDC) began to record the statistics regarding ectopic pregnancy, reporting 17,800 cases. By 1992, the number of ectopic pregnancies had increased to 108,800. Concurrently, however, the case-fatality rate decreased from 35.5 deaths per 10,000 cases in 1970 to 2.6 per 10,000 cases in 1992.
Problem
Ectopic pregnancy is derived from the Greek word ektopos, meaning out of place, and it refers to the implantation of a fertilized egg in a location outside of the uterine cavity, including the fallopian tubes, cervix, ovary, cornual region of the uterus, and the abdominal cavity. This abnormally implanted gestation grows and draws its blood supply from the site of abnormal implantation. As the gestation enlarges, it creates the potential for organ rupture because only the uterine cavity is designed to expand and accommodate fetal development. Ectopic pregnancy can lead to massive hemorrhage, infertility, or death.
Frequency
Since 1970, the frequency of ectopic pregnancy has increased 6-fold, and it now occurs in 2% of all pregnancies. An estimated 108,800 ectopic pregnancies in 1992 resulted in 58,200 hospitalizations with an estimated cost of $1.1 billion.
Etiology
Multiple factors contribute to the relative risk of ectopic pregnancy. In theory, anything that hampers the migration of the embryo to the endometrial cavity could predispose women to ectopic gestation. The most logical explanation for the increasing frequency of ectopic pregnancy is previous pelvic infection; however, most patients presenting with an ectopic pregnancy have no identifiable risk factor. The following risk factors have been linked with ectopic pregnancy:
Pelvic inflammatory disease
The most common cause is antecedent infection caused by Chlamydia trachomatis. Patients with chlamydial infection have a range of clinical presentations, from asymptomatic cervicitis to salpingitis and florid pelvic inflammatory disease (PID). More than 50% of women who have been infected are unaware of the exposure. Other organisms causing PID, such as Neisseria gonorrhoeae, increase the risk of ectopic pregnancy. A history of salpingitis increases the risk of ectopic pregnancy 4-fold. The incidence of tubal damage increases after successive episodes of PID (ie, 13% after 1 episode, 35% after 2 episodes, 75% after 3 episodes).
History of prior ectopic pregnancy
After one ectopic pregnancy, a patient incurs a 7- to 13-fold increase in the likelihood of another ectopic pregnancy. Overall, a patient with prior ectopic pregnancy has a 50-80% chance of having a subsequent intrauterine gestation, and a 10-25% chance of a future tubal pregnancy.
History of tubal surgery and conception after tubal ligation
Prior tubal surgery has been demonstrated to increase the risk of developing ectopic pregnancy. The increase depends on the degree of damage and the extent of anatomic alteration. Surgeries carrying higher risk of subsequent ectopic pregnancy include salpingostomy, neosalpingostomy, fimbrioplasty, tubal reanastomosis, and lysis of peritubal or periovarian adhesions.
Conception after previous tubal ligation increases a women's risk of developing ectopic pregnancies. Thirty-five to 50% of patients who conceive after a tubal ligation are reported to experience an ectopic pregnancy. Failure after bipolar tubal cautery is more likely to result in ectopic pregnancy than occlusion using suture, rings, or clips. Failure is attributed to fistula formation that allows sperm passage. Ectopic pregnancies following tubal sterilizations usually occur 2 or more years after sterilization, rather than immediately after. In the first year, only about 6% of sterilization failures result in ectopic pregnancy.
Use of fertility drugs or assisted reproductive technology
Ovulation induction with clomiphene citrate or injectable gonadotropin therapy has been linked with a 4-fold increase in the risk of ectopic pregnancy in a case-control study. This finding suggests that multiple eggs and high hormone levels may be significant factors.
One study has demonstrated that infertility patients with luteal phase defects have a statistically higher ectopic pregnancy rate than patients whose infertility is caused by anovulation. The risk of ectopic pregnancy and heterotopic pregnancy (ie, pregnancies occurring simultaneously in different body sites) dramatically increases when a patient has used assisted reproductive techniques to conceive, such as in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). In a study of 3000 clinical pregnancies achieved through in vitro fertilization, the ectopic pregnancy rate was 4.5%, which is more than double the background incidence. Furthermore, studies have demonstrated that up to 1% of pregnancies achieved through IVF or GIFT can result in a heterotopic gestation, compared to an incidence of 1 in 30,000 pregnancies for spontaneous conceptions.
Use of an intrauterine device
The presence of an inert copper-containing or progesterone intrauterine device (IUD) traditionally has been thought to be a risk factor for ectopic pregnancy. However, only the progesterone IUD has a rate of ectopic pregnancy higher than that for women not using any form of contraception. The modern copper IUD does not increase the risk of ectopic pregnancy. Nevertheless, if a woman ultimately conceives with an IUD in place, it is more likely to be an ectopic pregnancy. The actual incidence of ectopic pregnancies with IUD use is 3-4%.
Increasing age
The highest rate of ectopic pregnancy occurs in women aged 35-44 years. A 3- to 4-fold increase in the risk for developing an ectopic pregnancy exists compared to women aged 15-24 years. One proposed explanation involves the myoelectrical activity in the fallopian tube, which is responsible for tubal motility. Aging may result in a progressive loss of myoelectrical activity along the fallopian tube.
Smoking
Cigarette smoking has been shown to be a risk factor for developing an ectopic pregnancy. Studies have demonstrated elevated risk ranging from 1.6-3.5 times that of nonsmokers. A dose-response effect also has been suggested. Based on laboratory studies in humans and animals, researchers have postulated several mechanisms by which cigarette smoking might play a role in ectopic pregnancies. These mechanisms include one or more of the following: delayed ovulation, altered tubal and uterine motility, or altered immunity. To date, no study has supported a specific mechanism by which cigarette smoking affects the occurrence of ectopic pregnancy.
Salpingitis isthmica nodosum
Salpingitis isthmica nodosum is defined as the microscopic presence of tubal epithelium in the myosalpinx or beneath the tubal serosa. These pockets of epithelium protrude through the tube, similar to small diverticula. Studies of serial histopathological sections of the fallopian tube have revealed that approximately 50% of patients treated with salpingectomy for ectopic pregnancy have evidence of salpingitis isthmica nodosum. The etiology of salpingitis isthmica nodosum is unclear, but proposed mechanisms include postinflammatory and congenital as well as acquired tubal changes such as observed with endometriosis.
Other
Other risk factors associated with increased incidence of ectopic pregnancy include previous diethylstilbestrol (DES) exposure, a T-shaped uterus, prior abdominal surgery, failure with progestin-only contraception, and ruptured appendix.
Pathophysiology
Most ectopic pregnancies are located in the fallopian tube (see Media file 1).Sites and frequencies of ectopic pregnancy. By Donna M. Peretin, RN. (A) Ampullary, 80%; (B) Isthmic, 12%; (C) Fimbrial, 5%; (D) Cornual/Interstitial, 2%; (E) Abdominal, 1.4%; (F) Ovarian, 0.2%; (G) Cervical, 0.2%.
The most common site is the ampullary portion of the tube, where over 80% occur. The next most common sites are the isthmic segment of the tube (12%), the fimbria (5%), and the cornual and interstitial region of the tube (2%). Nontubal sites of ectopic pregnancy are a rare occurrence, with abdominal pregnancies accounting for 1.4% of ectopic pregnancies and ovarian and cervical sites accounting for 0.2% each.
Presentation
The classic clinical triad of ectopic pregnancy is pain, amenorrhea, and vaginal bleeding. Unfortunately, only 50% of patients present typically. Patients may present with other symptoms common to early pregnancy, including nausea, breast fullness, fatigue, low abdominal pain, heavy cramping, shoulder pain, and recent dyspareunia. Astute clinicians should have a high index of suspicion for ectopic pregnancy in any woman who presents with these symptoms and who presents with physical findings of pelvic tenderness, enlarged uterus, adnexal mass, or tenderness.
Remember, however, that only 40-50% of patients with an ectopic pregnancy present with vaginal bleeding, 50% have a palpable adnexal mass, and 75% may have abdominal tenderness. Approximately 20% of patients with ectopic pregnancies are hemodynamically compromised at initial presentation, which is highly suggestive of rupture. Fortunately, using modern diagnostic techniques, most ectopic pregnancies may be diagnosed prior to rupturing.
Numerous conditions may have a presentation similar to an extrauterine pregnancy. The most common of these are appendicitis, salpingitis, ruptured corpus luteum cyst or ovarian follicle, spontaneous abortion or threatened abortion, ovarian torsion, and urinary tract disease. Intrauterine pregnancies with other abdominal or pelvic problems such as degenerating fibroids must also be included in the differential diagnosis.
Indications
Medical therapy
Medical therapy involving methotrexate may be indicated in certain patients. A number of factors must be considered. The patient must be hemodynamically stable, with no signs or symptoms of active bleeding or hemoperitoneum. Furthermore, she must be reliable, compliant, and able to return for follow-up. Another factor is size of the gestation, which should not exceed 3.5 cm at its greatest dimension on ultrasound (US) measurement. She should not have any contraindications to the use of methotrexate.
Surgical therapy
Within the last 2 decades, a more conservative surgical approach to unruptured ectopic pregnancy using minimally invasive surgery has been advocated to preserve tubal function (see Surgical Therapy). Laparoscopy has become the recommended approach in most cases. Laparotomy is usually reserved for patients who are hemodynamically unstable or patients with cornual ectopic pregnancies. It also is a preferred method for surgeons inexperienced in laparoscopy and in patients where laparoscopic approach is difficult (eg, secondary to the presence of multiple dense adhesions, obesity or massive hemoperitoneum). In a patient who has completed childbearing and no longer desires fertility, in a patient with a history of an ectopic pregnancy in the same tube, or in a patient with severely damaged tubes, total salpingectomy is the procedure of choice.
Expectant management
Candidates for successful expectant management are asymptomatic and have no evidence of rupture or hemodynamic instability. Furthermore, they should portray objective evidence of resolution, such as declining bhCG levels. They must be fully compliant and must be willing to accept the potential risks of tubal rupture.
Relevant Anatomy
See Pathophysiology.
Contraindications
Medical therapy
A bhCG level of greater than 15,000 IU/L, fetal cardiac activity, and free fluid in the cul-de-sac on US (presumably representing tubal rupture) are contraindications to medical therapy with methotrexate. Other contraindications to the use of methotrexate include documented hypersensitivity to methotrexate; breastfeeding; immunodeficiency; alcoholism; alcoholic liver disease or any liver disease; blood dyscrasias; leukopenia; thrombocytopenia; anemia; active pulmonary disease; peptic ulcer disease; and renal, hepatic, or hematologic dysfunction.
Surgical therapy
Surgical treatment in cases in which the pregnancy is located on the cervix, ovary, or in the interstitial or the cornual portion of the tube is often associated with increased risk of hemorrhage, often resulting in hysterectomy or oophorectomy. In these cases, treatment with methotrexate is an especially attractive option.
In cases involving uncontrolled bleeding and hemodynamic instability, conservative treatment methods are avoided in favor of radical surgery.
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References
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Further Reading
Keywords
tubal pregnancy, extrauterine pregnancy, ectopic gestation, pelvic inflammatory disease, PID, Chlamydia trachomatis, salpingitis, Neisseria gonorrhoeae, salpingostomy, neosalpingostomy, fimbrioplasty, tubal reanastomosis, tubal ligation, clomiphene citrate, injectable gonadotropin therapy, in vitro fertilization, IVF, gamete intrafallopian transfer, GIFT, intrauterine device, IUD, salpingitis isthmica nodosum, pain
amenorrhea, vaginal bleeding, methotrexate, pregnancy-related death, abnormally implanted gestation, pelvic infection, cigarette smoking, diethylstilbestrol exposure, DES exposure, T-shaped uterus, prior abdominal surgery, failure with progestin-only contraception, ruptured appendix, adnexal mass, culdocentesis, hematosalpinx, hemoperitoneum, tubal rupture, uterine rupture, shock, disseminatedintravascular coagulopathy, DIC, laparoscopic salpingectomy
