Pathophysiology And Epidemiology

Fertilization of the oocyte usually occurs in the ampullary segment of the fallopian tube. In normal pregnancy, the zygote passes along the fallopian tube and implants into the endometrium of the uterus, with subsequent development of the placenta. An EP occurs when the zygote is implanted in any location other than the uterus; 95 percent of ectopic pregnancies occur in the fallopian tube. Extratubal sites include the abdominal cavity, cervix, and ovary. Abdominal ectopic pregnancies most commonly derive from early rupture or abortion of a tubal pregnancy, with subsequent reimplantation in the peritoneal cavity.

The fallopian tube is 10 to 12 cm long and is divided into four anatomic segments (proximal to distal): interstitial (cornual), isthmic, ampullary, and fimbrial. The ampullary segment is the longest. The most common site for EP is the ampullary segment, and the second most common site the isthmic segment. Interstitial (cornual) EP is uncommon (>3 percent) and fimbrial EP is rare. Operative description of tubal rupture reveals that it is more common with isthmic than with ampullary implantations. Ectopic pregnancies that have identifiable embryos or fetuses are more frequently associated with rupture. Rupture during the first few weeks of pregnancy is usually located in the isthmic segment of the tube, whereas interstitial rupture is seen later in pregnancy, typically at 9 to 16 weeks of gestation.

Tubal gestations that reach stages of fetal viability are rare (<5 percent of cases), and live-born offspring are extreme rarities. A normal placenta is found in only about 10 percent of ectopic pregnancies, possibly accounting for the much higher incidence of a blighted ovum in extrauterine pregnancies. Tubal abortion occurs when the vascular supply to the placenta is disrupted with bleeding into the fallopian tube and hematoma formation. Intermittent distention of the fallopian tube with blood can occur with leakage of blood from the fimbriated end of the fallopian tube into the peritoneal cavity. The aborting EP and associated hematoma can be completely or partially extruded out of the end of the fallopian tube or through a rupture site in the tubal wall. Tubal rupture is thought to be spontaneous; however, precipitating factors may include trauma associated with coitus or a bimanual examination.

EP represents about 2 percent of pregnancies. The postulated etiology of EP can be divided into two main categories: (1) mechanical or anatomic alterations in the tubal transport mechanism and (2) functional/hormonal factors that alter the fertilized ovum. Possible causes of mechanical or anatomic alterations in tubal transport include pelvic inflammatory disease (PID), previous surgical procedures on the fallopian tube, previous EP, intrauterine contraceptive devices (IUDs), previous induced abortions, peritubal adhesions (secondary to postabortal or puerperal infection, appendicitis, or endometriosis), and diethylstilbestrol (DES) exposure (possibly resulting in tubular diverticula or hypoplasia). PID results in damage to the mucosa of the fallopian tube. The most common cause of PID is infection resulting from sexually transmitted diseases. PID has been reported to increase the risk of EP six- to sevenfold. Each episode of PID increases the probability of EP. PID represents the most common and clear-cut risk factor in the development of EP.1

Tubal ligation is also a risk factor for EP. The more tissue-destructive the ligation procedure, the higher the EP rate. Extrauterine pregnancy rates as high as 51 percent of pregnancies have been reported with laparoscopic tubal electrocautery, as compared with rates of 12 percent using nonlaparoscopic methods. Infertility surgery on the fallopian tube has a reported 2 to 7 percent incidence of subsequent EP. Any patient who requires surgery for treatment of an EP is also at a higher risk of developing a subsequent EP. In general, future pregnancies following any prior tubal surgery should be suspected of being ectopic. It is not clear whether this higher incidence of EP is secondary to the underlying disease state or a result of the surgical procedure. IUDs have also been implicated in EP, with 3 to 4 percent of pregnancies occurring with an IUD in place estimated to be ectopic. Increased risk of EP is independent of the type of device. Following discontinuation of the IUD, the risk of EP is no longer significantly increased. Functional and hormonal mechanisms associated with an increased incidence of EP include assisted reproduction with chemical ovulation induction (clomiphene citrate, follicle-stimulating hormone, luteinizing hormone), gamete intrafallopian transfer (GIFT) and in vitro fertilization, altered tubal motility from the effects of estrogen and progesterone, and inherent defects in the fertilized ovum.

The incidence of EP has increased over the last two decades from 4.5 per 1000 reported pregnancies (0.45 percent) in 1970 to 19.7 per 1000 reported pregnancies (nearly 2 percent) in 1992. Reported pregnancies included live births, legally induced abortions, and ectopic pregnancies. An overestimation of the incidence of EP is possible, since the denominator, reported pregnancies, could be biased by lack of reporting of illegally terminated pregnancies or undetected spontaneous abortions. Some possible reasons postulated for the increased incidence of EP include the increased incidence of sexually transmitted tubal infections, unsuccessful tubal sterilizations, assisted reproductive techniques, previous pelvic surgery, and more sensitive and earlier diagnostic techniques. Overall, EP is more common in nonwhite than white women and in women above 35 years of age.1

The case-fatality rate per 10,000 ectopic pregnancies decreased from 35.5 in 1970 to 8.8 in 1980 to 3.8 in 1989. This trend was observed in both white and nonwhite women. However, nonwhite women overall had a 3.4 times greater risk of death than white women. Teenagers were the age group with the highest mortality rate. The observed decreased mortality is attributed largely to improved diagnostics and also a heightened awareness among medical personnel. However, EP remains the leading cause of maternal death in the first trimester of pregnancy and is the second leading cause of maternal mortality overall. 1

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