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Ectopicw
Ectopicw
tubes (approximately 97.7%), cervix, ovary, cornual region of the uterus, and abdominal cavity. Of tubal pregnancies, the ampulla is the most common site of implantation (80%), followed by the isthmus (12%), fimbria (5%), cornua (2%), and interstitia (23%). (See the image below.)
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%; and (G) Cervical, 0.2%. In ectopic pregnancy (the term ectopic is derived from the Greek word ektopos, meaning out of place), the 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 (see the images below). (See Etiology and Prognosis.)
A 12-week interstitial gestation, which eventually resulted in a hysterectomy. Courtesy of Deidra Gundy, MD, Department of Obstetrics and Gynecology at Medical College of Pennsylvania and Hahnemann University (MCPHU).
A 12-week interstitial gestation, which eventually resulted in a hysterectomy. Courtesy of Deidra Gundy, MD, Department of Obstetrics and Gynecology at Medical College of Pennsylvania and Hahnemann University (MCPHU). In 1970, the Centers for Disease Control and Prevention (CDC) began to record 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. (See Epidemiology.) The increased incidence of ectopic pregnancy has been partially attributed to improved ability in making an earlier diagnosis. Ectopic pregnancies that previously would have resulted in tubal abortion or complete, spontaneous reabsorption and remained clinically undiagnosed are now detected. (See Presentation, DDx, and Workup.) In the 1980s and 1990s, medical therapy for ectopic pregnancy was implemented; it has now replaced surgical therapy in many cases.[1, 2, 3] As the ability to diagnose ectopic pregnancy
improves, physicians will be able to intervene sooner, preventing life-threatening sequelae and extensive tubal damage, as well as, it is hoped, preserving future fertility. (See Treatment and Medication.)
Implantation sites
The faulty implantation that occurs in ectopic pregnancy occurs because of a defect in the anatomy or normal function of either the fallopian tube (as can result from surgical or infectious scarring), the ovary (as can occur in women undergoing fertility treatments), or the uterus (as in cases of bicornuate uterus or cesarean delivery scar). Reflecting this, most ectopic pregnancies are located in the fallopian tube; the most common site is the ampullary portion of the tube, where over 80% of ectopic pregnancies occur. (See Etiology.) Nontubal ectopic pregnancies are a rare occurrence, with abdominal pregnancies accounting for 1.4% of ectopic pregnancies and ovarian and cervical sites accounting for 0.2% each. Some ectopic pregnancies implant in the cervix (< 1%), in previous cesarean delivery scars, or in a rudimentary uterine horn; although these may be technically in the uterus, they are not considered normal intrauterine pregnancies.[4] About 80% of ectopic pregnancies are found on the same side as the corpus luteum (the old, ruptured follicle), when present.[5] In the absence of modern prenatal care, abdominal pregnancies can present at an advanced stage (>28 wk) and have the potential for catastrophic rupture and bleeding.[6]
Etiology
An ectopic pregnancy requires the occurrence of 2 events: fertilization of the ovum and abnormal implantation. Many risk factors affect both events; for example, a history of major tubal infection decreases fertility and increases abnormal implantation. Multiple factors contribute to the relative risk of ectopic pregnancy. In theory, anything that hampers or delays the migration of the fertilized ovum (blastocyst) to the endometrial cavity can predispose a woman to ectopic gestation. The following risk factors have been linked to ectopic pregnancy: Tubal damage - Which can be the result of infections such as pelvic inflammatory disease (PID) or salpingitis (whether documented or not) or can result from abdominal surgery or tubal ligation or from maternal in utero diethylstilbestrol (DES) exposure History of previous ectopic pregnancy Smoking - A risk factor in about one third of ectopic pregnancies; smoking may contribute to decreased tubal motility by damage to the ciliated cells in the fallopian tubes Altered tubal motility - As mentioned, this can result from smoking, but it can also occur as the result of hormonal contraception; progesterone-only contraception and progesterone intrauterine devices (IUDs) have been associated with an increased risk of ectopic pregnancy History of 2 or more years of infertility (whether treated or not)[7] - Women using assisted reproduction seem to have a doubled risk of ectopic pregnancy (to 4%), although this is mostly due to the underlying infertility[8] History of multiple sexual partners[7] Maternal age - Although this is not an independent risk factor[7] 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.[9]
A 2009 literature review found 56 reported cases of ectopic pregnancy (by definition), dating back to 1937, after hysterectomy.[10]
Smoking
Cigarette smoking has been shown to be a risk factor for ectopic pregnancy development. Studies have demonstrated an elevated risk ranging from 1.6 to 3.5 times that of nonsmokers. A doseresponse effect has also 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, and altered immunity. To date, however, no study has supported a specific mechanism by which cigarette smoking affects the occurrence of ectopic pregnancy.
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 with an incidence of 1 in 30,000 pregnancies for spontaneous conceptions.[16]
Increasing age
The highest rate of ectopic pregnancy occurs in women aged 35-44 years. A 3- to 4-fold increase in the risk of developing an ectopic pregnancy exists compared with women aged 15-24 years. One proposed explanation suggests that aging may result in a progressive loss of myoelectrical activity in the fallopian tube; myoelectrical activity is responsible for tubal motility.
DES exposure
Before 1971, several million women were exposed in utero to DES, which was given to their mothers to prevent pregnancy complications. In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes, including infertility, spontaneous abortion, and ectopic pregnancy.[18]
Other
Other risk factors associated with increased incidence of ectopic pregnancy include anatomic abnormalities of the uterus such as a T-shaped or bicornuate uterus, fibroids or other uterine tumors, previous abdominal surgery, failure with progestin-only contraception, and ruptured appendix.[9]
Epidemiology
Occurrence in the United States
The incidence of ectopic pregnancy is reported most commonly as the number of ectopic pregnancies per 1000 conceptions. Since 1970, when the reported rate in the United States was 4.5 cases per 1000 pregnancies, the frequency of ectopic pregnancy has increased 6-fold, with ectopic pregnancies now accounting for approximately 1-2% of all pregnancies. Consequently, the prevalence is estimated at 1 in 40 pregnancies, or approximately 25 cases per 1000 pregnancies. These statistics are based on data from the US Centers for Disease Control and Prevention (CDC), which used hospitalizations for ectopic pregnancy to determine the total number of ectopic pregnancies. Looking at raw data, 17,800 hospitalizations for ectopic pregnancies were reported in 1970. This number rose to 88,000 in 1989[19] but fell to 30,000 in 1998. An estimated 108,800 ectopic pregnancies in 1992 resulted in 58,200 hospitalizations, with an estimated cost of $1.1 billion. Changes in the management of ectopic pregnancy, however, have made it difficult to reliably monitor incidence (and therefore mortality rates).[20] A review of hospital discharges in California found a rate of 15 cases per 1,000 in 1991, declining to a rate of 9.3 cases per 1,000 in 2000,[21] but a review of electronic medical records (inpatient and outpatient) from a large health maintenance organization (HMO) in northern California found a stable rate of 20.7 cases per 1,000 reported pregnancies from 1997-2000.[22] This suggests that the incidence of ectopic pregnancy in the United States remained steady at about 2% in the 1990s, despite the shift to outpatient treatment. The above data raise the question of whether the number of ectopic pregnancies is declining or whether many ectopic pregnancies are now being treated in ambulatory surgical centers or are even being addressed with medical therapy, without admission. Some authors believe the latter is true, but truly accurate statistics are lacking. Approximately 85-90% of ectopic pregnancies occur in multigravid women. In the United States, rates are nearly twice as high for women of other races compared with white women.
International occurrence
The increase in incidence of ectopic pregnancy in the 1970s in the United States was also mirrored in Africa, although data there tend to be hospital based rather than derived from nationwide surveys, with estimates in the range of 1.1-4.6%.[23]
The United Kingdom estimated the incidence of ectopic pregnancy at about 11.1 per 1,000 reported pregnancies from 1997 to 2005, compared with 9.6 per 1,000 from 1991 to 1993.[24]
Prognosis
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 the death of the fetus. Without timely diagnosis and treatment, ectopic pregnancy can become a life-threatening situation.[26] The evidence in the literature reporting on the treatment of ectopic pregnancy with subsequent reproductive outcome is limited mostly to observational data and a few randomized trials comparing treatment options. Assessment of successful treatment and future reproductive outcome with various treatment options is often skewed by selection bias. For example, comparing a patient who was managed expectantly with a patient who received methotrexate or with a patient who had a laparoscopic salpingectomy is difficult. A patient with spotting, no abdominal pain, and a low initial betahuman chorionic gonadotropin (-HCG) level that is falling may be managed expectantly, whereas a patient who presents with hemodynamic instability, an acute abdomen, and high initial -HCG levels must be managed surgically. These 2 patients probably represent different degrees of tubal damage; thus, comparing the future reproductive outcomes of the 2 cases would be flawed.
In an earlier study, Maymon et al, after reviewing 20 years of ectopic pregnancy treatment, concluded that conservative tubal surgery provided no greater risk of recurrent ectopic pregnancy than the more radical salpingectomy.[30] The modern pelvic surgeon has been led to believe that the treatment of choice for unruptured ectopic pregnancy is salpingostomy, sparing the affected fallopian tube and thereby improving future reproductive outcome. However, if the treating surgeon has neither the laparoscopic skill nor the instrumentation necessary to atraumatically remove the trophoblastic tissue via linear salpingostomy, then salpingectomy by laparoscopy or laparotomy is not the wrong surgical choice. Leaving a scarred, charred fallopian tube behind after removing the ectopic pregnancy but requiring extensive cautery to control bleeding does not preserve reproductive outcome.
The average success rates for the single-dosage methotrexate regimen are reported to be from 8894%. In a study by Stovall and Ling, 113 patients (94%) were treated successfully, 4 (3.3%) of whom needed a second dose.[34] No adverse effects were encountered. Furthermore, 87.2% of these patients achieved a subsequent intrauterine pregnancy, whereas 12.8% experienced a subsequent ectopic pregnancy.[34] Other studies have reported similar results, with some mild adverse effects and lower reproductive outcomes. A meta-analysis that included data from 26 trials demonstrated a success rate of 88.1% with the single-dose methotrexate regimen and a success rate of 92.7% with the multiple-dose regimen.[35] A small, randomized clinical trial also demonstrated the single-dose regimen to have a slightly higher failure rate.[36] A hybrid protocol, involving 2 equal doses of methotrexate (50 mg/m2) given on days 1 and 4 without the use of leucovorin, has been shown to be an effective and convenient alternative to the existing regimens.[37]
Complications
Complications of ectopic pregnancy can be secondary to misdiagnosis, late diagnosis, or treatment approach. Failure to make the prompt and correct diagnosis of ectopic pregnancy can result in tubal or uterine rupture (depending on the location of the pregnancy), which in turn can lead to massive hemorrhage, shock, disseminated intravascular coagulopathy (DIC), and death. Ectopic pregnancy is the leading cause of maternal death in the first trimester, accounting for 9-13% of all pregnancyrelated deaths. In the United States, an estimated 30-40 women die each year from ectopic pregnancy. Any time a surgical approach is chosen as the treatment of choice, consider the complications attributable to the surgery, whether it is laparotomy or laparoscopy. These include bleeding, infection, and damage to surrounding organs, such as the bowel, bladder, and ureters, and to the major vessels nearby. Infertility may also result secondary to loss of reproductive organs after surgery. Also consider the risks and complications secondary to anesthesia. Make the patient aware of these complications, and obtain the appropriate written consents.
Mortality
In the United States, ectopic pregnancy is estimated to occur in 1-2% of all pregnancies and accounts for 3-4% of all pregnancy-related deaths.[38] It is the leading cause of pregnancy-related mortality during the first trimester in the United States. In a review of deaths from ectopic pregnancy in Michigan, 44% of the women who died were either found dead at home or were dead on arrival at the emergency department.[39] Virtually all ectopic pregnancies are considered nonviable and are at risk of eventual rupture and resulting hemorrhage. In addition to the immediate morbidity caused by ectopic pregnancy, the woman's future ability to reproduce may be adversely affected as well. However, patients who are diagnosed with ectopic pregnancy before rupture have a low mortality rate and also have a chance at preserved fertility. From 1970 to 1989, the US mortality rate for ectopic pregnancies dropped from 35.5 deaths to 3.8 deaths per 10,000 ectopic pregnancies.[19] If the overall incidence of ectopic pregnancy remained stable in the 1990s, then the mortality rate dropped to 3.19 deaths per 10,000 ectopic pregnancies by 1999.[40] Surveillance data for pregnancy-related deaths in the United States from 1991-1999 showed that ectopic pregnancy was the cause of 5.6% of 4200 maternal deaths. Of these deaths, 93% occurred via hemorrhage.[25]
During 19992008, the ectopic pregnancy mortality rate in the United States was 0.6 deaths per 100,000 live births. The CDC reported a higher rate in Florida, 2.5 deaths per 100,000 live births during 2009-2010. The 11 ectopic pregnancy deaths in Florida during 2009-2010 contrasted with the total number of deaths (14) identified in national statistics for 2007. There was a high prevalence of illicit drug use among the women who died in Florida.[38] The mortality rate reported in African hospital-based studies varied from 50-860 deaths per 10,000 ectopic pregnancies; these were almost certainly underestimates resulting from underreporting of maternal deaths and misclassification of ectopic pregnancies as induced abortions.[23] Using data from 1997 to 2002, the World Health Organization (WHO) estimated that ectopic pregnancy was the cause of 4.9% of pregnancy-related deaths in the industrialized world.[41] Ectopic pregnancy caused 26% of maternal deaths in early pregnancy in the United Kingdom from 2003-2005, second only to venous thromboembolism, despite a relatively low mortality rate of 0.035 per 10,000 estimated ectopic pregnancies.[24]