EctopicChp18Novak07.doc

Berek & Novaks Gynecology, 14th EditionCopyright 2007 Lippincott Williams & WilkinsChapter 18 Page 601-635Early Pregnancy Loss and Ectopic PregnancyThomas G. Stovall As many as 30% of pregnancies may be spontaneously lost. Following an ectopic pregnancy, there is a 10-fold increase in the risk of a subsequent ectopic pregnancy. Single-dose methotrexate appears to be the treatment of choice if medical therapy is indicated and selected. Unless the patient has documented cardiac activity in the ectopic, medical therapy should be instituted unless all the treatment criteria are met and the patient has had at least two hCG levels and a transvaginal ultrasound. Surgical management and medical therapy appear to be equivalent in a randomized comparison.An abnormal gestation can be either intrauterine or extrauterine. Extrauterine or ectopic pregnancy occurs when the fertilized ovum becomes implanted in tissue other than the endometrium. Although most ectopic gestations are located in the ampullary segment of the fallopian tube, such pregnancies may also occur in other sites (Table 18.1). Abnormal intrauterine pregnancy often results in pregnancy loss early in gestation. Such losses can be related to a number of factors. With both abnormal intrauterine and extrauterine gestation, early recognition is key to diagnosis and management.Abnormal Intrauterine PregnancySpontaneous AbortionAnembryonic gestation, inevitable abortion, incomplete abortion, and completed abortion are types of first-trimester abortions. About 15% to 20% of known pregnancies terminate in spontaneous abortion. With the use of serial human chorionic gonadotropin (hCG) measurements to detect early subclinical pregnancy losses, the percentage increases to 30%. About 80% of spontaneous pregnancy losses occur in the first trimester; the incidence decreases with each gestational week. In a study of 347 patients with a first-trimester pregnancy documented by ultrasonography, the overall rate of pregnancy loss was 6.1% to 4.2% in patients without bleeding and 12.4% in patients with bleeding (1). In women who have had one prior spontaneous abortion, the rate of spontaneous abortion in a subsequent pregnancy is about 20%; in women who have had three consecutive losses, the rate is 50%. The causes of this condition are varied and most often unknown (Table 18.2). Patients should be reassured that, in most cases, spontaneous abortion does not recur.Table 18.1 Definitions of Types of Abnormal Intrauterine and Extrauterine PregnanciesExtrauterine PregnancyTubal pregnancyA pregnancy occurring in the fallopian tube鈥攎ost often these are located in the ampullary portion of the fallopian tubeInterstitial pregnancyA pregnancy that implants within the interstitial portion of the fallopian tubeAbdominal pregnancyPrimary abdominal pregnancy鈥攖he first and only implantation occurs on a peritoneal surfaceSecondary abdominal pregnancy鈥攊mplantation originally in the tubal ostia, subsequently aborted, and then reimplanted onto a peritoneal surfaceCervical pregnancyImplantation of the developing conceptus in the cervical canalLigamentous pregnancyA secondary form of ectopic pregnancy in which a primary tubal pregnancy erodes into the mesosalpinx and is located between the leaves of the broad ligamentHeterotopic pregnancyA condition in which ectopic and intrauterine pregnancies coexistOvarian pregnancyA condition in which an ectopic pregnancy implants within the ovarian cortexAbnormal Intrauterine PregnancyIncomplete abortionExpulsion of some but not all of the products of conception before 20 completed weeks of gestationComplete abortionSpontaneous expulsion of all fetal and placental tissue from the uterine cavity before 20 weeks of gestationInevitable abortionUterine bleeding from a gestation of less than 20 weeks, accompanied by cervical dilation but without expulsion of placental or fetal tissue through the cervixAnembryonic gestationAn intrauterine sac without fetal tissue present at more than 7.5 weeks of gestationFirst-trimester fetal deathDeath of the fetus in the first 12 weeks of gestationSecond-trimester fetal deathDeath of the fetus between 13 and 24 weeks of gestationRecurrent spontaneous abortionThe loss of more than three pregnancies before 20 weeks of gestationThreatened AbortionThreatened abortion is defined as vaginal bleeding before 20 weeks of gestation. It occurs in about 30% to 40% of all pregnancies. The bleeding is usually light and may be associated with mild lower abdominal or cramping pain. It is often not possible to differentiate clinically between threatened abortion, completed abortion, and ectopic pregnancy in an unruptured tube. The differential diagnosis in these patients includes consideration of possible cervical polyps, vaginitis, cervical carcinoma, gestational trophoblastic disease, ectopic pregnancy, trauma, and foreign body. On physical examination, the abdomen usually is not tender, and the cervix is closed. Bleeding can be seen coming from the os, and usually there is no cervical motion or adnexal tenderness. Although most patients experience bleeding at 8 to 10 weeks of gestation, the actual loss usually occurs before 8 weeks of gestation. Only 3.2% of patients experience a pregnancy loss after 8 weeks of gestation (2).Table 18.2 Potential Causes of Spontaneous Pregnancy LossPathologic (blighted) ovum anembryonic gestationEmbryonic anomaliesChromosomal anomaliesIncreased maternal ageUterine anomaliesIntrauterine deviceTeratogenMutagenMaternal diseasePlacental anomaliesExtensive maternal traumaUnless the patient has an intrauterine pregnancy documented by ultrasonography, eliminating the possibility of an ectopic pregnancy, evaluation of a threatened abortion should include serial measurements of hCG. Endovaginal ultrasonography can detect a gestational sac at an hCG level of 1,000 to 2,000 mIU/mL. By 7 weeks of gestation, a fetal pole with fetal cardiac activity can be seen. When a gestational sac is visualized, subsequent loss of the pregnancy occurs in 11.5% of patients. If a yolk sac is present, the loss rate is 8.5%; with an embryo of 5 mm, the loss rate is 7.2%; with an embryo of 6 to 10 mm, the loss rate is 3.2%; and when the embryo is 10 mm, the loss rate is only 0.5%. The fetal loss rate after 14 weeks of gestation is about 2% (3). Transvaginal measurement of gestational sac size is useful in differentiating viable from nonviable intrauterine pregnancies. A mean sac diameter greater than 13 mm without a visible yolk sac or a mean sac diameter greater than 17 mm lacking an embryo predicts nonviability in all cases (4).There is no effective therapy for a threatened intrauterine pregnancy. Bed rest, although advocated, is not effective. Progesterone or sedatives should not be used. All patients should be counseled and reassured so that they understand the situation. Vaginal infection, if present, should be treated.Inevitable AbortionWith an inevitable abortion, the volume of bleeding is often greater than with other types of abortion, and the cervical os is open and effaced, but no tissue has been passed. Most patients have crampy lower abdominal pain, and some have cervical motion or adnexal tenderness. When it is certain that the pregnancy is not viable because the cervical os is dilated or excessive bleeding is present, suction curettage should be performed. Blood type and Rh determination and a complete blood count should be obtained if there is any concern about the amount of bleeding. Rh0(D) immune globulin (RhoGAM) should be given either before or after the uterus is evacuated if the patients blood is Rh negative.Incomplete AbortionAn incomplete abortion is a partial expulsion of the pregnancy tissue. Before 6 weeks of gestation, the placenta and fetus are generally passed together, but after this time, they often are passed separately. Although most patients have vaginal bleeding, only some have passed tissue. Lower abdominal cramping is invariably present, and the pain may be described as resembling labor. On physical examination, the cervix is dilated and effaced, and bleeding is present. Often, clots are admixed with products of conception. If the bleeding is profuse, the patient should be examined promptly for tissue protruding from the cervical os; removal of this tissue with a ring forceps reduces the bleeding. A vasovagal bradycardia may occur and responds to removal of the tissue. All patients with an incomplete abortion should undergo suction curettage as quickly as possible. A complete blood count, maternal blood type, and Rh determination should be obtained; Rh-negative patients should receive Rh0(D) immune globulin.If the patient is febrile, broad-spectrum antibiotic therapy should be administered before suction curettage is performed to reduce the incidence of postabortal endometritis and pelvic inflammatory disease, thereby reducing potential deleterious effects on fertility. The antibiotic regimen chosen should be similar to the regimens used for treatment of pelvic inflammatory disease (PID). In patients who do not have clinical signs of infection, prophylactic antibiotic therapy should be instituted. Suggested regimens include doxycycline (100 mg orally twice daily), tetracycline (250 mg orally four times daily for 5 days) or another antibiotic of similar spectrum.Ectopic GestationIncidenceThe most comprehensive data available on ectopic pregnancy rates have been collected by the Centers for Disease Control and Prevention (5). These data show a significant increase in the number of ectopic pregnancies in the United States during the past 20 years (Fig. 18.1 figures could not be shown in this Microsoft word file). In 1989, the latest year for which statistics were published, an estimated 88,400 ectopic pregnancies occurred, at a rate of 16 ectopic pregnancies per 1,000 reported pregnancies. These numbers represent a fivefold increase compared with the 1970 rates. The highest rates occurred in women aged 35 to 44 years (27.2 per 1,000 reported pregnancies). When the data are analyzed by race, the risk for ectopic pregnancy among African Americans and other minorities (20.8 per 1,000) is 1.6 times greater than the risk among whites (13.4 per 1,000). In 1988, 44 deaths were attributed to complications of ectopic pregnancy, which represents 15% of all maternal deaths. The risk for death is higher for African Americans and other minorities than for whites (6). For both races, teenagers have the highest mortality rates, but the rate for African American and other minority teenagers is almost five times that of white teenagers. After an ectopic pregnancy, there is a 7- to 13-fold increase in the risk of a subsequent ectopic pregnancy. The chance that a subsequent pregnancy will be intrauterine is 50% to 80%, and the chance that the pregnancy will be tubal is 10% to 25%; the remaining patients will be infertile (7,8,9). Many variables make accurate assessment of risk difficult (e.g., size and location of the ectopic pregnancy, status of the contralateral adnexa, treatment method, and history of infertility).Etiology and Risk FactorsTubal damage results from inflammation, infection, and surgery. Inflammation and infection may cause damage without complete tubal obstruction. Complete blockage may result from salpingitis, incomplete tubal ligation, tubal fertility surgery, partial salpingectomy, or congenital midsegment tubal atresia (10,11,12,13,14). Damage to the mucosal portion of the tube or fimbria accounts for about one half of all tubal pregnancies (15). Tubal diverticula may result in abnormalities that entrap the blastocyst or impede transport (16,17). Tubal pregnancy may occur in a blocked tube with contralateral tubal patency, with the sperm migrating across the abdomen to fertilize an egg released from the blocked side. Myoelectrical activity is responsible for propulsive activity in the fallopian tube (16). This activity facilitates movement of the sperm and ova toward each other and propels the zygote toward the uterine cavity. Estrogen increases smooth muscle activity, and progesterone decreases muscle tone. Aging results in progressive loss of myoelectrical activity along the fallopian tube, which may explain the increased incidence of tubal pregnancy in perimenopausal women (16). Hormonal control of the muscular activity in the fallopian tube may explain the increased incidence of tubal pregnancy associated with failures of the morning-after pill, minipill, progesterone-containing intrauterine devices (IUDs), and ovulation induction. Blighted ova occur more commonly in tubal conceptions than in intrauterine conceptions, although there is no increase in the incidence of chromosomal abnormalities in ectopic pregnancies (18).Independent factors consistently shown to increase the risk for tubal pregnancy include the following: Previous laparoscopically proven PID Previous tubal pregnancy Current IUD use Previous tubal surgery for infertilityMany other risk factors, including contraceptive choice, prior surgery, previous pregnancies, and fertility status, also have been identified.Pelvic InfectionThe relationship of PID, tubal obstruction, and ectopic pregnancy is well documented (13,19). In a study of 415 women with laparoscopically proven PID, the incidence of tubal obstruction increased with successive episodes of PID: 13% after one episode, 35% after two, and 75% after three (19). Furthermore, after one episode of PID, the ratio of ectopic pregnancy to intrauterine pregnancy was 1 in 24, a sixfold increase over the incidence for women with laparoscopically negative results (1 in 147). In a prospective study of 1,204 patients followed until first pregnancy after infection, 47 of 746 (6%) women with laparoscopically documented PID had a tubal gestation, which is significantly higher than the 0.9% incidence that occurred in the control group (20).Chlamydia is an important pathogen causing tubal damage and subsequent tubal pregnancy. Because many cases of chlamydia salpingitis are indolent, cases may not be recognized or, if recognized, may be treated on an outpatient basis. Chlamydia has been cultured from 7% to 30% of patients with tubal pregnancy (7,21). A strong association between chlamydia infection and tubal pregnancy has been shown with serologic tests for chlamydia (22,23,24,25). Conception is three times as likely to be tubal in women with anti-Chlamydia trachomatis titers higher than 1:64 than in those women whose titers were negative (7,26).Contraceptive UseInert and copper-containing IUDs prevent both intrauterine and extrauterine pregnancies (27,28). Women who conceive with an IUD in place, however, are 0.4 to 0.8 times more likely to have a tubal pregnancy than those not using contraceptives. Because IUDs prevent implantation more effectively in the uterus than in the tube, a woman conceiving with an IUD is 6 to 10 times more likely to have a tubal pregnancy than if she conceives without using contraception (27,28).With copper IUDs, 4% of contraceptive failures are tubal pregnancies. Progesterone IUDs are less effective than copper IUDs in preventing tubal pregnancy; 17% of failures result in tubal pregnancy. Furthermore, the rate of ectopic pregnancy in women using progesterone IUDs is higher than in women not using contraceptives: 1.9 per 100 woman-years (versus 0.5 for copper IUDs) (29). This finding suggests that failures occur for different reasons. Although all IUDs prevent intrauterine implantation, copper IUDs prevent fertilization by cytotoxic and phagocytic effects on the sperm and oocytes. Progesterone-containing IUDs are probably less effective in preventing conception.Duration of IUD use does not increase the absolute risk for tubal pregnancy (1.2 per 1,000 years of exposure), but with increasing use, there is an increase in the percentage of pregnancies that are tubal (30). With the exception of the Dalkon shield, for which past use of an IUD is associated with a twofold increased risk (31), the link between past use of IUDs and the risk of tubal pregnancy is unclear. One study showed that previous use of an IUD for longer than 2 years was associated with a fourfold risk, but this risk was present for only the first year after discontinuation of IUD use (27). However, subsequent studies have found no increased risk for tubal pregnancy following IUD use (30,32).The risk of the pregnancy being ectopic with combination oral contraceptive use has been calculated to be 0.5 to 4% (27,28,33). Past use of oral contraceptives does not increase the subsequent risk for ectopic pregnancy (8). Progesterone-only contraceptives, including oral contraceptives (minipill) and subdermal implants (Norplant), protect against both intrauterine and ectopic pregnancy when compared with no contraceptive use. If a pregnancy does occur, however, the chance of the pregnancy being ectopic is 4% to 10% for the minipill (34,35) and up to 30% if pregnancy occurs while implants are in place (36,37). Condom and diaphragm use protects against both intrauterine and ectopic pregnancy, and there is no increased incidence of ectopic pregnancy (30,33,38).SterilizationThe greatest risk of pregnancy, including ectopic pregnancy, occurs in the first 2 years after sterilization (39). Despite a greater proportion of poststerilization failures resulting in ectopic pregnancy, the absolute rate of ectopic pregnancy is decreased after sterilization. Calculating cumulative lifetime risk for ectopic pregnancy according to method of contraception, sterilized women have a lower cumulative risk for ectopic pregnancy than IUD users or nonusers of contraception, and women using barrier methods or oral contraceptives have the lowest risk (40).The