Ectopic Pregnancy: Clinical Manifestations and Diagnosis
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1/17/2016Ectopic pregnancy: Clinical manifestations and diagnosis Official reprint from UpToDate® www.uptodate.com ©2016 UpToDate® Ectopic pregnancy: Clinical manifestations and diagnosis Author Togas Tulandi, MD, MHCM Section Editor Robert L Barbieri, MD Deputy Editor Sandy J Falk, MD, FACOG All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Dec 2015. | This topic last updated: Sep 02, 2015. INTRODUCTION — An ectopic pregnancy is an extrauterine pregnancy. Almost all ectopic pregnancies occur in the fallopian tube (98 percent) [1], but other possible sites include: cervical, interstitial (also referred to as cornual; a pregnancy located in the proximal segment of the fallopian tube that is embedded within the muscular wall of the uterus), hysterotomy scar, intramural, ovarian, or abdominal. In addition, in rare cases, a multiple gestation may be heterotopic (include both a uterine and extrauterine pregnancy). The diagnosis of ectopic pregnancy is based upon a combination of measurement of the serum quantitative human chorionic gonadotropin (hCG) and findings on transvaginal ultrasonography (TVUS). The clinical manifestations and diagnosis of ectopic pregnancy will be reviewed here. This topic will focus mainly on the diagnosis of tubal pregnancy. The surgical treatment of ectopic pregnancy is reviewed elsewhere. Related topics regarding ectopic pregnancy are discussed in detail separately, including: ● Epidemiology, risk factors, and pathology (see "Ectopic pregnancy: Incidence, risk factors, and pathology") ● Management with methotrexate (see "Ectopic pregnancy: Choosing a treatment and methotrexate therapy") ● Surgical treatment (see "Ectopic pregnancy: Surgical treatment") ● Expectant management (see "Ectopic pregnancy: Expectant management") ● Diagnosis and management of uncommon sites (see "Abdominal pregnancy, cesarean scar pregnancy, and heterotopic pregnancy") CLINICAL PRESENTATION — The most common clinical presentation of ectopic pregnancy is first trimester vaginal bleeding and/or abdominal pain [2]. Ectopic pregnancy may also be asymptomatic. Normal pregnancy discomforts (eg, breast tenderness, frequent urination, nausea) are sometimes present in addition to the symptoms specifically associated with ectopic pregnancy. There may be a lower likelihood of early pregnancy symptoms, because progesterone, estradiol, and human chorionic gonadotropin (hCG) may be lower in ectopic pregnancy than in normal pregnancy [35]. In a retrospective study of 2026 pregnant women who presented to the emergency department with first trimester vaginal bleeding and abdominal pain, 376 (18 percent) were diagnosed with ectopic pregnancy. Of these 376 women, 76 percent had vaginal bleeding and 66 percent had abdominal pain [6]. In a populationbased registry of ectopic pregnancy from France, the incidence of rupture was 18 percent [7]. Clinical manifestations of ectopic pregnancy typically appear six to eight weeks after the last normal menstrual period, but can occur later, especially if the pregnancy is in an extrauterine site other than the fallopian tube. An ectopic pregnancy may be unruptured or ruptured at the time of presentation to medical care. Tubal rupture (or rupture of other structures in which an ectopic pregnancy is implanted) can result in lifethreatening hemorrhage. Any symptoms suggestive of rupture should be noted. These include severe or persistent abdominal pain or symptoms suggestive of ongoing blood loss (eg, feeling faint or loss of consciousness). Based upon the concern about the risk of rupture at the time or after presentation, clinicians should consider ectopic pregnancy as a diagnosis in any woman of reproductive age with vaginal bleeding and/or abdominal pain http://www.uptodate.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=search… 1/19 the fallopian tube) has ruptured and whether the patient is hemodynamically stable. However. but may occur as a single episode or continuously.uptodate. ● Perform additional testing to guide further management (eg. pretreatment testing for methotrexate therapy). (See "Ectopic pregnancy: Incidence. Determine the site of the ectopic pregnancy. the pain may be in the middle or upper abdomen. DIAGNOSTIC EVALUATION Overview — The main goals and steps of the evaluation of a woman with a suspected ectopic pregnancy are: ● Confirm that the patient is pregnant (see 'Human chorionic gonadotropin' below). In cases in which there is intraperitoneal blood that reaches the upper abdomen or in rare cases of abdominal pregnancy. (See "Prenatal assessment of gestational age and estimated date of delivery". and the pain may be continuous or intermittent. a woman who presents with hemodynamic instability and an acute abdomen that is not explained by another diagnosis. Bleeding occurs in many other conditions in early pregnancy. A populationbased French study identified four factors that increased the risk of rupture when an ectopic pregnancy was suspected: (1) never having used contraception. The timing. However. and pathology". (2) history of tubal damage and infertility.) Risk factors for ectopic pregnancy should be elicited. blood type and antibody screen. The onset of the pain may be abrupt or slow. and severity of abdominal pain vary. some women may misinterpret bleeding as normal menses. prior tubal ligation. character. (3) induction of ovulation. and in vitro fertilization (IVF) (table 1). section on 'Risk factors'. particularly if amenorrhea of >4 weeks preceded the current vaginal bleeding; (3) in rare cases. Blood pooling in the posterior culdesac (pouch of Douglas) may cause an urge to defecate. the pregnancy is heterotopic). (See 'Differential diagnosis' below. The vaginal bleeding associated with ectopic pregnancy is typically preceded by amenorrhea.) http://www. at least 10. ● Determine whether the pregnancy is intrauterine or ectopic (in rare cases. History — A menstrual history should be taken and the estimated gestational age should be calculated. and (4) high level of human chorionic gonadotropin (hCG. over 50 percent of women are asymptomatic before tubal rupture and do not have an identifiable risk factor for ectopic pregnancy [8].1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis who has the following characteristics: (1) pregnant. The overall rate of tubal rupture in this series was 18 percent. Failure to diagnose ectopic pregnancy before tubal rupture limits the treatment options and increases maternal morbidity and mortality. The pain may be dull or sharp; it is generally not crampy.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=search… 2/19 . but rupture may also present with mild or intermittent pain. The pain may be mild or severe. If there is sufficient intraabdominal bleeding to reach the diaphragm. (See 'Clinical presentation' above. including prior ectopic pregnancy. ● Determine whether the structure in which the pregnancy is implanted (most commonly. It may be diffuse or localized to one side.) The history should focus on the presence and characteristics of vaginal bleeding and abdominal pain.000 IU/L) [7]. risk factors. Tubal rupture may be associated with an abrupt onset of severe pain. but does not have a confirmed intrauterine pregnancy (IUP); (2) pregnancy status uncertain. Vaginal bleeding — The amount and timing of vaginal bleeding vary and there is no bleeding pattern that is pathognomonic for ectopic pregnancy. Bleeding may range from scant brown staining to hemorrhage. This is particularly true in women who have irregular menses or who do not keep track of menstrual cycles. there may be referred pain that is felt in the shoulder. and there is no pain pattern that is pathognomonic for ectopic pregnancy. and may not realize they are pregnant prior to developing symptoms associated with ectopic pregnancy.) Abdominal pain — The pain associated with ectopic pregnancy is usually located in the pelvic area. Bleeding is typically intermittent. current use of an intrauterine device. serial http://www.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis The medical and surgical history should be reviewed. but will likely be smaller than appropriate for gestational age. (See 'Heterotopic pregnancy' below and 'Interstitial pregnancy' below. whenever possible. TVUS alone (without measurement of hCG) can exclude or diagnose an ectopic pregnancy only if one of the following findings is present: ● Findings diagnostic of an intrauterine pregnancy (IUP.uptodate. ● Findings diagnostic of a pregnancy at an ectopic site (gestational sac with a yolk sac or embryo). Cardiac activity may or may not be present. renal or hepatic disease). The rare exceptions are heterotopic pregnancies and misdiagnoses of an IUP (ie.) TVUS can also detect findings that are suggestive. and/or abdominal tenderness. In the great majority of cases. since excessive pressure may rupture an ectopic pregnancy. it may be because the gestation is too early to be visualized on ultrasound. the abdomen may be distended and diffuse or localized tenderness to palpation and/or rebound tenderness may be found on examination. Transvaginal ultrasound — TVUS is the most useful imaging test for determining the location of a pregnancy. (See "Initial management of trauma in adults". vital signs. If so. In young. The ultrasound should be performed by a clinician with expertise in gynecologic ultrasound and with the evaluation of ectopic pregnancy. or incidental uterine pathology (most commonly. but not diagnostic. a rupture rate of 50 percent was found with 80 percent occurring before the third trimester [10]. In either case. The focus should be on obstetric history and pelvic or abdominal surgical history and medical comorbidities that are potential contraindications for surgery or methotrexate therapy (eg. However. Findings on examination may include cervical motion. section on 'Circulation'. Diagnostic testing — The tests used to diagnose an ectopic pregnancy are a combination of serum quantitative hCG level and transvaginal ultrasound (TVUS) (algorithm 1 and table 2). The uterus may be somewhat enlarged.) The abdominal examination is often unremarkable or may reveal lower abdominal tenderness. section on 'Contraindications'. of ectopic pregnancy.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=search… 3/19 . Palpation of the adnexa should be performed with only a small degree of pressure. The speculum examination is used to confirm that the uterus is the source of bleeding (rather than a cervical or vaginal lesion) and to assess the volume of bleeding by noting the quantity of blood in the vagina and presence or absence of active bleeding from the cervix. (See "Ectopic pregnancy: Choosing a treatment and methotrexate therapy". since this may impact treatment. a pseudosac is formed that may appear to be a gestational sac (see "Ultrasonography of pregnancy of unknown location". A bimanual pelvic examination is performed; the examination is often unremarkable in a woman with a small. rare cases of heterotopic pregnancy. assessing the vital signs should include an evaluation for postural change. An adnexal mass is the most common ultrasound finding in ectopic pregnancy and is present in 89 percent or more of cases [1113]. adnexal. either two findings above excludes or diagnoses an ectopic gestation.) Physical examination — Vital signs should be measured and hemodynamic stability assessed. may be normal early in the course of significant bleeding due to compensatory mechanisms [9]. Uterine enlargement in women with ectopic pregnancy may be due to endocrine changes of pregnancy. interstitial pregnancy or rudimentary horn pregnancy). In a review of 568 cases of rudimentary uterine horn pregnancies from 1900 to 1999. including postural changes. A complete pelvic examination should be performed. depending upon the hCG level or a suspicion of rupture. a gestational sac alone is not sufficient for diagnosis. If rupture with significant bleeding has occurred. Women with hemodynamic instability and suspected ectopic pregnancy require emergency surgery. TVUS should be performed as part of the initial evaluation and may need to be repeated. In some ectopic gestations. An adnexal mass is noted in some women. uterine fibroids). gestational sac with a yolk sac or embryo). unruptured ectopic pregnancy. section on 'Pseudosac'). healthy patients with blood loss. If TVUS is nondiagnostic. The hCG concentration in a normal IUP rises in a curvilinear fashion until about 41 days of gestation. The hCG result varies across different assays and laboratories. tubal abortion. a small amount of fluid is present in many women and a small amount of blood may be present in other conditions (eg. Ultrasound evaluation for ectopic pregnancy versus IUP is discussed in detail separately. ● The slowest recorded rise over 48 hours associated with a viable IUP was 53 percent. cesarean scar pregnancy. A decreasing hCG concentration is most consistent with a failed pregnancy (eg.) Studies in viable IUPs have reported the following changes in serum hCG [17.1 days in early pregnancy. However. anembryonic pregnancy.4 to 2.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis measurements of the serum hCG concentration should be taken until the hCG discriminatory zone is reached [14].) Either ultrasound or other abdominal imaging modalities are used for evaluation in the rare cases of abdominal pregnancy.19]. Once a pregnancy is confirmed. section on 'Pregnancy'. The intraassay and interassay variabilities depend http://www. spontaneously resolving ectopic pregnancy. but not all. only 21 percent of ectopic pregnancies were associated with hCG levels that followed the minimum doubling time of a viable IUP (defined in this series as ≥53 percent increase over two days) [18]. hCG can be detected in serum and urine as early as eight days after the luteinizing hormone surge (approximately 21 to 22 days after the first day of the last menstrual period in women with 28day cycles). and heterotopic pregnancy". the hCG concentration rises by at least 66 percent every 48 hours during the first 40 days of pregnancy; only 15 percent of viable pregnancies have a rate of rise less than this threshold. the serum hCG is then repeated serially (typically every two days) to assess whether the increase in concentration is consistent with an abnormal pregnancy.18]: ● The mean doubling time for the hormone ranges from 1.) In pregnant women.) Human chorionic gonadotropin — Measurement of hCG is performed initially to diagnose pregnancy and then followed to assess for ectopic pregnancy. ● In 85 percent of viable IUPs. if the hCG is above the discriminatory zone and transvaginal ultrasound shows no evidence of an intrauterine pregnancy and the presence of findings that suggest an ectopic pregnancy. and then declines until reaching a plateau in the second and third trimesters [15]. complete or incomplete abortion). section on 'Diagnostic evaluation'. spontaneous abortion). after which it rises more slowly until approximately 10 weeks.uptodate. hCG is measured serially (every 48 to 72 hours) to determine whether the increase is consistent with an abnormal pregnancy. A ruptured ovarian cyst is another condition that is common in pregnant women and may result in a small or large amount of blood. A finding of echogenic fluid (consistent with blood) in the pelvic culdesac and/or abdomen is consistent with rupture. (See 'Transvaginal ultrasound' above. It is not possible to determine whether a pregnancy is normal from a single hCG level because there is a wide range of normal levels at each week of pregnancy [16]. A serum hCG that does not rise appropriately is consistent with an abnormal pregnancy.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=search… 4/19 . For followup. the diagnosis of ectopic pregnancy can be made after a single measurement of hCG in combination with transvaginal ultrasound. (See "Abdominal pregnancy. The initial test to diagnose pregnancy may be either a urine or serum hCG.) The ultrasound examination is also used to evaluate whether rupture of the tube or other structure has occurred. if ectopic pregnancy is suspected. arrested pregnancy. In one series. The hCG concentration rises at a much slower rate in most. Rupture is indicated by ultrasound findings of free fluid (blood) in the abdominal cavity. (See 'Clinical protocol' below. as an example. (See "Clinical manifestations and diagnosis of early pregnancy". A single hCG measurement alone cannot confirm the diagnosis of ectopic or normal pregnancy. section on 'Serum pregnancy test' and "Human chorionic gonadotropin: Testing in pregnancy and gestational trophoblastic disease and causes of low persistent levels". In some cases. ectopic and nonviable IUPs [18. (See "Ultrasonography of pregnancy of unknown location". 1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis on the type of assay. The number of serial measurements to use to make the diagnosis has not http://www. Thus. the presence of physical factors (eg.4 percent. In addition.22]. an IUP or ectopic pregnancy can be diagnosed by TVUS. respectively [23]. and the laboratory characteristics of the hCG assay used.2 and 93.25 percent.) The most common protocol is to measure the hCG every two days.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=search… 5/19 . the discriminatory zone is a serum hCG level of 1500 or 2000 IU/L with TVUS. In one representative study. if present. Also. respectively [20]. multiple gestation). However. Clinical protocol — The clinical protocol for the evaluation for an ectopic pregnancy includes assessment with serum hCG and TVUS: ● HCG below the discriminatory zone – A serum hCG concentration <1500 or 2000 IU/L (or another value. section on 'False positive test or "phantom hCG"'. the possibility of falsely positive or negative hCG test results should be considered [21. At that time. they are 10. we find that measurement every 72 hours is more practical than every 48 hours. (See "Human chorionic gonadotropin: Testing in pregnancy and gestational trophoblastic disease and causes of low persistent levels". the correct level to use for the discriminatory zone is controversial. In one study. Another cause for variation of the discriminatory zone is that it is dependent upon the skill of the ultrasonographer.4 to 2. As noted above. the quality of the ultrasound equipment. and for an hCG level of >2000 IU/L. In our practice. Setting the discriminatory zone at 2000 IU/L instead of 1500 IU/L minimizes the risk of interfering with a viable IUP.87 and 6.1 days and slowest recorded rise over 48 hours associated with a viable IUP was 53 percent. but TVUS is the standard modality used to evaluate ectopic pregnancy. In most institutions. the mean hCG doubling time is 1.9 and 95. The hCG level may be rising slowly or may plateau at or very close to the previous level. before deciding on methotrexate treatment. It is important to note that there is a variation in the level of hCG across pregnancies for each gestational age and the discriminatory levels are not always reliable. the protocol is as follows: • hCG is rising normally (increasing by at least 53 percent in 48 hours OR doubling in 72 hours) – The patient should be evaluated with TVUS when the hCG reaches the discriminatory zone. The clinician can be reasonably certain that a normal IUP is not present. • hCG is rising. the same laboratory should be used for serial measurements. (See 'Human chorionic gonadotropin' above. but NOT normally – The lack of a normal rise in hCG across three measurements (the initial serum quantitative hCG and two additional serial measurements) is consistent with an abnormal pregnancy (an ectopic gestation or IUP that will ultimately abort). the discriminatory zone for the institution should be used) should be followed by repeated measurement of quantitative hCG to follow the rate of rise. section on 'False negative test (hook effect)' and "Human chorionic gonadotropin: Testing in pregnancy and gestational trophoblastic disease and causes of low persistent levels". 185 of 188 (98 percent) IUPs in women with hCG above 1500 IU/L were visualized [25]. and allowing 72 hours for doubling helps to avoid misclassifying those viable pregnancies with slower than average doubling times. Accordingly. the intraassay and interassay coefficient of variation were 4. but increases the risk of delaying diagnosis of an ectopic pregnancy. for a viable IUP. The use of 1500 or 2000 IU/L as the discriminatory zone is based upon observations that an intrauterine gestational sac could be detected by TVUS in patients with serum hCG concentrations as low as 800 IU/L and was usually identified by expert ultrasonographers at concentrations above 1500 to 2000 IU/L [24].uptodate. interpretation of serial hCG concentrations is more reliable when the assays are performed in the same laboratory. The level is higher for transabdominal ultrasound (approximately 6500 IU/L).) Discriminatory zone — The discriminatory zone is the serum hCG level above which a gestational sac should be visualized by TVUS if an IUP is present. The reported sensitivity and specificity of hCG of >1500 IU/L are 15.2 percent. one has to be sure that there is no possibility of a viable intrauterine pregnancy. fibroids. Thus. women with a suspected ectopic pregnancy should be counseled about possible outcomes of the evaluation.uptodate. If there are findings that confirm an IUP. however. progesterone measurements merely confirm diagnostic impressions already obtained by hCG measurements and transvaginal sonography. or feeling faint. some clinicians administer methotrexate and others perform curettage to exclude an IUP and thereby avoid medical therapy of nonviable IUP [27]. These include the new onset of or a significant worsening of abdominal pain. In our experience. the TVUS should be repeated. To followup with these patients. We do not routinely measure serum progesterone. Ancillary diagnostic tests — Additional diagnostic tests have been used in women with suspected ectopic pregnancy. that the definition of a low progesterone is unclear. Some data suggest that use of three serial measurements is more effective than two measurements [26]. a progesterone <3. Patients who are being followed for suspected ectopic pregnancy should be counseled about the risk of rupture and should be advised to call if symptoms associated with rupture occur. For women with bleeding or pain and an inconclusive pelvic ultrasound. If an adnexal mass is not visualized. In patients with an abnormal rise in hCG. It should be noted. measurement of serum progesterone may be useful in a patient with abdominal pain and bleeding and who has a serum hCG level below that expected for her gestational age.) • hCG is decreasing – A decreasing hCG is most consistent with a failed pregnancy (eg. A metaanalysis of 26 cohort studies including 9436 women in the first trimester of pregnancy evaluated use of a single measurement of serum progesterone for the diagnosis of a nonviable pregnancy [29]. (See 'Curettage' below. If TVUS does not reveal an IUP and shows a complex adnexal mass. a progesterone <10 ng/mL (31. tubal abortion.2 to 19. spontaneous abortion. since there is no proven discriminatory level for multiple gestations. vaginal hemorrhage. The diagnosis of ectopic pregnancy is less certain if no complex adnexal mass can be visualized. the results of TVUS guide management. an ectopic pregnancy is excluded and the patient should be managed as a failed pregnancy. However. then medical or surgical treatment is administered for a presumed ectopic pregnancy. since there is variability in the level of expertise among ultrasonographers. Furthermore.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis been well studied. The sensitivity and specificity of a low serum progesterone concentration for predicting a nonviable pregnancy in spontaneously pregnant patients are different from those in infertile patients who have undergone controlled ovarian hyperstimulation for IVF or intrauterine insemination [30]. In addition. Curettage — The intrauterine location of a pregnancy is diagnosed with certainty if trophoblastic tissue is http://www. If an adnexal mass consistent with an ectopic pregnancy is visualized. ● hCG above the discriminatory zone – For women with a quantitative serum hCG above the discriminatory zone. Except in selected cases. If an IUP is still not observed on TVUS. including viable IUP or the end of a pregnancy with treatment for ectopic pregnancy. an extrauterine pregnancy is almost certain.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=search… 6/19 .8 nmol/L) had a sensitivity of 67 percent and a specificity of 96 percent. For women with bleeding or pain alone. For these reasons. The predictive value of a low serum progesterone for identifying nonviable pregnancies varies with the patient population. Treatment of ectopic pregnancy should be instituted.1 nmol/L) had a sensitivity of 75 percent and a specificity of 98 percent. a serum hCG >1500 IU/L without visualization of intrauterine or extrauterine pathology may represent a multiple gestation. then the pregnancy is abnormal. Progesterone — Serum progesterone concentrations are higher in viable IUPs than in ectopic pregnancies and IUPs that are destined to abort [28]. weekly hCG concentrations should be measured until the result is undetectable.2 to 6 ng/mL (10. our next step in this clinical scenario is to repeat the TVUS examination and hCG concentration two days later. spontaneously resolving ectopic pregnancy). such tests do not provide additional clinically useful information. a medical approach confers additional risk and has no proven benefit. However. risk of recurrence) and for future decisionmaking. Historically. (See "Ectopic pregnancy: Choosing a treatment and methotrexate therapy". (See "Ectopic pregnancy: Choosing a treatment and methotrexate therapy" and "Intrauterine adhesions". Some experts have recommended performing curettage only on women with both a hCG concentration below the discriminatory zone and a low doubling rate [34. a culdocentesis positive for blood is nondiagnostic. serum hCG levels can be followed postcurettage if histopathology does not confirm the clinical impression. laparoscopy is used to confirm the diagnosis if hCG and ultrasound results are ambiguous. Blood type and screen — A Rh(D) typing and antibody screen should be drawn if not previously performed during the current pregnancy. (See "Culdocentesis". If curettage is performed. Therefore. In this situation.uptodate. In contrast. section on 'Alterations in hemostasis'. In severe cases. Moreover.35]. Rh(D) type. (See "Massive blood transfusion". pretreatment laboratory tests should be drawn. section on 'Pretreatment testing'. the authors' preference was to perform curettage in these patients to be more certain of the diagnosis. Approximately 30 percent of these patients have a nonviable intrauterine gestation and the remainder have an ectopic pregnancy [35. Blood in the posterior culdesac may be from bleeding from an unruptured or ruptured tubal pregnancy. (See "Prevention of Rh(D) alloimmunization". we and others believe it is more practical and less invasive to continue observation or administer one dose of methotrexate than to perform curettage [37. if heavy bleeding is suspected. A decision analysis comparing the cost/complication rates in patients who undergo diagnostic curettage before administration of methotrexate with those who do not have a curettage concluded there was no significant benefit of one approach over the other [36].1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis obtained by uterine curettage. false negatives can occur: chorionic villi are not detected by histopathology in 20 percent of curettage specimens from elective termination of pregnancy [31].) If significant bleeding is suspected. a sample should be sent to the blood bank for crossmatching for potential transfusion.38]. pretreatment testing typically includes a complete blood count and renal and liver function tests.) If ectopic pregnancy is diagnosed and treatment with methotrexate is considered.33]. (See 'Transvaginal ultrasound' above http://www. and felt this information was useful prognostically (eg.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=search… 7/19 . curettage carries a risk of intrauterine adhesion formation. In addition. the use of curettage as a diagnostic tool is limited by the potential for disruption of a viable pregnancy. The side effects of one dose of methotrexate are negligible. Pipelle endometrial biopsy is even less sensitive than curettage for detection of villi; sensitivities reported in two small series were 30 and 60 percent [32. culdocentesis was used to detect blood in the posterior culdesac; however. this finding can be easily demonstrated with transvaginal ultrasound. Pretreatment laboratory tests — For women treated with methotrexate. hCG levels should drop by at least 15 percent the day after evacuation [27].) Other tests — Rarely. Knowing the results of curettage avoids unnecessary methotrexate treatment of the 30 percent of patients without ectopic pregnancy.) Additional testing — Additional testing is performed to evaluate the patient’s hemodynamic status. If methotrexate treatment is a possibility. a complete blood count is part of the pretreatment laboratory evaluation. measurement of platelets or coagulation tests may also be indicated. When an IUP has been evacuated. Obviously.) DIAGNOSIS — The diagnosis of ectopic pregnancy is a clinical diagnosis made based upon serial serum human chorionic gonadotropin (hCG) testing and transvaginal ultrasound (TVUS). but it may also be the result of a ruptured ovarian cyst. Women with bleeding in pregnancy who are Rh(D)negative should be given antiD immune globulin. An ectopic pregnancy detected at laparoscopy should be treated immediately by surgery. Complete blood count — Women with suspected ectopic pregnancy should be evaluated for anemia with a hemoglobin and/or hematocrit.36]. the patient is followed until the hCG is above the discriminatory zone. but in most institutions it is 1500 to 2000 IU/L (see 'Discriminatory zone' above and 'Clinical protocol' above): ● Below the discriminatory zone • If the serial hCG level does not rise appropriately across at least three measurements 48 to 72 hours apart and there is no evidence on TVUS that confirms an IUP. or other sites further support the diagnosis. but are not diagnostic on their own (see 'Transvaginal ultrasound' above). believed to be related to implantation) Spontaneous abortion Gestational trophoblastic disease Cervical. as appropriate (table 3). The gestational sac is an early finding and is suggestive of. uterine curettage is performed to confirm the absence of an IUP (see 'Curettage' above). The differential diagnosis of bleeding or pain early in pregnancy also includes [39]: ● ● ● ● ● Physiologic (ie. hypotension and shock. In selected cases. histologic confirmation is obtained following treatment. ovary. In selected cases.) Histologic confirmation of the diagnosis is not typically required. section on 'Peritoneal free fluid'. and eventually. The presence of a gestational sac with a yolk sac or embryo is diagnostic of a pregnancy.uptodate. (See "Differential diagnosis of genital tract bleeding in women" and http://www. or uterine pathology Subchorionic hematoma Nonuterine sources of bleeding can be identified by physical examination. the pregnancy is considered abnormal. the presence or absence of peritoneal free fluid is not a reliable indicator of whether an ectopic pregnancy has ruptured. However. This is referred to as a pregnancy of unknown location and 8 to 40 percent are ultimately diagnosed as ectopic pregnancies [23]. A presumptive diagnosis of ectopic pregnancy can be made and the patient may be treated. (See "Ultrasonography of pregnancy of unknown location". Screening for cervical cancer should also be performed. Ultrasound findings suggestive of an ectopic pregnancy in the fallopian tube. but does not fully confirm. In the absence of a definitive sonogram confirming an IUP or histopathologic findings. • If the serial serum hCG level is rising appropriately. vaginal.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis and 'Human chorionic gonadotropin' above. Abdominal examination findings include tenderness and possible peritoneal signs. the diagnosis of rupture can be made by direct visualization. The typical finding on TVUS is free blood in the peritoneal cavity. ● Above the discriminatory zone – The diagnosis is made based upon the absence of TVUS findings that diagnose an IUP OR findings at an extrauterine site that confirm an ectopic pregnancy. uterine curettage is performed to confirm the absence of an intrauterine pregnancy (IUP) prior to methotrexate therapy.) For women who undergo surgery. The typical findings of rupture are abdominal pain. Diagnostic criteria — The diagnostic criteria depend upon the relationship to the hCG discriminatory zone (serum hCG level above which a gestational sac should be visualized by TVUS if an IUP is present). shoulder pain due to diaphragmatic irritation by blood in the peritoneal cavity. Ruptured versus nonruptured ectopic pregnancy — Diagnosis of rupture of the structure within which the ectopic gestation is implanted (usually the fallopian tube) is a clinical diagnosis. DIFFERENTIAL DIAGNOSIS — The classic symptoms of ectopic pregnancy are vaginal bleeding and abdominal pain. it is sometimes impossible to differentiate between an ectopic pregnancy and an early failed intrauterine gestation. The hCG level of the discriminatory zone varies. an IUP (see 'Transvaginal ultrasound' above). If an ectopic pregnancy is treated surgically.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=search… 8/19 . so vaginal bleeding is a common symptom. On ultrasound examination. the diagnosis is suggested by visualization of both an ectopic pregnancy and IUP or the presence of echogenic fluid in the posterior culdesac in the presence of an IUP. and include cervical. ovarian cyst rupture. and heterotopic pregnancy". (See "Abdominal pregnancy. leiomyomas. ovarian torsion. especially in patients who have undergone IVF and who experience abdominal pain or vaginal bleeding. and abdominal pregnancy. Levels of over 9000 IU/L have been described for intrauterine triplet pregnancies unobserved by transvaginal ultrasound (TVUS) [40]. but can be at another location. clinical manifestations. (See "Overview of the etiology and evaluation of vaginal bleeding in pregnant women" and "Spontaneous abortion: Risk factors. endometriosis. ● Interstitial pregnancy accounts for up to 1 to 3 percent of ectopic pregnancies [45. ovarian neoplasms. clinical features. while abdominal or rudimentary horn pregnancies can continue to develop late in gestation [41. When the human chorionic gonadotropin (hCG) concentration is unusually high for the gestational age. all women with first trimester bleeding should be evaluated by transvaginal ultrasonography.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis "Screening for cervical cancer". such as the cervix. if a transvaginal sonogram reveals an IUP.uptodate. gestational trophoblastic disease should be suspected.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=search… 9/19 . the serum human chorionic gonadotropin (hCG) level could be higher than 1500 mIU/mL and yet ultrasound examination will not reveal an intrauterine pregnancy (IUP) [14]. appendicitis. rudimentary uterine horn.42]. diverticulitis. section on 'Heterotopic pregnancy'. except among women conceiving through in vitro fertilization (IVF). ovarian. and pregnancyrelated conditions. pelvic inflammatory disease. Heterotopic tubal pregnancies have been reported as late as 16 weeks of gestation. the endometrium often responds to ovarian and placental production of pregnancyrelated hormones. We suggest that women with a confirmed IUP who are experiencing abdominal pain or vaginal bleeding undergo serial TVUS examinations every week until the possibility of a concomitant tubal ectopic pregnancy can be eliminated. kidney stones. cesarean scar pregnancy. http://www. The diagnosis and management of heterotopic pregnancy are discussed separately.) SPECIAL ISSUES Multiple gestation — In women with an intrauterine multiple pregnancy. These ectopic pregnancy sites are uncommon.) Even if another source of bleeding is identified. cesarean scar pregnancy.46]. and diagnosis". Heterotopic pregnancy (combined intrauterine and extrauterine pregnancy) is rare. ● Cervical pregnancy is estimated to occur in 1/2500 to 1/18. Thus. (See "Diagnostic approach to abdominal pain in adults".000 pregnancies and accounts for 1 percent of ectopic pregnancies [44]. endometritis. Serial hCG concentrations are not interpretable in the presence of both a viable intrauterine and ectopic pregnancy. and diagnostic evaluation" and "Hydatidiform mole: Epidemiology. Heterotopic pregnancy — The investigation for ectopic pregnancy can be terminated. should be considered. The evaluation of first trimester vaginal bleeding is outlined in the algorithm (algorithm 2) and is discussed separately. or even bilaterally [43]. (See "Abdominal pregnancy. and heterotopic pregnancy". interstitial. but also the adnexa of women who conceive following IVF.) The differential diagnosis of lower abdominal pain in women includes urinary tract infection. etiology.) Early diagnosis of heterotopic pregnancy is difficult because of lack of symptoms. under most circumstances. The extrauterine pregnancy is usually in the fallopian tube. hysterotomy scar.) Uncommon sites of ectopic pregnancy — The possibility that an ectopic pregnancy may occur in a nontubal location. a high index of suspicion for this diagnosis is important. The ultrasonographer should carefully examine not only the uterus. Regardless of the location. (See "Ultrasonography of pregnancy of unknown location". (See "Ultrasonography of pregnancy of unknown location". vaginal bleeding) [53].4 percent of ectopic pregnancies [48]. an interstitial pregnancy appears as a gestational swelling lateral to the insertion of the round ligament (figure 1) [46]. Although the maternal mortality rate associated with tubal pregnancy is decreasing. An interstitial pregnancy can be difficult to distinguish on ultrasound from an IUP that is eccentrically positioned. The normal pattern of the rise in serum hCG in early pregnancy is discussed below. all of which were before 12 weeks [54].) The diagnosis of ovarian pregnancy is typically made at the time of surgery. (See "Ectopic pregnancy: Incidence. The goal is to establish the diagnosis early to avoid rupture. section on 'Ovarian pregnancy'.5 percent because of misdiagnosis of these gestations as IUPs.uptodate. or in one side of a septated or partially septated uterus [46]. including those with an IVF pregnancy. as these pregnancies are usually treated by surgical excision of the involved organs. the rate for interstitial pregnancies remains at 2 to 2. ● Abdominal pregnancy accounts for up to 1. For women who are monitored in this way. Other clinical manifestations are the same as for all ectopic gestations (pelvic or abdominal pain. (See "Abdominal pregnancy. This type of pregnancy is extremely rare with less than 50 reported cases in the literature [51].000 pregnancies and accounts for 1 to 3 percent of ectopic pregnancies [47]. a rudimentary horn of a unicornuate uterus.50]. although an average delay of only four days in comparison with tubal pregnancies was reported in a large series [53].) Interstitial pregnancy — The interstitial portion of the fallopian tube is the proximal segment that is embedded within the muscular wall of the uterus. Ovarian pregnancy — Sonographic diagnosis of an ovarian pregnancy is difficult. The exact diagnosis is not clinically important. we monitor women at high risk of ectopic pregnancy (table 1) with laboratory and imaging studies. Strict histopathological criteria are used to distinguish ovarian pregnancies from those originating in the fallopian tube. and heterotopic pregnancy".com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc… 10/19 . Rates of maternal mortality have been reported as high as 20 percent [41. The unique anatomic location of an interstitial pregnancy often leads to a delay in diagnosis. risk factors. but differentiation from a hemorrhagic ovarian cyst or pregnancy in the distal fallopian tube can be difficult. The exceptions to this are women at high risk of an ectopic pregnancy.) Grossly. A pregnancy implanted at this site is called an interstitial pregnancy (figure 1); the term cornual pregnancy is also widely used to describe a pregnancy at this location. Other sites — Diagnosis and management of cesarean scar and abdominal pregnancy are discussed in detail separately. cesarean scar pregnancy. the term cornual pregnancy referred only to pregnancies implanted in either the horn of a bicornuate uterus. pregnancy after reconstructive surgery of the fallopian tube. Originally. These pregnancies can go undetected until an advanced age and often result in severe hemorrhage [49]. (See 'Human chorionic gonadotropin' above. and pathology". and start with the first missed menses or after embryo transfer for IVF. or prior history of ectopic pregnancy. We use the same protocol as for the diagnosis of ectopic pregnancy.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis ● Ovarian pregnancy occurs in 1/2100 to 1/60. Ultrasound may suggest the diagnosis preoperatively [47].) Screening asymptomatic women — Routine prenatal care does not include serial measurement of serum hCG. This is in contrast to previous reports that rupture of interstitial pregnancy occurred late in pregnancy. A series of cases of interstitial pregnancy reported to a surgical registry included 14 patients with tubal rupture. Methotrexate treatment has been successful in case reports [52]. Ultrasound evaluation for interstitial pregnancy is discussed in detail separately. Interstitial pregnancy presents with rupture in approximately 20 to 50 percent of cases [5456]. Ultrasound evaluation for ovarian pregnancy is discussed in detail separately.) In our practice. (See "Ectopic http://www. ● Intramural pregnancy refers to pregnancy implanted within the myometrium of the uterus. an ectopic pregnancy may present with an abnormal rise in hCG. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest. Alternatively. We encourage you to print or email these topics to your patients. In rare cases. hysterotomy scar. over 50 percent of women are asymptomatic before tubal rupture and do not have an identifiable risk factor for ectopic pregnancy. may cause tubal obstruction [60]. or abdominal. ● Rupture – Tubal rupture is usually associated with profound hemorrhage.) ● Basics topics (see "Patient information: Ectopic pregnancy (The Basics)") ● Beyond the Basics topics (see "Patient information: Ectopic (tubal) pregnancy (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS ● An ectopic pregnancy is an extrauterine pregnancy. section on 'Monitoring for pregnancy'. These articles are best for patients who want a general overview and who prefer short. ● Spontaneous resolution – The incidence of spontaneous resolution of an ectopic pregnancy is unknown. easytoread materials. risk factors. especially those who have risk factors (table 1). It is difficult to predict which patients will experience uncomplicated spontaneous resolution. and pathology"." The Basics patient education pieces are written in plain language. Potential candidates are hemodynamically stable women with an initial hCG concentration less than 2000 IU/L that is declining [59]. a tubal abortion may occur. Almost all ectopic pregnancies occur in the fallopian tube (98 percent).1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis pregnancy: Incidence. However. and they answer the four or five key questions a patient might have about a given condition. or it may regress spontaneously. less commonly. Ruptured ectopic pregnancy is the major cause of pregnancyrelated maternal mortality in the first trimester [57]. a multiple gestation may be heterotopic (include both a uterine and extrauterine pregnancy). In one older (1955) series of 119 hospitalized patients with typical ectopic pregnancy symptoms. (See 'Clinical presentation' above. and more detailed. not requiring further treatment. abdominal pregnancy) or on the ovary (ie. (See 'Introduction' above and 'Uncommon sites of ectopic pregnancy' above. interstitial. Beyond the Basics patient education pieces are longer. Gestational products left in the fallopian tube may resorb completely or. ovarian. Most of these deaths occur prior to hospitalization or proximate to the woman's arrival in the emergency department. Tubal abortion may be accompanied by severe intraabdominal bleeding. Here are the patient education articles that are relevant to this topic.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc… 11/19 . section on 'Risk factors' and "In vitro fertilization". ● Abortion – Tubal abortion refers to expulsion of the products of conception through the fimbria. or by minimal bleeding. ovarian pregnancy). more sophisticated. without surgical or medical intervention (except opiates) [58]. an ectopic pregnancy in the fallopian tube can progress to a tubal abortion or tubal rupture. "The Basics" and "Beyond the Basics. at the 5th to 6th grade reading level. These articles are written at the 10th to 12th grade reading level and are best for patients who want indepth information and are comfortable with some medical jargon. which can be fatal if surgery is not performed expeditiously to remove the ectopic gestation. INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials. This can be followed by resorption of the tissue or by reimplantation of the trophoblasts in the abdominal cavity (ie. but other possible sites include: cervical.) ● Abdominal pain and vaginal bleeding are the most common symptoms of ectopic pregnancy.uptodate. necessitating surgical intervention. Salpingectomy is the most common surgical approach when the tube has ruptured. Ectopic pregnancy should be suspected in any women of reproductive age with these symptoms.) ● The key components of the evaluation of a woman with suspected ectopic gestation are a transvaginal http://www.) NATURAL HISTORY — If left untreated. 57 were safely managed expectantly. The hCG level of the discriminatory zone varies.) Use of UpToDate is subject to the Subscription and License Agreement. the diagnosis is made based upon ultrasound findings that confirm either an intrauterine or extrauterine pregnancy (gestational sac with a yolk sac or embryo).com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc… 12/19 .1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis ultrasound (TVUS) examination and quantitative human chorionic gonadotropin (hCG) level. A diagnosis of ectopic pregnancy cannot be made based upon a single hCG result.uptodate.) ● The diagnosis of ectopic pregnancy is a clinical diagnosis made based upon serial hCG testing and TVUS. and for pretreatment evaluation for potential methotrexate therapy.) ● The diagnostic criteria depend upon the relationship to the hCG discriminatory zone (serum hCG level above which a gestational sac should be visualized by TVUS if an intrauterine pregnancy [IUP] is present).) • If the serial hCG is rising abnormally (does not increase by at least 53 percent in 48 hours OR doubling in 72 hours) and is below the discriminatory zone. Histologic confirmation of the diagnosis is not typically required.) ● Additional testing is performed to evaluate for anemia. • If the hCG is above the discriminatory zone. (See 'Clinical protocol' above. but in most institutions it is 1500 to 2000 IU/L. for Rh(D) blood typing. (See 'Ruptured versus nonruptured ectopic pregnancy' above. The hCG is measured serially every 48 to 72 hours.0 http://www. Topic 5487 Version 25. ● Diagnosis of rupture of the structure within which the ectopic gestation is implanted (usually the fallopian tube) is a clinical diagnosis made primarily based upon a finding of echogenic fluid (consistent with blood) in the pelvic culdesac and/or abdomen combined with the presence of abdominal pain and/or tenderness. (See 'Additional testing' above. (See 'Transvaginal ultrasound' above and 'Human chorionic gonadotropin' above and 'Diagnosis' above. (See 'Discriminatory zone' above and 'Diagnostic criteria' above. the diagnosis is made based upon the hCG pattern. Murray H.000). Tulandi T.000 versus 3. Am J Epidemiol 2003; 157:185.8 Smoking 2. the risk of ectopic pregnancy varies according to the type of ART procedure. Risk factors for ectopic pregnancy: a meta analysis. Fertil Steril 2007; 87:303.uptodate. Bossuyt PMM.0139 Tubal pathology 3.33. 1 Women who undergo ART are at much higher risk of heterotopic pregnancy than women who conceive naturally (152/100. the woman's reproductive health characteristics.12. 2.13.9 Previous pelvic/abdominal surgery 0.4/100. Baakdah H.3 to 6.44. Ectopic pregnancy risk with assisted reproductive technology procedures.5 Tubal ligation 3.525 In utero DES exposure 2. Coste J.145 Infertility 1.8 Vaginal douching 1. Bardell T. Obstet Gynecol 2006; 107:595. A comparison of heterotopic and intrauterineonly pregnancy outcomes after assisted reproductive technologies in the United States from 1999 to 2002.933. 2. et al. et al. Schieve LA.83. Ankum WM. 3.5 For women undergoing assisted reproductive technology (ART) procedures. and estimated embryo implantation potential. Peterson HB. Shojaei T. Schieve LA.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis GRAPHICS Risk factors for ectopic pregnancy Degree of risk High Moderate Low Risk factors Odds ratio Previous ectopic pregnancy 9. et al.7 History of pelvic inflammatory disease 2. CMAJ 2005; 173:905. Fertil Steril 1996; 65:1093.413 Current IUD use 1. chlamydia) 2. 2 References: 1. Risk factors for ectopic pregnancy: a comprehensive analysis based on a large casecontrol. Peterson HB.0 Multiple sexual partners 1.13. Graphic 82282 Version 5. Clayton HB.0 http://www.1 Early age of intercourse (<18 years) 1. populationbased study in France. Bouyer J. Mol BWJ.347 Previous tubal surgery 6. Clayton HB. Van Der Veen F.011. Diagnosis and treatment of ectopic pregnancy.128 Previous cervicitis (gonorrhea.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc… 13/19 . Adapted from: 1. Graphic 80606 Version 2.uptodate.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis Tests for suspected ectopic pregnancy EP: ectopic pregnancy; IUP: intrauterine pregnancy;TVS: transvaginal ultrasound; hCG: human chorionic gonadotropin.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc… 14/19 .0 http://www. Journal of Family Practice 2006; 55:388. Data from: Ramakrishnan.uptodate. DC. Graphic 80277 Version 3. * Mass or fluid in cul de sac for βhCG ≥1500 mIU/mL and ≥2000 mIU/mL. K.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc… 15/19 .0 http://www. Scheid.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis Significance of features associated with ectopic pregnancy Features SN (percent) SP (percent) Clinical features Estimated gestational age <70 days 95 27 Vaginal bleeding 69 26 Abdominal pain 97 15 Abdominal tenderness 85 50 Peritoneal signs 23 95 Cervical motion tenderness 33 91 Adnexal tenderness 69 62 Adnexal mass 5 96 100 89 Separate from ovary 93 99 Cardiac activity 20 100 Yolk sac or embryo 37 100 Tubal ring/yolk sac or embryo 65 99 Any 63 69 Echogenic 56 96 95 98 Transvaginal ultrasound No intrauterine gestational sac Adnexal mass Fluid in pouch of Douglas Colorflow Doppler βhCG combined with transvaginal ultrasound Empty uterus ≥1000 mIU/mL 4396 86100 ≥1500 mIU/mL 4099 8496 ≥2000 mIU/mL 3848 8098 ≥1000 mIU/mL 73 85 ≥1500 mIU/mL 4664 9296 ≥2000 mIU/mL 55 96 Adnexal mass* Sn: sensitivity; Sp: specificity; βhCG: beta human chorionic gonadotropin. Ectopic pregnancy: Forget the "classic presentation" if you want to catch it sooner: A new algorithm to improve detection. choriocarcinoma) Infection: Cervicitis Vulva Benign growths: Skin tags Sebaceous cysts Condylomata Angiokerataoma Cancer Vagina Benign growths: Gartner duct cysts Polyps Drugs Contraception: Hormonal contraceptives Intrauterine devices Postmenopausal hormone therapy Anticoagulants Tamoxifen Corticosteroids Chemotherapy Phenytoin Antipsychotic drugs Antibiotics (eg.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc… 16/19 .uptodate. motor vehicle accident) Leiomyomas (fibroids) Straddle injuries Endometrial polyps Cancer: Endometrial adenocarcinoma Sarcoma Infection: Pelvic inflammatory disease Endometritis Ovulatory dysfunction Cervix Benign growths: Cervical polyps Ectropion Endometriosis Cancer: Invasive carcinoma Metastatic (uterus. due to toxic epidermal necrolysis or StevensJohnson syndrome) Systemic disease Diseases involving the vulva: Crohn's disease Behcet's syndrome Pemphigoid Pemphigus Erosive lichen planus Lymphoma Bleeding disorders: von Willebrand disease Thrombocytopenia or platelet dysfunction Acute leukemia Some coagulation factor deficiencies Advanced liver disease Thyroid disease Adenosis (aberrant glandular tissue) http://www.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis Causes of abnormal genital tract bleeding in women Genital tract disorders Uterus Benign growths: Trauma Sexual intercourse Sexual abuse Endometrial hyperplasia Foreign bodies (including intrauterine device) Adenomyosis Pelvic trauma (eg. 0 http://www.uptodate.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc… 17/19 .1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis Cancer Polycystic ovary syndrome Vaginitis/infection: Chronic liver disease Bacterial vaginosis Cushing's syndrome Sexually transmitted diseases Hormonesecreting adrenal and ovarian tumors Atrophic vaginitis Upper genital tract disease Renal disease Fallopian tube cancer Emotional or physical stress Ovarian cancer Smoking Pelvic inflammatory disease Excessive exercise Pregnancy complications Diseases not affecting the genital tract Urethritis Bladder cancer Urinary tract infection Inflammatory bowel disease Hemorrhoids Other Endometriosis Vascular tumors and anomalies in the genital tract Graphic 74527 Version 8. 1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis Algorithm vaginal bleeding * This step may be omitted in women who are known to have an intrauterine pregnancy.0 http://www. Proceed directly to ultrasound examination.uptodate.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc… 18/19 . Graphic 68130 Version 2. com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc… 19/19 .0 http://www.uptodate.1/17/2016 Ectopic pregnancy: Clinical manifestations and diagnosis Normal female reproductive anatomy Graphic 55921 Version 2.
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