**Differential Diagnosis of Ectopic Pregnancy - Morbidity and Mortality**

Panagiotis Tsikouras et al.,\*

*Department of Obstetrics and Gynecology , Democritus University of Thrace Greece* 

### **1. Introduction**

The term ectopic pregnancy refers to a gestation in which the fertilized ovum implants on any tissue other than the endometrial membrane lining the uterine cavity. Fig 1 presents the various types of ectopic pregnancy and their relative frequencies The classic clinical symptoms of ectopic pregnancy are pelvic pain, amenorrhea, and vaginal bleeding , spotting (40-50%). However, only 50% of patients present typical symptomatology. Patients may present with other symptoms common to early pregnancy, including nausea (frequently after rupture), breast fullness, fatigue, abdominal pain, heavy cramping, shoulder pain, and recent dyspareunia . Physical findings during examination should be pelvic unilateral tenderness, especially on movement of cervix (75%), enlarged uterus or palpable adnexal mass; crepitant mass on one side or in culde-sac (50%). Approximately 20% of patients with ectopic pregnancies are hemodynamically compromised at initial presentation, which is highly suggestive of rupture. Body temperature ranges from 37.2 to 37.8 0C while the pulse is variable: normal before but rapid after rupture. Today, using modern diagnostic techniques, most ectopic pregnancies may be diagnosed prior to rupturing [1].

Diagnosis of ectopic pregnancy has been greatly improved by the advent of rapid serum beta-human chorionic gonadotropin (beta-HCG) tests and then the widespread adoption of transvaginal pelvic ultrasonography (TVUS) [2].

Serum beta-HCG levels can definitively rule out pregnancy if negative, although there have been case reports of pathology-proven ruptured ectopic pregnancy and hemorrhagic shock despite an undetectable serum beta-HCG [3]. In the early stages of a normal intrauterine pregnancy (IUP), the serum beta-HCG rises along a well-defined curve. Therefore, serial beta-HCG tests can be useful for determining the ultimate location of a pregnancy of unknown location. The lower limit of normal rise in beta-HCG (using a 99% confidence interval) is 53% in 2 days [4]. Patients with a beta-HCG level that falls more than 50% in 2

<sup>\*</sup> Marina Dimitraki1, Alexandros Ammari1, Sofia Bouchlariotou1, Stefanos Zervoudis2,

Panagiotis Oikonomidis2, Constantinos Zakas2, Theodoros Mylonas1, Anastasios Liberis1, Vasileios Liberis1 and Georgios Maroulis1

*<sup>1</sup>Department of Obstetrics and Gynecology , Democritus University of Thrace, Greece* 

*<sup>2</sup>Department of Obstetrics and Gynecology, Rhea Hospital, Athens, Greece*

Differential Diagnosis of Ectopic Pregnancy - Morbidity and Mortality 5

Research is ongoing concerning CA 125, pregnancy-associated plasma protein-A, vascular endothelial growth factor and creatine kinase. None of them have yet shown superiority to serial beta-HCG measurements in distinguishing between intrauterine pregnancy and

Furthermore , pelvic sonography is the imaging test of choice to investigate early pregnancy complaints. As sonogram findings of early normal IUP development (<7 weeks) are well correlated with beta-HCG level, the absence of a normal IUP on sonogram together with a

Pelvic sonography is usually conducted first using the transabdominal approach (which can reliably identify intrauterine pregnancies at a beta-HCG level above 6500 mIU/mL), and then the transvaginal approach (which can extend the discriminatory zone down to 1500 mIU/mL). M-mode imaging is useful for measuring the fetal heart rate. Color Doppler ultrasonography can help identify some ectopic pregnancies by identifying a placental blood flow pattern in the adnexa. Τhe following sonographic findings are of special interest : An intrauterine gestational sac containing a yolk sac, or fetal pole: A definitive IUP virtually rules out ectopic pregnancy (aside from heterotopic pregnancies). An intrauterine gestational sac larger than 16 mm without a fetal pole, or larger than 8 mm without a yolk sac; or an intrauterine fetal pole larger than 5 mm without heart motion: These findings are indicative of failed intrauterine pregnancy. A gestational sac with a mean sac diameter less than 5 mm greater than the crown-rump length has an 80% risk of pregnancy loss [11]. An extrauterine sac containing a yolk sac or a fetal pole, with or without heart motion Fig 2: Although definitive for ectopic pregnancy, only 16-32% of ectopics have this finding on

Fig. 2. Vaginal Ultrasound showing gestational sac with yolk sac in extra uterine location.

beta-HCG level above the discriminatory zone virtually rules out a normal IUP.

ectopic pregnancy [10].

transvaginal sonogram [12].

days are at low risk of having an ectopic pregnancy [5].As ruptured ectopic pregnancies have been reported at a wide range of beta-HCG levels, the beta-HCG level should not be a factor in determining whether or not transvaginal ultrasonography should be performed**. (**The prevalence of false-positive serum hCG results is low, with estimates ranging from 0.01-2%. False-positive serum hCG results are usually due to interference by non-hCG substances or the detection of pituitary hCG. Some examples of non-hCG substances that can cause false-positive results include human LH, antianimal immunoglobulin antibodies, rheumatoid factor, heterophile antibodies, and binding proteins. Most false-positive results are characterized by serum levels that are generally less than 1000 mIU/mL and usually less than 150 mIU/mL[6].)

Fig 1. Various types of ectopic pregnancy and their relative frequencies

Serum progesterone levels tend to be stable over time during the first trimester and concentrations are higher in normal intrauterine pregnancy. A single serum progesterone level has been used alone to discriminate between normal and failing intrauterine pregnancies, but it cannot accurately discriminate between intrauterine and ectopic pregnancies [7]. Levels of <5ng/ml are associated with a viable pregnancy in 0.16% of cases . Low progesterone levels in combination hCG levels is "essentially 100% predictive of a�with an abnormal rise in nonviable pregnancy" (intra or extrauterine) . A progesterone level of less than 15 ng/ml is seen in: 81% of ectopics, 93% of abnormal intrauterine pregnancies, 11% of normal intrauterine pregnancies [8].

The human chorionic gonadotropin (hCG) ratio of hemoperitoneum to venous serum (RP/V) has been demonstrated to improve early diagnosis of ectopic pregnancy, according to a recent study. Investigators observed that the RP/V was higher in ectopic pregnant subjects (median 4.07) than in patients with hemoperitoneum and intrauterine pregnancy (hIUP; median 0.6), with 1.0 as their suggested threshold value for differential diagnosis [9].

days are at low risk of having an ectopic pregnancy [5].As ruptured ectopic pregnancies have been reported at a wide range of beta-HCG levels, the beta-HCG level should not be a factor in determining whether or not transvaginal ultrasonography should be performed**. (**The prevalence of false-positive serum hCG results is low, with estimates ranging from 0.01-2%. False-positive serum hCG results are usually due to interference by non-hCG substances or the detection of pituitary hCG. Some examples of non-hCG substances that can cause false-positive results include human LH, antianimal immunoglobulin antibodies, rheumatoid factor, heterophile antibodies, and binding proteins. Most false-positive results are characterized by serum levels that are generally less than 1000 mIU/mL and usually less

Fig 1. Various types of ectopic pregnancy and their relative frequencies

pregnancies, 11% of normal intrauterine pregnancies [8].

Serum progesterone levels tend to be stable over time during the first trimester and concentrations are higher in normal intrauterine pregnancy. A single serum progesterone level has been used alone to discriminate between normal and failing intrauterine pregnancies, but it cannot accurately discriminate between intrauterine and ectopic pregnancies [7]. Levels of <5ng/ml are associated with a viable pregnancy in 0.16% of cases . Low progesterone levels in combination hCG levels is "essentially 100% predictive of a�with an abnormal rise in nonviable pregnancy" (intra or extrauterine) . A progesterone level of less than 15 ng/ml is seen in: 81% of ectopics, 93% of abnormal intrauterine

The human chorionic gonadotropin (hCG) ratio of hemoperitoneum to venous serum (RP/V) has been demonstrated to improve early diagnosis of ectopic pregnancy, according to a recent study. Investigators observed that the RP/V was higher in ectopic pregnant subjects (median 4.07) than in patients with hemoperitoneum and intrauterine pregnancy (hIUP;

median 0.6), with 1.0 as their suggested threshold value for differential diagnosis [9].

than 150 mIU/mL[6].)

Research is ongoing concerning CA 125, pregnancy-associated plasma protein-A, vascular endothelial growth factor and creatine kinase. None of them have yet shown superiority to serial beta-HCG measurements in distinguishing between intrauterine pregnancy and ectopic pregnancy [10].

Furthermore , pelvic sonography is the imaging test of choice to investigate early pregnancy complaints. As sonogram findings of early normal IUP development (<7 weeks) are well correlated with beta-HCG level, the absence of a normal IUP on sonogram together with a beta-HCG level above the discriminatory zone virtually rules out a normal IUP.

Pelvic sonography is usually conducted first using the transabdominal approach (which can reliably identify intrauterine pregnancies at a beta-HCG level above 6500 mIU/mL), and then the transvaginal approach (which can extend the discriminatory zone down to 1500 mIU/mL). M-mode imaging is useful for measuring the fetal heart rate. Color Doppler ultrasonography can help identify some ectopic pregnancies by identifying a placental blood flow pattern in the adnexa. Τhe following sonographic findings are of special interest : An intrauterine gestational sac containing a yolk sac, or fetal pole: A definitive IUP virtually rules out ectopic pregnancy (aside from heterotopic pregnancies). An intrauterine gestational sac larger than 16 mm without a fetal pole, or larger than 8 mm without a yolk sac; or an intrauterine fetal pole larger than 5 mm without heart motion: These findings are indicative of failed intrauterine pregnancy. A gestational sac with a mean sac diameter less than 5 mm greater than the crown-rump length has an 80% risk of pregnancy loss [11]. An extrauterine sac containing a yolk sac or a fetal pole, with or without heart motion Fig 2: Although definitive for ectopic pregnancy, only 16-32% of ectopics have this finding on transvaginal sonogram [12].

Fig. 2. Vaginal Ultrasound showing gestational sac with yolk sac in extra uterine location.

Differential Diagnosis of Ectopic Pregnancy - Morbidity and Mortality 7

intrauterine pregnancy or products of conception. Pelvic examination may note dilation of the cervix, as well as presence of tissue at the cervical os. Consecutive serum chorionic gonadotrophin levels often do not rise appropriately (66% in 48 hours), and progesterone levels often <15.9 nmol/L (<5 ng/mL). Acute appendicitis: Anorexia and periumbilical pain followed by nausea, RLQ (Right Lower Quadrant) abdominal pain, tenderness localizing at Mc Burney' s point; rebound tenderness and vomiting usual , precedes shift of pain to right lower quadrant. Vaginal bleeding in appendicitis occur unrelated to menses , temperature is 37.2-37.8 C and pulse are variable. No masses founded by pelvic examination. Ultrasound sensitivity of 85% to 90% and specificity of 92% to 96%; may show appendix with outer diameter >6 mm, no compressibility, lack of peristalsis, or periappendiceal fluid. WBC >10,000 cells/ μl ( rarely normal) ;red cell count normal; sedimentation rate slightly elevated. Ovarian torsion: Sudden onset, severe, unilateral lower abdominal pain that worsens intermittently over many hours. Peritoneal signs are often absent. Ovarian enlargement secondary to impaired venous and lymphatic drainage is the most common sonographical finding in ovarian torsion. Absence of arterial blood flow may also be used for diagnostic purposes, but this is often absent in the early stages of torsion. PID (pelvic inflammatory disease) or tubo-ovarian abscess: Lower abdominal tenderness on palpation, pain usally in both lower quadrants, with or without rebound, adnexal tenderness, adnexal masses only when pyosalpinx or hydrosalpinx is present and cervical motion tenderness. May also have body temperature >38.4°C?[ MORE THAN 38 ] and abnormal cervical or vaginal discharge. Occurrence of hypermenorrhea or metrorrhagia or both. Nausea and vomiting are infrequent . Although rare in pregnancy, can occur in the first 12 weeks of gestation before the decidua seals off the uterus from ascending bacteria. WBC often >10,000 cells/mm3 ; red cell count normal; sedimentation rate normal. Ultrasound not used in uncomplicated PID, but is a valuable adjunct in diagnosis of tubo-ovarian abscess. Ruptured corpus luteal cyst or follicle : Non-specific nausea, vomiting, low fever, and pelvic pain, which is often sharp, intermittent, sudden in onset, and severe unilateral ,becoming general with progressive bleeding. At times the ruptured cyst may lead to profuse bleeding and result in haemorrhagic shock. Period delayed, then bleeding , often with pain. Temperature not over 37.2 ; pulse normal unless blood loss marked, then rapid. Laboratory findings : white cell count normal to 10.000 /μl ; red cell count normal ; sedimentation normal. Doppler ultrasonography usually diagnostic, especially when transvaginal and transabdominal modalities are used together. Nephrolithiasis: Classically writhing in pain, pacing about, and unable to lie still, in contrast to a patient with peritoneal irritation, who remains motionless to minimise discomfort. Often presents with unilateral or bilateral flank pain. Haematuria (presence of >1 RBC/hpf) and pyuria (>5 WBC/hpf on a centrifuged specimen) common. Due to potential risks to the fetus, the only imaging modalities used in pregnant women are ultrasonography (direct visualisation of the stone, hydroureter > 6 mm in diameter, and perirenal urinoma suggesting calyceal rupture) and MRI (if ultrasound is non-diagnostic). UTI (urinary tract disease): Dysuria with accompanying urinary urgency, frequency, and abdominal discomfort along the surface of the bladder. May have pyuria (>5 WBC/hpf on a centrifuged specimen). Presence of nitrites is highly specific for a UTI, but its

Finally , bowel colitis ,inguinal or crural hernia and muscular pain should be included in the

Ectopic pregnancy is responsible for a significant proportion of maternal mortality and morbidity. According to the WHO, ectopic pregnancy accounts for 0.1 to 4.9% of the total

absence should not exclude the diagnosis.

differential diagnosis of abdominal pain in lower quadrants.

Tubal ring is a thick-walled cystic structure in the adnexa, independent of the ovary and uterus, and is highly predictive of ectopic pregnancy [13].It can sometimes be confused with a corpus luteum cyst when the ovary is not well visualized. The corpus luteum cyst wall tends to be thinner and less echogenic than the endometrium and the cyst tends to contain clear fluid [14]. When surrounded by free fluid, it can sometimes be confused with a hemorrhagic ovarian cyst [15]. A complex adnexal mass is the sign most frequently found in ectopic pregnancies [16]. It can be somewhat cystic-appearing or entirely solid in nature, surrounded by free fluid, and ill-defined. If it cannot be moved independently of the ovary, it is unlikely to be an ectopic pregnancy [17]. A moderate amount of anechoic free fluid (tracking more than one third of the way up the posterior wall of the uterus), or any echogenic free fluid, has a higher chance of being ultimately diagnosed as an ectopic pregnancy [18].

Culdocentesis is the transvaginal needle aspiration of fluid from the posterior cul-de-sac of Douglas. A positive result means aspiration of 0.5 ml of nonclotting blood, while negative result is accociated with aspiration of 0.5 ml of serous fluid.. If no fluid is aspirated ,the test is inadequate. In positive cases ,if the hematocrit of aspirated fluid is over 15%, ruptured ectopic pregnancy is possible ,while a hematocrit of aspirated fluid below 15% is usually in favor of other causes of intraabdominal hemorrhage, such as hemorrhagic corpus luteum cyst, tubal reflux of intrauterine blood , previous attempt at culdocentesis or(19-21). A positive culdocentesis is found in 70-90% of cases in ectopic pregnancy. A positive culdocentesis indicates the presence of a hemoperitoneum ,(21) but does not give the source of the blood and does not necessarily indicate tubal rupture .The volume of blood recovered does not correlate with the volume of the hemoperitoneum. A positive culdocentesis test in combination with a positive pregnancy test predicts the presence of an ectopic pregnancy, in approximately 95% of cases. (22-3) However double decidual sac sign, or gestational sac <8 mm without yolk sac or fetal pole is in favor of the diagnosis of ectopic pregnancy. While considered diagnostic of IUP by experienced sonographers, this can be easily confused with the pseudogestational sac found in ectopic pregnancy (caused by breakdown of stimulated endometrial lining) and lead to falsely ruling out of ectopic pregnancy [12]. The pseudogestational sac (seen in 10-20% of ectopic pregnancies [24] can be differentiated by its central location in the uterus, oval shape, thin echogenic rim, and lack of double decidual sac sign [11]. A thin endometrial stripe (<8 mm) appears to be somewhat predictive of eventual diagnosis of ectopic pregnancy in patients with a beta-HCG below 1,000 mIU/Ml [25] but there is sufficient overlap with eventual failed IUPs and normal IUPs that this is a poor diagnostic test [26].

 Numerous conditions may have a presentation similar to an extrauterine pregnancy (EP). The most common differential diagnosis hemmoragic are: a ruptured corpus luteum cyst or ovarian follicle (RC), and a spontaneous abortion or threatened abortion (SA). Other differential diagnosis are appendicitis (A), salpingitis(S), ovarian torsion(OT), and urinary tract disease(UD): cystitis, ureteric colic. Intrauterine pregnancies with other abdominal or pelvic problems such as degenerating fibroids must also be included in the differential diagnosis.

Specifically, differential diagnosis of ectopic pregnancy includes : Miscarriage (Includes anembryonic gestation, threatened abortion, incomplete abortion, complete abortion, missed abortion.) Often presents with vaginal bleeding in the first trimester, accompanied by abdominal discomfort secondary to uterine contractions. History may yield disappearance of pregnancy symptoms such as breast tenderness and nausea. Ultrasound shows

Tubal ring is a thick-walled cystic structure in the adnexa, independent of the ovary and uterus, and is highly predictive of ectopic pregnancy [13].It can sometimes be confused with a corpus luteum cyst when the ovary is not well visualized. The corpus luteum cyst wall tends to be thinner and less echogenic than the endometrium and the cyst tends to contain clear fluid [14]. When surrounded by free fluid, it can sometimes be confused with a hemorrhagic ovarian cyst [15]. A complex adnexal mass is the sign most frequently found in ectopic pregnancies [16]. It can be somewhat cystic-appearing or entirely solid in nature, surrounded by free fluid, and ill-defined. If it cannot be moved independently of the ovary, it is unlikely to be an ectopic pregnancy [17]. A moderate amount of anechoic free fluid (tracking more than one third of the way up the posterior wall of the uterus), or any echogenic free fluid, has a higher chance of being ultimately diagnosed as an ectopic

Culdocentesis is the transvaginal needle aspiration of fluid from the posterior cul-de-sac of Douglas. A positive result means aspiration of 0.5 ml of nonclotting blood, while negative result is accociated with aspiration of 0.5 ml of serous fluid.. If no fluid is aspirated ,the test is inadequate. In positive cases ,if the hematocrit of aspirated fluid is over 15%, ruptured ectopic pregnancy is possible ,while a hematocrit of aspirated fluid below 15% is usually in favor of other causes of intraabdominal hemorrhage, such as hemorrhagic corpus luteum cyst, tubal reflux of intrauterine blood , previous attempt at culdocentesis or(19-21). A positive culdocentesis is found in 70-90% of cases in ectopic pregnancy. A positive culdocentesis indicates the presence of a hemoperitoneum ,(21) but does not give the source of the blood and does not necessarily indicate tubal rupture .The volume of blood recovered does not correlate with the volume of the hemoperitoneum. A positive culdocentesis test in combination with a positive pregnancy test predicts the presence of an ectopic pregnancy, in approximately 95% of cases. (22-3) However double decidual sac sign, or gestational sac <8 mm without yolk sac or fetal pole is in favor of the diagnosis of ectopic pregnancy. While considered diagnostic of IUP by experienced sonographers, this can be easily confused with the pseudogestational sac found in ectopic pregnancy (caused by breakdown of stimulated endometrial lining) and lead to falsely ruling out of ectopic pregnancy [12]. The pseudogestational sac (seen in 10-20% of ectopic pregnancies [24] can be differentiated by its central location in the uterus, oval shape, thin echogenic rim, and lack of double decidual sac sign [11]. A thin endometrial stripe (<8 mm) appears to be somewhat predictive of eventual diagnosis of ectopic pregnancy in patients with a beta-HCG below 1,000 mIU/Ml [25] but there is sufficient overlap with eventual failed IUPs and normal IUPs that this is a

 Numerous conditions may have a presentation similar to an extrauterine pregnancy (EP). The most common differential diagnosis hemmoragic are: a ruptured corpus luteum cyst or ovarian follicle (RC), and a spontaneous abortion or threatened abortion (SA). Other differential diagnosis are appendicitis (A), salpingitis(S), ovarian torsion(OT), and urinary tract disease(UD): cystitis, ureteric colic. Intrauterine pregnancies with other abdominal or pelvic problems such as degenerating fibroids must also be included in the differential

Specifically, differential diagnosis of ectopic pregnancy includes : Miscarriage (Includes anembryonic gestation, threatened abortion, incomplete abortion, complete abortion, missed abortion.) Often presents with vaginal bleeding in the first trimester, accompanied by abdominal discomfort secondary to uterine contractions. History may yield disappearance of pregnancy symptoms such as breast tenderness and nausea. Ultrasound shows

pregnancy [18].

poor diagnostic test [26].

diagnosis.

intrauterine pregnancy or products of conception. Pelvic examination may note dilation of the cervix, as well as presence of tissue at the cervical os. Consecutive serum chorionic gonadotrophin levels often do not rise appropriately (66% in 48 hours), and progesterone levels often <15.9 nmol/L (<5 ng/mL). Acute appendicitis: Anorexia and periumbilical pain followed by nausea, RLQ (Right Lower Quadrant) abdominal pain, tenderness localizing at Mc Burney' s point; rebound tenderness and vomiting usual , precedes shift of pain to right lower quadrant. Vaginal bleeding in appendicitis occur unrelated to menses , temperature is 37.2-37.8 C and pulse are variable. No masses founded by pelvic examination. Ultrasound sensitivity of 85% to 90% and specificity of 92% to 96%; may show appendix with outer diameter >6 mm, no compressibility, lack of peristalsis, or periappendiceal fluid. WBC >10,000 cells/ μl ( rarely normal) ;red cell count normal; sedimentation rate slightly elevated. Ovarian torsion: Sudden onset, severe, unilateral lower abdominal pain that worsens intermittently over many hours. Peritoneal signs are often absent. Ovarian enlargement secondary to impaired venous and lymphatic drainage is the most common sonographical finding in ovarian torsion. Absence of arterial blood flow may also be used for diagnostic purposes, but this is often absent in the early stages of torsion. PID (pelvic inflammatory disease) or tubo-ovarian abscess: Lower abdominal tenderness on palpation, pain usally in both lower quadrants, with or without rebound, adnexal tenderness, adnexal masses only when pyosalpinx or hydrosalpinx is present and cervical motion tenderness. May also have body temperature >38.4°C?[ MORE THAN 38 ] and abnormal cervical or vaginal discharge. Occurrence of hypermenorrhea or metrorrhagia or both. Nausea and vomiting are infrequent . Although rare in pregnancy, can occur in the first 12 weeks of gestation before the decidua seals off the uterus from ascending bacteria. WBC often >10,000 cells/mm3 ; red cell count normal; sedimentation rate normal. Ultrasound not used in uncomplicated PID, but is a valuable adjunct in diagnosis of tubo-ovarian abscess. Ruptured corpus luteal cyst or follicle : Non-specific nausea, vomiting, low fever, and pelvic pain, which is often sharp, intermittent, sudden in onset, and severe unilateral ,becoming general with progressive bleeding. At times the ruptured cyst may lead to profuse bleeding and result in haemorrhagic shock. Period delayed, then bleeding , often with pain. Temperature not over 37.2 ; pulse normal unless blood loss marked, then rapid. Laboratory findings : white cell count normal to 10.000 /μl ; red cell count normal ; sedimentation normal. Doppler ultrasonography usually diagnostic, especially when transvaginal and transabdominal modalities are used together. Nephrolithiasis: Classically writhing in pain, pacing about, and unable to lie still, in contrast to a patient with peritoneal irritation, who remains motionless to minimise discomfort. Often presents with unilateral or bilateral flank pain. Haematuria (presence of >1 RBC/hpf) and pyuria (>5 WBC/hpf on a centrifuged specimen) common. Due to potential risks to the fetus, the only imaging modalities used in pregnant women are ultrasonography (direct visualisation of the stone, hydroureter > 6 mm in diameter, and perirenal urinoma suggesting calyceal rupture) and MRI (if ultrasound is non-diagnostic). UTI (urinary tract disease): Dysuria with accompanying urinary urgency, frequency, and abdominal discomfort along the surface of the bladder. May have pyuria (>5 WBC/hpf on a centrifuged specimen). Presence of nitrites is highly specific for a UTI, but its absence should not exclude the diagnosis.

Finally , bowel colitis ,inguinal or crural hernia and muscular pain should be included in the differential diagnosis of abdominal pain in lower quadrants.

Ectopic pregnancy is responsible for a significant proportion of maternal mortality and morbidity. According to the WHO, ectopic pregnancy accounts for 0.1 to 4.9% of the total

Differential Diagnosis of Ectopic Pregnancy - Morbidity and Mortality 9

[7] Mol BW, Lijmer JG, Ankum WM, van der Veen F, Bossuyt PM. The accuracy of single

[8] Lipscomb GH, Stovall TG, Ling FW. Non surgical treatment of ectopic pregnancy. NEJM

[9] Wang Y, Zhao H, Teng Y, Lu L, Tong J. Human chorionic gonadotropin ratio of

[10] Cabar FR, Fettback PB, Pereira PP, Zugaib M. Serum markers in the diagnosis of tubal

[11] Dighe M, Cuevas C, Moshiri M, Dubinsky T, Dogra VS. Sonography in first trimester

[12] Patel MD. "Rule out ectopic": Asking the right questions, getting the right answers.

[13] Brown DL, Doubilet PM. Transvaginal sonography for diagnosing ectopic pregnancy:

[14] Stein MW, Ricci ZJ, Novak L, Roberts JH, Koenigsberg M. Sonographic comparison of

[15] Hertzberg BS, Kliewer MA, Bowie JD. Adnexal ring sign and hemoperitoneum caused

[16] Frates MC, Brown DL, Doubilet PM, Hornstein MD. Tubal rupture in patients with

[17] Blaivas M. Color doppler in the diagnosis of ectopic pregnancy in the emergency

[18] Dart R, McLean SA, Dart L. Isolated fluid in the cul-de-sac: how well does it predict

[19] Glezerman M, Press F, Carpman M. Culdocentesis is an obsolete diagnostic tool in

[20] Wyte CD.Diagnostic modalities in the pregnant patient. Emerg Med Clin North Am.

[21] Falfoul A, Makni MY, Bellasfar M, Tnani M, Kaabar N, Kharouf M. [The role of

[23] Nyberg DA, Laing FC, Filly RA, Uri-Simmons M, Jeffrey RB Jr. Ultrasonographic

cases].J Gynecol Obstet Biol Reprod (Paris). 1991;20(7):917-22. French. [22] Romero R, Copel JA, Kadar N, Jeanty P, Decherney A Hobbins JC. Value of

suspected ectopic pregnancy.Arch Gynecol Obstet. 1992;252(1):5-9

positivity criteria and performance characteristics. J Ultrasound Med. Apr

the tubal ring of ectopic pregnancy with the corpus luteum. J Ultrasound Med. Jan

by hemorrhagic ovarian cyst: pitfall in the sonographic diagnosis of ectopic

ectopic pregnancy: diagnosis with transvaginal US. Radiology. Jun 1994;191(3):769-

department: is there anything beyond a mass and fluid?. J Emerg Med. May

Cartwright PS, Vaughn B, Tuttle D. Culdocentesis and ectopic pregnancy. J Reprod

culdocentesis in the diagnosis of ectopic pregnancy. Prospective study of 478

culdocentesis in the diagnosis of ectopic pregnancy.Obstet Gynecol. 1985

differentiation of the gestational sac of early intrauterine pregnancy from the pseudogestational sac of ectopic pregnancy. Radiology. Mar 1983;146(3):755-9.

analysis. Hum Reprod. Nov 1998;13(11):3220-7.

pregnancy. Clinics (Sao Paulo). Oct 2008;63(5):701-8.

bleeding. J Clin Ultrasound. Jul-Aug 2008;36(6):352-66.

pregnancy. AJR Am J Roentgenol. Nov 1999;173(5):1301-2.

ectopic pregnancy?. Am J Emerg Med. Jan 2002;20(1):1-4.

200;343(18):1325-1329

1994;13(4):259-66.

2004;23(1):57-62.

2002;22(4):379-84.

1994 Feb;12(1):9-43. Review

Med. 1984 Feb;29(2):88-91.

Apr;65(4):519-22

72.

pregnancy*.* Fertil Steril. 2008 .

Ultrasound Q. Jun 2006;22(2):87-100.

serum progesterone measurement in the diagnosis of ectopic pregnancy: a meta-

hemoperitoneum versus venous serum improves early diagnosis of ectopic

maternal deaths worldwide. [27] The range varies in different regions of the world, exhibiting the highest prevalence in developed countries. Table 1 . [27] It should be mentioned at this point that in developing countries, hemorrhage is the leading cause of maternal deaths.

It is responsible for an enormous amount of hospital admissions, surgical interventions and blood transfusions worldwide.

The mortality rate has declined from 35.5 maternal deaths per 10,000 ectopic pregnancies in 1970 to only 3.8 maternal deaths per 10,000 ectopic pregnancies in 1989. [28]Mortality from ectopic pregnancy is the commonest cause of maternal death, replacing mortality resulting from illegal abortion. [29]


Table 1. Variability of maternal deaths due to ectopic pregnancy in different regions of the world.

Studies have shown that African-American women have a mortality ratio 3 to 18 times higher than white women [29-30]

 Delay of treatment and misdiagnosis are the main factors that lead to mortality. Approximately 50 percent of ectopic pregnancies are misdiagnosed at the initial visit to an emergency department. [31-2]

The significant fall of maternal mortality is due to modern diagnostic advances and minimally invasive treatments.

#### **2. References**


maternal deaths worldwide. [27] The range varies in different regions of the world, exhibiting the highest prevalence in developed countries. Table 1 . [27] It should be mentioned at this point that in developing countries, hemorrhage is the leading cause of

It is responsible for an enormous amount of hospital admissions, surgical interventions and

The mortality rate has declined from 35.5 maternal deaths per 10,000 ectopic pregnancies in 1970 to only 3.8 maternal deaths per 10,000 ectopic pregnancies in 1989. [28]Mortality from ectopic pregnancy is the commonest cause of maternal death, replacing mortality resulting

> World Region Percentage (%) Asia 0.1 Africa 0.5 Latin America 0.5 Developed countries 4.9

Table 1. Variability of maternal deaths due to ectopic pregnancy in different regions of the

Studies have shown that African-American women have a mortality ratio 3 to 18 times

 Delay of treatment and misdiagnosis are the main factors that lead to mortality. Approximately 50 percent of ectopic pregnancies are misdiagnosed at the initial visit to an

The significant fall of maternal mortality is due to modern diagnostic advances and

[1] Vicken PS., Wood E, Ectopic Pregnancy, emedicine.medscape.com Updated: Mar 8, 2011 [2] Cohen HL, Moore WH. History of emergency ultrasound. J Ultrasound Med. Apr

[3] Grynberg M, Teyssedre J, Andre C, Graesslin O. Rupture of ectopic pregnancy with

[4] Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, Hummel AC, Guo W. Symptomatic

[5] Dart RG, Mitterando J, Dart LM. Rate of change of serial beta-human chorionic

[6] Ackerman R, Deutsch S, Krumholz B. Levels of human chorionic gonadotropin in unruptured and ruptured ectopic pregnancy. Obstet Gynecol 1982;60:13-14.

negative serum beta-hCG leading to hemorrhagic shock. Obstet Gynecol. Feb

patients with an early viable intrauterine pregnancy: HCG curves redefined. Obstet

gonadotropin values as a predictor of ectopic pregnancy in patients with indeterminate transvaginal ultrasound findings. Ann Emerg Med. Dec

maternal deaths.

world.

blood transfusions worldwide.

higher than white women [29-30]

emergency department. [31-2]

minimally invasive treatments.

2004;23(4):451-8.

2009;113(2 Pt 2):537-9.

1999;34(6):703-10.

Gynecol. Jul 2004;104(1):50-5.

**2. References** 

from illegal abortion. [29]


**Part 2** 

**Causes of Ectopic Pregnancy** 


**Part 2** 

**Causes of Ectopic Pregnancy** 

10 Ectopic Pregnancy – Modern Diagnosis and Management

[24] Dart RG, Dart L, Mitchell P, Berty C. The predictive value of endometrial stripe

[25] Seeber B, Sammel M, Zhou L, Hummel A, Barnhart KT. Endometrial stripe thickness

[26] Goldner TE, Lawson HW, Xia Z, Atrash HK. Surveillance for ectopic pregnancy--United

[27] Dorfman SF. Epidemiology of ectopic pregnancy. Clin Obstet Gynecol. 1987 Mar;30(1):

[28] Anderson FW, Hogan JG, Ansbacher R. Sudden death: ectopic pregnancy mortality.

[29] Abbott J, Emmans LS, Lowenstein SR. Ectopic pregnancy: ten common pitfalls in

[30] Kaplan BC, Dart RG, Moskos M, Kuligowska E, Chun B, Adel Hamid M, et al. Ectopic

pregnancy: prospective study with improved diagnostic accuracy. Ann Emerg Med

at ultrasonography. Acad Emerg Med. Jun 1999;6(6):602-8.

States, 1970-1989. MMWR CDC Surveill Summ 1993.

Reprod Med. Sep 2007;52(9):757-61.

Obstet Gynecol. 2004 Jun;103(6):1218-23.

diagnosis. Am J Emerg Med 1990;8:515-22.

74. Review.

173-80.

1996;28:10-7.

thickness in patients with suspected ectopic pregnancy who have an empty uterus

and pregnancy outcome in first-trimester pregnancies with bleeding, pain or both. J

Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006 Apr 1;367(9516):1066-

**2** 

 *Australia* 

**Tubal Damage, Infertility and Tubal Ectopic** 

Infertility is a worldwide health problem with one in six couples suffering from this condition and with a major economic burden on the global healthcare industry. Estimates of the current global infertility rate suggest that 15% of couples are infertile (Zegers-Hochschild *et al.,* 2009) defined as: (1) failure to conceive after one year of unprotected sexual intercourse (i.e. infertility); (2) continual failure of implantation at subsequent cycles of assisted reproductive technology; or (3) persistent miscarriage events without difficulty conceiving (natural conceptions). Tubal factor infertility is among the leading causes of female factor infertility accounting for 7-9.8% of all female factor infertilities. Tubal disease directly causes from 36% to 85% of all cases of female factor infertility in developed and developing nations respectively and is associated with polymicrobial aetiologies. One of the leading global causes of tubal factor infertility is thought to be symptomatic (and asymptomatic in up to 70% cases) infection of the female reproductive tract with the sexually transmitted pathogen, *Chlamydia trachomatis*. Infection-related damage to the Fallopian tubes caused by *Chlamydia* accounts for more than 70% of cases of infertility in women from developing nations such as sub-Saharan Africa (Sharma *et al.,* 2009). Bacterial vaginosis, a condition associated with increased transmission of sexually transmitted infections including those caused by *Neisseria gonorrhoeae* and *Mycoplasma genitalium* is present in two thirds of women with pelvic inflammatory disease (PID). This review will focus on (1) the polymicrobial aetiologies of tubal factor infertility and (2) studies involved in screening for, and treatment and control of, Chlamydial infection to prevent PID and the associated sequelae of Fallopian tube inflammation that may lead to infertility and ectopic

In the absence of functional Fallopian tubes, couples may only conceive through *in vitro* fertilisation procedures. Women with tubal factor infertility may be defined as women who have either (1) damaged/occluded Fallopian tubes or (2) have history of salpingectomy. Ectopic pregnancy is only relevant if the Fallopian tubes remain *in situ*. Previous studies

**1. Introduction** 

pregnancy.

**2. Tubal factor infertility** 

**Pregnancy:** *Chlamydia trachomatis* **and** 

**Other Microbial Aetiologies** 

*Institute of Health and Biomedical Innovation, (IHBI),* 

Louise M. Hafner and Elise S. Pelzer

*Queensland University of Technology (QUT)* 
