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Unusual ectopic pregnancies


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  • 1. Unusual ectopic pregnancies: A retrospective analysis of 65 cases Nan Shan1 , Dan Dong1 , Weiguo Deng2 and Yan Fu1 1 Department of Obstetrics and Gynecology, First Hospital of Jilin University, and 2 Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, China Abstract Aim: The aim of this study was to retrospectively investigate unusual ectopic pregnancies (EP) and compare them with fallopian ones. Material and Methods: A total of 1000 cases of ectopic pregnancies were analyzed, including 65 unusual cases. We discussed distribution, incidence, risk factors, examinations, treatments and prognoses. Results: Ovarian pregnancy was associated with placement of intrauterine device and pelvic inflammatory diseases. Extratubal EP have a high rate of misdiagnosis and presented more serious manifestations. Some unusual EP could be diagnosed by ultrasonography. Ovarian pregnancy was usually manifested as positive culdocentesis. Most of the unusual EP underwent surgery, except some early cervical and corneal pregnancies. Conclusion: Although extratubal pregnancies are difficult to diagnose, some histories and auxiliary examina- tions could make diagnosis easier for clinical physicians. Surgery is still the most effective approach for treatment of unusual EP, while conservative treatment of mifepristone combined with methotrexate or curet- tage could be used for early diagnosis and treatment of cervical pregnancy. Key words: cervical pregnancy, cornual pregnancy, methotrexate conservative treatment, ovarian pregnancy, unusual ectopic pregnancies. Introduction Nearly 95% of ectopic pregnancies (EP) are implanted in the various segments of the fallopian tubes. The remaining 5% implant in the ovary, peritoneal cavity, or within the cervix.1 When the blastocyst implants or develops in pelvic areas other than the tubes, the preg- nancy is considered an unusual EP. Compared with tubal ones, extratubal EP are atypical in history or symptoms, appear belatedly and might be more dan- gerous. Early diagnosis of extratubal EP is extremely difficult. We analyzed a 10-year series of consecutive cases in order to evaluate unusual EP retrospectively as a whole, and thus to make a forward investigation for future therapy. Methods From January 2000 to January 2010, 1000 cases of EP (935 tubal pregnancies, 65 extratubal pregnancies) were diagnosed and treated in our center. Diagnosis was essentially clinical and based on history, clinical signs and symptoms, physical examination, human chorionic gonadotrophin (hCG) assessment either in urine or in serum, and transvaginal ultrasound. In some cases, a diagnostic curettage was performed to Received: November 7 2012. Accepted: April 4 2013. Reprint request to: Dr Yan Fu, Department of Obstetrics and Gynecology, First Hospital of Jilin University, Changchun 130021, China. Email: bs_bs_banner doi:10.1111/jog.12146 J. Obstet. Gynaecol. Res. Vol. 40, No. 1: 147–154, January 2014 © 2013 The Authors 147 Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology
  • 2. remove intrauterine trophoblastic tissues. The major treatments included surgeries and conservative thera- pies, such as mifepristone combined with methotrexate (MTX) or curettage. c2 -test was used to examine the correlation between categorical factors, including the distribution, inci- dence, risk factors, examinations, treatments and prog- noses. Statistical analysis was performed on spss 13.5. P < 0.05 was considered statistically significant. Results Incidence The sites of implantation are listed in Table 1. Mean maternal age upon diagnosis was 30.9 years (20–47), and in 31 cases (47.7%), it was less than 30 years. Risk factors Of the 1000 EP, 44.6% of women were primigravid, and others reported previous pregnancies, of which 17.6% had a history of cesarean sections. Based on their histories, most patients had fertility-reducing risk factors, such as usage of intrauterine devices (IUD, 16.3%), pelvic inflammatory diseases (19.6%), curettage (56.8%) and previous ectopic pregnancy (5.4%). Only one patient underwent in vitro fertilization (IVF). As shown in Table 2, patients with a history of pelvic inflammatory diseases showed particularly significant differences among ovarian (c2 = 13.5, P < 0.01), cornual (c2 = 10.2, P < 0.01) and tubal pregnancies. Placement of IUD was significantly associated with ovarian preg- nancy (c2 = 25.2, P < 0.01) in comparison with other unusual EP. Comparison of misdiagnosis rates In our investigation, the 10-year rate of tubal preg- nancy misdiagnosis was 1.4%, which was much lower than that of extratubal ones (c2 = 440.7, P < 0.01). Among extratubal EP, cornual (c2 = 20.5, P < 0.01) and cervical (c2 = 4.0, P < 0.05) pregnancies had lower rates of misdiagnosis due to the help of ultrasound examination. Comparison of clinical manifestations As shown in Tables 3 and 4, EP patients showed clinical manifestations, such as a definitely delayed Table 1 Sites of implantation in EP Site Case Age Parity (above 2) (%) Ratio (%) Ratio (%) of unusual EP Tube 935 32.4 Ϯ 4.9 515 (51.5%) 93.5 — Ovarian 29 29.1 Ϯ 5.9 16 (55.2%) 2.90 44.6 Cornual 21 32.4 Ϯ 5.4 13 (61.9%) 2.10 32.3 Cervical 8 32 Ϯ 7.5 6 (75%) 0.80 12.3 Rudimentary horn 1 20 0 0.10 4.6 Abdominal 3 29.6 Ϯ 4.9 1 (33.3%) 0.30 3.1 Tubal stump 2 26 Ϯ 5 1 (50%) 0.20 1.5 Cesarean scar 1 30 1 (100%) 0.10 1.5 Total 1000 32.3 Ϯ 6.8 553 100 100 EP, ectopic pregnancy. Table 2 Risk factors Site (n) Pelvic inflammatory diseases (%) Cesarean section IUD Pregnancy (above 2) (%) Curettage (%) Ectopic pregnancy (%) Ovarian (29) 13 (44.8%)** 2 8 (27.5%) 16 (55.2%) 16 (55.2%) 1 (3.4%) Cornual (21) 10 (47.6%)** 3 1 (4.7%) 13 (61.9%) 12 (57.1%) 0 Cervical (8) 4 (50%) 1 1 6 (75%) 5 (62.5%) 0 Abdominal (3) 1 (33.3%) 1 0 1 (33.3%) 1 (33.3%) 0 Tubal stump (2) 1 (50%) 0 0 1 (50%) 1 (50%) 1 Cesarean scar (1) 0 1 0 1 (100%) 1 (100%) 0 Tube (935) 167 (17.9%**) 167 153 (16.4%) 515 (55.1%) 532 (56.9%) 53 (5.7%) *P < 0.05; **P < 0.01. IUD, intrauterine device. N. Shan et al. 148 © 2013 The Authors Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology
  • 3. menstruation over a month (85.5%), abdominal pain (62.8%), vaginal bleeding (83.3%), cervical motion pain (51.7%), abdominal bleeding (39.4%) and shock (13%). Unusual EP showed more severe abdominal bleeding (P < 0.05), abdominal muscle tension (P < 0.01), sec- ondary anemia (P < 0.01) or shock (P < 0.01) than tubal pregnancies. According to the implantation sites, EP showed spe- cific signs and symptoms: patients with ovarian preg- nancy were observed with more abdominal bleeding than cornual (c2 = 10.7, P < 0.01) or cervical (c2 = 13.6, P < 0.01) pregnancies. Ovarian EP also presented more serious secondary anemia (c2 = 9.5, P < 0.01) and obvious cervical motion pain compared with corneal ones. Abdominal pain was significantly different between cervical and tubal pregnancies (c2 = 8.0, P < 0.01). Auxiliary examinations In our study, women were observed with positive hCG both in urine (94.5%) and serum (91.4%). Some patients were admitted to hospital as an emergency so they provided urine hCG instead of serum hCG as a diag- nostic method of pregnancy before treatment. About 46.9% of the patients showed positive culdocen- tesis, and 94.1% of the patients were diagnosed by ultrasonography. Culdocentesis was more meaningful for ovarian pregnancy than for corneal pregnancy (c2 = 14.7, P < 0.01). Ultrasound examinations were significantly meaningful for tubal (c2 = 526.9, P < 0.01), cervical (c2 = 10.5, P < 0.01) and cornual (c2 = 30.0, P < 0.01) pregnancies (Table 5). Treatments As shown in Table 6, most women with unusual EP underwent surgery, except those with cervical and corneal pregnancies, which were treated with conser- vative approaches, including methotrexate therapy and curettage. During operations, we found 82.8% (24/29) of ovarian pregnancies had active hemorrhage, which could prove its hazard. Discussion Incidence and related factors The incidence of unusual EP ranges from 4.9% to 10.1%,2 and in our study, it was 6.5% and consistent Table 3 Clinical manifestation (1) Site (n) Amenorrhea (n) Period (day) Vaginal bleeding (n) (%) Abdominal pain (n) (%) Shock (n) Ovarian (29) 28 42.6 Ϯ 9.8 21 (72.4%) 29 (100%) 9 (32.1%) Cornual (21) 19 66.2 Ϯ 15 13 (68.4%) 18 (94.7%) 7 (36.8%) Rudimentary horn (1) 1 65 0 1 (100%) 0 Abdominal (3) 3 50 Ϯ 18.7 2 (66.7%) 3 (100%) 0 Tubal stump (2) 2 55.7 Ϯ 13.8 1 (50%) 2 (100%) 1 Cesarean scar (1) 1 54 1 (100%) 1 (100%) 0 Cervical (8) 7 83.9 Ϯ 28.1 7 (87.5%) 1 (12.5%) 1 Tubal (935) 794 50.9 Ϯ 11.9 788 (84.2%) 573 (61.3%**) 112 (1.2%) *P < 0.05; **P < 0.01. Table 4 Clinical manifestation (2) Site (n) Abdominal bleeding (n) (%) Anal inflation (n) Abdominal muscle tension (n) Cervical motion pain (n) (%) Secondary anemia (n) (%) Ovarian (29) 23 (79.3%)** 11 6 18 (62.1%)** 21 (72.4%)* Cornual (21) 7 (33.3%) 3 2 2 (9.5%) 8 (38%) Rudimentary horn (1) 0 0 0 0 0 Abdominal (3) 3 (100%) 1 2 1 (33.3%) 3 (100%) Tubal stump (2) 1 (50%) 2 0 0 2 (100%) Cesarean scar (1) 1 (100%) 1 0 1 (100%) 1 (100%) Cervical (8) 0** 0 0 0 7 (87.5%) Tubal (935) 359 (3.8%**) 203 (21.7%) 540 (57.8%**) 495 (52.9%) 357 (38.2%) *P < 0.05; **P < 0.01. Unussual ectopic pregnancies © 2013 The Authors 149 Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology
  • 4. with the reports. Although this incidence is low, the danger and mobility from an extratubal pregnancy is higher than normal pregnancy. Moreover, the success rate for a subsequent pregnancy will be reduced after EP. In our series, the most common site of implantation in EP is the tube, followed by the ovary, corn, cervix and abdomen. The rarest site is the cesarean scar. Ovarian pregnancy is very rare, accounting for 0.3%– 3.0% of EP,3 and its incidence in our investigation was 3.1%. Ovarian pregnancy is generally believed to be associated with pelvic inflammatory diseases and pre- vious surgery in the pelvic cavity. We found 44.8% of the cases (13/29) had a history of pelvic inflammatory diseases, and 55.2% (16/29) had a history of delivery or curettage. Patients with a history of pelvic inflamma- tory diseases showed a significant difference in ovarian than corneal and tubal pregnancies. Furthermore, even without inflammatory history, pelvic surgeries may also cause ovarian inflammation and thicken the albug- inea, which could lead to a relative lack of follicular fluid pressure. Finally, it would generate ovulation dis- order. Ovum might be detained in the broken follicles and fertilized just in the ovary. Reportedly, the use of IUD seems to be dispropor- tionately associated with ovarian pregnancy.4,5 In our series, 10 out of 29 patients had a history of IUD place- ment (27.6%), which indicated statistical relevance between IUD and ovarian pregnancy, and suggested that IUD placement may change some manners in the pathophysiological environment of the ovary. IUD was hypothesized to successfully prevent all pregnancies, except ovarian ones.6 Therefore, the history of IUD placement is useful if a patient is suspected of ovarian pregnancy. However, it was reported that the incidence rate of PID among IUD users as reported from different studies depends heavily on the definition used and the means available for diagnosing PID. It varies from 1 per 100 to 1 per 1000 woman-years – a tenfold difference – in different studies. PID risk has been found to be sixfold higher in the first month after IUD insertion than it is thereafter. Beyond the first month or so after insertion, the incidence of PID is low among women using IUD and at a level that appears similar to that for women in general.7 The incidence of cervical pregnancy is less than 1% of all EP,8,9 varying from 1/10003 to 1/18 000.4 the cause may be associated with the following factors: (i) cesar- ean section and usage of IUD might interfere with the implantation of blastocyst; (ii) repeated endometrial curettages might damage the endometrium or form a scar, and thus retard the pass and implantation of blas- tocyst at cervix (in our series, 75% of the cases [6/8] reported a history of induced abortion or cesarean section and placement of IUD, which suggested that intrauterine surgeries could be an important cause for cervical pregnancy); and (iii) with the development of reproductive technology, embryo transfer as in vitro fertilization is also a substantial cause. Misdiagnosis rate The misdiagnosis rate of extratubal pregnancies is quite high (96.6%). Ovarian and tubal pregnancies are difficult to distinguish, even by ultrasound, because their clinical manifestations are similar. In our investi- gation, only one case of ovarian pregnancy was diag- nosed by ultrasound. Reportedly, all 24 cases of ovarian pregnancies in six hospitals were preoperatively mis- diagnosed.10 However, positive culdocentesis results were more common in patients with ovarian pregnan- cies than with cornual pregnancies, probably because a Table 5 Auxiliary examination Site (n) Serum hCG (n) Urine hCG (n) Culdocentesis positive (n) Ultrasound Diagnosis (n) fetal heart movement Persistent hCG secretion Cases of misdiagnosis Ovarian (29) 17 (58.6%) 25 (86.2%) 20** (69%) 1 (3.4%) 1 (3.45%) 6 (20.7%) 28 (96.6%**) Cornual (21) 13 (61.9%) 13 (61.9%) 3 (14.3%) 12 (57.1%) 0 0 5 (23.8%**) Cervical (8) 6 (75%) 5 (62.5%) 0 5 (62.5%) 0 0 2 (25%*) Rudimentary horn (1) 1 (100%) 1 (100%) 0 1 (100%) 0 1 (100%) 0 Abdominal (3) 2 (66.7%) 2 (66.7%) 0 0 2 (66.7%) 0 3 (100%) Tubal stump (2) 0 2 (100%) 1 (50%) 0 0 0 2 (100%) Cesarean scar (1) 1 (100%) 1 (100%) 0 0 0 0 1 (100%) Tubal (935) 874 (93.5%) 896 (95.8%) 445 (47.6%) 922 (98.6%) 38 (4.06%) 0 13 (1.4%**) Total 914 (91.4%) 945 (94.5%) 46.9 (46.9%) 941 (94.1%) 41 (4.1%) 7 (0.7%) 54 (5.4%) *P < 0.05; **P < 0.01. hCG, human chorionic gonadotrophin. N. Shan et al. 150 © 2013 The Authors Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology
  • 5. patient upon admission already had her ovary ruptured and suffered from severe abdominal hemorrhage. Cornual pregnancy was often misdiagnosed as an intrauterine pregnancy because its implantation site is so close to the uterine cavity and lesions are difficult to scrape during curettage. With the improvement of ultrasound technology, cornual and cervical pregnan- cies can be more accurately diagnosed. In our investi- gation, 57.1% (12/21) of cornual pregnancies and 75% (6/8) of cervical pregnancies were diagnosed by ultra- sound, and their misdiagnosis rates (23.8% and 25%, respectively) were obviously lower than that of other extratubal pregnancies. Ultrasound is considered as the most important examination method as it can detect an extrauterine pregnancy with a sensitivity of 89% and a specificity of 99.8%.11 Therefore, ultrasound examination should be encouraged during early gesta- tion in order to screen for ectopic pregnancy in a timely manner. Ultrasound examination before abortion and villus check after curettage are highly recommended. Uterine contents should be included in pathological examination. Serum b-hCG and ultrasound should be closely monitored without villus. Pregnancy on a cesarean scar can be easily misdiag- nosed as inevitable abortion or cervical pregnancy due to the low implantation site of the blastocyst. It shows similar early manifestations as intrauterine pregnancy, threatened abortion, trophoblastic tumor or cervical pregnancy. It could cause vaginal bleeding during curettage if misdiagnosed as intrauterine pregnancy. The diagnosis of pregnancy on cesarean scar is depen- dent on ultrasound, especially the uterine longitudinal sonogram. Ultrasound could reveal the correlation between cesarean scar and blastocyst clearly and thereby provide an objective and reliable diagnosis. Auxiliary examination was helpless in abdominal pregnancy, and our cases were all confirmed by surgery. Clinical manifestations More obvious cervical motion pain was observed besides abdominal pain, vaginal bleeding and amenor- rhea in ovarian pregnancy. Ovarian tissues lack muscles but are rich in vessels. When an ovary is rup- tured, severe abdominal hemorrhage, secondary anemia (21/29, 72.4%) or even shock (9/29, 31.0%) may occur. In cervical pregnancy, the endocervix is eroded by trophoblast, and the pregnancy proceeds to develop in the fibrous cervical wall. The higher the trophoblast is Table6Treatments SiteConservative treatment No treatment LaparotomyAdnexectomySubtotal resectionof uterus HysterectomyCurettageLaparoscopic resection Tube(935)113(12.1%)30(3.2%)531(56.8%)5(0.5%)000261(27.9%) Ovarian(29)0020(69%)1(3.4%)0009(31%) Cornual(21)5(23.8%)1(4.8%)7(33.3%)1(4.8%)5(23.8%)1(4.8%)5(23.8%)0 Cervical(8)6(75%)0001(12.5%)3(37.5%)2(25%)0 Abdominal(3)003(100%)1(33.3%)0000 Rudimentaryhorn(1)001(100%)00000 Tubalstump(2)001(50%)00000 Cesareanscar(1)00001(100%)000 Unussual ectopic pregnancies © 2013 The Authors 151 Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology
  • 6. implanted in the cervical canal, the higher capacity it has to grow and hemorrhage. Some diagnostic criteria for cervical pregnancy are: 1 Clinical signs and symptoms: recurring vaginal bleeding without pain was observed during early gestation, often followed by uncontrolled hemor- rhage. In our investigation, 87.5% (7/8) of cases were observed with vaginal bleeding, involving three cases of emergency. 2 Gynecological examination: cervix is dilated; cervical canal increasingly thickens like barrel. Doctors could see or even touch placenta in cervix. Two cases pre- sented cervical dilation and another two cases showed a flabby cervix. The examination may cause severe hemorrhage, so it should be deliberated before examination. 3 Serum b-hCG assessment and ultrasound examina- tion. Quantitative serum hCG in cervical pregnancy is often present below the normal pregnancy due to poor blood supply. Compared with other unusual EP, cervical pregnancy showed atypical abdominal pain or bleeding. This may be the result of early admission. In abdominal pregnancy, with either tubal abortion or intraperitoneal rupture, the entire conceptus may be extruded from the tube. If an early conceptus is expelled essentially undamaged into the peritoneal cavity, its placental attachment may persist, or it may be reimplanted almost anywhere and grow as an abdomi- nal pregnancy. This is unusual, and most small concep- tuses can be reabsorbed. They may occasionally remain in the cul-de-sac for years as an encapsulated mass, or even become calcified to form a lithopedion.11 All our cases are secondary. The first one occurred due to rupture of tubal pregnancy, and then the con- ceptus developed on the posterior wall of bladder. The second one was from rupture of rudimentary horn pregnancy and the conceptus grew in Douglas’ space on the ligament of the right iliac fossa. The last one happened due to tubal interstitial pregnancy and the conceptus dropped into the abdominal cavity. During the operation, the fetus was found alive in the abdomi- nal cavity surrounded by blood. The placenta was attached to the greater omentum. Treatment and prognosis Twenty-eight out of 29 women with ovarian preg- nancies underwent surgery by resection of the ovarian wedge or partial oophorectomy. Most reports advocate preserving ovarian tissues as much as possible. Doctors cut off the affected annex only under serious damages. In the past, it was suggested to cut off the uterine corpus to avoid rupture of cornual pregnancy, and hysterectomy was recommended if necessary. In our study, seven cases (33.3%) underwent lesion resection on corpus; and five cases (23.8%) received sub- total hysterectomy due to ruptures. In recent years, many successful cases of conservative treatment were reported. We treated five patients with conservative therapies, including mifepristone, curettage and MTX, which achieved excellent results. However, some reports also pointed out that conservative treat- ment for patients in this type of pregnancy with long- time amenorrhea and abdominal pain may not succeed easily. Before 12 weeks’ gestation, invasion of trophoblastic cells in the cervical wall is not deep enough, so conser- vative treatments for cervical pregnancy can be suc- cessful.12 Treatments include: (i) hysterectomy and subtotal hysterectomy (they are operated only after failure of conservative treatments or uncontrolled hem- orrhage [they were used in three cases]); and (ii) con- servative treatments (the key was early diagnosis and treatment). Recently, the use of curettage and hysterec- tomy has been reduced gradually. They are only used as alternative therapies for MTX and uterine artery embolization. Reportedly, MTX can be used by sys- temic or local injection. It could reach a high effect of 80%.13 Usage of both mifepristone and MTX was better than single MTX for cervical pregnancy, as the former showed a high success rate and lower toxicity.14 This method could enhance the toxicity to trophoblast cells and kill the embryo effectively. In our investigation, four cases of conservative treat- ments and two cases of curettage were successful. However, vaginal bleeding may still occur after con- servative treatments. Doctors should closely monitor patients’ conditions. One patient underwent hysterec- tomy after conservative treatment due to recurring vaginal bleeding. Rudimentary horn in the uterus is the result of devel- opmental defects on lower segment in the duct of Muller, which caused unequal formation on both sides. A small appendage formed next to the normal uterus and connected it through a bunch of fibrous tissues.15 Compared with the normal uterus, the rudimentary uterus has thicker muscles (most hypoplasia) with dense vessels. Thus, severe hemorrhage often occurs after the rupture of pregnancy. N. Shan et al. 152 © 2013 The Authors Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology
  • 7. For rudimentary horn uterine pregnancy, general considerations are to excise the rudimentary horn in the uterus.16,17 Gynecologists should excise both rudi- mentary horn and its ipsilateral tube to avoid future tubal pregnancy.18 They should do the same in abdo- minal surgeries, once a rudimentary horn uterus is identified. One patient in our group underwent resection of rudimentary horn uterus and ipsilateral salpingectomy. In abdominal pregnancy, blastocyst may invade into maternal organs or vessels, and thus cause bleeding or rupture of maternal organs. It should be immediately treated upon diagnosis. Three cases underwent resec- tion of lesions in the abdomen and one suffered ipsi- lateral salpingectomy. Cesarean scar pregnancy accounted for 6.1% of the ectopic pregnancies with a history of cesarean section.19 The isthmus had poor muscles due to the uterine scar but had rich proliferations of connective tissues and vessels. If the incision site is ruptured, or the placenta is separated, uncontrolled bleeding would occur. Hysterectomy is needed if necessary.20 Surgical treat- ment, including laparotomy and hysterotomy, were attempted with success.21 Conservative treatments include systemic or direct injection of MTX.22,23 The combination of MTX, uterine artery embolization and laparoscopic excision, followed by hysteroscopy to assess scar integrity, was reported.24 In conclusion, although extratubal pregnancies are difficult to diagnose, some histories and auxiliary examinations could make diagnosis easier for clinical physicians. IUD placement and history of pelvic inflammatory disease were closely related to ovarian pregnancy. Ultrasonography is meaningful for diagno- sis of tubal, cervical and corneal pregnancies, whereas ovarian pregnancy is usually manifested with positive culdocentesis. Surgery is still the most effective approach for unusual ectopic pregnancies, while conservative treat- ments, such as mifepristone combined with MTX or curettage, could be used for early diagnosis and treat- ment of cervical pregnancy. With the globally increasing incidence of sexually transmitted diseases, the prevalence of unusual ectopic pregnancy is anticipated to increase. Their rarity, the complex history and atypical clinical characteristics of the condition may cause them to be ignored by an unsuspecting clinician. Thus, high-level awareness should be maintained at all times by clinicians. This can reduce the mortality and morbidity associated with these emergencies. Acknowledgments We would like to take this opportunity to thank to all authors who have contributed to this paper. Disclosure None. References 1. Cunningham FG, Leveno KJ, Bloom SL. Williams Obstetrics. McGraw-Hill: New York, 2010; 23 edn. 2. Yao B, Chen R. 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