Three-dimensional Ultrasound Imaging in the Diagnosis of Ectopic Pregnancy

INTRODUCTION

Ectopic pregnancy has remained a major cause of maternal morbidity and mortality. The incidence of EPs, denominated as the number of EPs per 1,000 pregnancies, varies from 6.4 to 20.7.^1–3 EP is diagnosed in 6–16% of women seeking help in emergency departments with bleeding and/or pain in the 1st trimester.⁴

Reflecting the impact of socioeconomic factors on public healthcare, mortality rates of EP could be reduced by 50% in industrialized countries, while EP still remains a leading cause of maternal death in Africa and Asia.^5,6 In 2009, an EP mortality ratio of 0.48 per 1,00,000 live births (0.08% of 100 EP) was established for the USA,³ compared to 1.4–2.79% in Nigeria and Ghana, probably resulting from delayed diagnosis and treatment.⁷ The lack of research productivity concerning EP in low-income countries and their missing presence in international scientific working groups in the field⁸ is another indirect sign that advances in diagnosis and management leading to earlier detection and better treatment of EP have reached developing countries only in urban areas. These advances include the serum beta hCG pregnancy test, TVS imaging, minimal invasive laparoscopic surgery, chemotherapy with methotrexate, and interventional radiology with UAE.

To date, TVS with high-resolution probes is an indispensable tool in any early pregnancy unit. One of its purposes there is to evaluate the spatial relationship of a suspicious mass—possibly representing an EP—to the inner genital organs, which is often difficult for nondynamic imaging such as CT and MRI. In contrast, TVS as a tool for “dynamic” investigation of structures within the pelvis can visualize whether the suspicious mass moves together or independently of ovary or uterus (sliding sign), by exerting gentle pressure with the tip of the US probe. Furthermore, with the tip of the TVS probe located in the topographic center of the pelvis/region of interest (ROI), image quality benefits from the ability to use close-range high frequencies with optimal resolution and image quality. Thirdly, TVS with color-, power-, and HD-flow Doppler technology is able to show increased blood flow in the ROI and to detect typical trophoblast flow characterized by low resistance indices and low velocities, with peak systolic velocity (PSV) greater at and above 20 cm/s, and pulsatility index (PI) lower than 1.⁹

With serum beta hCG levels of 0–750 U/L at 1 week before the first missed period, and 200–7,000 U/L at 1 week after the first missed period, the threshold for sonographic visibility of the trophoblast is usually reached as early as 5 weeks after the last menstrual period (LMP).¹⁰

The term “visibility threshold” refers to visualization of an intrauterine trophoblast using TVS which is achievable transvaginally already at a serum beta hCG of 1,400 mIU/mL vs 4,500 mIU/mL with transabdominal ultrasound (TUS) probes (Fig. 1).

Given all these improvements, modern TVS has led to a diagnostic paradigm change from “negative for intrauterine GS” or “pregnancy of unknown location” (PUL) to a high percentage of positive identification of the site of the EP. High resolution TVS is able to visualize 75% of all EPs during the first assessment, and even 87–99% of tubal EPs.¹¹ Last but not least, transvaginal 3D ultrasound has created another diagnostic platform, with identification of new, equally efficient ways of diagnosing EP.

HISTORY

The first successful treatment of tubal pregnancy with salpingectomy was described in 1884 by Tait (1845–1899).¹² As a result of improvements of surgical techniques, changing the approach from open salpingectomy to laparoscopy,^13,14 technological innovations in the field of ultrasonography (Fig. 2)^15–17 and biochemistry with the production of an antiserum highly specific to the P-subunit of hCG,¹⁸ mortality rates could be reduced from 72 to 90% in 1880–0.14% in 1990,^19,20 and this in spite of a six-fold increase of EP numbers, for example, in the US between 1970 and 1992.²¹

The increasing incidence of EP has to be attributed mainly to the following factors: more common pelvic inflammatory disease (PID) with tubal damage as a result of spreading chlamydia salpingitis,²² ever rising popularity of cesarean section,²³ and general availability and usage of assisted reproduction techniques.²⁴ Most tellingly, one of the first IVF attempts in history in 1976 resulted in an EP.²⁵

EP LOCATIONS

The sites of EP can be divided into two groups: 96% of EPs are found in the fallopian tubes, named after the 16th century Italian anatomist Gabriele Fallopio. The remaining 4% of EPs include uterine, ovarian, and abdominal locations.²⁶ It is this small group of nonfallopian EPs which is mainly responsible for morbidity and mortality: the mortality rate for interstitial pregnancy, for example, was found to be 15 times higher than the mortality rate of tubal ectopic.²⁷

TUBAL ECTOPIC PREGNANCY

The great majority of EPs (96%) implants within the fallopian tube. In 1,800 surgically treated cases, the distribution along the tube was found to be the following: 70% in the ampulla, 12% in the isthmus, and 11.1% fimbrial²⁶ (Fig. 3). Other than the uterus, the fallopian tube has limitations of both vascularization and compliance, which explains that tubal ectopic pregnancies (TEPs) have a lower percentage of viable embryos and rupture earlier, at 6–8 weeks after the LMP, than uterine EPs (12–16 weeks). Under normal circumstances, the tube cannot be visualized by ultrasound. If, however, the tube is dilated by an ectopic trophoblast, this section of the tube becomes visible, and trophoblast flow can be demonstrated using color Doppler. In 70–85% of cases, corpus luteum (C. luteum) and TEP are ipsilateral (Fig. 4).

The best approach to identification of the ectopic trophoblast is therefore visualization of the ovaries and determination of the site of the C. luteum. The next step consists in careful exploration of the surroundings of the ovary containing the C. luteum, looking for an adjacent inhomogeneous mass. Once this mass is seen, gentle pressure with the tip of the probe on the structures between ovary and the mass can provide knowledge whether or not the mass and the ovary are connected (sliding sign). Now color Doppler mode is activated and used to demonstrate C. luteum neoangiogenesis in the ovary, the “ring of fire.” The adjacent mass is interrogated in the same way to verify a similar vascular ring signal representing the trophoblast flow. Finally, 3D mode can give an idea of the spatial arrangement of ovary and mass and deliver additional proof that the mass, now identified as trophoblast, is not part of the ovary, but of the fallopian tube (Fig. 5).

OVARIAN ECTOPIC PREGNANCY

Ovarian ectopic pregnancy (OEP) results from the implantation of the trophoblast into the ovary, which happens in up to 3% of all EPs, or once in 7,000–15,000 pregnancies.²⁶ As per histological evidence, the implantation may occur intra- or extrafollicular;²⁸ however, this classification makes no difference for sonographic appearance and clinical manifestation. Like in other EPs, clinical symptoms may include vaginal bleeding and abdominal pain, with positive pregnancy test. Sonographic indicators for OEP are subtler than in other EPs. With a positive pregnancy test and the provisional diagnosis “PUL” overshadowing this clinical scenario, successful management depends on the cooperation between the main responsible obstetrician, sonographer, laparoscopic surgeon, and pathologist,²⁹ the first three often being the same person. Ovarian ectopic pregnancy appearance in TVS can be misinterpreted as ovarian endometriosis or as C. luteum, and even during laparoscopy, it usually presents as a hemorrhagic or ruptured C. luteum cyst.³⁰ 3D ultrasound can demonstrate a small hypoechoic mass representing the gestational sac (GS), bulging from the ovarian cortex and being surrounded by a thick hyperechoic ring (“bagel sign”).³¹ The addition of color/power Doppler will highlight trophoblast flow within this hyperechoic ring and will eventually visualize a “ring of fire” of an adjacent C. luteum graviditatis right next to it. Thus, 3D power Doppler ultrasound is able to establish OEP diagnosis by visualizing ectopic trophoblast and C. luteum within the same ovarian volume.³¹ The interested reader can find excellent images in the publication of Ghi, Banfi, Marconi, Pilu, et al. “Picture of the month-three dimensional sonographic diagnosis of ovarian pregnancy.” Ultrasound Obstet Gynecol 2005;26:102–104.³¹

UTERINE ECTOPIC PREGNANCIES

All uterine ectopic pregnancies have higher beta hCG levels and higher rates of embryonic viability in common compared to TEP and OEP, which is a limiting factor for the use of methotrexate in uterine ectopic pregnancies.

CORNUAL/INTERSTITIAL PREGNANCY

Cornual/interstitial pregnancy (IEP) the term “cornual” is often used as synonym for “interstitial” EP. Strictly spoken, the cornual pregnancy (1% of all EPs) describes the location of an EP in the horn of a bicornuate or septate uterus, whereas an IEP (2–4% of all EPs) is defined as located in the interstitial or intra-myometrial section of the fallopian tube³² (Fig. 6). In an emergency laparotomy situs, this differentiation may be rather difficult (Fig. 7). This intramural section of the tube may under ideal sonographic conditions and careful exploration of the 3D volume, for example, by 3D tomographic ultrasound imaging (TUI), be visualized as a hyperechoic thin line in the cornual area. In IEP, the medial section of this line can be seen connecting the apex of the cornual endometrial angle with the medial aspect of the ectopic GS, as the “interstitial line” (Fig. 8).³³

Another sonographic marker for IEP is the “claw sign”.³⁴ The myometrium, separating the central endometrium from the cornual mass in the lateral uterine fundus, forms a “claw” around this mass, with a remaining myometrial mantle of less than 5-mm thickness in the fundal area around the ectopic GS (Fig. 9). Particularly because IEP occurs significantly more frequently after assisted reproduction, a delay of diagnosis and treatment is unfortunately common and one of the reasons for a mortality rate 15 times higher (2–2.5%) than in TEP (0.14%),²⁷ (Fig. 7).

In analogy to the rather ominous naming of the arterio-arterial anastomosis of obturator artery and inferior epigastric artery as “corona mortis”, the severity of hemorrhage in IEP may be explained by the arterio-arterial anastomosis of the tubal branch of the ovarian artery and the uterine artery (Fig. 10).

Next to color Doppler mode for identification of cornual trophoblast flow (Fig. 11), 3D multiplanar (Fig. 9) and 3D tomographic imaging are excellent tools to deliver the decisive proof, which endometrium and trophoblast are separated by a layer of myometrium (Fig. 12).

Various treatment options have been described in the literature for IEP.²⁹ Of our three cases, one was ruptured and required emergency laparotomy with cornual resection. Of the other two, one was managed with laparoscopic cornual resection, the other with laparotomy and cornual resection (Fig. 13).

CESAREAN SCAR ECTOPIC PREGNANCY

Cesarean scar ectopic pregnancy (CSEP) occurs in up to 0.05% of all pregnancies and is found in 0.15% of women who had a previous lower segment cesarean section (LSCS). In women after at least one LSCS, CSEP accounts for 6.1% of all EPs.³⁵ This rare form of uterine EP is defined by a trophoblast location in the niche of a lower segment cesarean scar, with the GS seen outside of the endometrium and surrounded only by myometrium and scar tissue (Fig. 14).

Clinical symptoms can occur already around 5 weeks post menstruation in form of painless vaginal bleeding. Cesarean scar ectopic pregnancy might be mistaken for an isthmic intrauterine pregnancy or an incipient miscarriage of an initially regularly placed intrauterine pregnancy, though an inevitable spontaneous abortion is usually accompanied by lower abdominal cramps. In abortion, TVS presents images of a deformed or collapsed GS and vertical sliding movements of products of conception along the long axis of the lower uterine and cervical segment during uterine contractions (sliding sign) which can be provoked by gentle pressure on the myometrium. In contrast, the ultrasonographic evidence of an immobile trophoblast located atypically in the level of the cesarean scar and surrounded by rich blood flow in 3D power Doppler has to be taken as unmistakable sign of a viable CSEP.³⁶ Demonstration of embryonic heart action within the GS, rather common, given the excellent blood supply in vicinity of the uterine arteries, is additional proof. More differential diagnostic clues will be provided by 3D surface rendering of the uterus in the sagittal axis: the ballooning of the cervix, as typically seen in a cervical pregnancy (see section “cervical pregnancy”), is absent in CSEP. Since the CSEP expands within the cesarean scar niche, the main mass of the GS is not placed centrally in the uterocervical axis but anteriorly of it. Finally, the myometrial layer between GS and Bladder is very thin or absent (Fig. 15).

CERVICAL ECTOPIC PREGNANCY

Cervical ectopic pregnancy (CEP), defined as the implantation of a fertilized ovum in the endocervical canal below the inner cervical os, is a rare condition, with an incidence below 0.1% of all EPs³⁴ (Fig. 16). This ectopic implantation happens to be in the level where the uterine arteries reach the side of the uterus. Clinicians have to be cautioned that clinical and sonographic presentation of miscarriage and cervical pregnancy often have such features in common as early pregnancy vaginal bleeding, speculum examination in both cases revealing an open external cervical os with a fleshy mass protruding,²⁹ a positive serum beta hCG test, and TVS demonstration of a dilated cervical canal with heteroechogenic content. The response however to an attempt of evacuation of alleged “retained products of conception” could be deleterious in a CEP, disrupting placentation, and causing massive hemorrhage and even emergency hysterectomy. On the contrary, there is also need to differentiate between isthmic pregnancy with intraendometrial implantation just above the inner cervical os, and cervical pregnancy, because of opposite prognosis of the two: while a viable isthmic pregnancy is likely to have a normal outcome, cervical pregnancy—as uterine ectopic pregnancy—has no chances of going to term and implies a high risk of maternal morbidity and mortality due to severe hemorrhage (Fig. 17).

3D vaginal sonography in combination with color Doppler has redefined the sonographic criteria of cervical pregnancy: 3D surface rendering with three orthogonal planes (sagittal, transversal, and coronal) shows an hourglass appearance of cervix, isthmus, and corpus uteri in the reconstructed image. The ballooned cervix contains the trophoblast, clearly located below a constricted isthmus.³⁶ With color/power Doppler mode added, atypically intense blood flow in the cervical area around the trophoblast can be demonstrated³⁷ (Fig. 18). The inclined reader may find further study material online: TheFetus.net.³⁸

ABDOMINAL ECTOPIC PREGNANCY

Against the backdrop of a positive serum beta hCG, the heteroechogenicity of a thickened endometrium, indicating a collection of debris and blood in the uterine cavity, resembles images of retained products of conception with a collapsed GS (pseudosac), in approximately 20% of all EPs.³⁹ It has therefor been argued that in the case of high and/or increasing serum beta hCG, a (diagnostic) curettage could provide histological clues—by demonstrating presence or absence of trophoblast villi within the endometrial tissue—to eventually abandon wrong assumptions of incomplete abortion, and in doing so, help to focus on the search for a PUL.^40,41 Depending on its location, an abdominal ectopic pregnancy (AEP) can be accompanied by various symptoms, ranging from renal or gallbladder colic to symptoms of appendicitis. In clinically symptomatic PUL, careful transabdominal sonographic exploration of perihepatic and perisplenic spaces, and of the paracolic gutters, is always required to look for and to quantify free fluid, i.e., hemoperitoneum, but also to identify a possible AEP. Besides a good ultrasound equipment, sonographic skills, and experience, a high degree of suspicion is needed in dealing with EPs. Abdominal pregnancy sites can be—in decreasing order of frequency—the pouch of Douglas (PoD), mesosalpinx, omentum, spleen, liver, and appendix.^42,43

Abdominal ectopic pregnancy occurs as rarely as once in 8,000–10,000 pregnancies and makes up for 1–1.5% of all EPs.^44,45 Maternal mortality rates are high, which is explained by an often advanced gestational age at discovery, severe hemorrhage at any time in case of placenta separation, and predominance of occurrences in developing countries with limitations of infrastructure and medical equipment. The following case presentation shall illustrate the specific challenges of an AEP (Fig. 19).

SUMMARY

Transvaginal high frequency 2D/3D ultrasound with color Doppler has emerged as the most important tool in diagnosing an EP. Applied in a dynamic real-time study of the pelvic organs, the TVS probe becomes the “seeing finger” of the examining clinician. The need of an experienced operator for the ultrasound machine in this encounter should not be conceived as disadvantage. If this operator is the gynecologist in charge himself, he may find the answers to all his diagnostic questions, while interrogating the ROI methodically using all diagnostic modalities from 2D over color Doppler to 3D and 3D color Doppler. Tomographic imaging with postprocessing of volumes in different planes can be very useful as shown in section “interstitial ectopic pregnancy”. Nevertheless, in analogy to CT and MRI, offline analysis of TVS generated 3D data sets does not match with the performance of 2D–3D real-time examination incorporating anamnestic data and clinical information during scanning.⁴⁶ Again: the excellent diagnostic potential of TVS, with 3D mode added, is based on interactive dynamic real-time examination.⁴⁷

DIAGNOSTIC HINTS AND PITFALLS

REFERENCES

1. Van Den Eeden SK, Shan J, Bruce C, et al. Ectopic pregnancy rate and treatment utilization in a large managed care organization. Obstet Gynecol 2005;105(5 Pt 1):1052. DOI: 10.1097/01.AOG.0000158860.26939.2d.

2. Hoover KW, Tao G, Kent CK. Trends in the diagnosis and treatment of ectopic pregnancy in the United States. Obstet Gynecol 2010;115(3):495. DOI: 10.1097/AOG.0b013e3181d0c328.

3. Stulberg DB, Cain LR, Dahlquist I, et al. Ectopic pregnancy rates and racial disparities in the Medicaid population, 2004-2008. Fertil Steril 2014;102(6):1671. DOI: 10.1016/j.fertnstert.2014.08.031.

4. Murray H, Baakdah H, Bardell T, et al. Diagnosis and treatment of ectopic pregnancy. CMAJ 2005;173(8):905. DOI: 10.1503/cmaj.050222.

5. Creanga AA, Shapiro-Mendoza CK, Bish CL, et al. Trends in ectopic pregnancy mortality in the United States: 1980–2007. Obstet Gynecol 2011;117(4):837–843. DOI: 10.1097/AOG.0b013e3182113c10.

6. Der EM, Moyer C, Gyasi RK, et al. Pregnancy related causes of deaths in Ghana: a 5-year retrospective study. Ghana Med J 2013;47(4):158–163.

7. Iklaki CU, Emechebe C, Njoku CO, et al. Review of Ectopic Pregnancy as a Cause of Maternal Morbidity and Mortality in a Developing Country. IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) 2015;14(8):86–91.e-ISSN: 2279-0853, p-ISSN: 2279-0861.

8. Brüggmann D, Kollascheck J, Quarcoo D, et al. Ectopic pregnancy: exploration of its global research architecture using density-equalising mapping and socioeconomic benchmarks. BMJ Open 2017;7(10): e018394. DOI: 10.1136/bmjopen-2017-018394.

9. Ouyang Y, Li X, Yi Y, et al. First-trimester diagnosis and management of Cesarean scar pregnancies after in vitro fertilization-embryo transfer: a retrospective clinical analysis of 12 cases. Reprod Biol Endocrinol 2015;13:126. DOI: 10.1186/s12958-015-0120-2.

10. https://www.healthdirect.gov.au/hcg-levels ,HealthDirect, a free medical service supported by the Australian government.

11. Winder S, Reid S, Condous G. Ultrasound diagnosis of ectopic pregnancy. AJUM 2011;14(2):29–33. DOI: 10.1002/j.2205-0140.2011.tb00192.x.

12. Tait RL. Five cases of extrauterine pregnancy operated upon at the time of rupture. Br Med J 1884;1:1250. DOI: 10.1136/bmj.1.1226.1250.

13. Kalk H. Erfahrungen mit der Laparoskopie (zugleich mit Beschreibung eines neuen Instrumentes). Z Klin Med 1929;111:303.

14. Hope RB. Differential diagnosis of ectopic gestation by peritonoscopy. Surg Gynecol Obstet 1937;64:229.

15. Donald I, Macvikar MB, Brown TG. Investigation of abdominal masses by pulsed ultrasound. The Lancet 1958;271(7032):1188–1195. DOI: 10.1016/S0140-6736(58)91905-6.

16. Timor-Tritsch IE, Farine D, Rosen MG. A close look at early embryonic development with the high-frequency transvaginal transducer. Am J Obstet Gynecol 1988;159(3):676–681. DOI: 10.1016/S0002-9378(88)80033-4.

17. Kurjak A, Jurkovic D, Alfirevic Z, et al. Transvaginal color Doppler imaging. J Clin Ultrasound 1990;18(4):227–234.

18. Armstrong E, Ehrlich P, Birken S, et al. Use of a highly sensitive and specific immunoradiometric assay for detection of human chorionic gonadotropin in urine of normal, nonpregnant, and pregnant individuals. J Clin Endocrinol Metab 1984;59(5):867–874. DOI: 10.1210/jcem-59-5-867.

19. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom, 2011.

20. Lurie S. The history of the diagnosis and treatment of ectopic pregnancy: a medical adventure. Eur J Obstet Gynecol Reprod Biol 1992;43(1):1–7. DOI: 10.1016/0028-2243(92)90235-Q.

21. The Institute of Obstetricians and Gynecologists, Royal College of Physicians in Ireland, and Directorate of Clinical Strategies and Programmes, Health Service Executive. Clinical Practice Guideline–The Diagnosis and Management of Ectopic Pregnancy. Version: 1.0 Guideline No: 33; Publication Date Nov. 2014, Revision Date Nov. 2017.

22. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2016. Atlanta, GA: US Department of Health and Human Services; 2017.

23. Centers for Disease Control and Prevention, Births - Method of delivery, 2015. https://www.cdc.gov/nchs/fastats/delivery.htm(accessed on May 05, 2017).

24. Li C, Zhao WH, Zhu Q, et al. Risk factors for ectopic pregnancy: a multi-center case-control study. BMC Pregnancy Childbirth 2015;15:187. DOI: 10.1186/s12884-015-0613-1.

25. Steptoe PC, Edwards RG. Reimplantation of the human embryo with subsequent tubal pregnancy. Lancet 1976;1:880–882. DOI: 10.1016/S0140-6736(76)92096-1.

26. Bouyer J, Coste J, Fernandez H, et al. Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases. Hum Reprod 2002;17(12):3224–3230. DOI: 10.1093/humrep/17.12.3224.

27. Tulandi T, Al-Jaroudi D. Interstitial pregnancy: results generated from the Society of Reproductive Surgeons registry. Obstet Gynecol 2004;103(1):47–50. DOI: 10.1097/01.AOG.0000109218.24211.79.

28. Seo MR, Choi SC, Bae J, et al. Preoperative diagnostic clues to ovarian pregnancy: retrospective chart review of women with ovarian and tubal pregnancy. Obstet Gynecol Sci 2017;60(5):462–468. DOI: 10.5468/ogs.2017.60.5.462.

29. Fylstra DL. Ectopic pregnancy not within the (distal) fallopian tube: etiology, diagnosis, and treatment. Am J Obstet Gynecol 2012;206(4):289–299.

30. Comstock C, Huston K, Lee W. The ultrasonographic appearance of ovarian ectopic pregnancies. Obstet Gynecol 2005;105(1):42–45. DOI: 10.1097/01.AOG.0000148271.27446.30.

31. Ghi T, Banfi A, Marconi R, et al. Picture of the month-three dimensional sonographic diagnosis of ovarian pregnancy. Ultrasound Obstet Gynecol 2005;26(1):102–104. DOI: 10.1002/uog.1933.

32. Lau S, Tulandi T. Conservative medical and surgical management of interstitial ectopic pregnancy. Fertil Steril 1999;72(2):207–215. DOI: 10.1016/S0015-0282(99)00242-3.

33. Yassin AS, Taha MS. Interstitial ectopic pregnancy, diagnosis and management: A case report and literature review. Ann Clin Case Rep 2017;2:1352.ISSN: 2474-1655.

34. Kao LY, Scheinfeld MH, Chernyac V, et al. Beyond ultrasound: CT and MRI of ectopic pregnancy. AJR Am J Roentgenol 2014;202(4):904–911. DOI: 10.2214/AJR.13.10644.

35. Ash A, Smith A, Maxwell D. Caesarean scar pregnancy. BJOG 2007;114(3):253–263. DOI: 10.1111/j.1471-0528.2006.01237.x.

36. Shih J-C. Cesarean scar pregnancy: diagnosis with 3-dimensional (3D) ultrasound and 3 D power Doppler. Ultrasound Obstet Gynecol 2004;23(3):305–309. DOI: 10.1002/uog.1005.

37. Ruano R, Reya F, Picone O, et al. Three-dimensional ultrasonographic diagnosis of a cervical pregnancy. Clinics (Sao Paulo) 2006;61(4):355–358. DOI: 10.1590/S1807-59322006000400014.

38. Lau WL, Cahn LL, Chan KS, et al. 3D ultrasound diagnosis of the cervical pregnancy.2011-2-23. TheFetus.net.

39. Ahmed AA, Brian DM, Calabrese P. Ectopic pregnancy and pseudo-sac. Fertil Steril 2004;81(5):1225–1228. DOI: 10.1016/j.fertnstert.2003.09.068.

40. Rubal L, Chang K. Do you need to definitely diagnose the location of a pregnancy of unknown location? The case for “yes”. Fertil Steril 2012;98(5):1078–1084. DOI: 10.1016/j.fertnstert.2012.09.033.

41. Reid S, Condous G. Is there a need to definitely diagnose the location of a pregnancy of unknown location? The case for “no”. Fertil Steril 2012;98(5):1085–1090. DOI: 10.1016/j.fertnstert.2012.09.032.

42. Parekh VK, Bhatt S, Dogra VS. Abdominal pregnancy: an unusual presentation. J Ultrasound Med 2008;27(4):679–681. DOI: 10.7863/jum.2008.27.4.679.

43. Abduljabbar N, Saquib S, Elhussein W. Successful management of abdominal pregnancy: two case reports. Oman Med J 2018;33(2):171–175. DOI: 10.5001/omj.2018.32.

44. Gibbs RS. Danforth’s obstetrics and gynecology,Philadelphia: Lippincott Williams and Wilkins; 2008; p. 84.

45. Atrash HK, Friede A, Hogue CJ. Abdominal pregnancy in the United States: frequency and maternal mortality. Obstet Gynecol 1987;69(3 Pt 1):333–337.

46. Infante F, Espada Vaquero M, Bignardi T, et al. Prediction of tubal ectopic pregnancy using offline of 3-dimensional transvaginal ultrasonographic data sets: an interobserver and diagnostic accuracy study. J Ultrasound Med 2018;37(6):1467–1472. DOI: 10.1002/jum.14489.

47. Testa AC, Van Holsbeke C, Mascilini F, et al. Dynamic and interactive gynecological ultrasound examination. Ultrasound Obstet Gynecol 2009;34(2):225–229. DOI: 10.1002/uog.7309.

48. Braunstein GD, Vaitukaitis JL, Carbone PP, et al. Ectopic production of human chorionic gonadotropin by neoplasms. Ann Intern Med 1973;78(1):39. DOI: 10.7326/0003-4819-78-1-39.