Intramural Ectopic Pregnancy

Intramural ectopic pregnancy (IEP) refers to an abnormal implantation of pregnancy within myometrium. The defining feature the presence of the gestational sac extending beyond the endometrial–myometrial junction, above the level of internal os and not within  the interstitial portion of  the Fallopian tube (1).

According to ESHRE’s classification, intramural ectopic pregnancy is a form of uterine ectopic pregnancy and should be subdivided into partial or complete forms(1).

• Partial IEP: The gestational sac invading the myometrium but also partly protruding into uterine cavity
• Complete IEP: The gestational sac completely implanted within the myometrium, without visible communication with the uterine cavity.

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The exact etiology and pathogenesis of intramural ectopic pregnancy are still unclear. It has been suggested that IEP may occur following any surgical procedures that could damage the endometrial-myometrial junction, such as myomectomy, hysteroscopy, in vitro fertilization (IVF) and dilatation and curettage. Other theories include external migration and implantation on the serosal surface of the uterus or implantation in a focus of adenomyosis (4-10).

Risk factors include a history of previous uterine curettage, uterine fibroid removal, Cesarean Section, intramural adenomyosis, In Vitro Fertilization and embryo transfer (3),(6),(8- 10).

In the 22 reported cases since 2000 by Kirk et al, nine (56%) had a previous uterine curettage, three (19%) were known to have adenomyosis, three (19%) were the result of IVF or IUI and four (25%) had either a previous myomectomy or caesarean section (11).

The risk of recurrence is extremely low. Women with a history of intramural pregnancy with successful preservation of the uterus should present for an early ultrasound scan in all future pregnancies to exclude recurrence.

Diagnosis of intramural ectopic pregnancies is challenging.  In general, it is diagnosed by transvaginal scan examination and confirmed by histological examination showing villous and trophoblast cells in the myometrium. The diagnosis of intramural pregnancy requires clear visualization of the endometrial–myometrial junction in order to delineate the endometrial cavity and detect extension of trophoblast into the myometrium. Three-dimension ultrasound and MRI are important non-invasive methods in diagnosing this type of ectopic pregnancy because of their value to define the relationship between the gestational sac and endometrial–myometrial junction.

Jurkovic D et at proposed the following criteria for the ultrasonographic diagnosis of intramural pregnancy: (1) gestational sac/products of conception located above the internal os and medial to the interstitial tube; (2) evidence of trophoblast breaching the endometrial–myometrial junction (partial intramural pregnancy) or completely confined to the myometrium (complete intramural pregnancy); (3) lack of decidual reaction in the vicinity of trophoblast; and (4) evidence of increased peri-trophoblastic blood flow on color Doppler examination (12)

• Cervical and Cesarean scar pregnancies are also characterized by trophoblast invading into the myometrium but located close to or below the level of the internal os. Identification of  the internal os is therefore important to distinguish intramural  pregnancy from these ectopic pregnancies. The uterine artery reaches the uterus at the level of the internal os and could be used as a landmark to define this level  (1).
• Interstitial ectopic pregnancy implants within the intramural portion of the Fallopian tube. The diagnosis of interstitial pregnancy is suggested when ultrasound images demonstrate eccentric implantation of the gestational sac at the superior fundic level of the uterus. Visualization of the interstitial line sign, a thin endometrial line extending directly to the center of the gestational sac, could help to confirm the diagnosis.  
• Cystic adenomyosis: The ectopic gestational sac is surrounded by an echogenic ring representing the trophoblastic tissue which is absent in cystic adenomyosis. In addition, on color Doppler ultrasound scan, the “ring of fire” sign or  peri-trophoblastic blood flow is not seen in cystic adenomyosis (1),(4),(10).
• Cystic degenerating fibroid: Cystic degenerating fibroid may have appearance of a mass with echogenic rim of tissue surrounding a sonolucent center like an empty gestational sac on B- Mode ultrasound scan. In such cases, colour Doppler could be used to demonstrate increased vascularity surrounding the gestational sac which is relatively sparse in fibroids (1),(5),(6),(9),(13).
• Gestational trophoblastic disease (GTD): The differential diagnosis between intramural pregnancy and GTD is clinically important due to their different treatment regimes. However, it may be difficult to distinguish an intramural pregnancy from GTD due to the similarity in ultrasound features and clinical course. GTD can present as a heterogeneous hypervascularity mass with an ill-defined border like a failed intramural pregnancy. Serum β-hCG levels is usually lower in ectopic pregnancy and rarely exceed 10,000 mIU/l (5),(9),(10).

Life-threatening complications can develop if intramural pregnancies are not diagnosed and treated at an early stage. Transvaginal ultrasound scan is always the first-hand diagnostic modality for all ectopic pregnancies. Early intramural pregnancies mostly have non-specific appearances however,  which can mimic other uterine ectopic pregnancies or even eccentrically located intracavity pregnancies. Hence, it is challenging to make timely and accurate diagnosis even with the most experienced sonographers. Clinicians, therefore, should be aware of the risk factors for such pregnancies. Three-dimension ultrasound and MRI should be considered  in uncertain cases.

Ectopic pregnancy is still a significant source of maternal morbidity and mortality.  Early diagnosis and management are the crucial steps for good outcome. In advanced cases, serious maternal morbidity might be due to either uterine rupture or an abnormally adherent placenta. Women should be managed in a high-risk obstetric unit in order to minimize the risk of severe adverse outcomes.

As with other types of ectopic pregnancy, treatment can be surgical, medical or expectant. Treatment strategies vary depending on individual clinical presentation: the location of the pregnancy, the depth of muscular invasion, the gestational age at diagnosis, serum β-HCG level and also patient’s reproductive history and desire of future fertility.

Failed, partial intramural pregnancy can be managed by dilatation and curettage but the procedure should be performed under ultrasound guidance to ensure that the tissue is completely removed and to minimize the risk of uterine perforation. Medical management, or in rare circumstances expectant management is more appropriate for complete intramural pregnancies or in cases which can not be accessible to transcervical surgical evacuation.  Methotrexate is the most commonly used drug and may be given locally or systemically (12)

Laparotomy or laparoscopy is also performed to excise the intramural pregnancy. Patients should be counseled about the risk of uterine rupture in the event of a future pregnancy if the surgical management was chosen. Carrying to term has also been described for live wanted intramural pregnancy. Le Petit reported a case of intramural ectopic pregnancy with live birth at 37 weeks of gestation (14). Women need to be informed that, if they continue with the pregnancy, they would almost definitely get the life-threatening risks such as: uterine rupture , abnormally adherent placenta with a high risk of requiring hysterectomy (6),(9),(15)

1.           ESHRE working group on Ectopic Pregnancy, Kirk E, Ankum P, Jakab A, Le Clef N, Ludwin A, Small R, Tellum T, Töyli M, Van den Bosch T, Jurkovic D. Terminology for describing normally sited and ectopic pregnancies on ultrasound: ESHRE recommendations for good practice. Hum Reprod Open. 2020 Dec 16;2020(4): hoaa055. doi: 10.1093/hropen/hoaa055. PMID: 33354626; PMCID: PMC7738750.

2.           Kong, L., Mao, N., Shi, Y., Ma, H., & Xie, H. (2017). Diagnosis and management of intramural ectopic pregnancy in the second trimester-a case report. BJR case reports, 3(4), 20160095. https://doi.org/10.1259/bjrcr.20160095

3.           Kyle K. Jensen, Chelsea Pyle, Bryan R. Foster, Roya Sohaey, and Karen Y. Oh. Adenomyosis in Pregnancy: Diagnostic Pearls and Pitfalls. RadioGraphics 2021 41:3, 929-944

4.           Lu, H.-F., Sheu, B.-C., Shih, J.-C., Chang, Y.-L., Torng, P.-L. and Huang, S.-C. (1997), Intramural ectopic pregnancy: Sonographic picture and its relation with adenomyosis. Acta Obstetricia et Gynecologica Scandinavica, 76: 886-889. https://doi.org/10.3109/00016349709024372

5.           Bannon K, Fernandez C, Rojas D, Levine EM, Locher S. Diagnosis and management of intramural ectopic pregnancy. J Minim Invasive Gynecol. 2013 Sep-Oct;20(5):697-700. doi: 10.1016/j.jmig.2013.02.023. PMID: 24034539.

6.           Panelli DM, Phillips CH, Brady PC. Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review.    Fertil Res Pract. 2015 Oct 15;1:15. doi: 10.1186/s40738-015-0008-z. PMID: 28620520; PMCID: PMC5424401

7.           Zhang Q, Xing X, Liu S, Xie X, Liu X, Qian F, Liu Y. Intramural ectopic pregnancy following pelvic adhesion: case report and literature review. Arch Gynecol Obstet. 2019 Dec;300(6):1507-1520. doi: 10.1007/s00404-019-05379-3. Epub 2019 Nov 15. PMID: 31729562.

8.           Chida, H., Kikuchi, A., Murai, M., Sasaki, Y., Kanasugi, T., Isurugi, C., Oyama, R. and Sugiyama, T. (2016), Intramural Pregnancy Implanted Into a Myometrial Defect Caused by Curettage: Diagnosis With Transvaginal Sonography and Preconception and Postconception Magnetic Resonance Imaging. Journal of Ultrasound in Medicine, 35: 2066-2067. https://doi.org/10.7863/ultra.15.11071

9.           Shen Z, Liu C, Zhao L, Xu L, Peng B, Chen Z, Li X, Zhou J. Minimally-invasive management of intramural ectopic pregnancy: an eight-case series and literature review. Eur J Obstet Gynecol Reprod Biol. 2020 Oct;253:180-186. doi: 10.1016/j.ejogrb.2020.08.021. Epub 2020 Aug 23. PMID: 32871441.

10.         Su, S., Chavan, D., Song, K., Chi, D., Zhang, G., Deng, X., Li, L., Kong, B."Distinguishing between intramural pregnancy and choriocarcinoma: A case report". Oncology Letters 13, no. 4 (2017): 2129-2132. https://doi.org/10.3892/ol.2017.5737

11.         Kirk, Emma; McDonald, Katie; Rees, Julia; Govind, Abha (2013). Intramural ectopic pregnancy: a case and review of the literature. European Journal of Obstetrics & Gynecology and Reproductive Biology, 168(2), 129–133. doi:10.1016/j.ejogrb.2012.12.036

12.         Memtsa, M.; Jamil, A.; Sebire, N.; Jauniaux, E.; Jurkovic, D. (2013). Diagnosis and management of intramural ectopic pregnancy. Ultrasound in Obstetrics & Gynecology, 42(3), 359–362. doi:10.1002/uog.12437

13.         Lone FW, Aziz AB, Khan MN, Pervez S. A case of intramural pregnancy: the importance of differentiation from fibroid uterus. Aust N Z J Obstet Gynaecol. 2001 Aug;41(3):337-8. doi: 10.1111/j.1479-828x.2001.tb01242.x. PMID: 11592555.

14.         Petit, L., Lecointre, C., & Ducarme, G. (2012). Intramural ectopic pregnancy with live birth at 37 weeks of gestation. Archives of Gynecology and Obstetrics, 287(3), 613–614. doi:10.1007/s00404-012-2549-2

15.         Jin H, Zhou J, Yu Y, Dong M. Intramural pregnancy: a report of 2 cases. The Journal of Reproductive Medicine. 2004 Jul;49(7):569-572. PMID: 15305831.

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