Interstitial Ectopic Pregnancy

An interstitial pregnancy occurs when the blastocyst implants in the interstitial part of the fallopian tube. The interstitial part is the most proximal portion of fallopian tube that lies within the myometrium, about 0.7mm wide and 1-2cm long [1]. 

Interstitial pregnancy accounts for 2–6.8% of all ectopic pregnancies [2]. The increase in the incidence of interstitial pregnancy is mostly due to improvements in ultrasound diagnosis and uptake of assisted reproductive techniques.

The term “Interstitial “pregnancy may be incorrectly interchanged with ‘cornual’ or ‘angular’ pregnancies. It is important to correctly differentiate between these terms, as the resultant maternal morbidity and mortality risks  vary greatly.

“Cornual pregnancy” refers to the presence of a gestational sac within a rudimentary horn of an unicornuate uterus, cornua of a bicornuate uterus, or upper lateral portion of a septate uterus [3]. 
‘Angular pregnancy’ occurs when an embryo is implanted medial to the utero-tubal junction, in the lateral angle of the uterine cavity. In a recent prospective study by Bollig and Schust [4] of 42 cases, they found that 80% of these pregnancies resulted in a live birth and 20% in miscarriage. There were no cases of uterine rupture, maternal death, abnormal placentation or hysterectomy. It was concluded that angular pregnancy is a variation of a normally implanted intrauterine pregnancy, rather than a form of ectopic pregnancy. The term angular pregnancy also should be abandoned according to recent  ESHRE  recommendation [5].

Interstitial pregnancy is a subtype of tubal ectopic pregnancy. It could be further classified as partial or complete. Partial interstitial pregnancies are those which are implanted within the interstitial part of the fallopian tube, but also partially protruding through the uterine tubal ostium into the uterine cavity. Complete interstitial pregnancy occurs when the gestational sac is completely implanted within the intramural portion of fallopian tube [5].
Most interstitial pregnancies tend to grow laterally into the proximal segment of the tube and ectopic pregnancies which are confined only to the interstitial segment of the fallopian tube are relatively rare [4].

Risk factors for interstitial pregnancy include previous ectopic pregnancy, tubal surgery, in vitro fertilisation (IVF), ovulation induction, or history of sexually transmitted disease. Hiersch et al. reported that 46% of the women with interstitial pregnancies treated in their hospital had conceived following assisted reproductive techniques [6].

Recurrence risk of interstitial pregnancy is rare.

Diagnosing interstitial pregnancy may be difficult, due to the similar presenting symptoms and signs with other ectopic pregnancies and difficulties in distinguishing an interstitial pregnancy from an eccentric intrauterine or isthmic tubal ectopic pregnancy on ultrasound imaging [3,4]. Even when interstitial pregnancy is suspected on ultrasound scan, laparoscopic findings may be negative in early stages and present a diagnostic dilemma.
Patients may present with abdominal pain and/or vaginal bleeding. Some patients may be asymptomatic or present with rupture and haemodynamic instability requiring immediate surgery.

A single measurement of the quantitative β hCG level alone cannot differentiate an intrauterine pregnancy from an ectopic pregnancy.  Therefore, serial quantitative β hCG levels correlated with serial transvaginal ultrasound findings are recommended to determine an early intrauterine pregnancy from ectopic pregnancy. An abnormal increasing of serial beta β hCG allows to recognize of an abnormal implantation but it’s not specific to interstitial pregnancy.

Pelvic sonography is the main method of diagnosis. The main characteristic feature of an interstitial ectopic pregnancy is a gestational sac located eccentrically outside the endometrial cavity of the uterus, in the region of the fundus with no or minimal identifiable myometrium on its lateral aspect.

The following ultrasound scan criteria may be used for the diagnosis of interstitial pregnancy, as articulated by RCOG [7]: (1) Empty uterine cavity, (2) Products of conception/gestational sac located laterally in the interstitial (intramural) part of the tube and surrounded by less than 5 mm of myometrium in all imaging planes, (3) Presence of the ‘interstitial line sign’.  ‘Interstitial line sign’ is an echogenic line that runs from the endometrial echo complex to the interstitial mass/gestational sac and has high sensitivity (80%) and specificity (98%) in diagnosis of interstitial pregnancy [8]. 

The 2D Doppler transvaginal US has higher sensitivity because it can reveal an intense peri-trophoblastic blood flow with numerous tortuous vessels.

The 3D scans are very useful in obtaining the coronal scans of the fundal region of the uterus, giving a better overview of the cornual regions of the uterus. Therefore, 3D ultrasound if available can be used to avoid misdiagnosis with early eccentric normal intrauterine pregnancy [3,7].
 

Most interstitial pregnancies expand into the isthmic part of the fallopian tube which is easy to diagnose. In some cases, interstitial pregnancies spread out medially and eventually start to protrude into the upper lateral aspect of the uterine cavity. These partial interstitial pregnancies are often very hard to differentiate from laterally implanted normally sited pregnancies (eccentric intrauterine pregnancy). 3D ultrasound is a useful diagnostic tool compared to other imaging modalities because it may depict the precise location of the interstitial gestational sac and differentiate it from eccentrically located intrauterine gestational sac [9]. 

Ectopic pregnancy is still the leading cause of haemorrhage-related maternal mortality in the first trimester. In interstitial pregnancy, the gestational sac is implanted in the intramural portion covered by the myometrium and proliferated blood vessel near the fallopian tube. Therefore, the rupture of interstitial pregnancies would cause severe hemorrhage in the abdominal cavity and may lead to  hypovolemic shock or even maternal death. Timely diagnosis is key to the successful management of patients with interstitial pregnancy. 

Surgical management is the main option for interstitial pregnancies. Increasingly, more conservative approaches are being used, such as cornuostomy instead of cornual resection, laparoscopy in place of laparotomy and hysterectomy only in cases with severely damaged uterus [2,7]. Cornuostomy is considered to cause less tubal damage than cornual resection and may have better pregnancy outcomes in future. Cornual resection disrupts the uterine architecture and cause a risk of uterine rupture in subsequent pregnancies. Liao et al. reported an incidence of subsequent uterine rupture and dehiscence after cornual resection of 30% [10]. Therefore, it should only be performed in ruptured cases or for patients not desiring future fertility. Cucinella et al.’s systematic review compared 156 cases of cornuostomy with 198 cases of cornual resection: the pregnancy rates were 72% vs. 62% respectively, of which  live birth rates  of 48% vs. 62% were found in the cornuostomy and cornual resection groups, respectively. The differences in the fertility outcomes and live birth rates between the two groups were not statistically significant [11].

Conservative management (expectant and medical management) should only be offered to patients who are haemodynamically stable and have no obvious risks of immediate rupture, such as large GS or rapidly increasing β-hCG levels. Close, stringent  follow-up allows expectant or medical management to be offered in appropriate patients. The best medical treatment regimen for interstitial pregnancy remains unknown. A report by Tulandi [12] included  32 cases of interstitial pregnancy: 8 cases were  treated with methotrexate (systemically n=4, locally under ultrasonographic guidance n=2, or under laparoscopic guidance n=2), 11 patients were treated by laparoscopy and 13 by laparotomy. Systemic methotrexate treatment failed in 3 patients, and they subsequently required surgery. Cassik et al. [13] published a case series of conservatively managed interstitial pregnancies. They found success rates for local methotrexate, systemic methotrexate and expectant management were 91%, 80% and 71% respectively although the numbers were too small to show a statistically significant difference. However, the 5/35 (14.3%) of the patients managed conservatively ultimately required surgical treatment, all of whom had β-hCG levels greater than 9000 IU/L.

Interstitial ectopic pregnancy is referred to one of the most dangerous types of ectopic pregnancy because it has the potential to cause life-threatening haemorrhage resulting in a 2–5% maternal mortality rate. Therefore, early diagnosis plays a vital role in management and reducing maternal complications. 

1.    Wright SD, Busbridge RC, Gard GB (2013) A conservative and fertility preserving treatment for interstitial ectopic pregnancy. Aust N Z J Obstet Gynaecol 53(2):211–213.
2.    Brincat, M., Bryant-Smith, A. & Holland, T.K. The diagnosis and management of interstitial ectopic pregnancies: a review. Gynecol Surg 16, 2 (2019)
3.    E.K. Arleo, E.M. DeFilippis. Cornual, interstitial, and angular pregnancies: clarifying the terms and a review of the literature, Clin Imag, 38 (6) (2014), pp. 763-770
4.    Bollig KJ, Schust DJ. Refining angular pregnancy diagnosis in the first trimester: a case series of expectant management. Obstet Gynecol 2020;135:175–184
5.    The ESHRE working group on Ectopic Pregnancy, Emma Kirk, Pim Ankum, Attila Jakab, Nathalie Le Clef, Artur Ludwin, Rachel Small, Tina Tellum, Mira Töyli, Thierry Van den Bosch, and Davor Jurkovic. Terminology for describing normally sited and ectopic pregnancies on ultrasound: ESHRE recommendations for good practice. Human Reproduction Open, Vol.00, No.0, pp. 1-21, 2020
6.    Hiersch L et al Effectiveness of medical treatment with methotrexate for interstitial pregnancy. Aust N Z J Obstet Gynaecol 54(6) (2014):576–580
7.    Diagnosis and management of ectopic pregnancy: green-top guideline No. 21. BJOG Int J Obstet Gynaecol 2016;123:e15–55. doi:10.1111/1471-0528.14189
8.    T.E. Ackerman, et al. Interstitial line: sonographic finding in interstitial (cornual) ectopic pregnancy Radiology, 189 (1) (1993), pp. 83-87
9.    Finlinson AR, Bollig KJ, Schust DJ. Differentiating pregnancies near the uterotubal junction (angular, cornual, and interstitial): a review and recommendations. Fertil Res Pract. 2020 May 4;6:8.
10.    Liao CY et al (2017) Cornual wedge resection for interstitial pregnancy and postoperative outcome. Aust N Z J Obstet Gynaecol 57(3):342–345
11.    Cucinella G et al Interstitial pregnancy: a ‘road map’ of surgical treatment based on a systematic review of the literature. Gynecol Obstet Investig (2014) 78:141–149 
12.    Tulandi T, Al-Jaroudi D. Interstitial pregnancy: results generated from the Society of Reproductive Surgeons Registry. Obstet Gynecol. 2004 Jan; 103(1):47-50.
13.    Cassik P et al Factors influencing the success of conservative treatment of interstitial pregnancy. Ultrasound Obstet Gynecol (2005) 26(3):279–282

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