Margaret Dziadosz1 , Ana Monteagudo1 and Ilan Timor-Tritsch1
Department of Obstetrics and Gynecology, New York University School of Medicine, 550 1st Avenve, 10016 New York, New York, USA
Interstitial pregnancyCornual pregnancyDiagnostic criteriaMethotrexateMultidose methotrexate
A 28-year-old woman, G2P0010, presented to her primary obstetrician with a complaint of amenorrhea and abdominal pain. Her last menstrual period was 10 weeks prior to presentation. Past history was significant for a single elective first trimester medical abortion and chlamydia that was treated 1 year prior. Physical examination revealed a tender gravid uterus, measuring 7 weeks in size with asymmetrical enlargement. The serum beta human chorionic gonadotropin (BhCG) level was 40,138 mIU/mL. Transvaginal ultrasound (TVUS) evaluation revealed the images presented in Fig. 11.1.
Transvaginal ultrasound (TVUS). a An empty uterine cavity (UC) with echogenic line (arrows) leading towards gestational sac (P). b 3D TVUS rendering showed thin myometrial edge marked with calipers abutting gestational sac (P). Note the empty uterine cavity (UC). c TVUS revealed vascularity surrounding the gestation (P). The uterine cavity was empty (UC). d3D TVUS tomographic rendering showed ectopic gestation denoted by P with empty uterine cavity (UC)
Diagnosis and Assessment
Our patient demonstrates common presentation of interstitial pregnancy . Interstitial pregnancy implants in the segment of fallopian tube that traverses the muscular wall of the uterus. Its incidence is estimated to be 2–4 % of ectopic pregnancies and 1 in 2500–5000 live births. It is also known as “cornual pregnancy,” found in the outermost horn of the uterus, though this term should be reserved for patients with bicornuate uterus. Due to the thickened diameter of the outermost fallopian extension, there is a potential for expansion. Though rupture most commonly occurs prior to 12 weeks in 22 % of patients, expansion allows many interstitial pregnancies to remain asymptomatic for upwards of 7–16 weeks [1−3].Mortality for undiagnosed condition reaches 2.5 %, which is sevenfold higher than for other ectopic locations. This is most commonly due to catastrophic hemorrhage involving late rupture .
Assessment should be initiated with TVUS, which is the primary method for diagnosis; it is not only cost effective but also readily available. An empty uterine sac, paucity of myometrium around the superior-lateral portion of the gestational sac (GS), a distance of at least 1 cm from the edge of the uterine cavity to the GS, and an interstitial line are key identifiers for correct diagnosis [5−8]. As described by Ackerman, the interstitial line is an echogenic line that runs from the endometrial cavity to the cornual region, abutting the interstitial mass or GS. Identification of these diagnostic markers yields specificity for interstitial pregnancy of 88–98 % (Fig. 11.2).
TVUS images concerning ectopic gestation. a TVUS reveals empty uterine cavity. b 3D TVUS confirms interstitial pregnancy. c Note empty uterine cavity (UC). d 3D TVUS reveals intrauterine gestation (P) in UC at left horn. TVUS transvaginal ultrasound. (Images courtesy of Dr. Ilan Timor)
Three-dimensional (3D) ultrasound is especially useful in the diagnosis of interstitial pregnancy (Figs. 11.2 and 11.3). Navigating in the orthogonal planes in order to generate the desired section is helpful. Using the tomographic, multi-sectional display allows systematic scrutiny. Employing the thick slice rendering of volume contrast imaging (VCI) enables the investigator to achieve a particularly sharp edge enhancement in order to differentiate the hyperechoic, decidualized endometrium from intervening myometrium and the eccentrically located GS. A 3D TVUS should be the diagnostic tool of choice for accurate diagnosis [6, 8].
TVUS images concerning for ectopic gestation. a TVUS reveals pregnancy (P) appears outside of UC. b 3D TVUS reveals intrauterine gestation in left horn. c TVUS concerning for empty UC. d 3D TVUS confirms interstitial pregnancy (P) with empty UC. Transvaginal ultrasound (TVUS), uterine cavity (UC). (Images courtesy of Dr. Ilan Timor)
When utilizing TVUS, color flow mapping should be employed to aid in identification of blood supply to the GS. In addition, the use of 3D ultrasonography, as demonstrated in Fig. 11.2 b, d and 11.3 b, d, as well as tomographic planning adds vital details of myometrial measure and exact pregnancy location.
If the rare event that 2D and 3D TVUS are inconclusive, MRI may be considered for diagnostic differentiation. Criteria are similar, including an eccentric GS, scant myometrial tissue surrounding the GS, and detection of the interstitial line .
If an interstitial or cornual pregnancy is identified without the presence of fetal cardiac activity, expectant management is a viable option. However, once positive fetal heart rate is identified, the risks of rupture and subsequent maternal morbidity necessitate other interventions .
Systemic MTX is the most widely utilized nonsurgical management to treat interstitial pregnancy . Single-dose therapy is often unsuccessful with BhCG values > 5000 mIU/mL. Multidose MTX therapy should be implemented as follows: day 0: obtain BhCG, complete blood count (CBC), amino transferase (AST), creatinine, type and screen Rh, Rhogam prn, MTX 50 mg/m2 body surface area (BSA), Administer single IM injection of calculated MTX dose; day 4: BhCG; and day 7: BhCG and administer second dose MTX if BhCG decreased < 15% from days 4–7 . This treatment choice has an overall success rate of 83 %, but carries risk of subsequent rupture with 10–20 % of patients requiring eventual surgical intervention.
Local MTX injection to the GS may also be employed. Various dose regimens of MTX for injection include (a) 1 mg/kg, (b) single dose of 100 mg, or (c) 50 mg/m2 BSA. Success rates of local injection by experienced providers reach 91 % [2, 6, 11, 12]. Benefits include a decreased side effect profile when compared to systemic treatment with a chemotherapeutic agent, tubal patency rate of 92 %, and avoidance of surgical intervention. In the rare event of heterotopic gestation, KCl 20 % is often preferred to MTX [8, 13].
Traditional treatment of interstitial or cornual ectopic pregnancy is surgical intervention. Historically, this involved exploratory laparotomy with subsequent cornual resection or hysterectomy. However, the current evolution of minimally invasive techniques dictates that optimal interventions should be performed via laparoscopy to decrease maternal morbidities. The most common approach remains cornual resection, where the pregnancy and cornua are resected en bloc via a circumferential incision with primary closure [6, 14, 15].
Interstitial pregnancy is most commonly diagnosed between 6.9 and 8.2 weeks gestation . Risk factors include tubal damage, prior salpingectomy , in vitro fertilization conception, and history of sexually transmitted infections. Half of the patients experience abdominal pain, 30 % have bleeding in the first trimester, and 30 % remain asymptomatic.
The patient in this case underwent local injection with MTX according to Fig. 11.4. Per protocol, a 21-gauge needle was introduced into the GS under ultrasound guidance with the assistance of an automated puncture device. Half of the prepared 100 mg MTX in 2 ml of solvent was injected and cardiac activity was noted to cease. The puncture site was observed for 5 minutes to monitor for any post-procedure bleeding . It is of vital importance to pass the needle through the myometrium in a fashion as to allow the point of least resistance to empty into the cavity and thereby avoiding leakage or rupture into the abdomen. Morison’s pouch was inspected and hemostasis was ensured. The patient experienced 2 weeks of progressively decreasing vaginal bleeding and declining BhCG without complications.
Proper technique for local injection of interstitial pregnancy. 
· 3D TVUS is the primary mode for diagnosis
· Interstitial line identification yields excellent specificity and sensitivity for diagnosis
· Less than 5 mm myometrial layer surrounding GS, empty uterine cavity, and < 1 cm of GS from uterine cavity edge are standard criteria for diagnosis.
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