Learning Objectives:After participating in this continuing professional development activity, the provider should be better able to:

1. Differentiate between cornual and interstitial ectopic pregnancy and propose diagnostic and treatment strategies.

2. Recommend best practices in medical or surgical management and shared decision-making.

3. Explain future pregnancy and health implications.

Ectopic pregnancy accounts for 1% to 2% of all pregnancies in the United States, and is one of the leading causes of maternal morbidity and mortality.1,2 Ectopic pregnancy causes approximately 6% of all maternal deaths, and up to 80% of those that occur in the first trimester.3 The fallopian tube is the most common implantation site, with only 5% to 10% of ectopic pregnancies occurring in nontubal locations.1,2,4 The true incidence of nontubal ectopic pregnancy is difficult to estimate, however, due to the lack of recent national surveillance data. The incidence of nontubal ectopic is likely rising with the increasing rates of cesarean delivery and assisted reproductive technology (ART).5

Nontubal ectopic pregnancies are commonly classified as cervical, interstitial, cornual, cesarean, ovarian, and abdominal pregnancies.4 There is no definitive consensus on the definition of interstitial and cornual pregnancy. These terms are often used interchangeably in the medical literature, but are also often defined as 2 distinct types of nontubal ectopic pregnancy. Based on current literature and for the purposes of our discussion, this article uses the following definitions.

Interstitial pregnancy is defined as a pregnancy that implants in the interstitial portion of the fallopian tube, at the junction of the fallopian tube and uterine myometrium.2,6 Interstitial ectopic pregnancies are rare, accounting for 2% to 4% of all ectopic pregnancies.1,5 However, the morbidity of interstitial ectopic pregnancies is high, with a mortality rate as high as 2.5% or 7 times greater than that of tubal ectopic pregnancy.1,6 The increased morbidity of interstitial pregnancy is often attributed to the interstitial location of the pregnancy, which is adjacent to highly vascular anatomy, including the anastomosis of the ovarian and uterine arteries.4,6 Therefore, rupture poses significant hemorrhage risk. The interstitial location is also believed to allow for asymptomatic growth and subsequent presentation at a later gestational age.4,6 Despite wide acceptance, data to support this asymptomatic growth hypothesis are limited.6

Cornual pregnancy refers to a pregnancy implanted in the cornua of a bicornuate or didelphys uterus, or within a rudimentary horn of a unicornuate uterus.1,2 Cornual pregnancies occur less frequently than interstitial pregnancy, and account for 0.2% to 2% of all ectopic pregnancies.2,7

Cornual and interstitial pregnancies often pose diagnostic and management challenges to providers. Multiple advances have led to new and innovative management options. As risk factors for these potentially morbid nontubal ectopic pregnancies rise, understanding the diagnosis and management of nontubal ectopic pregnancy is increasingly important.

Risk Factors

Risk factors for ectopic pregnancy are well established. Common risk factors include older than 35 years, smoking, history of prior ectopic pregnancy, history of pelvic infection, presence of intrauterine device, and history of ART.1,4 Interstitial and cornual ectopic pregnancies have similar risk factors to tubal ectopic pregnancies.7 In addition, a history of bilateral or ipsilateral salpingectomy is a risk factor for interstitial pregnancy.1,2,6 A history of prior interstitial pregnancy also increases risk of developing a subsequent interstitial ectopic, with a recurrence rate reported as high as 9%.1 Despite the well-established risks, providers should be aware that approximately 50% of women with ectopic pregnancy have no known or identifiable risk factors.7

Clinical Presentation

Clinical presentation of tubal and nontubal ectopic pregnancy is nonspecific. The classic presentation is a positive pregnancy test and abdominal pain with or without vaginal spotting. Among women who present to the emergency department with vaginal bleeding or pain in the first trimester, the rate of ectopic pregnancy is 18%.8 Patients may also be asymptomatic or have mild symptoms. A patient presenting with a positive pregnancy test and an acute abdomen, tachycardia, and hypotension should raise immediate concern for a ruptured ectopic pregnancy.

In cornual and interstitial pregnancies, the location of implantation may allow asymptomatic growth until later gestational ages.6 Patients with these conditions are therefore theoretically more likely to present with ruptured ectopic gestations and require surgical intervention. Providers should maintain a high clinical suspicion for cornual and interstitial pregnancy, as a timely diagnosis is imperative to decrease maternal mortality and morbidity.

Diagnostic Evaluation

Providers should obtain a full medical history and perform a physical examination. Physical exam findings may include abdominal tenderness, vaginal bleeding, cervical motion tenderness, or a tender adnexal mass. If a urine pregnancy test is positive, a quantitative serum [beta]-human chorionic gonadotropin ([beta]-hCG) should be obtained. Transvaginal ultrasound should be performed. Intrauterine gestational sac and yolk sac should be seen by 5 to 6 weeks' gestation in a normally developing intrauterine pregnancy. Serum [beta]-hCG can also be used to aid in diagnosis.8 A discriminatory level of [beta]-hCG is defined by the American College of Obstetricians and Gynecologists (ACOG) as the level at which a gestational sac should be visualized on transvaginal ultrasound. This level has been debated, but use of a conservative measurement of 3500 mIU/mL can be considered. The absence of a gestational sac on transvaginal ultrasound when serum hCG is above the discriminatory level is concerning for nonviable pregnancy.8

If transvaginal ultrasound imaging is inconclusive, and the patient has stable vital signs with well-controlled pain, serial serum [beta]-hCG levels may be used to differentiate normal from abnormal pregnancy. A repeat serum hCG is recommended after 48 hours. The minimum rate of expected increase after 48 hours for viable intrauterine pregnancy is dependent on initial serum hCG value: 49% for an initial [beta]-hCG level of less than 1500 mIU/mL, 40% for an initial [beta]-hCG level of 1500 to 3000 mIU/mL, and 33% for an initial [beta]-hCG level greater than 3000 mIU/mL.8 For spontaneous early pregnancy loss, a decrease in serum [beta]-hCG of 21% to 35% is observed in 95% of women.8 However, decreasing [beta]-hCG values do not definitively rule out ectopic pregnancy. Repeat imaging should be performed as indicated in the routine management of pregnancy of unknown location.

Imaging

Transvaginal Ultrasound

Imaging with transvaginal ultrasound is the gold standard for diagnosis of ectopic pregnancy. It is widely accepted that ectopic pregnancy may not be identifiable on imaging at initial presentation. However, transvaginal ultrasound combined with serial serum [beta]-hCG is reported to have as high as 96% sensitivity and 97% specificity for diagnosing ectopic pregnancy.9 Findings suspicious of ectopic pregnancy include a pseudogestational sac in the uterus, a thin endometrial stripe, free fluid in the pelvis, and/or an adnexal mass.1,9 Clinical suspicion is heightened if there is no gestational sac and [beta]-hCG is above the discriminatory zone. The rate of ectopic pregnancy in these cases is as high as 70%.8 However, there are various factors affecting the discriminatory zone, which may result in a gestational sac visible only at higher [beta]-hCG levels. Examples of such factors include obesity, uterine pathology such as fibroids, and multiple gestations.1

Interstitial Ectopic Pregnancy

The criteria for diagnosing interstitial ectopic pregnancy on transvaginal ultrasound are well established (Table 1). Trimor-Tritsch described the following 3 criteria: (1) an empty uterine cavity; (2) eccentrically located gestational sac more than 1 cm from the uterine cavity; and (3) a thin, less than 5-mm myometrial layer surrounding the gestational sac. These criteria were shown to be 88% to 93% specific and 40% sensitive for the diagnosis of interstitial pregnancy.5 The presence of an interstitial line, an echogenic line extending from the endometrial cavity to the interstitial mass or gestational sac, was later described by Ackerman et al, and is 98% specific and 80% sensitive for interstitial ectopic pregnancy.2,5 An example of an interstitial ectopic pregnancy can be seen in Figure 1.

Figure 1. Interstitial ectopic pregnancy on ultrasound. Findings: a 5.6-cm mass, eccentrically located within right cornua separate from the endometrium with increased hyperemia, and hematoma within the cul-de-sac. The findings are suspicious for interstitial ectopic pregnancy.

Table 1. Ultrasound Criteria for Interstitial and Cornual Ectopic Pregnancies

Cornual Ectopic Pregnancy

Cornual pregnancy is diagnosed by the presence of a pregnancy occurring in the horn of an anomalous uterus (Table 1). Transvaginal ultrasound findings consist of an eccentrically located gestational sac surrounded by a rim of myometrium. This gestational sac is located separate from the uterine cavity, often defined as more than 1 cm from the lateral wall of the endometrial cavity.2,7,9

MRI

Although transvaginal ultrasound is the gold standard for diagnosis of ectopic pregnancy, there are limitations to ultrasound which can pose diagnostic challenges. These include operator skill and experience, bowel gas interference, large body habitus, small field of view, and the inability to definitively differentiate hemorrhage from other fluids.9

Additional imaging may be considered with MRI when ultrasound findings are inconclusive (Figure 2). Interstitial pregnancy appears on MRI as a gestational sac located lateral to the cornua, surrounded by myometrium with an intact junctional zone between the cavity and the gestational sac. Advantages of MRI include multiplanar imaging, excellent soft tissue characterization, and lack of ionizing radiation. MRI can be used in suspected ectopic pregnancies to identify fresh hemorrhage, accurately locate the implantation site with spatial resolution, diagnose congenital uterine anomalies, assist in surgical planning, and differentiate possible ectopic pregnancy from other acute intra-abdominal processes. Clinicians may consider MRI to aid in diagnosis of complex cases, define location, and assist in surgical planning. A noncontrast technique should be used, as gadolinium crosses the placenta and may be damaging to a developing pregnancy. Providers should be aware that CT has no role in diagnosis or management of suspected ectopic pregnancy.9

Figure 2. Interstitial ectopic pregnancy on MRI. Findings: a 5.2-cm heterogeneous mass within the right cornual region of the uterus with a central cystic area with hemorrhage in the pelvis. Given clinical history of pregnancy and pelvic pain, the finding probably represents a ruptured interstitial ectopic pregnancy, with a necrotic uterine fibroid considered less likely.

Management

The management of tubal and nontubal ectopic pregnancy varies significantly and is often dictated by a combination of clinical presentation, patient preference, resources, and clinician practice. Management options include expectant, medical, procedural, or surgical approaches. A recent study showed 78.4% of all ectopic pregnancies were managed surgically.10 This study highlighted the disparities present in management of ectopic pregnancy, specifically demonstrating differences in management type by race and insurance status. Medicaid recipients and uninsured women were less likely to receive medical management than commercially insured women and, if undergoing surgery, less likely to undergo tube-sparing salpingostomy. In addition, Black and Hispanic patients were less likely to undergo tubal conservative surgery than White women.10 These disparities highlight the need for standardization of care in the management of ectopic pregnancy. Providers should be aware of all available and recommended best practices for management of ectopic pregnancy.

Traditional management for interstitial and cornual ectopic pregnancy has been laparotomy with cornual resection or hysterectomy. Advances in imaging technology, pharmacology, and surgical practices have led to earlier diagnosis and the development of newer, more conservative management options. Providers should be aware of all nonsurgical and surgical management options. Overall management decision is dependent on hemodynamic stability, size of ectopic, titer of [beta]-hCG, available resources, and patient preference.

The management of interstitial and cornual ectopic pregnancy is discussed later. Given the rare nature of cornual ectopic pregnancies, robust evidence for the effectiveness of nonsurgical management is not available. It is the opinion of the authors of this review that medical and other procedural management options proposed for interstitial pregnancies can be applied to cornual pregnancies with appropriate shared decision-making.

Nonsurgical Management

Expectant Management

Expectant management for interstitial and cornual ectopic is not recommended due to the high risk of rupture and subsequent morbidity and mortality. However, cases of successful expectant management have been reported in the literature.6 Expectant management can be considered if ultrasound findings are inconclusive, the patient is hemodynamically stable and has no barriers are identified for close interval follow-up and is highly desires of expectant management. This is most appropriate in asymptomatic patients with spontaneously declining [beta]-hCG levels. Benefits to expectant management include avoidance of chemotherapy and surgery, and preservation of potential fertility. For the rare cornual ectopic pregnancy, fetal survival with rudimentary uterine horn pregnancy is reported at approximately 5%.5 Risks of expectant management include uterine rupture and life-threatening hemorrhage. Patients should be counseled extensively about these risks.

Expectant management should consist of close surveillance with repeat [beta]-hCG and imaging.6,7 In cornual ectopic pregnancies, serial ultrasound evaluation demonstrating a surrounding myometrial thickness of less than 5 mm is concerning for impending rupture.5 Strict return precautions should be given to all patients, and risks of rupture and life-threatening hemorrhage, tubal rupture, and emergency surgery should be discussed. Due to these risks, expectant management should be limited to patients with 24-hour access to facilities and surgeons with adequate expertise to care for a hemorrhagic emergency.6

Medical Management

Medical management is a well-reported treatment modality for interstitial ectopic pregnancy in hemodynamically stable patients without signs of rupture who can participate in follow-up. Medical management was traditionally limited to systemic methotrexate in single- or multidose regimens. Management options have expanded to include local injections and adjuncts to methotrexate.

Methotrexate

Methotrexate is widely accepted as a nonsurgical treatment for ectopic pregnancy. Methotrexate is a dihydrofolate reductase inhibitor, which functions by disrupting DNA and RNA synthesis. Before administration of methotrexate, patients should undergo a workup including a complete blood count, evaluation of hepatic and renal function, blood type and screen, [beta]-hCG, and transvaginal ultrasound. Absolute contraindications to methotrexate administration include intrauterine pregnancy, renal or hepatic impairment, pulmonary disease, immunodeficiency, peptic ulcer disease, breastfeeding, and moderate to severe leukopenia, anemia, or thrombocytopenia. Relative contraindications include high [beta]-hCG concentration, ectopic pregnancy more than 4 cm, detection of fetal cardiac activity, and refusal of blood transfusion.8 Common side effects of methotrexate include pelvic pain, nausea, headache, abdominal pain, and dermatitis. Less common side effects include mucositis, diarrhea, and alopecia.1,8 Patients will likely experience vaginal spotting. Before administration, patients should be counseled regarding the risk of rupture and should avoid strenuous activity, intercourse, and medications/foods that decrease efficacy including folic acid and nonsteroidal anti-inflammatory drugs.8

Methotrexate can be administered in single- or multidose regimens for the treatment of ectopic pregnancy (Table 2). Treatment with single-dose regimens is generally limited to patients presenting with low initial [beta]-hCG values.11 The treatment of interstitial pregnancy with single- and multidose regimens has comparable success rates, ranging from 66% to 100%.1,2,4 A recent case study of 18 patients reported 77% success rate of management of interstitial/cornual ectopic pregnancy with systemic methotrexate only.12 Successful treatment has been reported with [beta]-hCG as high as 100,000 mIU/mL. Most data support the use of a multidose regimen of methotrexate (Table 2), and some series have reported safe use of up to 3 courses of therapy. After administration, serum [beta]-hCG levels should be monitored. Failure of appropriate [beta]-hCG level decrease and resolution may require additional treatment, as outlined in Table 2. Approximately 10% to 20% of interstitial pregnancies treated with methotrexate will have rising [beta]-hCG and ultimately require surgical management.6

Table 2. Methotrexate Treatment Protocols for Ectopic Pregnancy

Methotrexate + Gefitinib

Successful treatment of interstitial ectopic pregnancy with systemic methotrexate in combination with gefitinib has been reported.13-15 Gefitinib is an oral epidermal growth factor receptor inhibitor proposed to increase the efficacy of methotrexate. A study reported treatment of 5 interstitial ectopic pregnancies with 1 or 2 doses of systemic methotrexate plus daily oral gefitinib 250 mg for 7 days. All patients tolerated the therapy well, had complete resolution of the ectopic with [beta]-hCG less than 15 mIU/mL within 25 to 67 days, and resumed menses within 6 weeks of resolution.13 There is one case of interstitial pregnancy with fetal cardiac activity and [beta]-hCG peaking as high as 20,000 mIU/mL successfully treated with this combination therapy.14 Of note, no serious adverse events or outcomes have been reported with this treatment. The most common side effects were transient acneiform rash, diarrhea, and dizziness.13,15 No long-term adverse side effects were observed and there were no significant hematologic, liver, or renal biochemical abnormalities. However, gefitinib is associated with the rare side effect of interstitial lung disease, occurring at an incidence of 0.3%. This risk is higher for male sex, Japanese descent, older than 55 years, and prolonged use. The administration of a short course of gefitinib to reproductive-age women without preexisting lung pathology is believed to be safe. Due to limited data and proposed increased risk, providers should avoid this treatment regimen in people of Japanese descent.15 Although promising, larger clinical trials are needed to further define the efficacy and safety of this combination therapy.

Methotrexate + Mifepristone

Successful treatment of interstitial ectopic pregnancies with systemic multidose methotrexate and 1-time oral mifepristone has been reported. Mifepristone is a steroidal antiprogestin that competitively binds progesterone receptors and can lead to decidual necrosis and cellular degeneration. The decidual effects are hypothesized to result in improved efficacy in the medical treatment of interstitial ectopic pregnancy.16 A case report and literature review reported 7 cases of successful treatment of interstitial pregnancy at an average of 6 weeks 4 days and with an average [beta]-hCG of 7683.85 mIU/mL.16 Additional clinical trials need to be performed to further explore the efficacy and safety of this regimen in management of interstitial ectopic.

Procedural Management

Uterine Artery Embolization

Uterine artery embolism (UAE) has been successfully used as an adjunctive therapy in management of interstitial and cornual ectopic pregnancies. Multiple cases of selective UAE on the side of the implanted pregnancy have been reported, followed by successful medical or surgical management.6 One recent study demonstrated successful management of interstitial pregnancy with uterine artery methotrexate infusion and embolism in combination with systemic methotrexate, reporting a 96% success rate and high posttreatment conception rates of 83%.17 Although cases of successful pregnancy have been reported after selective UAE, effect on future fertility is largely unknown and patients should be counseled appropriately. There are insufficient data to routinely recommend the use of UAE as an adjunct to medical or surgical management.

Local Injection

Multiple studies have reported successful treatment of interstitial pregnancy with medical injection directly into the pregnancy under ultrasound, hysteroscopic or laparoscopic guidance.6 The benefits of local injection include avoiding the risks associated with surgery and possibly maintaining tubal patency and/or fertility preservation.6 Tubal patency and live birth have been reported after treatment with local injection for interstitial pregnancy.7 Types of local injections most studied include methotrexate, potassium chloride (KCl), hyperosmolar glucose, and etoposide.7 Various injected dosages and volumes have been reported (Table 3). Local injection of methotrexate is best studied, with case series reporting success rates ranging from 86% to 100%.1,7 KCl is a cardiotoxic agent, and consequently is preferred for management of interstitial pregnancy when fetal cardiac activity is noted.6 Both KCl and hyperosmolar glucose may be preferable in heterotopic pregnancy and in circumstances where there is significant risk of toxicity with systemic administration of methotrexate.7 Etoposide is a topoisomerase II inhibitor that causes breaks in DNA and leads to arrest in cellular division. There are case reports describing etoposide injection for successful management of tubal and nontubal pregnancy.7

Table 3. Ultrasound-Guided Injection: Medical and Doses

Ultrasound-guided local injection (USGI) is the least invasive option for direct injection. One case series of 14 interstitial/cornual ectopic treated with USGI with and without systemic methotrexate reported a 100% success rate in comparison to 77% in 18 cases treated with systemic methotrexate alone.12 Candidates for USGI include patients who desire future fertility, want to avoid systemic therapy or surgery, or have a heterotopic pregnancy and desire preservation of the intrauterine gestation. USGI should be considered only in patients who are hemodynamically stable without signs of rupture or impending rupture, have no contraindications to the chosen regimen, and can undergo close follow-up with prolonged monitoring.7 Dolinko et al7 recommend transvaginal USGI using a dual lumen to allow for aspiration of gestational sac contents followed by injection of the cytotoxic agent in an equal volume. The authors encourage documenting a minimal amount of free fluid in the pelvis on transvaginal ultrasound before and after injection to ensure that rupture has not occurred.7

Although local injection appears to have comparable or improved success rates compared to medical management alone, patients must undergo an additional procedure often with imaging. In addition, these procedures require a level of expertise and are associated with added cost. Physicians with expertise should discuss the risks and potential benefits of USGI with appropriate candidates and consider it as a management option for interstitial and cornual pregnancies.

Surgical Management

Traditionally, patients with interstitial and cornual pregnancy were treated with laparotomy and cornual resection or hysterectomy. The advances in imaging have allowed for earlier diagnosis, and subsequent development of additional surgical management options for stable patients presenting with interstitial and cornual ectopic pregnancy. Surgery is indicated in patients with interstitial or cornual pregnancy who are hemodynamically unstable, have findings concerning for ruptured ectopic, who failed medical or local management, or who prefer surgical management.1 A recent retrospective case series of nontubal ectopic pregnancies revealed primary surgical management was required in almost 60% of interstitial cases.18

Laparoscopy

Laparoscopic management of interstitial and cornual pregnancy is becoming widely accepted as a first-line management option. A recent systematic review and meta-analysis of interstitial pregnancy demonstrated laparoscopy was associated with an almost 10-fold decrease in blood loss, decreased operative time, and decreased hospital stay compared with the traditional management of laparotomy.19 Moawad et al6 reported a cumulative success rate of 85% (164/192 patients) with use of laparoscopic techniques to treat interstitial ectopic pregnancy. Laparoscopic approaches include cornuostomy and cornual resection. Multiple hemorrhagic reduction techniques have been described as adjuncts to laparoscopy and are discussed next.

Transcervical Approach

Successful transcervical management of interstitial pregnancy has been described. Few case reports have described management with transcervical suction evacuation under laparoscopic and transrectal ultrasound guidance.6 Hysteroscopic resection of interstitial pregnancy under laparoscopic visualization also has been described.4,5,20,21

Cornuostomy

Cornuostomy is the laparoscopic management option recommended for interstitial pregnancies less than 3.5 cm. This method was first described in 1995. The method is similar to the linear salpingostomy technique used for distal tubal ectopic pregnancy.6 The affected cornua is injected with dilute vasopressin to minimize blood loss and aid in visualization during dissection. A linear incision is made over the ectopic pregnancy. The gestation is carefully dissected away from the cornua using a combination of blunt, sharp, or hydrodissection techniques. The gestation is removed without removing the surrounding myometrium. The cornua is then closed with absorbable interrupted or continuous sutures.1,2,4-6 Alternative methods for closure include use of a loop or purse string suture, fibrin glue, and spontaneous closure after using electrocautery.6

Cornual Resection

Cornual resection is recommended for management of interstitial ectopic pregnancy more than 4 cm and all cornual pregnancies.2,5 This surgical technique was first described in 1998.5 Dilute vasopressin is injected circumferentially into the myometrium, beneath and lateral to the site of the ectopic pregnancy, to minimize blood loss. A circumferential incision is then made approximately 1 to 2 cm around the cornual pregnancy using scissors or an energy source. The cornual pregnancy is dissected away from underlying tissue and removed. The adjacent fallopian tube is also removed at the time of cornual resection. The myometrium and serosa are then closed in layers, using a similar technique to laparoscopic myomectomy (Figure 3).1,4-6

Figure 3. Laparoscopic cornual wedge resection of interstitial ectopic pregnancy. (Surgical photographs courtesy of Dr. Christine Foley.)

Cornuostomy and cornual resection have similar clinical outcomes, and there is no clinically proven superior method for management of interstitial pregnancy. Lee et al22 reported no difference among postoperative hemoglobin, major complications, or incidence of persistent pregnancy. Notably, cornuostomy did have shorter operative time.22

Reducing Hemorrhage

Multiple techniques to reduce hemorrhage have been successfully used as adjuncts to the surgical management of cornual and interstitial pregnancy. Placement of an endoloop around the cornua was first described in 1999 and has subsequently been successfully reported in the literature. Laparoscopic management of interstitial pregnancy with locally injected vasopressin is accepted as a safe and effective method to minimize blood loss.23 Dosing of vasopressin can range from 10 units in 10 to 100 mL of normal saline.6 Uterine artery blockage, via embolization or intraoperative occlusion, has also been reported.6,24

Laparotomy

Traditionally, interstitial and cornual ectopic pregnancies were managed by laparotomy with cornual wedge resection or total abdominal hysterectomy. Exploratory laparotomy remains the preferred treatment approach for marked hemodynamically unstable patients with suspected rupture when expeditious laparoscopy cannot be performed.2,4,6 Laparotomy is also preferred if an expert laparoscopic surgeon is unavailable. Hysterectomy should be performed in women with uncontrolled hemorrhage.4,6 It is also reasonable to consider hysterectomy based on patient preference with shared decision-making.

Posttreatment Surveillance and Management

Posttreatment Surveillance

Patients who undergo nonsurgical management of interstitial pregnancy should be followed with serial [beta]-hCG until resolution. Follow-up [beta]-hCG levels should be drawn according to the widely accepted protocol for single- or multiple-dose methotrexate (Table 2). There are minimal data to support best practices post-procedure for patients who undergo USGI. Dolinko et al7 recommend pelvic rest and avoidance of strenuous exercise, in addition to following [beta]-hCG to resolution.

After surgical management of interstitial or cornual ectopic, there is no clear guideline for surveillance of [beta]-hCG. In patients who underwent conservative surgical management such as cornuostomy, Moawad et al6 recommend surveillance with serial [beta]-hCG until resolution. Providers may also consider following [beta]-hCG levels weekly until products of conception are confirmed on pathology. Patients who undergo definitive management with hysterectomy or cornual wedge resection do not need postoperative serology testing.

Posttreatment Counseling

The recurrence rate of cornual and interstitial pregnancy is unknown. However, a review of 53 cases of prior interstitial ectopic pregnancies reported a recurrence rate as high as 9.4% after medical or surgical management.1 Therefore, patients should be counseled regarding the higher risk of recurrent ectopic pregnancy.

Patients who desire future fertility and undergo methotrexate therapy should avoid conception until resolution of [beta]-hCG. Experts recommend patients delay conception for 3 months after the last dose of methotrexate, although there are limited data to support this recommendation.1,8,11

Labor Considerations

Cesarean delivery after 37 weeks is widely recommended in patients who underwent surgical management of interstitial or cornual pregnancy to reduce the risk of uterine rupture.2,6 Successful vaginal deliveries have been reported after medical management of nontubal ectopic pregnancies. The strength of the myometrium surrounding the prior ectopic remains unknown, and there is a risk of uterine rupture during labor. There are 3 existing reports of uterine rupture after prior interstitial pregnancy after both expectant and surgical management.1,6

Summary

Cornual and interstitial ectopic pregnancies are rare forms of nontubal ectopic pregnancies with increased morbidity and mortality. Timely recognition and diagnosis is critical to reduce risk of rupture and life-threatening hemorrhage. Traditional management with laparotomy has been supplemented by the development and implementation of less morbid management options including systemic methotrexate, ultrasound-guided injection, embolization procedures, or surgery. Preferred surgical approaches include cornual resection or cornuostomy. In cases of surgical management, a laparoscopic approach is preferred if a surgeon with appropriate expertise is available. Laparotomy is reserved for hemodynamically unstable patients when expeditious laparoscopy cannot be safely performed. Providers should be aware of all available management options to inform best clinical practices. Factors dictating management are multifactorial, and patient presentation, clinical resources, and patient preference should be considered. After management, patients should undergo counseling regarding risks of recurrence and implications in future pregnancies.

Practice Pearls

* Ectopic pregnancy accounts for 1% to 2% of all pregnancies in the United States and is the lead cause of maternal mortality in the first trimester.

* The most common site of ectopic pregnancy is the fallopian tube. Approximately 5% to 10% of ectopic pregnancies implant in nontubal locations.

* Cornual and interstitial pregnancies are rare forms of nontubal pregnancy with increased mortality.

* Transvaginal ultrasound is the gold standard imaging modality for workup of suspected nontubal ectopic pregnancy.

* There is a lack of robust level I evidence to dictate management of cornual and interstitial ectopic pregnancy.

* Interstitial pregnancy has been successfully managed medically with systemic or locally injected methotrexate.

* In surgical management of interstitial and cornual ectopic pregnancy, a laparoscopic approach is preferred if a skilled laparoscopic surgeon is available.

* Cornual resection and cornuostomy have comparable outcomes in the management of interstitial pregnancy.

* Laparotomy is reserved for management of hemodynamically unstable patients when expedited laparoscopy cannot be performed by a skilled surgeon.

References