Management and Therapy of Early Pregnancy Complications: First and Second Trimesters

5. Non-tubal Ectopic Pregnancies: Diagnosis and Management

Louise P. King Jessica Kuperstock2Leonardo Resta Andrea Tinelli4, 5, 6, 7   and Camran Nezhat 

(1)

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School and Center for Bioethics, Boston, MA, USA

(2)

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

(3)

Section of Pathological Anatomy, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy

(4)

Department of Obstetrics and Gynecology, Vito Fazzi Hospital, Lecce, Italy

(5)

Laboratory of Human Physiology, The International Translational Medicine and Biomodelling Research Group, Department of Informatics and Applied Mathematics, Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow Region, Russia

(6)

Institute of Physics and Technology (State University), Moscow, Russia

(7)

Division of Experimental Endoscopic Surgery, Imaging, Technology and Minimally Invasive Therapy, Department of Obstetrics & Gynecology, Vito Fazzi Hospital, Lecce, Italy

(8)

Center for Special Minimally Invasive Surgery, Stanford Medical Center, Palo Alto, CA, USA

Louise P. King (Corresponding author)

Email: lpking@bidmc.harvard.edu

Leonardo Resta

Email: leonardo.resta@uniba.it

Andrea Tinelli

Email: andreatinelli@gmail.com

Camran Nezhat

Email: nezhatinstitute@gmail.com

5.1 Diagnosis and Management

5.1.1 Incidence

Non-tubal ectopic pregnancies include those pregnancies occurring outside the uterus and tubes. Up to 98 % of ectopic pregnancies occur in the fallopian tubes. By contrast, non-tubal ectopic pregnancies occur with the following frequencies: 2.4 % interstitial, 12 % isthmic, 70 % ampullary, 11.1 % fimbrial, 3.2 % ovarian, and 1.3 % abdominal [1].

5.1.2 Definitions

There is some confusion regarding terminology when discussing non-tubal pregnancy [2]. The terms “interstitial” and “cornual” pregnancy are frequently used synonymously. Additionally, the term “cornual” pregnancy is sometimes used to described pregnancies in bicornuate or septate uteri, while Williams Obstetrics defines a cornual pregnancy as one occurring in the upper and lateral uterine cavity of an anatomically normal uterus [23] (Fig. 5.1).

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Fig. 5.1

Three images of cornual ectopic (Courtesy of Dr. Deborah Levine, MD, Boston, Massachusetts). (a) Transverse transabdominal sonogram shows a right horn (short arrow) and smaller left horn (long arrow) with the gestational sac. (b) Transvaginal sonogram shows the pregnancy in the left horn (arrow) adjacent to the ovary (O). Note how the myometrium is very thin posterior to the gestational sac. (c) Slightly angled axial T2-weighted MR image shows the right horn of the uterus (short arrow) and left horn with the gestational sac (long arrow). On other images, the left horn was seen to be atrophic and did not communicate with the cervix

Angular pregnancy is a term not frequently used but defines a pregnancy just medial to the uterotubal junction, in the lateral angle of the uterine cavity, displacing the round ligament upward and outward [2]. An angular pregnancy can migrate to become a normal intrauterine pregnancy (Fig. 5.2).

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Fig. 5.2

Three images of angular pregnancy (Courtesy of Dr. Deborah Levine, MD, Boston, Massachusetts). (a) Transabdominal image of the uterus in a patient 6 weeks and 5 days pregnant by dates shows the endometrial cavity to appear normal without a gestational sac in the midline. (b) Transvaginal image angled to the right shows that the gestational sac is high and on the right. There is only 4 mm of myometrium (calipers) between the sac and the uterine serosa (not shown is the yolk sac and 3 mm embryo). (c) Coronal reconstructed image shows that the gestational sac is high on the right but does communicate with the endometrial cavity. The patient was closely followed. Two weeks later the sac was still in a high position with only 3 mm of myometrium around it on the right. By 9 weeks the concerning appearance had resolved and the gestational sac was centrally located in the uterus. The pregnancy was delivered at term

By contrast, an interstitial pregnancy is found lateral to the round ligament [2] (Fig. 5.3).

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Fig. 5.3

Five images of interstitial pregnancy (Courtesy of Dr. Deborah Levine, MD, Boston, Massachusetts). (a) Transabdominal sagittal image of the uterus shows empty endometrial cavity. (b) Transabdominal transverse image of the uterus shows empty endometrial cavity and the gestational sac off to the right, separate from the endometrial cavity. (c) Transvaginal image shows a gestational sac on the right, without endometrium surrounding it laterally compatible with interstitial ectopic pregnancy. (d) Transvaginal image shows a CRL in the ectopic pregnancy of 22 mm corresponding to 8 weeks and 5 days, which is almost 4 weeks greater than age by dates of 5 weeks and 1 day. (e) M-mode shows live ectopic pregnancy with a heart rate of 178 beats per minute

An abdominal pregnancy is defined by lack of myometrium around the outside of the gestational sac or its location remote from the uterus (Fig. 5.4).

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Fig. 5.4

Three images of abdominal pregnancy (Courtesy of Dr. Deborah Levine, MD, Boston, Massachusetts). (a) Transabdominal image shows a retroflexed uterus (UT) and mass/ectopic pregnancy (arrow) above it. (b) Transvaginal image shows the gestational sac (arrow) to be completely outside of the uterus. (c) Crown rump length of 3.3 cm in the live ectopic. Note that there is no myometrium around the outside of the gestational sac

Using correct and clear terminology is becoming increasingly important. Traditionally, laparoscopy was the gold standard for the diagnosis of an ectopic pregnancy. However, increasingly, the use of imaging and serum assays has made laparoscopy for the purpose of diagnosis less important [2]. For this chapter, we will use the following definitions. Interstitial will refer to a pregnancy implanted within the proximal portion of the fallopian tube embedded within the muscular wall of the uterus. Cornual will refer to a pregnancy in a bicornuate or septate uterus. Angular will refer to an intrauterine pregnancy implanted medial to the uterotubal junction. Ovarian will refer to a pregnancy occurring within the ovary itself. Abdominal will refer to pregnancies occurring on the peritoneal surface or abdominal viscera.

5.1.3 Risk Factors

The risks factors for non-tubal ectopic pregnancy are the same as for tubal ectopics. They are addressed in detail in prior chapters. In short, prior history of medically treated ectopic and disruption of tubal or pelvic anatomy from infection, prior surgery, or endometriosis are the major risk factors. Cervical and interstitial pregnancies are also encountered more frequently following in vitro fertilization at a rate of 1.6 % as compared to 19 per 1000 in the general population [4].

5.1.4 Diagnosis by Imaging and Serum Testing

The diagnosis of an ectopic pregnancy is made using a combination of serum human chorionic gonadotropin (hCG) and findings on transvaginal ultrasound. Discussion of diagnosis of specific non-tubal ectopic pregnancies can be found in the following sections. The most common presentation remains first trimester vaginal bleeding with or without abdominal pain [5]. Multiple algorithms exist to guide testing for suspected ectopic pregnancy and have been reviewed in depth elsewhere [6].

5.2 Interstitial Ectopic Pregnancy

5.2.1 Incidence and Diagnosis

Interstitial pregnancies are rare, accounting for only 2–4 % of tubal pregnancies [7]. However, because these pregnancies implant in a portion of the fallopian tube that traverses the muscular wall of the uterus, they are surrounded by thicker tissue with a great capacity to expand (Fig. 5.5a) [27]. Thus, interstitial pregnancies may remain asymptomatic for longer than those found in other portions of the fallopian tube as the muscular wall expands to accommodate. Interstitial pregnancies are less likely to present with vaginal bleeding. Rupture later in pregnancy, as late as 7–16 weeks, can result in catastrophic hemorrhage given the abundant vascular supply in this area of the uterus fed by both the uterine and ovarian arteries [7].

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Fig. 5.5

(a) Laparoscopic image of interstitial pregnancy at 6 weeks. (b) Ultrasonographic transvaginal uterine section of an interstitial pregnancy, with a chorionic sac greater than 1 cm separate from the lateral edge of the uterine cavity with a thin myometrial layer. (c) A figure representing an interstitial pregnancy at 6 weeks

As mentioned above, interstitial, cornual, and angular pregnancies can be managed very differently. Both cornual and angular pregnancies can potentially be viable intrauterine pregnancies. Thus, it is important to ensure that communication with your radiologist is clear and the diagnosis is established appropriately with high-resolution ultrasound or diagnostic laparoscopy if necessary.

Ultrasound findings will include an empty uterine cavity and a chorionic sac greater than one centimeter separated from the lateral edge of the uterine cavity with a thin myometrial layer (Fig. 5.5b, c) [8]. 3D ultrasound or MRI will allow for more accurate diagnosis if interstitial pregnancy is suspected and the patient is stable [9]. Findings on MRI will include a heterogenous mass with intermediate/high T2 hyperintensity surrounded by myometrium which is T2 hypodense or an intact junctional zone which is hypodense, adjacent to T2 bright endometrium. There should be an “interstitial line sign” or echogenic line in the corneal region bordering the midportion of the sac found in both ultrasound and MRI [79]. In between 56 and 71 %, diagnosis can be reliably made ahead of surgery [7].

Assuming a conclusive diagnosis is not made by imaging, at laparoscopy an angular pregnancy will appear as an asymptomatic bulge deflecting the round ligament laterally (Fig. 5.6), while an interstitial pregnancy will appear lateral to the round ligament [7].

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Fig. 5.6

Interstitial pregnancy

5.2.2 Risk Factors

Risk factors for interstitial pregnancy include in vitro fertilization, ovulation induction, uterine anomalies, prior salpingectomy, history of prior ectopic pregnancy, and history of prior infection [10].

5.2.3 Treatment

5.2.3.1 Surgical Treatment

In the past, interstitial pregnancy was treated with exploratory laparotomy and wedge resection. Wedge resection involved removal of the pregnancy and surrounding myometrium (Fig. 5.7). Given the highly vascular nature of this area of the uterus, total abdominal hysterectomy was sometimes required (Fig. 5.8a, b) [7].

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Fig. 5.7

Interstitial pregnancy to treat by wedge resection, involving removal of the pregnancy and surrounding myometrium

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Fig. 5.8

Total abdominal hysterectomy for an interstitial pregnancy (highlighted in the red ring); (a) uterus in two midsections, with multiple intramural fibroids

5.2.3.2 Laparoscopy

Laparoscopic wedge resection is now possible especially earlier in gestation (Fig. 5.9a, b). The area around the ectopic should be injected with a solution of vasopressin ahead of resection. Resection can be accomplished with cold scissors or an energy source such as the harmonic scalpel or LigaSure. The fallopian tubes and mesosalpinx can be removed if necessary during the resection. The defect is usually closed in a manner similar to that used during myomectomy with layering of suture to achieve hemostasis and restore anatomy [7].

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Fig. 5.9

(a) Ectopic pregnancy resection can be accomplished by cold scissors. (b) The ectopic pregnancy is laparoscopically completely removed

A minicornual excision or cornuotomy (Fig. 5.10a) can be undertaken during which an elliptical incision is made along the long axis of the pregnancy after vasopressin is injected. The area is “de-roofed” by excising the myometrial layer. The pregnancy is shelled out (Fig. 5.10b) and judicious cautery or suturing is used (Fig. 5.10c) to control bleeding, thus preserving to some extent the myometrium and vascular supply [7911]. The risk taken when performing a salpingotomy or cornuotomy is that the cornual area will become weak and allow for future rupture.

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Fig. 5.10

(a) Cornuotomy by a laparoscopic monopolar croquet needle. (b) Laparoscopic pregnancy is shelled out by Johannes clamps. (c) Laparoscopic suturing of the cornual edges

5.2.3.3 Hysteroscopy

Successful hysteroscopic resection has been described. Using atraumatic graspers from a laparoscopic approach, the interstitium is pushed into the cavity allowing hysteroscopic resection using a 90° loop and electrocautery [1213].

Thus, multiple approaches have been described to surgical treatment of interstitial ectopic pregnancies but the optimal surgical treatment has yet to be established. Further study is warranted.

5.2.3.4 Management of Potential Hemorrhage

The key to any successful surgical treatment of interstitial pregnancy is to minimize blood loss. Given the highly vascular nature of these lesions, significant hemorrhage can occur quickly. Multiple methods to decrease blood loss have been described. Vasopressin solutions can be injected into the myometrium at the base of lesion ahead of dissection. One suggested dose of vasopressin is 10 units diluted in 10–100 ml of normal saline solution. As with myomectomy, the total dose used should not exceed 4 units to avoid risk of bradycardia, cardiovascular collapse, and death [1415]. Vasopressin should not be used in women with contraindications such as cardiovascular, vascular, or renal disease. Care should be taken to avoid intravascular injection.

The ascending branch of uterine artery can be occluded by suture ligation or electrocautery ahead of dissection with suture. Sutures can be placed under the pregnancy ahead of dissection [7]. However, this technique as with suture closure of the defect can result in anatomic distortion and tubal occlusion. Patients should be informed of this possibility ahead of surgery.

5.2.3.5 Ancillary Treatments

A variety of ancillary techniques have also been described in the literature. In 2015, Takeda et al. described diagnosis of an unruptured interstitial pregnancy by MRI that was treated by initial devascularization with transcatheter arterial chemoembolization. Thereafter, the interstitial gestational products were removed hysteroscopically under laparoscopic guidance. The patient subsequently had a successful pregnancy delivered by cesarean section and the authors noted that the interstitial portion of her uterine wall was well preserved [8].

In their review, Fornazari et al. describe various interventional radiology procedures that can assist or fully treat non-tubal ectopic pregnancies [16]. Methotrexate can be directly injected into the gestational sac, ensuring high local concentrations and lowering the risk of systemic toxicity. In the presence of contraindications to methotrexate (liver disease, severe pulmonary disease, blood dyscrasia, or others), potassium chloride and hyperosmolar glucose can be injected. Alternatively, methotrexate can be infused into the uterine arteries followed by microsphere embolization. This would ensure direct exposure of the embryo to a high dose of methotrexate, consequently, greater ischemia and trophoblastic degeneration, and reduction of side effects. Neither of these techniques has been studied rigorously to date and further study is warranted.

5.2.3.6 Medical Treatment

Experience with systemic medical treatment of interstitial ectopic pregnancy has been described in the literature although case reports are limited. Success rates have been reported as high as 83 % for systemic combined with local treatment [17]. By contrast, a retrospective study of 31 patients with ultrasound-guided local injection and systemic methotrexate for viable unruptured interstitial pregnancies noted a success rate of only 66.7 % [18]. As up to 30 % of patients may require urgent surgery posttreatment, patients must be watched closely should they opt for medical management. Other agents used for medical therapy have very limited evidence (KCl, etoposide, and actinomycin). Further study is warranted.

5.3 Angular Pregnancies

As described earlier in this chapter, angular pregnancy is a term not commonly used. There are minimal case reports in the literature. Expectant management while likely not appropriate for interstitial pregnancy given the risk of catastrophic rupture is potentially appropriate for angular pregnancy (Fig. 5.11). Angular pregnancies can proceed forward to intrauterine pregnancies that may end in miscarriage or potentially term gestation. Thus, accurate diagnosis by high-level imaging is essential (Fig. 5.12). Case reports have described multiple treatment modalities including suction curettage under laparoscopic guidance [19], hysteroscopic resection [20], diagnostic hysteroscopy and laparoscopy with salpingectomy and cornuostomy and subsequent adjuvant methotrexate [21], and methotrexate alone [22]. Some of these case reports likely address interstitial pregnancies. Careful use of terminology should be encouraged to avoid confusion in the literature.

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Fig. 5.11

Interstitial pregnancy with its catastrophic rupture and embryo expulsion of pregnancy

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Fig. 5.12

Figure shows an interstitial pregnancy with the embryo inside

5.4 Cornual Ectopic Pregnancy

5.4.1 Diagnosis

The classic definition of cornual ectopic pregnancy is one that arises in one horn of a bicornuate or septate uterus (Fig. 5.13) [2]. Others, including Williams Obstetrics, would define a corneal pregnancy as one arising in the cornual region of a normal uterus (Fig. 5.14), aka upper and lateral uterine cavity, while still others would define this entity as one in the rudimentary horn of a unicornuate uterus [23]. Given this confusion in definitions, review of the literature surrounding this type of ectopic is difficult. It can be treated laparoscopically.

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Fig. 5.13

Cornual ectopic pregnancy arises in one horn of a bicornuate or septate uterus

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Fig. 5.14

Cornual ectopic pregnancy at laparoscopy (Courtesy of Dr. Ceana Nezhat, Atlanta, Georgia)

5.4.2 Treatment

In 2009, Chetty described treatment of a pregnancy in a rudimentary horn by either laparotomy or laparoscopic excision of the rudimentary horn [23]. A small review is available describing medical treatment in 27 cases of unusual ectopics including six cornual ectopics treated with KCl injection. Three were treated with transvaginal ultrasound guidance; three were treated with transabdominal ultrasound guidance. Five of the six resolved over a course of between 1 and 5 months of treatment. The final case was heterotopic. She underwent a D&C for an intrauterine pregnancy yet unfortunately she subsequently suffered a cornual rupture [24].

Clearly, further study is warranted using agreed-upon universal definitions to define the appropriate treatment in suspect cornual ectopic pregnancies. The need for intervention is likely driven by the underlying anatomy of the patient in question. While a pregnancy in a bicornuate uterus can potentially proceed with expectant management, a pregnancy in a rudimentary horn may require urgent or semi-urgent surgical evaluation. Mullerian anomalies can present along a spectrum between a true bicornuate and a rudimentary horn; thus the ultimate treatment for any particular patient will depend greatly on the judgment of the surgeon. Consultation with radiologists and surgeons familiar with this entity and with experience in management is encouraged.

5.5 Ovarian Ectopic Pregnancy

5.5.1 Incidence and Diagnosis

Diagnosis of ovarian ectopic pregnancy is made by ultrasound findings including a normal and intact ipsilateral tube with a gestational sac located in the area of the ovary (Fig. 5.15). The ovary and the gestational sac are usually found to be connected to a uterine ovarian ligament. After surgical excision, histology will confirm the presence of placental tissue mixed with the ovarian cortex [2325].

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Fig. 5.15

Image shows an ovarian pregnancy with a normal and intact ipsilateral tube with a gestational sac located in the area of the ovary

The risk exists that this entity on ultrasound will be confused with a luteal cyst, thus leading to a delay in diagnosis and the potential for catastrophic rupture. Preoperative diagnosis is correct less than 30 % of the time and it is mainly by ultrasounds (Fig. 5.16) [26]. Laparoscopy is thus more frequently required for diagnosis and subsequent treatment in ovarian ectopic pregnancy (Fig. 5.17a–c) [27]. When doubt exists, consultation with radiologists and surgeons familiar with this entity and with experience in management is encouraged if possible.

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Fig. 5.16

Left ovarian ectopic pregnancy at 7 weeks of gestation with a well-detected embryo

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Fig. 5.17

(a) Laparoscopic treatment of a right ovarian pregnancy; (b) schematic representation of ovarian pregnancy (upper part of the figure) and its removal from the ovary (the lower part of the figure); (c) hemostatic coagulation of the edges of the ovary where it was placed in the ovarian pregnancy

5.5.2 Risk Factors

Risk factors for ovarian ectopic pregnancy include the presence of an IUD, exposure to assisted reproductive technology, a history of endometriosis, pelvic inflammatory disease, and prior surgery [10].

5.5.3 Treatment

Surgical treatment is the method of choice for ovarian ectopic pregnancy. Typically, in early gestations, ovarian wedge resection is possible so as to preserve ovarian tissue for future pregnancies and hormonal function. Various reports have described laparoscopic techniques to proceed with resection. Use of electrocautery or cold dissection with scissors and subsequently bipolar cautery to achieve hemostasis is reasonable [2528]. Oophorectomy is advised and likely required for safe management of advanced gestations.

One case report exists of systemic methotrexate treatment of unruptured ovarian ectopic diagnosed at laparoscopy. However, given the risk of rupture and significant hemorrhage from this potentially highly vascular entity, this is not a common practice [29].

5.6 Abdominal Ectopic Pregnancy

5.6.1 Incidence

Abdominal ectopic pregnancy represents 1–4 % of all ectopic pregnancies [10]. Symptoms include lower abdominal pain, possibly localized pain to the site of implantation, and occasionally palpable fetal parts [10]. Secondary implantation of a ruptured tubal ectopic is a more common etiology for an abdominal ectopic pregnancy as compared to primary implantation in the abdomen [30].

Major complications of abdominal ectopic pregnancy are common and include massive hemorrhage, DIC, ARDS, pulmonary edema or embolism, sepsis, potential perforation into the bowel with intestinal obstruction, fistula formation, and potential perforation of the bladder, vagina, or abdominal wall [31]. The maternal mortality rate for abdominal ectopic pregnancy is eight times higher than for any other ectopic [3233]. Fetal survival is reported to be only 20–40 % in advanced cases, while perinatal mortality approaches 95 % in some series (Fig. 5.18) [31].

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Fig. 5.18

atypical presentation of abdominal pregnancy, with a dead fetus in the second trimester

5.6.2 Diagnosis

Diagnostic criteria by imaging include: (1) bilaterally normal tubes and ovaries with no evidence of recent rupture, (2) no uteroperitoneal fistula, and (3) early pregnancy (less than 12 weeks) with trophoblastic attachments solely to the peritoneal surface [30]. Imaging can be by ultrasound (Fig. 5.19) but frequently MRI is required to establish diagnosis. Characteristic ultrasound features of abdominal ectopic pregnancy are an empty uterus adjacent to the bladder, absence of any myometrium surrounding the fetus, a poorly visualized placenta, an unusual fetal lie, relative oligohydramnios, fetal parts found adjacent to maternal abdominal contents, and an extrauterine placenta [10]. Up to 50 % of cases will be missed antenatally contributing to the high maternal and perinatal mortality.

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Fig. 5.19

Abdominal gestational sac revealed during transvaginal ultrasound. The unusual location of the pregnancy was particularly evident in the dynamic modality of the ultrasonographic examination (Courtesy of Dr. Sandro Gerli, Department of Obstetrics and Gynecology, University of Perugia, Italy)

Frequently, the diagnosis is not made preoperatively and surgeons must maintain a high index of suspicion at time of laparoscopy. In a retrospective review of abdominal ectopic pregnancies, none of 11 abdominal ectopics were diagnosed preoperatively [34]. A separate case report noted an abdominal wall ectopic pregnancy was initially misdiagnosed as endometriosis at the time of diagnostic laparoscopy and later found appropriately diagnosed upon repeat laparoscopy [35]. Our colleague, Prof. Leonardo Resta, reports two rare cases of spleen pregnancy (Figs. 5.205.215.22 and 5.23) and omental pregnancy (Figs. 5.245.25 and 5.26), documented by histological samples.

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Fig. 5.20

Thirty-eight-year-old woman with an intrauterine device (IUD) since 10 years. She underwent surgical treatment for abdominal pain and hemoperitoneum. Macroscopic view of the hemorrhagic focus (3.5 cm) in the lower pole of the spleen

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Fig. 5.21

General histological view of the hemorrhagic focus in the spleen

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Fig. 5.22

Area of the spleen implantation of chorionic villi. The different sizes and histological aspects of the villi are related to the insufficient arterial modification, the consequent low amount of maternal blood to the placenta, and the precocious loss of the embryo

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Fig. 5.23

Evident partial invasion of the arterial wall by the extravillar trophoblastic cells in the bed of the spleen pregnancy

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Fig. 5.24

Thirty-year-old woman, previously treated with a bilateral salpingo-oophorectomy for subsequent tubal pregnancies, was submitted to a medically assisted insemination. At 10 weeks ultrasonography revealed a normal intrauterine pregnancy and a second pregnancy in the omentum. An omentectomy was performed. The large section of the omentum reveals the hemorrhagic pattern of the omental localization

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Fig. 5.25

This picture witnesses the deficient modification of the omental arteries in the bed of the pregnancy by the extravillar trophoblastic cells. A part of the arterial muscle cells is conserved and the trophoblastic cells are absent in the arterial lumen

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Fig. 5.26

Consequence of the deficient arterial modification is documented by the presence of (a) ischemic villi and (b) hemorrhagic foci

5.6.3 Risk Factors

No studies have clearly defined the risk factors for abdominal ectopic pregnancies other than those for other ectopic pregnancies. Thus, risk factors include prior history of a medically treated ectopic, and disruption of tubal or pelvic anatomy from infection, prior surgery, or endometriosis is the major risk factor. Abdominal ectopic pregnancies have been described after ART, specifically after IUI [36], after IVF [37], and after Clomid [38].

5.6.4 Surgical Treatment

Laparoscopic treatment of abdominal ectopic pregnancy is generally feasible and safe given the appropriate level of skill. Advanced gestations or ectopic pregnancies that have implanted in highly vascular or anatomically difficult areas may require laparotomy for treatment.

A retrospective review describes surgical treatment of eleven abdominal ectopic pregnancies. Five were treated laparoscopically and six were treated by laparotomy. Laparoscopy was associated with less operative time, blood loss, and hospital stay [34].

An operative technique will again depend upon the presentation and anatomical location of the lesion. Various reports have described the use of hydrodissection [39], electrocautery, and single-site surgery [40].

Case reports do exist of laparoscopic treatment of advanced gestations. Rahaman and colleagues described a 21-week gestation abdominal ectopic pregnancy that was initially treated with preoperative uterine artery embolization. Thereafter the group proceeded with laparoscopically assisted delivery through a 6 cm midline incision. The placenta was left in situ. The patient was treated with postoperative methotrexate 50 mg/m^2 × 4 doses at an interval of every 3 weeks [31].

Rahaman and colleagues addressed the controversial issue of management of the placenta in these cases [31]. Complete removal is clearly preferred if possible. However, given likely vascularization this may lead to catastrophic hemorrhage. Alternatives to removal include ligating the cord close to the placenta and allowing resorption; however, this process can take years. The risks of leaving the placenta in situ include secondary hemorrhage, abscess formation, peritonitis, intestinal obstruction, wound dehiscence, and amniotic fluid cyst formation. The retained placenta can provide an excellent nexus for infection. In a review of five abdominal ectopic pregnancies with placentas left in situ and treated with methotrexate, all developed intra-abdominal infections. Further study is warranted to determine the optimal course in these cases with regard to the placenta [4142].

As with interstitial ectopic pregnancies, control of blood loss is essential to successful treatment. Meticulous control of blood supply recruited by the ectopic pregnancy and placenta is paramount. Case reports have described use of FloSeal to control bleeding after partial omentectomy [43] as well as use of the PlasmaJet to vaporize residual tissue and achieve hemostasis [35]. Uterine artery embolization is a reasonable first step ahead of surgery, depending on anatomical location of the abdominal ectopic pregnancy [44].

Expectant management is not advised although case reports exist including one abdominal ectopic diagnosed at the time of cesarean section for breech [3445].

Various authors have described failed attempts at medical management including failure of methotrexate [4647]. However, Cobellis and colleagues have described three cases of abdominal ectopic pregnancy diagnosed laparoscopically and thereafter successfully treated with intravenous methotrexate [48].

In short, the optimal mode of treatment for abdominal ectopic pregnancy, a fairly heterogenous condition that can affect multiple organs in the abdominal cavity, is not yet known. Consultation with experienced surgeons is recommended especially in later gestations. Further study is warranted.

5.7 Conclusion

Non-tubal ectopic pregnancies are rare but can be dangerous. Although a few review articles exist, our comprehensive review of the literature noted a significant number of case reports available in the literature. Thus, although rare, experience with this entity exists.

To determine the optimal mode of treatment and assess the use of adjuvant and ancillary modalities including the ones from our colleagues in interventional radiology, further study or a registry is warranted.

A first step toward achieving protocols for treatment in these rare presentations would be to establish a common nomenclature as proposed by Arleo and colleagues [2].

Given the dangers inherent in treatment of interstitial, some cornual, and abdominal ectopic pregnancies, consultation with experts in radiology, surgery, and potentially interventional radiology is highly encouraged, especially when confronted with later gestations.

Acknowledgment

The authors wish to thank Prof. Leonardo Resta, Department of Emergency and Organ Transplantation (DETO), Section of Pathological Anatomy, University of Bari, Italy (e-mail: leonardo.resta@uniba.it).

References

1.

Bouyer J, Coste J, Shojaei T, Pouly JL, Fernandez H, Gerbaud L et al (2003) Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France. Am J Epidemiol 157(3):185–194PubMed

2.

Arleo EK, DeFilippis EM (2014) Cornual, interstitial, and angular pregnancies: clarifying the terms and a review of the literature. Clin Imaging 38(6):763–770PubMed

3.

Cunningham FGLK BS, Hauth JC, Rouse DJ, Spong CY (2009) Williams obstetrics. McGraw-Hill, New York

4.

Perkins KM, Boulet SL, Kissin DM, Jamieson DJ (2015) Risk of ectopic pregnancy associated with assisted reproductive technology in the United States, 2001–2011. Obstet Gynecol 125(1):70–78PubMedPubMedCentral

5.

Alkatout I, Honemeyer U, Strauss A, Tinelli A, Malvasi A, Jonat W et al (2013) Clinical diagnosis and treatment of ectopic pregnancy. Obstet Gynecol Surv 68(8):571–581PubMed

6.

Tulandi T (2015) Ectopic pregnancy: clinical manifestations and diagnosis. Up to date; 2015 uptodate.com

7.

Moawad NS, Mahajan ST, Moniz MH, Taylor SE, Hurd WW (2010) Current diagnosis and treatment of interstitial pregnancy. Am J Obstet Gynecol 202(1):15–29PubMed

8.

Takeda A, Koike W, Hayashi S, Imoto S, Nakamura H (2015) Magnetic resonance imaging and 3-dimensional computed tomographic angiography for conservative management of proximal interstitial pregnancy by hysteroscopic resection after transcatheter arterial chemoembolization. J Minim Invasive Gynecol 22(4):658–662PubMed

9.

Warda H, Mamik MM, Ashraf M, Abuzeid MI (2014) Interstitial ectopic pregnancy: conservative surgical management. JSLS 18(2):197–203PubMedPubMedCentral

10.

Ghaneie A, Grajo JR, Derr C, Kumm TR (2015) Unusual ectopic pregnancies: sonographic findings and implications for management. J Ultrasound Med 34(6):951–962PubMed

11.

Moon HS, Choi YJ, Park YH, Kim SG (2000) New simple endoscopic operations for interstitial pregnancies. Am J Obstet Gynecol 182(1 Pt 1):114–121PubMed

12.

Nezhat CH, Dun EC (2014) Laparoscopically-assisted, hysteroscopic removal of an interstitial pregnancy with a fertility-preserving technique. J Minim Invasive Gynecol 21(6):1091–1094PubMed

13.

Lin K, Xu K, Wu R, Lin J (2014) A new fertility-preserving surgery for interstitial pregnancy involving hysteroscopic removal under laparoscopic guidance. Int J Gynecol Obstet 124(3):256–257

14.

Nezhat F, Admon D, Nezhat CH, Dicorpo JE, Nezhat C (1994) Life-threatening hypotension after vasopressin injection during operative laparoscopy, followed by uneventful repeat laparoscopy. J Am Assoc Gynecol Laparosc 2(1):83–86PubMed

15.

Dillon TF, Marbury BE, Bonsnes RW, Douglas RG, Du Vigneaud V (1958) Vasopressin as a hemostatic in gynecologic surgery; a preliminary report. Obstet Gynecol 11(4):363–371PubMed

16.

Fornazari VA, Szejnfeld D, Elito Junior J, Goldman SM (2015) Interventional radiology and endovascular surgery in the treatment of ectopic pregnancies. Einstein (Sao Paulo) 13(1):167–169

17.

Lau S, Tulandi T (1999) Conservative medical and surgical management of interstitial ectopic pregnancy. Fertil Steril 72(2):207–215PubMed

18.

Smorgick N, Vaknin Z, Pansky M, Halperin R, Herman A, Maymon R (2008) Combined local and systemic methotrexate treatment of viable ectopic pregnancy: outcomes of 31 cases. J Clin Ultrasound 36(9):545–550PubMed

19.

Kambhampati L, Kitova-John M, Allahdin S, Voigt S (2012) Suction curettage under laparoscopic vision for advanced angular pregnancy. J Obstet Gynaecol 32(6):601–602PubMed

20.

Rapisarda V, Santonocito V, Biondo L, Lombardo G, Carastro D, Zarbo G (2010) Angular pregnancy at the sixth week of a patient with ICSI and embryo transfer in womb. Giornale Italiano di Ostetricia e Ginecologia 32(2):107–108

21.

Ciavattini A, Cere I, Tsiroglou D, Caselli FM, Tranquilli AL (2007) Angular-interstitial pregnancy treated with minimally invasive surgery after adjuvant methotrexate medical therapy. JSLS 11(1):123–126PubMedPubMedCentral

22.

Landucci L, Gentile T, Lauri M, Piccioni MG, Framarino Dei Malatesta M (2006) The intra-lesion therapy under ecographic guidance in the angular ectopic pregnancy: analysis of the two cases. Giornale Italiano di Ostetricia e Ginecologia 28(9):434–436

23.

Chetty M, Elson J (2009) Treating non-tubal ectopic pregnancy. Best Pract Res Clin Obstet Gynaecol 23(4):529–538PubMed

24.

Doubilet PM, Benson CB, Frates MC, Ginsburg E (2004) Sonographically guided minimally invasive treatment of unusual ectopic pregnancies. J Ultrasound Med 23(3):359–370PubMed

25.

Samal S, Gupta S, Mahapatro A (2015) Laparoscopic management of primary ovarian pregnancy. J Gynecol Surg 31(1):43–45

26.

Oron G, Tulandi T (2013) A pragmatic and evidence-based management of ectopic pregnancy. J Minim Invasive Gynecol 20(4):446–454PubMed

27.

Olaru F, Narad V, Olaru C, Erdelean D, Corpade A (2014) Ovarian pregnancy on an endometriosis area. J Minim Invasive Gynecol 21(6):S129

28.

Tinelli A, Hudelist G, Malvasi A, Tinelli R (2008) Laparoscopic management of ovarian pregnancy. JSLS 12(2):169–172PubMedPubMedCentral

29.

Shamma FN, Schwartz LB (1992) Primary ovarian pregnancy successfully treated with methotrexate. Am J Obstet Gynecol 167(5):1307–1308PubMed

30.

Hong JH, Shin JH, Song KJ, Lee HJ, Kim IS, Lee JK et al (2008) Laparoscopic management of primary omental pregnancy. J Minim Invasive Gynecol 15(5):640–641PubMed

31.

Rahaman J, Berkowitz R, Mitty H, Gaddipati S, Brown B, Nezhat F (2004) Minimally invasive management of an advanced abdominal pregnancy. Obstet Gynecol 103(5 Pt 2):1064–1068PubMed

32.

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

33.

Tulandi T, Saleh A (1999) Surgical management of ectopic pregnancy. Clin Obstet Gynecol 42(1):31–38PubMed

34.

Shaw SW, Hsu JJ, Chueh HY, Han CM, Chen FC, Chang YL et al (2007) Management of primary abdominal pregnancy: twelve years of experience in a medical centre. Acta Obstet Gynecol Scand 86(9):1058–1062PubMed

35.

Diab Y, Shakir F (2012) Case report-management of an abdominal pregnancy using the plasmajet device. Gynecol Sur 9(1):S34

36.

Kar S (2011) Primary abdominal pregnancy following intra-uterine insemination. J Hum Reprod Sci 4(2):95–99PubMedPubMedCentral

37.

Koyama S, et al., A case of abdominal pregnancy following in vitro fertilization and embryo transfer treated with laparoscopic surgery, Gynecology and Minimally Invasive Therapy (2015), http://dx.doi.org/10.1016/j.gmit.2015.04.006

38.

Baba T, Endo T, Ikeda K, Takenami N, Shimizu A, Morishita M et al (2012) Simultaneous presentation of tubal and primary abdominal pregnancies following clomiphene citrate treatment. Arch Gynecol Obstet 286(2):395–398PubMed

39.

Dennert IM, van Dongen H, Jansen FW (2008) Ectopic pregnancy: a heart beating case. J Minim Invasive Gynecol 15(3):377–379PubMed

40.

Ma K, Zhang Y, Feng Z, Yang X, Yin L (2014) Successful single-port laparoscopic management of abdominal pregnancy in the cul-de-sac. J Minim Invasive Gynecol 21(6):S166–S167

41.

Rahman MS, Al-Suleiman SA, Rahman J, Al-Sibai MH (1982) Advanced abdominal pregnancy – observations in 10 cases. Obstet Gynecol 59(3):366–372PubMed

42.

Raff GJ, Rothenberg JM, Golichowski AM (2010) Minimally invasive management an advanced abdominal pregnancy. J Minim Invasive Gynecol 17(6):S125

43.

Gorry A, Morelli ML, Olowu O, Shahid A, Odejinmi F (2012) Laparoscopic management of abdominal ectopic pregnancy using FLOSEAL Hemostatic Matrix. Int J Gynecol Obstet 117(1):83–84

44.

Saveljeva G, Kurcer M, Breusenko V, Kapranov S, Krasnova I, Aksenova V et al (2009) Endovascular surgery in obstetrics and gynecology. Int J Gynecol Obstet 107:S329

45.

Gomez E, Vergara L, Weber C, Wong AE, Sepulveda W (2008) Successful expectant management of an abdominal pregnancy diagnosed at 14 weeks. J Matern Fetal Neonatal Med 21(12):917–920PubMed

46.

Anderson PM, Opfer EK, Busch JM, Magann EF (2009) An early abdominal wall ectopic pregnancy successfully treated with ultrasound guided intralesional methotrexate: a case report. Obstet Gynecol Int 2009:247452PubMedPubMedCentral

47.

Zinger M, Rosenfeld D (2001) Failed treatment of abdominal pregnancy with methotrexate: a case report. J Reprod Med 46(4):392–394PubMed

48.

Cobellis L, Stradella L, Messalli EM (2000) Contribution to the choice of therapy in abdominal pregnancy. Panminerva Med 42(2):159–161PubMed