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Abdominal pregnancy, cesarean scar pregnancy, and heterotopic pregnancy

INTRODUCTION — Ectopic pregnancy is estimated to occur in 1 to 2 percent of pregnancies. Over 90 percent are located in the fallopian tube, while the remainder implant in locations such as the abdomen, cesarean (hysterotomy) scar, cervix, and ovary. Given the rarity of implantation at these sites, much of the information surrounding diagnosis and treatment of these pregnancies has been derived from small observational studies and case reports. This makes the optimal approach to their evaluation and management difficult to determine.

Abdominal pregnancy, cesarean scar pregnancy, and heterotopic pregnancy will be reviewed here. The goal is to prompt clinicians to think of these diagnoses and to make suggestions for management, especially for avoiding catastrophe.

The diagnosis and management of ectopic pregnancies at other locations are discussed separately.  

ABDOMINAL PREGNANCY — Abdominal pregnancy refers to a pregnancy that has implanted in the peritoneal cavity, external to the uterine cavity and fallopian tubes. The estimated incidence is 1 per 10,000 births  and 1.4 percent of ectopic pregnancies . There are reports of abdominal pregnancy occurring after hysterectomy .

Potential sites include the omentum, pelvic sidewall, broad ligament, posterior cul-de-sac, abdominal organs (eg, spleen, bowel, liver), large pelvic vessels, diaphragm, and the uterine serosa .

It is not known whether abdominal pregnancies are a result of secondary implantation from an aborted tubal pregnancy or the result of intraabdominal fertilization of sperm and ovum, with primary implantation in the abdomen . A third, iatrogenic mechanism was suggested by a case report of abdominal pregnancy after in vitro fertilization (IVF) in a patient without oviducts because of two previous salpingectomies  . The location of the pregnancy was attributed to uterine perforation by the IVF transfer catheter.

Risk factors for abdominal pregnancy include tubal damage, pelvic inflammatory disease, endometriosis, assisted reproductive techniques, and multiparity.

Clinical manifestations — Because of the variable location in the abdomen, abdominal pregnancy is associated with a wide range of signs and symptoms. In contrast to tubal ectopic pregnancies, abdominal pregnancies may go undetected until an advanced gestational age; some pregnancies go all the way to term. In such cases, fetal movement may be appreciated and may be painful, and the fetus may assume an unusual lie. When the pregnancy implants on bowel, nausea and vomiting may be prominent symptoms. Vaginal bleeding is less frequent than in tubal ectopic pregnancies; however, vaginal bleeding may occur since the endometrium still responds to changes in pregnancy hormones . Some women present with an acute abdomen and shock due to severe intraabdominal hemorrhage from placental separation or rupture of maternal blood vessels or viscera . In rare cases, the pregnancy may be diagnosed after a failed induction due to lack of myometrial response to oxytocin stimulation . Bowel obstruction and formation of fistulae are other rare presentations.

Diagnostic evaluation — All women of reproductive age with abdominal pain, vaginal bleeding, or menstrual abnormalities should be tested for pregnancy. Once pregnancy is established, the location of the pregnancy (intrauterine or extrauterine) is typically made by ultrasound examination .

A high index of suspicion is important for making a diagnosis of abdominal pregnancy. The classic ultrasound finding is the absence of myometrial tissue between the maternal bladder and the pregnancy . An empty uterus may be visualized. Other findings suggestive of the diagnosis include poor definition of the placenta, oligohydramnios, and unusual fetal lie.

An early abdominal pregnancy may be difficult to distinguish from a tubal pregnancy if it implants in the vicinity of the adnexa  . An advanced abdominal gestation may be misinterpreted as being intrauterine if the ultrasonographer does not evaluate the myometrium during the examination. Computed tomography and magnetic resonance imaging can be useful for confirming the diagnosis, distinguishing anatomic relationships and potential vascular connections, and assessing placental adherence  .

Abdominal pregnancies may cause an elevation of the maternal serum alpha-fetoprotein concentration, but this is a rare cause of this laboratory abnormality  .

In contrast to tubal pregnancies, women with abdominal pregnancies often do not have an abnormal trend in serial hCG values.  

Differential diagnosis — Differential diagnosis includes ectopic pregnancy in other locations, intrauterine pregnancy in a rudimentary uterine horn, abruptio placenta, and uterine rupture.

Treatment — If the abdominal pregnancy is diagnosed at an early gestational age (first trimester), operative laparoscopy is an option  . Preoperative selective arterial embolization may help prevent hemorrhage during attempts to remove the placenta  . We suggest avoiding laparoscopy when the abdominal pregnancy has implanted on a vascular surface, due to the risk of uncontrollable hemorrhage during the procedure. Rapid vascular control during major hemorrhage is easier to establish at laparotomy. In contrast to the tubal ectopic pregnancies, primary methotrexate therapy of early gestations has had minimal success  . This may be due to the more advanced gestational age at which these pregnancies are discovered.

Abdominal pregnancies, even when advanced, are interrupted at diagnosis, as the potential for delivery of a healthy infant is poor and the risk of maternal complications is high. If the diagnosis is made late in pregnancy, a viable infant may be delivered via laparotomy. Expectant management to gain fetal maturity has been attempted and has been successful in a few cases  . If this is attempted, very close maternal monitoring is essential.

The mainstay of treatment of advanced abdominal pregnancy is surgery, but the optimal approach has not been determined. The fetus can be delivered easily; the key issue is how to manage the placenta.

Removal of the placenta can lead to life-threatening maternal hemorrhage. We prefer ligating the umbilical cord and leaving the placenta in situ. The patient can then be followed without further intervention, or active intervention using arterial embolization or methotrexate can be instituted to hasten involution .

In some cases, both the fetus and placenta have been left in situ to avoid surgery and potential placental disruption and hemorrhage. One report described sonographically guided feticide of a 14.5 week gestation to prevent further development and initiate the process of natural resorption . The gestational sac involuted very slowly; the amniotic fluid volume still appeared normal at six months after the procedure, but was diminished at the nine-month postprocedure examination.

HCG levels decline in the first few months postdelivery, but it takes years for the placental mass to be absorbed. Long-term complications related to the inflammatory changes caused by the necrotic placenta include abscess formation, sepsis, delayed hemorrhage, intestinal or ureteral obstruction, fistula involving abdominal viscera, and wound dehiscence . These complications occur despite loss of intraplacental vascular flow.

It has been hypothesized that methotrexate administration causes rapid destruction of the abdominal placenta, resulting in accumulation of a large amount of necrotic tissue  . This provides a favorable medium in which colonic bacteria can grow, and increases the frequency of maternal complications. The rate of degeneration of the placenta in the absence of methotrexate administration is much slower, theoretically enabling resorption to take place slowly and with less risk of serious complications. However, methotrexate can be administered in select cases of retained placenta (ie, patients with persistently elevated serum hCG levels), with close monitoring for signs of infection.

An alternative approach is to ligate the placental blood supply and then try to remove the placenta  . However, this should only be done if there are no other reasonable options. This is generally difficult because the placenta can be implanted on one or more vital organs or large blood vessels, and the normal mechanism to stem blood loss from the placental bed (contraction of the uterus) is absent. There is a significant risk of uncontrollable hemorrhage if the placenta is disturbed. Transfusion, pelvic packing, uterine artery occlusive catheters  , and use of Military Anti-Shock Trousers have been used to try to prevent exsanguination.  

Outcome — An accurate assessment of the incidence of any outcome is difficult to determine since most reports consist of one or only a few cases gathered over a period of decades. Maternal death is usually the result of uncontrollable hemorrhage, and has been reported in as many as 20 percent of cases. Fetal deformations and perinatal death occur more often than maternal death . Common abnormalities include facial and/or cranial asymmetry, joint abnormalities (eg, talipes equinovarus), hypoplastic limbs, and central nervous system malformations. Pregnancies with some vascular attachment to the uterus seem to be associated with a higher chance of fetal survival .

A case series of 10 abdominal pregnancies revealed difficulty in making the diagnosis; only 6/10 were diagnosed preoperatively. Complication reported included hemorrhage requiring transfusion in 9/10 women and preeclampsia in 3/10  .

There is no good information about future fertility after abdominal pregnancy.

Rarely, the fetus from an unrecognized abdominal pregnancy may die and calcify. The resulting lithopedion ("stone child") may not be detected for decades and may cause a variety of complications (intra-abdominal abscess, adhesions, mass, or fistula)  . In most cases, the lithopedion can be identified on a plain film of the abdomen, often as an incidental finding.

CESAREAN SCAR PREGNANCY — Ectopic pregnancy in a previous cesarean (hysterotomy) scar occurs in about 1 in 2000 pregnancies and accounts for 6 percent of ectopic pregnancies among women with a prior cesarean delivery . The incidence does not appear to correlate with the number of cesarean deliveries.

The pregnancy is located in the scar and is surrounded by myometrium and connective tissue. The mechanism for implantation in this location is believed to be migration of the embryo through either a wedge defect in the lower uterine segment or a microscopic fistula within the scar  .

Adenomyosis, in vitro fertilization, previous dilation and curettage, and manual removal of the placenta are purported risk factors  .

Clinical manifestations — In symptomatic patients, the clinical presentation ranges from vaginal bleeding with or without pain to uterine rupture and hypovolemic shock  .

Diagnostic evaluation — As discussed above, all women of reproductive age with abdominal pain, uterine bleeding, or menstrual abnormalities should be tested for pregnancy. Once pregnancy is established, the location of the pregnancy (intrauterine or extrauterine) is typically made by ultrasound examination. A high index of suspicion is important for making a diagnosis of cesarean scar pregnancy.

The diagnosis is made by sonographically visualizing an enlarged hysterotomy scar with an embedded mass, which may bulge beyond the anterior contour of the uterus . Other findings include presence of trophoblast between the bladder and the anterior uterine wall, no fetal parts in the uterine cavity, absence of myometrium between the gestational sac and the bladder, Doppler evidence of perfusion of the peritrophoblastic vasculature, and discontinuity of the anterior uterine wall in the sagittal plane . Attention should be directed at determining the extent of invasion into adjacent pelvic structures, such as the bladder. Magnetic resonance imaging and hysteroscopy have been used to further evaluate pregnancy location, but are not mandatory for making the diagnosis .

Differential diagnosis — Differential diagnosis includes cervical ectopic pregnancy and placenta accreta .

Treatment — There are too few reported cases on which to base a specific treatment recommendation. Treatment should be tailored to the individual patient. Desire for future fertility, size and gestational age of the pregnancy, and hemodynamic stability should be considered when determining a treatment plan.

Options include wedge resection of the ectopic pregnancy via laparotomy or laparoscopy, hysteroscopic excision, local injection of 5 mEq potassium chloride into the sac, and local or systemic methotrexate administration (local administration is preferable if fetal cardiac activity is present) .

Disadvantages of medical therapy are slow resolution of the pregnancy (which can take months), with risk of rupture and hemorrhage; hysterectomy may be necessary. Advantages of surgical resection are that it provides an opportunity to both remove the pregnancy and repair the defect, and avoids the risk of hemorrhage from rupture if medical therapy fails. Expectant management is not a good option because of the risk of rupture and maternal death  

In one of the largest series (n = 18 cases of cesarean scar pregnancy), management included transvaginal surgical evacuation, medical treatment with local injection of 25 mg methotrexate into the exocelomic cavity, and expectant management . Curettage was successful in five of eight cases (63 percent), but three women suffered significant bleeding (500 to 1000 mL) which required the insertion of a Foley catheter to tamponade the uterine cavity to achieve hemostasis. Methotrexate was successful in five of seven cases (71 percent), but the two failures required emergent surgery to control hemorrhage over 1000 mLs. Expectant management was successful in only one of three cases .

Uterine artery embolization (UAE) has been used to reduce the risk of subsequent hemorrhage in patients who are to undergo conservative surgery or methotrexate injection  . Dilation and curettage as first line therapy, without UAE, can result in perforation and catastrophic hemorrhage . In a randomized trial, 72 women with cesarean scar pregnancy who underwent suction curettage were pretreated with either UAE or systemic methotrexate  . UAE pretreatment was associated with significantly decreased blood loss (37 versus 416 mL) and length of hospitalization (12 versus 40 days). A relatively new approach is use of hysteroscopy to remove cesarean scar pregnancies under direct visualization. In a series of five cases, only one had bleeding requiring intrauterine Foley tamponade and one required methotrexate for plateaued serum hCG levels. Hysteroscopic management has been described with ultrasound and laparoscopic guidance .

Virtually all cesarean scar pregnancies have been diagnosed and treated in the first trimester. Local excision, if possible, or hysterectomy may be the safest approaches, as uterine rupture and maternal death from exsanguination can occur during attempted medical therapy, but medical management of early cesarean scar pregnancy is also a reasonable approach. Even if complete resolution of the cesarean scar pregnancy occurs, the patient remains at risk of serious complications (eg, uterine rupture, placenta accreta, severe hemorrhage) in a subsequent pregnancy  

Second trimester cervical scar pregnancies are rare. As in advanced tubal ectopic pregnancies, medical treatment of second trimester cervical scar pregnancies probably has a much lower success rate than medical treatment of first trimester cervical scar pregnancies. Therefore, we suggest surgical management of advanced cesarean scar pregnancies and consider medical treatment an investigational approach.

Outcome — Some of these pregnancies may be partially implanted in the uterine cavity and proceed to term, while others implant deep in the scar and are predisposed to rupture in the first trimester.

In subsequent pregnancies, recurrent scar implantation may occur  . There are reports of successful term pregnancy after a cesarean scar pregnancy ; however, uterine rupture (resulting in maternal or fetal death) and placenta accreta have also been reported . Patients should be counseled about the probable weakened nature of the cesarean scar, and should undergo repeat cesarean delivery . Early ultrasound should be performed in subsequent pregnancies in order to establish the location of implantation .

HETEROTOPIC PREGNANCY — Heterotopic pregnancy refers to the presence of simultaneous pregnancies at two different implantation sites. Most often these sites are a combination of intrauterine and ectopic pregnancies, rather than two ectopic pregnancies . The majority of ectopic pregnancies occur in the fallopian tube (90 percent); however, implantation in the cervix, ovary, interstitial (cornual) tubal segment, abdomen, and previous cesarean scar has been reported .

The estimated incidence of heterotopic pregnancy is dependent upon the rates of ectopic pregnancy and dizygotic twinning. Heterotopic pregnancy used to be rare, estimated to occur in 1 in 30,000 pregnancies . With the advent of assisted reproduction techniques (ART), including super-ovulation, intrauterine insemination, and in vitro fertilization, the overall incidence of heterotopic pregnancy has risen to approximately 1 in 3900 pregnancies . An analysis of all registered ART pregnancies in the United States from 1999 to 2002 reported an incidence of heterotopic pregnancy of 1.5 per 1000 ART pregnancies .

The increased incidence in these pregnancies may be related to the high proportion of patients with tubal disease, high levels of estradiol and progesterone, or high numbers of transferred embryos or ovulated oocytes in this population  . Other factors, such as volume and viscosity of transfer medium and the technique of embryo transfer, may also play a role  . A history of pelvic inflammatory disease has also been cited as a predisposing factor for heterotopic pregnancy  .

Clinical manifestations — The clinical presentation of heterotopic pregnancies closely mimics the symptoms of threatened abortion and ectopic pregnancy in other locations. Symptoms include abdominal pain, adnexal mass, peritoneal irritation, and an enlarged uterus . These patients are often diagnosed at a more advanced gestational age (eg, 16 weeks) than isolated tubal pregnancy because when an intrauterine gestation is observed on ultrasound, the possibility of an additional ectopic pregnancy is generally not considered. Given the high potential for misdiagnosis, there is a high incidence of rupture at presentation . Rupture can result in acute abdomen and hemodynamic shock.

Diagnostic evaluation — As discussed above, all women of reproductive age with abdominal pain, uterine bleeding, or menstrual abnormalities should be tested for pregnancy. Once pregnancy is established, the location of the pregnancy is typically made by ultrasound examination  .

Signs suggestive of heterotopic pregnancy are a complex adnexal mass or fluid in the pelvis. If the clinician has a low suspicion for heterotopic pregnancy after visualizing an intrauterine pregnancy, the ectopic pregnancy may be falsely labeled a corpus luteum cyst. Advanced ectopic gestations containing a yolk sac or fetal pole with cardiac activity make this diagnosis easier to make . The presence of free fluid within the abdomen may be a sign of tubal rupture, but may be falsely labeled ascites associated with ovarian hyperstimulation syndrome  . HCG levels are not useful, as they primarily reflect the intrauterine pregnancy.

Ultrasound evaluation for heterotopic pregnancy is discussed in detail separately.  

Surgical evaluation continues to play a key role in the diagnosis of heterotopic pregnancies. Some patients will present with severe pain or hemodynamic instability that makes surgical evaluation and treatment necessary. In the stable patient, laparoscopy offers the advantage of minimally invasive evaluation, while limiting the impact to a coexistent intrauterine fetus.

Differential diagnosis — The differential diagnosis of uterine bleeding and pain in a patient with an intrauterine pregnancy should include threatened abortion, heterotopic pregnancy, and ruptured corpus luteum. Patients undergoing ART, with persistent pain, and free fluid in the pelvis despite an intrauterine pregnancy, should be evaluated for heterotopic pregnancy. Appendicitis, nephrolithiasis, and urinary tract infection may also present with abdominal pain early in pregnancy.

Treatment — Treatment of the ectopic pregnancy should be tailored to the site of implantation and should utilize the least invasive therapy in order to preserve the concomitant intrauterine pregnancy.

Systemic medical therapy (eg, methotrexate) is contraindicated in the presence of a viable intrauterine gestation.

Salpingectomy is the standard surgical approach of a coexistent tubal pregnancy, and should be the first line of treatment in patients with hemodynamic instability or other signs of tubal rupture  . A laparoscopic approach is desirable if the patient is hemodynamically stable.  

In expert hands, if the pregnancy has not ruptured, then local injection into the sac under sonographic guidance is an effective treatment. Substances for injection should have high therapeutic effectiveness with low toxicity to the concurrent intrauterine pregnancy, and produce no lasting damage to the fallopian tube  . Two options are potassium chloride (KCL) and hyperosmolar glucose . A literature review of 11 cases of heterotopic pregnancy treated with KCL injection noted six cases (55 percent) failed this therapy and required surgical intervention  . A report of a cervical pregnancy treated with KCL injection was complicated by delayed bleeding, which was controlled by placement of cervical stay sutures . The co-existing intrauterine pregnancy progressed to term. A heterotopic cesarean scar pregnancy combined with an intrauterine pregnancy was successfully treated by selective embryo reduction by aspiration  .

Outcome — One in three coexistent intrauterine pregnancies spontaneously abort; this rate is higher than that in singleton intrauterine pregnancy .