Mariam Savabi, MD, MPH

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Since the 1960s there has been a worldwide increase in primary cesarean deliveries from 5% to 32%.

 North America has the second highest rate of cesareans in the world, which has resulted in high rates of repeat cesarean deliveries and worsening maternal morbidity including surgically-related infections, bowel and bladder injury, transfusions, hysterectomy, abnormal placentation, and cesarean scar pregnancy (CSP).

 While CSP is a rare outcome of pregnancies, and the incidence is not well known, there have been estimates based on different populations of 1:1800-1:2216.

 CSP has been associated with a history of prior cesarean that causes dehiscence of a portion of the uterine wall.

CSP is considered an ectopic pregnancy and can carry very serious consequences, including hemorrhage, abnormal placentation, and uterine rupture.

 Due to the rarity of the condition and the possible serious consequences it requires specialized care to manage appropriately. The number of prior cesarean deliveries does not seem to correlate with risk of CSP and a meta-analysis found that 52% of such pregnancies were in women with one prior cesarean.

 This review examines the literature on CSP regarding pathophysiology, signs and symptoms, ultrasound diagnosis, management options, and future fertility for women with the condition.


	To better understand CSP, an appreciation of placental development is important. As a brief overview, at the time of implantation, the blastocyst results in modification of endometrial stromal cells, which enhances the decidualization reaction. The decidua, in turn, is able to regulate endometrial receptivity to modulate architectural changes that facilitate immune and vascular cell function to further trophoblastic invasion.

 Trophoblasts continue to invade until meeting the decidua basalis in which a zone of fibrinoid degeneration is created, described as the Rohr stria and Nitabuch layer.

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Prior uterine scar tissue from a cesarean often results in absence of the decidua basalis or partial disruption with a faulty layer of fibrinoid degeneration.

 In the setting of CSP, the pregnancy is not surrounded by or implanting into the decidualized endometrium, but rather, embeds in fibrous scar tissue and myometrium.

 The pregnancy is abnormal from the moment of implantation and management requires careful consideration.

Most patients with CSP are asymptomatic. Symptoms can, however, include light vaginal bleeding that is either painless or associated with mild to moderate abdominal pain.

 There are no signs or symptoms that are pathognomonic for CSP.

Diagnosis is performed using transvaginal ultrasound (TVUS). Transabdominal ultrasound has been used to diagnose CSP but TVUS continues to be the imaging modality of choice. 
	 

Figure 1 shows four ultrasonographic findings that have been described as diagnostic of CSP:

1. Empty uterine cavity with bright hyperechoic endometrial stripe

3. Intrauterine mass in the anterior part of the uterine isthmus

4. Absence of the myometrium, absent or thin between the bladder and gestational sac, measuring less than 5 mm

Using 3D sonography of the lower uterine segment may help to clarify this pathological entity (Figures 2 and 3). Magnetic resonance imaging (MRI) may be an option for diagnosis and evaluation, but the literature appears to demonstrate that overall, TVUS with color Doppler is superior and that MRI should be reserved for inconclusive or difficult-to-diagnose cases.

 Once a diagnosis is made, management should be multidisciplinary, and management options should be reviewed with the patient.

Because CSP is rare, management has largely been described in the literature in case reports and small cases series, as summarized here. We will outline different treatment options that have been most frequently chosen including what we do in our institution. 

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There are multiple considerations for management of CSP.  Goals of care are to treat the CSP with complete resolution and to ensure the mother’s safety. Keys to optimizing clinical outcomes include identification and termination of an early gestation and a multidisciplinary approach to management.


	Methotrexate (MTX) is standard treatment for many types of ectopic pregnancy and has also been used to treat CSP effectively. Patients who are pain-free, hemodynamically stable, and have an unruptured CSP < 8 weeks’ gestation are candidates for MTX.

 This type of medicine stops cells from dividing. It can be used as a way (other than surgery) to treat a pregnancy that’s implanted outside the uterus (ectopic pregnancy). The drug can be given via intra-sac or local injection, as systemic therapy, or in a combination of systemic therapy and intra-sac injection.

Local injection appears to work well but additional surgical treatment or systemic medical management often is required (Table 1). Administration of a single injection of MTX, potassium chloride (KCL), hyperosmolar glucose, or crystalline trichosanthin under TVUS or transabdominal ultrasound guidance has been used.

Systemic MTX is commonly used for tubal or cervical ectopic pregnancies. Reassuring results have been reported with systemic regimens, with and without intra-sac medication injections, for CSP. Both single-dose and multidose protocols have been used.

 The standard single-dose regimen for MTX is 50 mg/m

 whereas the multidose protocol includes four doses of MTX 1 mg/kg given on Days 1, 3, 5, and 7 with alternating days of folinic acid
	0.1 mg/kg.

 Patients with ectopic pregnancies and HCG levels < 5000 mIU/mL appear to respond best to systemic MTX.

In many case series, a combination of systemic therapy and intra-sac injections have been used as first-line management of CSP. In these regimens, the intra-sac injections have been done primarily with KCL or methotrexate at the doses shown in Table 1.


	We strongly caution against performing uterine curettage as first-line treatment for CSP. The pregnancy is often not in the uterine cavity so the products of conception may not be accessible, resulting in failure of the procedure. In addition, risk of uterine rupture and hemorrhage associated with the procedure is increased because of the thinness of the myometrial layer.

 Uterine curettage, however, can be considered after successful medical management, which is usually performed when Doppler ultrasound does not demonstrate active blood flow around the gestational sac.

Hysteroscopy (HSC) can also be used to guide uterine curettage. Some providers have evaluated CSP with HSC and coagulated vasculature noted around the CSP.

 In a case series by Pan et al, HSC was used in conjunction with laparoscopy.

 If anterior myometrial thickness was < 3 mm on ultrasound, laparoscopy was performed prior to HSC to dissect bladder peritoneum from the lower uterine segment to attempt to remove the bladder from the site of surgical management and decrease risk of injury. In this case series, 44 patients were successfully treated with removal of products of conception.

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	Uterine artery embolization (UAE) has been chosen by providers as a first-line approach in managing CSP to theoretically decrease risk of hemorrhage before ultimate management with surgery.

 In the event that UAE is considered for treatment of a CSP, consideration should be given to a patient’s plans for future fertility because information is limited on fertility after the procedure.


	In a small case series, a double uterine balloon was presented as a minimally invasive option for managing CSP.

 This technique is novel and appears to have very high success rates overall. Briefly, a double balloon catheter was placed into the uterus under ultrasound guidance. Each balloon was inflated, with the lower uterine segment balloon placed to compress the CSP.  The patient was then appropriately monitored and returned over the next few days for reevaluation with ultrasound. Once embryonic cardiac activity had ceased, the catheter was removed. With this procedure, treatment of CSP was successful and neither medication or dilation and curettage was needed in the published case series.


	Occasionally, patients fail to respond to all the above-mentioned procedures or they have severe abdominal pain (suspicious for uterine rupture) with bleeding. In these cases, hysterectomy should be considered (Figure 4).

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Very little information exists with which to guide patients with CSP about future fertility. In a few case series, patients with CSP have undergone scar resection.

 The procedure has been performed with laparoscopic excision, CO2 laser, or ultrasound knife, with suture reapproximation of the myometrium afterwards in all cases.

Data are limited regarding fertility after these procedures, but all patients who did achieve fecundity appeared to deliver via planned cesarean.

 eight of 18 patients with CSP treated with unclear methods went on to become pregnant again. Two of the eight ended up with a repeat CSP, for an incidence of 25%. The remaining six patients all had cesarean deliveries, four of which were uncomplicated and two emergent. The reasons for the emergent cesareans were placental abruption at 34 weeks’ gestation in one case and nonreassuring fetal status at 41 weeks in the other case. 

Currently there is no evidence to indicate that a pregnancy has an affinity to locate in the cesarean delivery scar. Given the unpredictability of CSP, it is important to offer patients who have received treatment a very early ultrasound in their next pregnancy to ensure there is no recurrence. Outcomes of pregnancies in women previously treated for CSP are unclear. 

The multiple challenges associated with managing a suspected CSP start with identification of the abnormal pregnancy. For best clinical outcomes, once a CSP is diagnosed, the following should be prioritized: (1) facilitating a multidisciplinary discussion to create an individualized treatment plan; (2) early gestational termination; and (3) disrupting trophoblastic invasion prior to surgical management. CSP is a complicated medical condition, but possible adverse outcomes can be avoided with a considerate approach to treatment. 

The authors report no potential conflicts of interest with regard to this article.

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