The Society for Maternal-Fetal Medicine consult series #49 on cesarean scar pregnancy

Q: What is cesarean scar pregnancy, and what is its incidence?

A: CSP occurs when an embryo implants in the fibrous scar tissue of a prior cesarean hysterotomy. Although sometimes called a “cesarean ectopic pregnancy,” these gestations are, in fact, within the uterine cavity and, unlike true ectopic pregnancies, may result in a liveborn infant. This condition presents a substantial risk for severe maternal morbidity complicated by challenges in securing timely diagnosis, as well as uncertainty regarding optimal treatment once identified.

The true incidence of CSP is unknown, as the condition is likely underdiagnosed and underreported. Reported single-center estimates of incidence range from 1:1800 to 1:2656 of overall pregnancies. Although relatively uncommon, reported international experience with CSP appears to be increasing, likely as a result of high contemporary cesarean delivery volume. Other factors, including improved imaging with ultrasound and magnetic resonance imaging (MRI), increased utilization of transvaginal ultrasonography (TVUS), and possibly increased physician awareness, may also contribute to a perceived increase in incidence.

Q: What is the pathogenesis of CSP?

A: Although the pathogenesis of CSP is incompletely understood, the mechanism has been postulated to involve blastocyst implantation within a microscopic dehiscence tract in the scar from a prior cesarean delivery. Due to the fibrous nature of scar tissue, these inherently deficient implantation sites are at risk for dehiscence, PAS, and hemorrhage as the CSP enlarges.

CSP and placenta accreta appear to have similar disease pathways and may exist along a common disease continuum. Histopathologic analyses for both groups are characterized by myometrial or scar tissue villous invasion with little or no intervening decidua.

Implantation patterns of CSP can be categorized as either endogenic (also referred to as “on the scar”) or exogenic (“in-the-niche”). Endogenic is defined as growing within the uterine cavity and exogenic as arising from a gestational sac deeply implanted into the scar that may grow toward the bladder or abdominal cavity (Figure 1).

These ultrasonographic appearances may influence obstetric prognosis. It has been suggested that early first-trimester determination of whether a CSP is growing “on the scar” or “in the niche” of the prior cesarean hysterotomy may be used to predict subsequent pregnancy outcomes. In one small, retrospective experience, patients with pregnancies growing “on the scar” had variable obstetric outcomes, whereas those with pregnancies growing “in the niche” all underwent hysterectomy with PAS at delivery.1

Q: How does CSP present clinically, and are there known risk factors?

A: Although second-trimester diagnoses have been reported, CSP usually presents in the first trimester. In one review of published CSP case series, the average gestational age at diagnosis was 7.5 +/- 2.5 weeks.2 The clinical presentation is variable, ranging from asymptomatic ultrasonographic detection to a presentation with uterine rupture and hemoperitoneum, typically in the absence of a timely diagnosis. In the review mentioned above, about one-third of cases were asymptomatic, and approximately one-third presented with painless vaginal bleeding. Nearly one-quarter of presentations involved pain, with or without bleeding. Women with a ruptured CSP may also present with hemodynamic collapse. 

Although by definition prior cesarean delivery is a prerequisite for CSP development and placenta previa may modify this risk, it is not clear if the number of prior cesarean deliveries further increases risk. A review of the literature reveals that 52% of CSP cases occur in women with a single prior cesarean delivery.3-5 Previous delivery for breech presentation appears to be a more common indication in women who later develop CSP. No published data exist regarding an association between hysterotomy closure technique and CSP.

Q: How is CSP diagnosed?

A: TVUS is the optimal modality for evaluation of suspected CSP, as it provides the highest image resolution (Figures 2 and 3). Grayscale combined with color Doppler ultrasound is recommended for CSP diagnosis. One group suggests combining TVUS with a transabdominal ultrasonogram with a full maternal bladder to provide a “panoramic view” of the uterus and the relationship between the gestational sac and bladder.6 The initial finding of a low, anteriorly located gestational sac should raise concern for a possible CSP and warrants further investigation. When evaluating women with suspected CSP, a high degree of clinical suspicion is needed as a missed or delayed diagnosis can result in uterine dehiscence, hemorrhage, loss of fertility, or maternal death. 

Diagnostic criteria have been proposed to enhance ultrasonographic detection of CSP.4,7,8 One approach proposes the following ultrasonographic criteria to diagnose CSP: (1) an empty uterine cavity and endocervix; (2) placenta, gestational sac, or both embedded in the hysterotomy scar; (3) a triangular ( ≤8 weeks of gestation) or rounded or oval (> 8 weeks of gestation) gestational sac that fills the scar “niche” (the shallow area representing a healed hysterotomy site); (4) a thin (1-3 mm) or absent myometrial layer between the gestational sac and bladder; (5) a prominent or rich vascular pattern at or in the area of a cesarean scar; and (6) an embryonic or fetal pole, yolk sac, or both with or without fetal cardiac activity (Figure 4). All of these criteria may not be observed. Especially with very early diagnosis and before fetal cardiac activity, the woman must have confirmation of pregnancy (for example, a positive pregnancy test result). Bulging or ballooning of the lower uterine segment in the midline sagittal transabdominal view has also been considered to be supportive of CSP diagnosis. 

Distinguishing CSP from other clinical entities with a similar ultrasonographic appearance is challenging. CSP may be misdiagnosed as either cervical ectopic pregnancy, spontaneous abortion in transit, or low implantation of an intrauterine pregnancy. Given the importance of prompt diagnosis, referral to an experienced center for a second opinion may be preferable to ongoing follow-up examinations that are likely to lead to a delay in diagnosis.

Q: Are other modalities useful for diagnosis?

A: Transvaginal three-dimensional (3D) ultrasound and 3D power ultrasound have been used in an attempt to enhance accuracy of CSP diagnosis. However, data are insufficient to support a benefit of routine use of 3D ultrasound for diagnosis or management of CSP. Magnetic resonance imaging (MRI) has been used as an adjunct to ultrasound for diagnosis of CSP, although its incremental benefit over ultrasound alone is unknown. MRI may provide useful information regarding the degree of invasion and whether there is evidence of PAS. Most authors do not recommend MRI as a routine component of CSP evaluation. In cases in which ultrasound imaging is inconclusive, MRI could be considered as an adjunct study. Given the risks associated with delayed diagnosis, use of multiple ultrasound imaging approaches, as well as modalities such as MRI, are likely preferable to serial ultrasound examinations.

Hysteroscopy and laparoscopy can be used to confirm a diagnosis at the time of planned operative intervention. With laparoscopic examination, CSP has been described as an ecchymotic bulge with a “salmon-red” appearance beneath the bladder at the level of the prior cesarean scar with an otherwise normal-appearing uterus.

Q: What is the natural history of CSP?

A: Although few recognized CSPs continue to a viable gestational age, some CSPs have resulted in live births often associated with PAS, cesarean hysterectomy, and massive hemorrhage at delivery. Series describing outcomes of expectantly managed CSPs all involve small case numbers and high hysterectomy rates, ranging from 50% to 100% and usually associated with PAS. In case series of women managed expectantly, most required additional treatment, and more than 50% had severe complications.9-13

Due to the high risk of severe maternal morbidity, expectant management is not recommended for a recognized CSP, and pregnancy termination is generally advised as soon as the diagnosis is confirmed. For cases in which a CSP is suspected but the diagnosis is not certain, short-interval follow-up, a second opinion, or additional imaging with MRI should be considered to make a timely diagnosis without undue delay. We recommend against expectant management of cesarean scar pregnancy (GRADE 1B).

An exception to the recommendation against expectant management involves early CSP that is definitively diagnosed as nonviable. In this situation, expectant management may be pursued with serial ultrasound surveillance, quantitative beta-hCG measurements, and monitoring for maternal symptoms such as bleeding or pelvic pain. It can take several months for a nonviable CSP to resolve spontaneously, and expectant management of nonviable CSP has been associated with development of a uterine arteriovenous malformation (AVM). Uterine AVM in this clinical context has been associated with persistent, severe vaginal bleeding and may require umbilical artery embolization or even hysterectomy.

Q: What CSP treatment modalities have been reported?

A: Surgical, medical, and minimally invasive therapies, as well as various combinations of such treatments, have been described, including hysteroscopy, laparoscopy, laparotomy, open surgery, transvaginal surgery, dilation and curettage (D&C, including both sharp and vacuum aspiration techniques), uterine artery embolization (UAE), methotrexate (MTX) (both local guided injection and systemic administration), direct potassium chloride (KCl) injection, needle-guided sac decompression, high-intensity focused ultrasound (HIFU), and use of balloon catheters, and combinations of these methods (Table 1).14-16

The optimal treatment is not known. Systematic reviews have been inconsistent with regard to identification of a single optimal CSP treatment modality that best balances procedural success and risks. Data regarding optimal CSP therapy consist primarily of case series with varying levels of clinical experience, institutional capability, provider skill, and case complexity. Randomized controlled trials comparing treatment approaches are limited, as are those comparing medical and surgical approaches.

CSP treatment decisions are guided by a principal goal of preserving maternal health, followed by a secondary goal of preserving fertility when possible. Management decisions should be determined after considering pregnancy viability, gestational age, maternal health, future family planning wishes, physician skill and experience, and institutional resources. Preferred management may differ between institutions based upon resources, personnel, and clinical experience. Even with efforts to tailor treatment strategies to individual patients and clinical presentations, there remains a substantial risk of complications with any management approach.

Q: What are the recommended treatment approaches for CSP?

A: Surgical treatment

Among surgical management options, transvaginal and laparoscopic CSP resection appear to have low complication rates.17-19 A potential advantage of these approaches is that the scar tissue can be excised and the surrounding myometrium reapproximated at the time of CSP removal. It is unknown if this practice decreases risk of CSP reoccurrence. 

D&C alone, without adjuvant treatments, has been associated with high complication rates, including hemorrhage and perforation, due to an inability to completely access and remove trophoblastic tissue outside of the endometrial cavity and because scar tissue contracts poorly after curettage.14 As with PAS, sharp curettage may sever deeply invading blood vessels, exposing the patient to ongoing bleeding. In addition to a high complication rate, additional treatment is reported to be required after 52% of D&C cases. It should be noted that the published literature incompletely distinguishes between sharp curettage and vacuum aspiration, which may provide different success and complication rates with CSP management.14 We suggest operative resection (with transvaginal or laparoscopic approaches when possible) or ultrasound-guided vacuum aspiration be considered for surgical management of CSP and that sharp curettage (D&C) alone be avoided (GRADE 2C).

While sharp curettage alone is not recommended as a primary CSP treatment, higher efficacy and lower complication rates have been reported with ultrasound-guided vacuum aspiration.20 Shirodkar placement as an adjunct to D&C has also been described, in which the cerclage suture is placed prior to D&C and only secured in the setting of hemorrhage to minimize bleeding.21

Gravid hysterectomy is an alternative surgical option that may be considered for definitive management of CSP. This approach may be particularly appropriate for early second-trimester CSP presentations or for women who do not desire future fertility.

A: Medical treatment

When pursuing medical treatment of CSP, local or intragestational injection of MTX is a preferred approach, with or without accompanying systemic MTX. Standalone systemic MTX is not recommended due to a higher reported risk of complications.7, 22 Although a small randomized trial of systemic versus local MTX demonstrated no difference in overall cure rates23, reviews suggest a high risk of complications with intramuscular MTX alone24, 25, and local MTX appears to be a more effective approach. In a literature review by Cheung et al, of 96 cases of intragestational MTX for CSP, success was achieved in 73.9% after a single local MTX injection and increased to 88.5% after an additional local or intramuscular MTX injection.25 Intragestational injection is typically performed with a 20-gauge needle under ultrasound guidance using a transvaginal approach. Sac aspiration may be performed prior to injection to verify appropriate needle placement. Optimal dosing for local MTX injection ranges from doses of 1 mg/kg of maternal weight to 50 mg. Varying dosages of systemic MTX have been reported in management of CSP; in general, these dosages are comparable to those used for ectopic pregnancy. We suggest intragestational MTX for medical treatment of CSP, with or without other treatment modalities (GRADE 2C). We recommend that systemic MTX alone not be used to treat CSP (GRADE 1C). 

When following women with CSP who have been treated medically, the gestational mass can take weeks to months to resolve. A transient increase in beta-hCG levels and CSP mass size can be observed after MTX therapy. One study of 22 women following local conservative CSP treatment reported a mean time to resolution of 88 days (range 26-177).8 An understanding of this anticipated posttherapy course may help to minimize unnecessary additional treatments. During the posttreatment observation period, patients should be monitored for concerning symptoms such as hemorrhage or uterine AVM development. Interval ultrasonographic surveillance may be helpful to observe for CSP resolution.

Intragestational KCl has also been described for treatment of CSP in a small number of cases. This approach may be particularly appropriate for management of CSP heterotopic pregnancies with a coexisting intrauterine pregnancy, as MTX exposure may have embryocidal or teratogenic consequences for the intrauterine cotwin. As with MTX, ultrasound-guided KCl injection can be accompanied by sac aspiration. Hysteroscopic and laparoscopic approaches for treating CSP heterotopic pregnancies have also been described.

A: Adjunct treatment options

UAE is a minimally invasive procedure that has been used in various combinations to treat CSP. It has been reported as a standalone procedure, as well as in combination with D&C, MTX, and hysteroscopy, which complicates comparisons between studies.14 UAE may be a uterine- and fertility-preserving procedure, although reported outcomes in the setting of CSP vary significantly, and its role as an adjunct to other management approaches requires further study.

Ultrasound-guided placement and inflation of balloon and Foley catheters to tamponade a CSP gestational sac complicated by bleeding or as a prophylactic measure has been reported.15, 16, 26 Limited experience shows that this technique may be well tolerated and efficacious, supporting a potential option that warrants further study. 

Q: How should CSP be managed in women who decline treatment?

A: Women who decline treatment of a CSP should be counseled about risk of significant obstetric complications, including PAS, massive hemorrhage, uterine rupture, severe maternal morbidity, and potentially maternal death. Management of such cases should include a very high index of suspicion for PAS with appropriate antepartum management and delivery planning. Women should be counseled regarding signs and symptoms of preterm labor or any symptoms suggesting uterine rupture. Repeat cesarean delivery is recommended between 34 0/7 and 35 6/7 weeks of gestation. As with other medically indicated late preterm births, betamethasone administration is recommended prior to delivery. In women who choose expectant management and continuation of a CSP, we recommend repeat cesarean delivery between 34 0/7 and 35 6/7 weeks of gestation (GRADE 1C).

As with PAS, delivery should occur at Level III or Level IV facilities with appropriate expertise and resources, including the capability to manage massive hemorrhage. A multidisciplinary team approach to delivery is recommended, and the team should be prepared for the potential need for cesarean hysterectomy and massive transfusion.

Q: How does a history of a CSP impact future pregnancies?

A: Women can become pregnant after uterine-preserving management of a CSP, although there appears to be an increased risk for recurrent CSP and other severe maternal morbidities. High rates of complications and severe maternal morbidity, including PAS, recurrent CSP, gravid hysterectomy, and uterine rupture, have been reported.27-30 Women considering pregnancy after a CSP should be informed that there is a significant risk of recurrence and severe maternal morbidity. We recommend that women with a CSP be advised of the risks of another pregnancy and counseled regarding effective contraceptive methods, including long-acting reversible contraception and permanent contraception (GRADE 1C).

Although a short interval between successful conservative CSP management and subsequent pregnancy may increase risk of recurrent CSP or PAS, there is no consensus about how long to wait before attempting another pregnancy for women who desire another pregnancy after counseling regarding the risks. Some experts have recommended waiting 12 to 24 months before attempting to become pregnant again, although there is limited supporting evidence.

Given the increased risk of CSP recurrence, some advocate evaluation of the uterus and cesarean scar by saline infusion sonohysterography prior to a subsequent pregnancy. However, it is not clear whether the detection of a defect is associated with higher risks and should influence counseling regarding the advisability of another pregnancy. Interpregnancy repair or revision of a cesarean scar has been reported using a variety of surgical modalities. However, data are insufficient to support a benefit to this practice.

Should a woman with a history of a CSP become pregnant, close ultrasonographic monitoring is recommended to confirm the presence of an intrauterine pregnancy and to exclude recurrent CSP or PAS. An initial ultrasound examination is recommended on presentation to prenatal care, ideally before 8 weeks of gestation, to confirm a normal intrauterine location. Repeat cesarean delivery is recommended between 34 0/7 to 35 6/7 weeks of gestation, prior to the onset of labor. Betamethasone administration is recommended prior to anticipated late preterm delivery. The delivery team should be prepared for obstetric hemorrhage and the potential need for cesarean hysterectomy.

Conclusion

Due to high worldwide cesarean delivery rates, an increased incidence of CSP has been recognized. CSP can be difficult to diagnose in a timely fashion, and this diagnosis should be considered in women with a prior cesarean delivery who are undergoing early first-trimester ultrasonography. Several surgical and medical treatments have been described for this disorder, but at this time, optimal management remains uncertain. For this reason, an international registry has been created for providers to submit data on diagnosis, natural history, and management (https://csp-registry.com).

References

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