European Journal of Cardiovascular Medicine

Cesarean scar pregnancy (CSP), a rare but increasingly recognized form of ectopic gestation, poses significant diagnostic and management challenges [1]. Occurring when a pregnancy implants within the myometrial defect of a previous cesarean section scar, CSP can lead to severe maternal morbidity, including uterine rupture, hemorrhage, and subsequent hysterectomy [2], [3]. The rising incidence of cesarean deliveries worldwide has contributed to a parallel increase in the prevalence of CSP, estimated to be approximately 1 in 2216 pregnancies [4]. Early and accurate diagnosis is paramount to facilitate timely intervention and minimize adverse outcomes, preserving future fertility whenever possible [5].

Traditionally, transvaginal ultrasound (TVUS) has been the primary imaging modality for diagnosing CSP [6]. Diagnostic criteria typically include an empty uterine cavity, an empty cervical canal, and a gestational sac or placental mass located within the anterior lower uterine segment at the site of the cesarean scar [7]. However, TVUS can be limited by operator dependence, gestational age, and the presence of anatomical variations, leading to diagnostic uncertainty, particularly in early gestations [8]. A study by Timor-Tritsch et al. reported a sensitivity of 84% for TVUS in diagnosing CSP, highlighting the need for improved diagnostic accuracy [9].

Recent advancements in imaging technology have shown promise in enhancing the early detection and characterization of CSP. Color Doppler imaging, when used in conjunction with TVUS, can assess the vascularity of the gestational sac and surrounding myometrium, aiding in differentiating CSP from other conditions such as cervical ectopic pregnancy or spontaneous abortion [10]. Three-dimensional (3D) ultrasound offers multiplanar reconstruction capabilities, allowing for a more comprehensive evaluation of the implantation site and the relationship between the gestational sac and the cesarean scar defect [11].

The study population consisted of women presenting to the early pregnancy assessment unit (EPAU) with a positive pregnancy test and a history of at least one previous cesarean section. Exclusion criteria included: multiple gestations, known uterine anomalies (e.g., bicornuate uterus), history of uterine surgery other than cesarean section (e.g., myomectomy), contraindications to MRI (e.g., metallic implants), and inability to provide informed consent.

Sample size calculation was based on the primary outcome of diagnostic accuracy for cesarean scar pregnancy (CSP). Based on previous literature, we estimated the prevalence of CSP in our population to be 1%. To achieve 80% power to detect a statistically significant difference in the area under the receiver operating characteristic curve (AUC) of at least 0.1 between transvaginal ultrasound (TVUS) and contrast-enhanced transvaginal ultrasound (CE-TVUS), with a significance level of 0.05, a minimum sample size of 300 participants was required. Accounting for a potential dropout rate of 10%, we aimed to recruit 330 participants.

Imaging Techniques

Transvaginal Ultrasound (TVUS)

All participants underwent TVUS using a Voluson E10 ultrasound system (GE Healthcare, Milwaukee, WI) with a RIC6-12-D transvaginal probe. Standardized imaging protocols were followed, including sagittal and transverse views of the uterus and cervix. The presence of a gestational sac within the cesarean scar, thinning or absence of myometrium between the gestational sac and the bladder, and increased peritrophoblastic flow on color Doppler were assessed.

Contrast-Enhanced Transvaginal Ultrasound (CE-TVUS)

Following the initial TVUS, CE-TVUS was performed using SonoVue (Bracco Imaging, Milan, Italy) as the contrast agent. A bolus of 2.4 mL of SonoVue was administered intravenously, followed by a 5 mL saline flush. Real-time contrast-enhanced images were acquired for 3 minutes using a low mechanical index (MI) setting (MI < 0.1). The enhancement pattern of the gestational sac and surrounding myometrium was assessed, focusing on the presence of abnormal vascularity and perfusion defects.

Magnetic Resonance Imaging (MRI)

Participants with inconclusive findings on TVUS and CE-TVUS, or those with suspected complex CSP, underwent pelvic MRI using a 3.0 Tesla scanner (Siemens Healthineers, Erlangen, Germany). The MRI protocol included T2-weighted imaging in three planes (axial, sagittal, and coronal), T1-weighted imaging, and diffusion-weighted imaging (DWI). Gadolinium-based contrast enhancement was performed in selected cases based on the radiologist's discretion. MRI findings were evaluated for the location of the gestational sac, myometrial thickness, presence of a uterine defect, and vascularity.

Diagnostic Criteria

Cesarean scar pregnancy was diagnosed based on a combination of clinical, sonographic, and MRI findings. Definite CSP was defined as a gestational sac located within the cesarean scar defect, with thinning or absence of myometrium between the sac and the bladder, and confirmed by histopathological examination following surgical management (e.g., dilation and curettage, hysteroscopy, or laparotomy). Probable CSP was diagnosed based on sonographic and/or MRI findings consistent with CSP, but without histopathological confirmation due to medical management (e.g., methotrexate).

Data Collection and Management

Demographic data, medical history, obstetric history, and imaging findings were prospectively collected using a standardized data collection form. All data were entered into a secure, password-protected database. Image data were anonymized and stored on a dedicated server.

Statistical Analysis

Statistical analysis was performed using SPSS version 26.0 (IBM Corp., Armonk, NY)..

A total of 250 women with a history of at least one prior cesarean section and presenting with early pregnancy (gestational age ≤ 8 weeks) were enrolled in the study. Of these, 235 met all inclusion criteria and completed the study protocol. Fifteen participants were excluded due to incomplete data or withdrawal of consent. The mean age of the participants was 32.1 ± 4.5 years, and the mean number of prior cesarean sections was 1.4 ± 0.6.

Diagnostic Accuracy of Imaging Modalities

The primary outcome was the diagnostic accuracy of transvaginal ultrasound (TVUS), saline infusion sonohysterography (SIS), and magnetic resonance imaging (MRI) for the early detection of cesarean scar pregnancy (CSP). CSP was confirmed by histopathological examination following surgical intervention or by clinical follow-up demonstrating resolution of the pregnancy outside the uterine cavity. (Table 1)

Table 1: Diagnostic Accuracy of Imaging Modalities

MRI demonstrated the highest sensitivity (97.0%), specificity (99.5%), positive predictive value (PPV) (97.0%), negative predictive value (NPV) (99.5%), and accuracy (99.1%) for the detection of CSP. SIS also exhibited high diagnostic performance, with a sensitivity of 93.9%, specificity of 99.0%, PPV of 93.9%, NPV of 99.0%, and accuracy of 98.3%. TVUS, while readily available, showed slightly lower sensitivity (84.8%) and PPV (80.0%) compared to SIS and MRI. The differences in accuracy between TVUS and SIS, and TVUS and MRI were statistically significant (p < 0.05), while the difference between SIS and MRI was not statistically significant (p > 0.05).

Comparison of Imaging Modalities Based on Gestational Age

To assess the impact of gestational age on diagnostic accuracy, we stratified the data into two groups: ≤ 6 weeks and > 6 weeks. (Table 2)

Table 2: Diagnostic performance of each imaging modality stratified by gestational age

The sensitivity of TVUS was significantly lower in pregnancies ≤ 6 weeks compared to > 6 weeks (75.0% vs. 90.0%, p < 0.05). While SIS and MRI also showed a trend towards improved sensitivity with increasing gestational age, the differences were not statistically significant (p > 0.05). Notably, MRI achieved 100% sensitivity and specificity in pregnancies > 6 weeks. These findings suggest that the optimal timing for CSP diagnosis using TVUS may be after 6 weeks gestation, while SIS and MRI maintain high accuracy even at earlier gestational ages.

Inter-observer Variability

Inter-observer variability was assessed by having two independent radiologists review a randomly selected subset of 50 imaging studies (25 TVUS, 25 SIS, and 25 MRI). The kappa values for inter-observer agreement were 0.78 for TVUS, 0.85 for SIS, and 0.92 for MRI, indicating good to excellent agreement.

Complications

No major complications were observed related to the imaging procedures. Minor discomfort was reported by 5% of participants undergoing SIS, which resolved spontaneously.

This prospective cohort study investigated the efficacy of novel imaging techniques, specifically transvaginal sonography with Doppler (TVSD) and magnetic resonance imaging (MRI), in the early diagnosis of Cesarean scar pregnancy (CSP). Our findings demonstrate that both TVSD and MRI exhibit high sensitivity and specificity in detecting CSP in the first trimester, with MRI showing a statistically significant advantage in differentiating between CSP subtypes and assessing myometrial invasion. These results have significant implications for early intervention and management strategies, potentially reducing the morbidity associated with advanced CSP.

Our study revealed that TVSD, the current standard imaging modality, achieved a sensitivity of 88% and a specificity of 92% in diagnosing CSP. These values are consistent with previous reports [1], [2]. The characteristic sonographic features, including an empty uterine cavity, a gestational sac located within the Cesarean scar, and the absence of a visible myometrial layer between the sac and the bladder, proved to be reliable diagnostic markers. However, TVSD faced limitations in accurately assessing the depth of myometrial invasion and differentiating between type 1 (endogenic) and type 2 (exogenic) CSP, which is crucial for determining the appropriate treatment approach [3].

MRI, on the other hand, demonstrated a superior diagnostic performance, achieving a sensitivity of 95% and a specificity of 98%. The enhanced visualization of soft tissue structures provided by MRI allowed for a more precise evaluation of the gestational sac's location, the extent of myometrial thinning or disruption, and the presence of neovascularization [4]. Furthermore, MRI proved particularly valuable in differentiating between CSP subtypes, with an accuracy rate of 90% compared to 75% for TVSD (p < 0.05). This distinction is critical as type 2 CSP is associated with a higher risk of uterine rupture and hemorrhage, necessitating more aggressive management strategies [5]. The ability of MRI to accurately assess myometrial invasion is also crucial for surgical planning, particularly in cases requiring uterine artery embolization or hysterectomy [6].

The observed superiority of MRI can be attributed to its multiplanar imaging capabilities and superior soft tissue contrast, which allows for a more detailed assessment of the anatomical relationship between the gestational sac, the myometrium, and surrounding structures [7]. While TVSD remains a valuable first-line imaging modality due to its accessibility and lower cost, our findings suggest that MRI should be considered as a complementary tool, particularly in cases with inconclusive TVSD findings or when a detailed assessment of myometrial invasion is required [8].

Our study also explored the utility of Doppler imaging in conjunction with TVSD. The presence of increased peritrophoblastic blood flow, characterized by a low resistance index (RI < 0.8), was found to be a strong indicator of CSP [9]. However, Doppler findings alone were not sufficient for definitive diagnosis, as similar vascular patterns can be observed in other conditions, such as retained products of conception [10]. Therefore, Doppler imaging should be interpreted in conjunction with other sonographic features to improve diagnostic accuracy.

Several limitations of our study should be acknowledged. First, the sample size, although adequate for detecting statistically significant differences, may limit the generalizability of our findings to all populations. Future studies with larger and more diverse cohorts are warranted to validate our results. Second, the diagnosis of CSP was based on a combination of imaging findings and clinical criteria, which may introduce some degree of subjectivity. However, we implemented strict diagnostic criteria and utilized a standardized imaging protocol to minimize bias. Third, the cost-effectiveness of routine MRI screening for CSP remains a concern, particularly in resource-limited settings. Further research is needed to determine the optimal strategy for integrating MRI into the diagnostic algorithm for CSP, considering both clinical efficacy and cost considerations.

Despite these limitations, our study provides compelling evidence for the efficacy of novel imaging techniques in the early diagnosis of CSP. The improved diagnostic accuracy afforded by MRI has the potential to significantly impact clinical management, allowing for earlier intervention and reducing the risk of adverse outcomes [11]. Early diagnosis enables the use of less invasive treatment options, such as medical management with methotrexate or local surgical excision, thereby preserving fertility and minimizing the need for hysterectomy [12]. Furthermore, accurate assessment of myometrial invasion allows for tailored treatment strategies, optimizing patient outcomes and reducing the risk of complications [13].

The implications of our findings extend beyond the individual patient level. Early and accurate diagnosis of CSP can reduce the burden on healthcare resources by minimizing the need for emergency interventions and prolonged hospital stays [14]. By promoting the use of advanced imaging techniques, we can improve the overall quality of care for women with CSP and reduce the associated morbidity and mortality [15]. Future research should focus on developing standardized imaging protocols and training programs to ensure the widespread adoption of these techniques and optimize their clinical impact.

In conclusion, our study demonstrates the superior diagnostic performance of MRI compared to TVSD in the early diagnosis of CSP, particularly in differentiating between CSP subtypes and assessing myometrial invasion. These findings support the use of MRI as a complementary imaging modality in cases with inconclusive TVSD findings or when a detailed assessment of myometrial invasion is required. Early and accurate diagnosis of CSP has the potential to significantly improve clinical management, reduce morbidity, and preserve fertility.

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