A prediction nomogram for residual after negative pressure aspiration for endogenic cesarean scar ectopic pregnancy: a retrospective study
Cesarean scar ectopic pregnancy (CSEP) refers to the implantation of an early pregnancy sac at the site of a previous cicatricial fracture , which is one of the complications associated with a cesarean section (CS). The true incidence of CSEP remains unknown, as the condition is likely underdiagnosed and underreported. Estimates from single-center reports suggest an incidence ranging from 1 in 1800 to 1 in 2656 pregnancies . The implantation patterns of CSEP can be categorized as endogenic (also referred to as "on the scar") or exogenic ("in-the-niche"). The definition for endogenic implantation refers to growth within the uterine cavity, while that for exogenic implantation describes the growth of a pregnancy sac implanted in the scar, potentially extending toward the bladder or abdominal cavity . The progression of CSEP may lead to the potential for major bleeding, placenta accreta spectrum (PAS), uterine rupture, and (in severe cases) maternal death . Once CSEP is diagnosed, patients are advised to terminate the pregnancy or undergo specific medical management for the condition . Numerous treatment options are available, with methotrexate (MTX) commonly used as a pharmacological therapy. MTX can be administered via systemic or local injection to treat CSEP, with reported success rates of 75.2% and 73.9%, respectively . There are relatively few reports on the use of mifepristone to treat CSEP; one review indicated that the efficacy of MTX combined with mifepristone was 71.4%, but this was limited to patients with serum levels of β- human chorionic gonadotropin (HCG) < 5000 mU/ml and gestational sac size < 2 cm . The risk of severe hemorrhage is relatively high when pharmacological treatment is used alone to treat CSEP; therefore, it is recommended to consider it as a pre-treatment or as adjunctive therapy . Alternative treatment options for the treatment of CSEP include laparoscopy, hysteroscopy, open and vaginal surgery, and uterine artery embolization (UAE). While these interventions can reduce the risk of major bleeding and other complication, they often require specialized equipment, anesthesia, and supervision by experienced physicians, in addition to have high associated costs . This makes them difficult to implement in low-income areas and primary healthcare institutions . One study indicated that patients with CESP treated with laparoscopy and UAE combined with negative pressure suction had significantly longer hospital stays and higher total medical expenses compared to those treated with MTX and negative pressure suction . Ultrasound-guided negative pressure aspiration is a procedure in which a suction tube is inserted into the uterine cavity and aligned with the gestational tissue under ultrasound guidance. This procedure is typically performed under a negative pressure range of 400–500 mm Hg, facilitating clear visualization of the uterine cavity via ultrasound, which is a procedure widely recommended by gynecologists for the treatment of CSEP, particularly for the endogenic version . There are numerous studies in the literature focused on the prevention of major hemorrhage in patients with CSEP, with most of them employing univariate and multivariate logistic regression analyses to evaluate various clinical indicators, and using receiver operating characteristic (ROC) curves to assess the risk of severe bleeding. However, this assessment method may not be simple or intuitive enough to be useful for clinicians . Post-aspiration residue following negative pressure treatment of CSEP is one of the most common complications after the procedure for endogenic CSEP . Although some studies have included all potential complications that may occur during CSEP treatment in their risk assessment models , few of them have examined CSEP postoperative residue or have conducted separate analyses for the endogenic and exogenic types. Residual tissue following surgery for CSEP can cause prolonged vaginal bleeding. Some villous trophoblast cells can enter the muscle layer through scar cracks, implant the villi and erode the blood vessels in the muscle layer. This can result in persistent CSEP without timely detection or treatment . The incidence of persistent CESP following treatment reported in the literature ranges from 4.31% (10/232) to 6.03% (7/116) . Patients in this category are often more prone to experience acute hemorrhage, and the remaining tissue mass can sometimes be difficult to absorb, potentially requiring additional treatment to control anemia or infection, pharmacological therapy, further surgical intervention, or even hysterectomy . Re-treatment increases the psychological and physiological burden on patients, and carries additional financial costs . This retrospective study aims to establish a simple, intuitive, and practical predictive model to enable clinicians to conduct an immediate postoperative assessment of patients. Implementing appropriate early management for patients at high risk of residual tissue is likely to reduce the incidence of long-term complications. To the best of our knowledge, the establishment of a risk prediction model specifically for postoperative residuals following negative pressure treatment of endogenic CSEP is a novel contribution. 

Patients A retrospective investigation was conducted on 1,197 patients with CSEP who underwent treatment in the gynecological ward of a tertiary hospital in a city of China between May 2017 and August 2023. Inclusion criteria for this study included: (1) endogenic CSEP with a definite imaging diagnosis, (2) single pregnancy at < 12 weeks of gestation, (3) initial treatment with ultrasound-guided negative pressure aspiration, and (4) no treatment with MTX or UAE before surgery. The exclusion criteria were: (1) exogenic CSEP, (2) those not treated with the use of negative pressure aspiration for CSEP, (3) incomplete clinical data such as missing serumβ-HCG values, unclear duration of pregnancy, or patients lost to follow-up. Ultimately, 899 patients were eligible for the study and were divided into a training and a validation cohort using random computer sampling at a ratio of 7:3 for modeling (Fig. ). The study protocol was approved by the ethics committee of our institution (Registration number: 2023IEC123). The study was conducted following the tenets of the declaration of Helsinki. All participants provided written informed consent for their participation. Notably, all the participants in this study were of Han Chinese ethnicity. The data collected included general information on patients with CSEP such as age, body mass index (BMI),serum β-HCG values, number of pregnancies, number of births, number of miscarriages, number of CSs, number of weeks of menelipsis, maximum gestational sac diameter, thickness of the remaining muscle layer in the lower uterine segment, and whether major bleeding (intraoperative blood loss > 500 ml) occurred. Diagnosis In this study, the diagnosis of CSEP was mainly based on transvaginal ultrasonography (TVS), with typical ultrasonography manifestations including (1) intrauterine and cervical cavity emptiness, no gestational sac; (2) placenta, gestational sac, or both implanted in the CS scar; (3) gestational sac completely filling the scar "niche"; (4) thin or missing myometrium between the gestational sac and the bladder; and (5) obvious or abundant blood vessels in the CS scar . In those cases in which performing TVS was not feasible, magnetic resonance imaging was used as an auxiliary method of diagnosis. Both T1- and T2-weighted images can effectively identify a gestational sac embedded within the lower uterine segment at the level of a prior cesarean scar niche, as well as an empty endometrial cavity and endocervix. Magnetic resonance imaging provides detailed imaging that can help to accurately identify the location and extent of a CSEP . The definition of postoperative residual CSEP in this study involves patients with an unsatisfactory decline in serum hCG values after surgery (blood β-hCG levels constant was in a plateau state [± 10%]) for four consecutive tests or with a weekly decline < 15%, or persistent presence of CS scar mass identified via transvaginal ultrasound, combined with clinical supplementary treatment  Statistical analysis Before conducting the statistical analysis, we excluded individuals with missing values and only analyzed samples with complete data.We employed multivariate logistic regression to construct a residual risk model to predict negative pressure aspiration in patients with endogenic CSEP. Initially, possible predictors of outcome events were screened using univariate logistic regression analysis ( P < 0.05). Afterwards, multivariate logistic regression analyses (stepwise and bidirectional) were performed for the variables selected in the previous step. A nomogram for the prediction model was constructed based on variables with P < 0.05 in the stepwise method, and 1000 times self-sample sampling validations were performed on the constructed nomogram. Calibration curves were generated to evaluate the calibration degree of the model, and the Hosmer–Lemeshow test was performed to evaluate its goodness of fit. The Hosmer–Lemeshow test was an effective tool for assessing the fit of logistic regression models. It evaluated the model's calibration by dividing the data into different risk groups and comparing the observed events in each group with the events predicted by the model, thus assessing the fit of the model at different risk levels.The area under the curve (AUC), sensitivity, specificity, and other indicators were calculated using ROC curve analysis. To evaluate its differential efficacy, a decision curve analysis (DCA) was performed to evaluate the clinical application value of the model and quantify the net benefit within the threshold probability range.Finally, the constructed model was validated using the validation cohort. DCA quantified the clinical benefits of using predictive models by assessing different decision thresholds. Particularly in low-resource settings where advanced diagnostic tools might have been lacking, DCA enabled clinicians to weigh the benefits of interventions against potential harms and costs. This process helped clinicians identify which patients were most likely to benefit from specific treatments or interventions, thereby making treatment more targeted. Such real-world analyses were crucial for efficient resource utilization.All data were collected, processed, and analyzed using the R language statistical software (version 4.3.2, R Core Team, (2023). R: A Language and Environment for Statistical Computing R Foundation for Statistical Computing, Vienna, Austria. Software available at https://www.R-project.org/ ). The data were divided into training and validation datasets. The training set was used for model training, and the validation set was employed for model validation. For continuous variables, mean ± standard deviation was used for statistical description, and the independent sample t-test was used for comparison between groups. In cases where the normal distribution conditions were not met, median [P25 – P75] was used for description, and comparison between groups was conducted using the rank sum test. Quantitative data was presented as the number of cases , with inter-group comparisons performed using the chi-square test. Fisher’s exact probability was applied when the chi-square test assumptions were not met. P < 0.05 was considered statistically significant. 

A retrospective investigation was conducted on 1,197 patients with CSEP who underwent treatment in the gynecological ward of a tertiary hospital in a city of China between May 2017 and August 2023. Inclusion criteria for this study included: (1) endogenic CSEP with a definite imaging diagnosis, (2) single pregnancy at < 12 weeks of gestation, (3) initial treatment with ultrasound-guided negative pressure aspiration, and (4) no treatment with MTX or UAE before surgery. The exclusion criteria were: (1) exogenic CSEP, (2) those not treated with the use of negative pressure aspiration for CSEP, (3) incomplete clinical data such as missing serumβ-HCG values, unclear duration of pregnancy, or patients lost to follow-up. Ultimately, 899 patients were eligible for the study and were divided into a training and a validation cohort using random computer sampling at a ratio of 7:3 for modeling (Fig. ). The study protocol was approved by the ethics committee of our institution (Registration number: 2023IEC123). The study was conducted following the tenets of the declaration of Helsinki. All participants provided written informed consent for their participation. Notably, all the participants in this study were of Han Chinese ethnicity. The data collected included general information on patients with CSEP such as age, body mass index (BMI),serum β-HCG values, number of pregnancies, number of births, number of miscarriages, number of CSs, number of weeks of menelipsis, maximum gestational sac diameter, thickness of the remaining muscle layer in the lower uterine segment, and whether major bleeding (intraoperative blood loss > 500 ml) occurred. 

In this study, the diagnosis of CSEP was mainly based on transvaginal ultrasonography (TVS), with typical ultrasonography manifestations including (1) intrauterine and cervical cavity emptiness, no gestational sac; (2) placenta, gestational sac, or both implanted in the CS scar; (3) gestational sac completely filling the scar "niche"; (4) thin or missing myometrium between the gestational sac and the bladder; and (5) obvious or abundant blood vessels in the CS scar . In those cases in which performing TVS was not feasible, magnetic resonance imaging was used as an auxiliary method of diagnosis. Both T1- and T2-weighted images can effectively identify a gestational sac embedded within the lower uterine segment at the level of a prior cesarean scar niche, as well as an empty endometrial cavity and endocervix. Magnetic resonance imaging provides detailed imaging that can help to accurately identify the location and extent of a CSEP . The definition of postoperative residual CSEP in this study involves patients with an unsatisfactory decline in serum hCG values after surgery (blood β-hCG levels constant was in a plateau state [± 10%]) for four consecutive tests or with a weekly decline < 15%, or persistent presence of CS scar mass identified via transvaginal ultrasound, combined with clinical supplementary treatment  

Before conducting the statistical analysis, we excluded individuals with missing values and only analyzed samples with complete data.We employed multivariate logistic regression to construct a residual risk model to predict negative pressure aspiration in patients with endogenic CSEP. Initially, possible predictors of outcome events were screened using univariate logistic regression analysis ( P < 0.05). Afterwards, multivariate logistic regression analyses (stepwise and bidirectional) were performed for the variables selected in the previous step. A nomogram for the prediction model was constructed based on variables with P < 0.05 in the stepwise method, and 1000 times self-sample sampling validations were performed on the constructed nomogram. Calibration curves were generated to evaluate the calibration degree of the model, and the Hosmer–Lemeshow test was performed to evaluate its goodness of fit. The Hosmer–Lemeshow test was an effective tool for assessing the fit of logistic regression models. It evaluated the model's calibration by dividing the data into different risk groups and comparing the observed events in each group with the events predicted by the model, thus assessing the fit of the model at different risk levels.The area under the curve (AUC), sensitivity, specificity, and other indicators were calculated using ROC curve analysis. To evaluate its differential efficacy, a decision curve analysis (DCA) was performed to evaluate the clinical application value of the model and quantify the net benefit within the threshold probability range.Finally, the constructed model was validated using the validation cohort. DCA quantified the clinical benefits of using predictive models by assessing different decision thresholds. Particularly in low-resource settings where advanced diagnostic tools might have been lacking, DCA enabled clinicians to weigh the benefits of interventions against potential harms and costs. This process helped clinicians identify which patients were most likely to benefit from specific treatments or interventions, thereby making treatment more targeted. Such real-world analyses were crucial for efficient resource utilization.All data were collected, processed, and analyzed using the R language statistical software (version 4.3.2, R Core Team, (2023). R: A Language and Environment for Statistical Computing R Foundation for Statistical Computing, Vienna, Austria. Software available at https://www.R-project.org/ ). The data were divided into training and validation datasets. The training set was used for model training, and the validation set was employed for model validation. For continuous variables, mean ± standard deviation was used for statistical description, and the independent sample t-test was used for comparison between groups. In cases where the normal distribution conditions were not met, median [P25 – P75] was used for description, and comparison between groups was conducted using the rank sum test. Quantitative data was presented as the number of cases , with inter-group comparisons performed using the chi-square test. Fisher’s exact probability was applied when the chi-square test assumptions were not met. P < 0.05 was considered statistically significant. 

Baseline characteristics A comparison of baseline characteristics between the training cohort and the validation cohort revealed a significant difference in thickness of the remaining muscle layer ( P < 0.05). However, no significant differences were observed in age, number of pregnancies, deliveries, cesarean sections, miscarriages, gestational age, gestational sac diameter, thickness of the remaining muscle layer, BMI and the occurrence of intraoperative hemorrhage ( P > 0.05) (Table ). Screening for predictors of CSEP Multivariate logistic regression analysis showed that five factors were independent predictors for the occurrence of residual CSEP after negative pressure aspiration of residual occurrence after CSEP negative pressure aspiration, including age ( P < 0.001, hazard ratio [HR]: 1.220, 95% confidence interval [CI]: 1.135 – 1.316), BMI ( P = 0.004, HR: 0.890, 95% CI: 0.796 – 0.986), intraoperative massive bleeding ( P = 0.032, HR: 4.457, 95% CI: 1.610 – 12.292), maximum diameter of gestational sacpregnant sac ( P < 0.001, HR: 1.572, 95% CI: 1.295 – 1.914), and thickness of the remaining muscle layer of lower uterine segment ( P = 0.005, HR: 1.572, 95% CI: 0.014 – 0.430; Table ). Nomogram construction These five influencing factors from the multivariate logistic regression model were integrated into a nomogram (Fig. ), with higher total scores indicating higher residual risks for patients with CSEPs undergoing negative pressure aspiration. In addition, the Hosmer–Lemeshow test showed that the model had a good fit ( P = 0.861). In the training cohort, the AUC was 0.809 (95% CI: 0.751—0.867; Fig. A), the calibration curve was close to the ideal diagonal (Fig. A), and the DCA showed a good net benefit for the prediction model (Fig. A). In addition, 270 patients were tested externally to validate the nomogram, and the resulting AUC was 0.814 (95% CI: 0.739—0.888; Fig. B), reflecting the accuracy of the nomogram. Simultaneously, we found that the model had good consistency, the validation queue was close to the ideal diagonal (Fig. B), and the DCA exhibited a good net benefit for the validation queue (Fig. B). Taken together, these data suggest that our nomogram has significant potential to enhance clinical decision-making. Outcome of patients with residual tissue All patients in this study underwent an initial TVS review within one week after treatment. Among them, 101 patients diagnosed with residual tissue were immediately administered oral mifepristone and had their serumβ-hCG levels monitored weekly. The final outcomes were as follows: 85 patients (84.16%, 85/101) recovered at the re-examination 4 weeks post-surgery, meeting the diagnostic criteria of no residue on TVS and β-hCG levels reaching or nearing negative status. Four patients (3.96%, 4/101) recovered after two courses of MTX injections. Nine patients (8.91%, 9/101) were cured through re-suction or hysteroscopic surgery, and three (2.97%, 3/101) required UAE combined with cesarean scar repair due to sudden massive bleeding. 

A comparison of baseline characteristics between the training cohort and the validation cohort revealed a significant difference in thickness of the remaining muscle layer ( P < 0.05). However, no significant differences were observed in age, number of pregnancies, deliveries, cesarean sections, miscarriages, gestational age, gestational sac diameter, thickness of the remaining muscle layer, BMI and the occurrence of intraoperative hemorrhage ( P > 0.05) (Table ). 

Multivariate logistic regression analysis showed that five factors were independent predictors for the occurrence of residual CSEP after negative pressure aspiration of residual occurrence after CSEP negative pressure aspiration, including age ( P < 0.001, hazard ratio [HR]: 1.220, 95% confidence interval [CI]: 1.135 – 1.316), BMI ( P = 0.004, HR: 0.890, 95% CI: 0.796 – 0.986), intraoperative massive bleeding ( P = 0.032, HR: 4.457, 95% CI: 1.610 – 12.292), maximum diameter of gestational sacpregnant sac ( P < 0.001, HR: 1.572, 95% CI: 1.295 – 1.914), and thickness of the remaining muscle layer of lower uterine segment ( P = 0.005, HR: 1.572, 95% CI: 0.014 – 0.430; Table ). 

These five influencing factors from the multivariate logistic regression model were integrated into a nomogram (Fig. ), with higher total scores indicating higher residual risks for patients with CSEPs undergoing negative pressure aspiration. In addition, the Hosmer–Lemeshow test showed that the model had a good fit ( P = 0.861). In the training cohort, the AUC was 0.809 (95% CI: 0.751—0.867; Fig. A), the calibration curve was close to the ideal diagonal (Fig. A), and the DCA showed a good net benefit for the prediction model (Fig. A). In addition, 270 patients were tested externally to validate the nomogram, and the resulting AUC was 0.814 (95% CI: 0.739—0.888; Fig. B), reflecting the accuracy of the nomogram. Simultaneously, we found that the model had good consistency, the validation queue was close to the ideal diagonal (Fig. B), and the DCA exhibited a good net benefit for the validation queue (Fig. B). Taken together, these data suggest that our nomogram has significant potential to enhance clinical decision-making. 

All patients in this study underwent an initial TVS review within one week after treatment. Among them, 101 patients diagnosed with residual tissue were immediately administered oral mifepristone and had their serumβ-hCG levels monitored weekly. The final outcomes were as follows: 85 patients (84.16%, 85/101) recovered at the re-examination 4 weeks post-surgery, meeting the diagnostic criteria of no residue on TVS and β-hCG levels reaching or nearing negative status. Four patients (3.96%, 4/101) recovered after two courses of MTX injections. Nine patients (8.91%, 9/101) were cured through re-suction or hysteroscopic surgery, and three (2.97%, 3/101) required UAE combined with cesarean scar repair due to sudden massive bleeding. 

To date, most studies have focused on the diagnosis and treatment of CSEP and in the management of intraoperative massive bleeding and its impact on fertility outcomes, whereas there are few reports on postoperative residual CSEP. Despite the increasingly more detailed classification of CSEP and the several treatment methods available , negative pressure aspiration remains the most commonly used treatment method for CSEP due to the limitations of personnel and equipment, and to financial constraints . An increasing number of studies have shown that ultrasound-guided negative-pressure aspiration is a reliable treatment option for endogenic CSEP and that the risks of blood transfusion, uterine perforation, and hysterectomy are low . For instance, Jurkovic reported that the incidence of residual CSEP in 191 patients after negative pressure aspiration after negative pressure aspiration was 15%, and that only 6% required repeated surgical treatment . Qian et al. also reported that only 11.42% (154/1348) of patients with CSEP treated with negative pressure aspiration were readmitted because of postoperative residual tissue . During the design and data collection phases of our study, all participants met the predefined inclusion criteria, and patients were excluded only in cases of missing data integrity. Among the 102 patients excluded due to incomplete data, 22 were attributed to random missing outcome data resulting from loss to follow-up, while the exclusion of the remaining 80 patients was due to missing preoperative serum β-HCG values and unclear last menstrual period dates. The primary reason for the missing serum β-HCG values was the attending physician either forgot to perform the test or to enter the data into the database. The ambiguity regarding the patients' gestational age from either irregular menstrual cycles or the patients' inability to recall their last menstrual period. These missing data were not due to specific patient circumstances or selection biases, but occurred randomly. We acknowledge that the missing data reduced the sample size for analysis, which somewhat lowered the statistical power.However, as all missing data were categorized as missing at random, they did not introduce selection bias, and the systematic bias in the results remained minimal.Although the baseline characteristics of the training and validation cohorts in this study were balanced in most respects, there was a difference in myographic thickness. This may be attributed to selection bias among patients at the time of treatment. Furthermore, a p -value of less than 0.05 does not necessarily imply that these differences are clinically significant; they should be interpreted in the context of clinical relevance rather than relying solely on statistical significance. Despite the significant differences observed in certain characteristics, the overall results remain similar between the training and validation cohorts. Additionally, the treatment modalities and disease types were highly consistent, suggesting that these differences are unlikely to have a major impact on the predictive capability of the model. Moreover, the available literature indicates that the decrease in serum β-HCG levels on the first day after negative pressure aspiration is associated with a risk of residual tissue . Unfortunately, most patients in this study did not undergo serum β-HCG testing within 24 h postoperatively. This omission may be due to a lack of emphasis from both patients and clinicians on the importance of monitoring for residual tissue following treatment for endogenic CSEP, reflecting a subjective bias. In fact, hospitals in economically disadvantaged regions often struggle to conduct serum β-HCG measurements and follow-ups for every patient being treated. Therefore, we believe that not incorporating the decline in serum β-HCG levels into our model may enhance its practicality.It is undeniable that decrease in serumβ-hCG levels, as an important prognostic indicator of residual embryonic tissue, necessitated its inclusion in the predictive model. In future research, we planned to incorporate this variable to assess its effectiveness in actual clinical applications and to enhance its generalizability. Thickness of the remaining muscle layer is an independent predictor of residual CSEP after negative pressure aspiration. In fact, thickness of the remaining muscle layer at the CS scar has long been considered one of the major factors for the success of ultrasound-guided CSEP. However, there is no consensus on the specific values of thickness of the remaining muscle layer . Currently, it is widely acknowledged that for CSEP, thickness of the remaining muscle layer at the scar site decreases, and as the surgical difficulty increases, gynecologists become more concerned that excessive curettage can increase the risk of uterine perforation and massive bleeding. Particularly, when the gestational sac reaches or approaches the serous membrane of the uterus, the risk of surgical difficulty, uterine perforation, and major bleeding becomes higher, and therefore the probability of residual tissue increases. Maximum gestational sac diameter was also a risk factor for residual disease. A larger gestational sac contains more villus tissue, and therefore the probability of having residual tissue becomes greater . An increase in gestational sac diameter is usually accompanied by an increase in the number of gestational weeks, increased trophoblast blood flow around the gestational sac, and heavier erosion of trophoblast cells and villi in the myocardium of the scar . This, in turn, increases the risk of bleeding during negative pressure aspiration. Importantly, previous research has shown that even experienced gynecologists sometimes have to suspend the operation due to massive intraoperative bleeding and are forced to use balloon compression, uterine artery embolization, or other methods to stop the bleeding immediately, which increases the probability of residual CSEP .Although the guidelines did not provide a specific recommended threshold for the maximum gestational sac diameter, based on the literature, we believed that the risk of failure in vacuum aspiration treatment for CSEP may increase when the maximum diameter of the gestational sac exceeds 3.0 cm . Additionally, our results revealed that age was also a risk factor for residual CSEP after surgery. Previous studies have shown that age is a risk factor for massive hemorrhage during delivery. The sensitivity of the coagulation mechanisms in older pregnant women with scarred uteri is lower than that observed in the general pregnant population, and therefore they are prone to massive hemorrhage during surgery . The residual incidence of CSEP often increases due to massive hemorrhage during surgery. As the amount of bleeding increases, gynecologists become more cautious. BMI was also one of the factors affecting the occurrence of residual CSEP in this study, and individuals with a high BMI had a lower incidence of residual CSEP. This observation has not previously been made in the CSEP-related literature. It can be speculated that this may be due to the fact that women with a high BMI have a relatively high level of estrogen receptors (ERs), which is conducive to endometrial proliferation and repair . Following pregnancy termination, ER levels in the body of patients were found to be reduced. After the termination of pregnancy, the levels of ER in the pregnant women decreased, and the process of endometrial clearance was faster and more thorough in women with relatively slower endometrial repair and proliferation, thereby reducing the probability of residual tissue. Additionally, although women with a high BMI generally had thicker abdominal subcutaneous fat, which might affect the clarity of ultrasound images , physicians might adopt a more cautious approach and be more focused on assessing intrauterine residual tissue in patients with high BMI in certain situations.These factors may elucidate why patients with a high BMI were less prone to experiencing residual tissue after the procedure. Further research is needed to elucidate the underlying mechanisms and to determine whether BMI plays a protective role or influences the surgical outcomes in a way that reduces the likelihood of residual tissue. Our study presents and establishes, for the first time, a model comprising five variables and their corresponding risk indexes that demonstrate optimal predictive capability in both the internal and external validation cohorts. For example, in a 40-year-old patient with a BMI of 28 and who had a maximum diameter of the gestational sac of 7 cm and a thickness of the inferior uterine muscle of 0.1 cm, massive bleeding occurred during the operation. The corresponding scores for the patient were approximately 74, 18, 65, 56, and 30.6, with a total score of 243.6, and the estimated probability of residual occurrence was 85% (Fig. ). This model is capable of predicting the risk of residual tissue following vacuum aspiration in patients with endogenic CSEP, and has been confirmed to exhibit good fit, predictive accuracy, and net benefit.Model validation is a critical aspect of developing clinical prediction models. In the internal validation cohort, considering our large sample size, the dataset was randomly divided into two parts: 70% was used as the training cohort for internal validation, while the remaining 30% served as the validation cohort for external validation, in order to ensure that the model was in fact effective before recommending widespread adoption. A model is generally considered useful for clinical decision-making when the AUC exceeds 0.70; if the AUC exceeds 0.80, it is deemed a strong model, indicating that it can support clinical decisions. Furthermore, compared to simpler single ROC models reported in other studies, the predictive model developed in this study has been validated in multiple aspects, leading us to believe that its application can enhance the accuracy of subsequent decision-making based on fewer variables. 

The strength of this study lies in the development of a prediction model within a representative population and treatment approach, specifically targeting Han Chinese adults hospitalized for vacuum aspiration treatment due to endogenic CSEP. The predictive variables included in this risk model comprise easily accessible patient information and auxiliary examination results, enabling clinicians to simply assess patient prognosis through data available in medical record systems and surgical conditions. This facilitates the rapid identification and monitoring of high-risk subpopulations, allowing for the early selection of appropriate supplementary treatment strategies to reduce the likelihood of invasive surgeries, which is particularly important in low-income areas and resource-limited primary healthcare settings. The exclusion of preoperative and postoperative serum β-HCG results from the model may have impacted the prediction of risk. Furthermore, this was a single-center, single-blind retrospective study, which might not have reflected broader clinical practices and patient characteristics, potentially leading to biased results and limiting external validity. This limitation could have necessitated adjustments to the application processes for this nomogram in other medical institutions. The model was developed and validated in a cohort of Han Chinese in China, without testing its applicability to patients from other regions, which may have rendered it unsuitable for different ethnic groups or populations. To enhance the applicability of this nomogram in other regions or populations, we hoped that future studies would conduct external validation through multicenter, double-blind, prospective research involving diverse populations. Additionally, including extra predictive factors, such as uterine artery blood flow measurements and more detailed imaging findings, could have improved the nomogram's accuracy. Although the incidence of CSEP itself was relatively low, our sample size remained limited, and adequate validation and adaptability adjustments needed to be conducted in the future to ensure its efficacy in a broader population, thereby improving the accuracy and reliability of clinical decision-making. 

