Background: Cesarean scar pregnancy (CSP) is one of the rarest ectopic pregnancies which may be associated with life-threatening complications. Owing to the rarity of CSP, little is known about it. This study aimed to evaluate the value of the first-trimester transvaginal sonography (TVS) diagnosis and the risk factors of CSP after in vitro fertilization-embryo transfer (IVF-ET)., Methods: This was a retrospective study of women undergoing IVF-ET between January 2013 and December 2018. Women who were diagnosed with a CSP using TVS and confirmed by surgery and histological examination were included. The clinical data and ultrasound findings were collected and analyzed. Univariate and multivariate logistic regression analyses were performed for evaluation of possible influence factors. Diagnostic parameters including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TVS were calculated for the diagnosis of CSP., Results: Overall, 75,438 consecutive women who underwent IVF-ET had received TVS during this period. Of these, 4,817 women (6.4%) had a history of cesarean section and 83 cases were found to have a CSP. Due to the absence of histological data, 19 cases treated conservatively were excluded. Finally, 64 cases were included, among whom 63 cases were correctly diagnosed [including 17 cases of heterotopic CSP (HCSP)] and 1 case was missed using TVS. Another 1 case of inevitable miscarriage was misdiagnosed as a CSP. The maternal age at the initial scan [34.0 (range, 26.0-44.0) years], the infertility duration [4.0 (range, 1-12) years], and the initial diagnostic time after ET [27 (range, 20-50) days] were recorded. A gestational sac (GS) was observed in all 63 cases during ultrasound examinations, including 28 with fetal pole, 25 with a yolk sac only, and 10 with an empty sac. The sensitivity and specificity of first-trimester TVS in diagnosing CSP were 98.44% and 99.98%, respectively; the PPV and NPV were 98.44% and 99.98%, respectively. Multivariate logistic regression analysis showed thinner endometrial thickness (ET) on transfer day [adjusted odds ratio (aOR): 0.83; 95% confidence interval (CI): 0.76-0.93, P<0.001] and multiple ET (aOR 53.60, 95% CI: 5.31-1,736.00, P=0.008) were independent risk factors for CSP and HCSP, respectively., Conclusions: First-trimester TVS performed by an experienced sonographer has a high sensitivity for making the correct diagnosis of CSP after IVF-ET, which is helpful for clinical intervention and avoiding severe complications. For patients with a history of cesarean section, thinner ET on the transfer day and bigger body mass index (BMI) seem to be risk factors for CSP; single blastocyst transfer should be recommended to decrease the possibility of HCSP. The clinical significance of this study still needs to be considered., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1239/coif). All authors report the funding from the Research Grant of CITIC-Xiangya (Nos. YNXM-202220 and YNXM-202310) and Hunan Provincial Grant for Innovative Province Construction (No. 2019SK4012). The authors have no other conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)