Efficacy and safety of perfluoropropane human albumin microspheres use in hysterosalpingo-contrast sonography for evaluating tubal patency: a prospective double-blind multicenter phase III study.

Background: Prospective clinical research on the use of ultrasound contrast agents for tubal patency assessment in hysterosalpingo-contrast sonography (HyCoSy) is limited. This study sought to evaluate the efficacy and safety of perfluoropropane human albumin microspheres as an ultrasound contrast agent for HyCoSy in assessing fallopian tube patency, using laparoscopy (LSC) as the gold standard. Methods: This prospective, double-blind, phase III study was conducted at 11 centers in China from April 2022 to April 2023 (ClinicalTrials.gov: CTR20220578). Infertile women aged between 18 and 45 years, who were scheduled for tubal patency testing, were eligible to participate in the study. The HyCoSy examination was performed by an experienced sonographer, and the image analysis was conducted by two experienced sonographers. Subsequently, within one menstrual cycle, LSC was performed by gynecologists who were blinded to the HyCoSy results. The accuracy of HyCoSy was calculated using the LSC results as the gold standard. In addition, a binary logistic regression model was applied to analyze the clinical and ultrasound factors associated with false-positive and false-negative results. Safety assessments were conducted before HyCoSy, within one week after HyCoSy, and before discharge from hospital following LSC. Results: A total of 120 participants were enrolled in the study, of whom 112 completed both HyCoSy and LSC. Two participants who had previously undergone unilateral salpingectomy, and one participant whose fallopian tube evaluation result was recorded as "uncertain" on one side by HyCoSy, resulting in a total of 221 fallopian tubes included in the efficacy analysis. Compared to LSC, the overall accuracy of HyCoSy was 88.24% (195/221). The total false-positive rate and false-negative rate were 3.62% (8/221) and 8.14% (18/221), respectively. The false-positive group had a higher proportion of previous ectopic pregnancy and a higher proportion of ovaries adjacent to the uterus (P=0.03, P=0.01), while the false-negative group had a higher incidence of contrast intravasation (P=0.046). In the safety assessment, pain and contrast intravasation were common treatment-emergent adverse events. Conclusions: Perfluoropropane human albumin microspheres can be used to effectively evaluate tubal patency through HyCoSy, and their diagnostic accuracy is good compared to the gold standard, LSC. Additionally, this contrast agent was associated with fewer and milder adverse reactions, making it suitable for clinical application.