Development and validation of a nomogram for predicting ectopic pregnancy in patients receiving double fresh cleavage stage embryo transfer

Ectopic pregnancy (EP) is a common yet fatal complication of in vitro fertilization-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI). We aim to establish and validate a nomogram in patients undergoing double fresh cleavage-stage embryo transfer, which remains a mainstream strategy in infertile patients. Data from 7456 patients were reviewed and divided into training and validation sets. Logistic analyses were conducted to identify the risk factors, with calibration and decision-curve analyses performed to evaluate model performance. The model divided patients into high- and low-risk groups, showing different 48-h serum beta-human chorionic gonadotropin (HCG) rising thresholds. It showed that Tubal factor infertility (Odds Ratio [OR] = 1.680, 95% Confidence Interval [CI] 1.129-2.500, P = 0.011), previous tubal surgery (OR = 2.667, 95% CI 1.772-4.015, P < 0.001), polycystic ovarian syndrome (PCOS) (OR = 1.809, 95% CI 1.169-2.799, P = 0.008), uterine malformation (OR = 5.663, 95% CI 1.524-21.043, P = 0.010), endometrial thickness (OR = 0.585, 95% CI 0.522-0.655, P < 0.001) and serum estradiol levels (OR = 1.000, 95% CI 1.000-1.000, P < 0.001) on triggering day were independent risk factors for EP after double fresh cleavage-stage embryo transfer. The area under curve (AUC) values for the training and validation sets were 0.768 (95% CI 0.732-0.805, P < 0.001) and 0.756 (95% CI 0.703-0.810, P < 0.001), respectively. The nomogram further divided all participants into high EP risk and low EP risk with a cut-off score of 86.1 based on the maximum value of Youden Index in order to investigate different subsequent interventions based on serum HCG level. Patients in high EP risk group suffered significantly higher incidence of EP (OR = 4.902, 95% CI 3.597-6.667, P < 0.001 and OR = 4.587, 95% CI 2.899-7.246, P < 0.001). Higher 48-h serum HCG rising thresholds (2.18 vs. 1.74 and 2.10 vs. 1.66) also applied to patients from high EP risk group. The nomogram effectively predicts individual EP probability in patients receiving double fresh cleavage-stage embryo transfer, thereby aiding screening high-risk patients.