Effectiveness of clinical touch, 2D, 3D, and 4D ultrasound guided embryo transfer: a systematic review and network meta-analysis of embryo transfer techniques

Objective: With the use of two-dimensional ultrasound (2D US) in embryo transfer (ET) procedures now a widely accepted practice, and preferred over clinical touch (CT), there is growing interest in whether three-dimensional (3D) and four-dimensional (4D) US provide better outcomes for ET compared with traditional 2D methods. We aim to perform a network meta-analysis (NMA) to compare the clinical efficacy and safety of CT, 2D transabdominal (TAUS), 2D transvaginal (TVUS), 3D, and 4D US-guided ET. Evidence Review: Randomized controlled trials (RCTs) indexed in PubMed, MEDLINE, EMBASE, clinical trial registries, and Cochrane Database of Systematic Reviews were searched from inception to December 2023. Identified RCTs were assessed for trustworthiness using the Trustworthiness in RAndomized Controlled Trials. Statistical analysis for pairwise was performed using Review Manager version 5.3 and NMAs were performed using STATA version 16. Random-effects modeling was used for data-pooling. Key outcomes included clinical pregnancy (CPRs) and live birth rates (LBRs), miscarriage rates, and ectopic pregnancy rates. Results: Twenty-five RCTs of high integrity assessing 8,884 ET outcomes comparing CT, 2D TAUS-, 2D TVUS-, 3D TAUS-, and 4D TVUS-guided ET were included. The NMA identified lower LBR with CT (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.59- 1.03) compared with 2D TAUS. There were no significant differences in LBR between other methods, including 2D TVUS vs. 2D TAUS (RR: 1.03, 95% CI: 0.61-1.74), and 3D TAUS vs. 2D TAUS (RR: 1.01, 95% CI: 0.78-1.32). Clinical touch-guided ET was associated with a lower CPR compared with 2D TAUS (RR: 0.83, 95% CI: 0.75-0.91). There was no significant CPR difference comparing 2D TVUS vs. 2D (RR: 0.98, 95% CI: 0.83-1.16), 3D TAUS vs. 2D TAUS (RR 0.98, 95% CI: 0.80-1.20). Four-dimensional TVUS did not show a significant difference in either LBR or CPR compared with 2D TAUS, 3D TAUS, or CT. Conclusion: For CPR, our study reinforces that ET guided by CT alone is inferior to 2D TAUS-guided transfer. However, when comparing 2D TAUS-, 2D TVUS-, 3D TAUS-, and 4D TVUS-guided ET, we found no evidence of significant differences in LBR, CPR, miscarriage rates, or ectopic pregnancy rates. The certainty of evidence for our primary outcome of CPR was rated as moderate, reflecting confidence in the results, but with notable concerns regarding study limitations and paucity of trials assessing the use of 3D and 4D US. (c) 2025 by American Society for Reproductive Medicine.