The BREACH Study: Hyaluronan-Enriched Transfer Medium Increases Live Birth Rates After Trophectoderm Biopsy of Euploid Blastocysts

Abstract Objective To evaluate whether hyaluronan-enriched transfer medium improves live birth rates in biopsied euploid blastocyst transfers and to examine the role of zona pellucida disruption in mediating this effect. Design Retrospective cohort study. Participants A total of 1,221 single frozen euploid blastocyst transfers performed between January 2011 and December 2024. Intervention Embryo transfer using hyaluronan-enriched transfer medium compared with standard zwitterionic-buffered transfer medium. All embryos underwent trophectoderm biopsy resulting in zona pellucida disruption. Main Outcome Measures Live birth rate. Secondary outcomes included biochemical pregnancy and clinical pregnancy rates. Results Hyaluronan-enriched transfer medium was associated with significantly higher live birth rates compared with standard medium (59.1% vs. 43.2%; absolute difference 15.9%, 95% confidence interval 10.3%–21.5%; relative risk 1.37, 95% confidence interval 1.22–1.54; P < 0.001). Clinical pregnancy and biochemical pregnancy rates were also significantly higher in the hyaluronan group (P < 0.001 for both comparisons). Sensitivity analysis restricted to first transfers per patient (n = 715) confirmed persistence of the live birth benefit (61.2% vs. 47.1%; absolute difference 14.1%, 95% confidence interval 6.9%–21.3%; relative risk 1.30, 95% confidence interval 1.13–1.49; P < 0.001). Maternal age was comparable between groups. Conclusion Use of hyaluronan-enriched transfer medium is associated with a clinically meaningful increase in live birth rates in biopsied euploid blastocyst transfers. Zona pellucida disruption created during trophectoderm biopsy may facilitate enhanced embryo-endometrial interaction, improving implantation efficiency.