Objective:
To determine whether a hyaluronan enriched transfer medium improves outcomes sufficiently to justify its cost compared with a low lactate embryo culture medium for transfer in frozen embryo transfer (FET).
Materials and Methods:
Retrospective multicenter cohort study of all FET cycles from two IVF centers. Transfers were performed using either a low lactate embryo culture medium supplemented with protein or a hyaluronan enriched transfer medium. Center 1 utilized low lactate medium in 2022–2023 and hyaluronan enriched medium in 2024–2025; Center 2 utilized low lactate medium in 2022–2024 and hyaluronan enriched medium in 2025. Primary outcomes were β-hCG positivity and implantation rate per transfer. Cost analysis was performed from a clinic perspective using actual media utilization and institutional pricing to derive cost per transfer and cost per implantation; all costs are reported in U.S. dollars (USD).
Comparisons between groups were performed using chi-square testing for proportions. Two-sided p-values were reported with statistical significance defined as p<0.05. Incremental cost-effectiveness ratios (ICERs) were calculated as the difference in cost between media divided by the difference in implantation rates, expressed as cost per additional implantation achieved.
Results:
Among 5,661 FETs, hyaluronan enriched medium did not improve implantation in either Center 1 (57.7% vs 56.3%, p=0.29) or Center 2 (62.6% vs 59.8%, p=0.64), despite a marginal increase in β-hCG in Center 1 only (64.1% vs 61.6%, p=0.047) and no difference in Center 2 (70.2% vs 68.6%, p=0.74). This occurred alongside a 13 to 16 times increase in cost per transfer ($2.90–$3.60 vs $46.10–$46.40) and more than 10 times higher cost per implantation (approximately $5.00–$6.00 vs $74.00–$80.00), yielding ICERs of approximately $1,250 (Center 1) and $1,360 (Center 2) per additional implantation without statistically significant improvement in implantation.
Conclusions:
Hyaluronan enriched transfer medium substantially increases cost without improving implantation in FET. A marginal increase β-hCG positivity rate in one center does not translate into meaningful clinical benefit. ICER analysis confirms poor cost-effectiveness.
Impact Statement:
These findings challenge the value of adhesion-based transfer strategies and support low lactate embryo culture medium for transfer as a high-value standard. Eliminating high-cost, low-yield interventions represents an immediate opportunity to improve the value of IVF care.