JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):6
Oral Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263520

O-06. Impact of Hyaluronic Acid on Clinical Outcomes in Single Frozen Blastocyst Transfers: A Prospective Observational Study

Mariana Nicolielo¹, Renata Fabiane Erberelli¹, Ana Luisa Menezes Campos², Matheus Teixeira Roque¹, Claudia Gomes¹, Thais Sanches Domingues¹, Michele Panzan¹, Eduardo Leme Alves Motta¹, João Pedro Junqueira Caetano², Dóris Spinosa Chéles¹, Mauricio Barbour Chehin¹, José Roberto Alegretti¹, Aline Rodrigues Lorenzon¹

¹ Huntington Medicina Reprodutiva - Eugin Group - São Paulo - SP - Brasil
² Huntington Pró-Criar Medicina Reprodutiva - Eugin Group - Belo Horizonte - MG - Brasil

Objective: The use of transfer media supplemented with hyaluronic acid or hyaluronan (commercially known as Embryo Glue®, Vitrolife) has recently gained renewed attention following the publication of the European Society of Human Reproduction and Embryology (ESHRE) guidelines on the use of “add-ons” in assisted reproduction. In these guidelines, a potential benefit was reported, but the evidence was limited to fresh embryo transfer cycles. Whether similar benefits extend to frozen embryo transfers remains uncertain. This study aimed to evaluate whether the use of Embryo Glue^® in frozen single embryo transfer (SET) cycles is associated with improved clinical pregnancy rates and to assess its impact on other reproductive outcomes.
Methods: We conducted a prospective, multicentric observational study between March and early July 2025 in two ART centers in Brazil. All frozen-thawed blastocyst SET performed during this period were included. Patients were allocated to either the Embryo Glue^® group (EG) or the standard transfer medium group (Control) according to routine clinical practice and patient choice. A total of 361 SET cycles were analyzed: 117 in the EG group and 244 in the Control group. Baseline and cycle characteristics assessed included female age, body mass index (BMI), proportion of autologous vs. donor oocyte cycles, use of preimplantation genetic testing for aneuploidy (PGT-A), type of endometrial preparation (natural or hormone replacement), proportion of top-quality embryos transferred (Gardner’s A and B grades only), number of embryo transfer attempts (≤2 vs. ≥3), and day of blastocyst transfer (Day 5 vs. non-Day 5). Reproductive outcomes included positive pregnancy rate (PPR, positive serum β-hCG), clinical pregnancy rate (CPR, presence of a gestational sac with fetal heartbeat on ultrasound), biochemical pregnancy rate (BPR, positive serum β-hCG without ultrasound evidence of gestation) and miscarriage rate (MR, pregnancy loss after clinical confirmation). Comparisons between groups were performed using Fisher’s exact test for categorical variables and Mann–Whitney U test for continuous variables, with p<0.05 considered statistically significant.
Results: The EG and Control groups were comparable in age (mean±SD: 38.7±4.6 vs. 38.8±4.7 years, p=0.88), BMI (23.6±2.8 vs. 23.8±3.9 kg/m², p=0.59), proportion of autologous cycles (84.6% vs. 79.1%, p=0.25), PGT-A use (70.9% vs. 70.1%, p=0.90), endometrial preparation type (hormonal replacement therapy 90.6% vs 86.9%, p=0.39), number of embryo transfer attempts (1.6±1.0 vs 1.7±1.0, p=0.27), and day of transfer (Day 5: 70.9% vs 73.9%, p=0.61). The proportion of top-quality embryos was higher in Control group (93.4% vs. 82.1%, p=0.001). The overall PPR was 57.3% in the EG group and 58.2% in Control group (p=0.91). CPR was 47.0% in the EG group versus 46.7% in the Control group (p=0.90). BPRs were 7.7% and 8.6% (p=0.84), and MRs were 2.6% and 2.9% (p=0.99) for the EG group and Control group, respectively. No statistically significant differences in reproductive outcomes were observed in any subgroup analysis (autologous and oocyte donated cycles, euploid and non-biopsied embryos, number of transfer attempts, day of blastocyst transfer or high and low-quality embryo transfer).
Conclusion: In this prospective observational study of frozen-thawed single blastocyst transfers, the use of Embryo Glue^® at transfer was not associated with a statistically significant improvement in clinical pregnancy, biochemical pregnancy, or miscarriage rates compared to standard transfer medium. While Embryo Glue^® may be safe for clinical use, its routine application in this patient population may not confer a measurable advantage in reproductive outcomes. Randomized controlled trials with larger sample sizes and stratification by patient and embryo characteristics are warranted to further clarify potential benefits in specific subgroups.