Does Vaginal Delivery of Concentrated Oxygen and Hyaluronic Acid Improve the Implantation Rate in Human IVF: A Proof-of-Concept Study

Objective: To determine whether a high concentration of oxygen and hyaluronic acid applied vaginally in the two weeks preceding embryo transfer may increase implantation rates in human IVF. Design: Retrospective, observational, non-randomized proof-of-concept study. CaressFlow treatment consisted of three 15 min vaginal sessions administered during the two weeks preceding embryo transfer, using oxygen at 93% ± 3%, a pressure of 1 ± 0.1 bar, a flow rate of 2 ± 0.2 L/min, and 0.2% sodium hyaluronate. Subjects: A total of 377 women with infertility and/or previous IVF failure undergoing single frozen–thawed blastocyst transfer were included. Of these, 161 received CaressFlow treatment and 216 served as untreated controls. Main Outcome Measures: Implantation rates after homologous and heterologous frozen blastocyst transfer. Results: Overall, implantation occurred in 94 of 161 treated patients (58.4%) compared with 92 of 216 controls (42.6%), corresponding to significantly higher odds of implantation in the CaressFlow group (OR 1.89, 95% CI 1.25–2.86; p = 0.0024). In the homologous subgroup, implantation occurred in 60 of 111 treated patients (54.1%) and 64 of 147 controls (43.5%); this difference was not statistically significant (OR 1.53, 95% CI 0.93–2.50; p = 0.0941). In the heterologous subgroup, implantation occurred in 34 of 50 treated patients (68.0%) compared with 28 of 67 controls (41.8%), corresponding to significantly higher odds of implantation following CaressFlow treatment (OR 2.96, 95% CI 1.37–6.38; p = 0.0050). Conclusions: In this retrospective proof-of-concept study, vaginal pretreatment with high-concentration oxygen and hyaluronic acid was associated with higher implantation rates following single frozen–thawed blastocyst transfer. The association was most pronounced in patients undergoing heterologous embryo transfer. Prospective randomized studies are required to confirm these findings and to clarify the underlying mechanisms.