Embryo Glue: The Use of Hyaluronan in Embryo Transfer Media

Abstract

EmbryoGlue is available to patients at many in vitro fertilization clinics, usually at an additional cost. The efficacy of hyaluronan-enriched transfer medium (HETM) is supported by moderate quality evidence that indicates a significant improvement in clinical outcomes such as live birth rates for patients, including poorer prognosis women (i.e., maternal age factor [>35 years] and recurrent implantation failure). An increased multiple pregnancy rate has been reported with the use of HETM; therefore, a single embryo transfer policy should be considered in conjunction with the use of EmbryoGlue. There is no evidence to suggest that HETM has any detrimental impact, and therefore the use of HETM in clinics may be justified for a specific demographic of patients. Further robust evidence, in the form of meta-analyses or large-scale randomized controlled trials, is needed to build a sufficient consensus regarding the benefit of hyaluronan supplementation in embryo transfer media.

Keywords

EmbryoGlue - embryo transfer - hyaluronic acid - hyaluronan

Publication History

Article published online:
25 May 2021

• References

• 1 Fouladi-Nashta AA, Raheem KA, Marei WF, Ghafari F, Hartshorne GM. Regulation and roles of the hyaluronan system in mammalian reproduction. Reproduction 2017; 153 (02) R43-R58
• 2 Kothapalli D, Zhao L, Hawthorne EA. et al. Hyaluronan and CD44 antagonize mitogen-dependent cyclin D1 expression in mesenchymal cells. J Cell Biol 2007; 176 (04) 535-544
• 3 Toole BP. Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer 2004; 4 (07) 528-539
• 4 Stern R, Asari AA, Sugahara KN. Hyaluronan fragments: an information-rich system. Eur J Cell Biol 2006; 85 (08) 699-715
• 5 Afify AM, Craig S, Paulino AF. Temporal variation in the distribution of hyaluronic acid, CD44s, and CD44v6 in the human endometrium across the menstrual cycle. Appl Immunohistochem Mol Morphol 2006; 14 (03) 328-333
• 6 Salamonsen LA, Shuster S, Stern R. Distribution of hyaluronan in human endometrium across the menstrual cycle. Implications for implantation and menstruation. Cell Tissue Res 2001; 306 (02) 335-340
• 7 Saito H, Kaneko T, Takahashi T, Kawachiya S, Saito T, Hiroi M. Hyaluronan in follicular fluids and fertilization of oocytes. Fertil Steril 2000; 74 (06) 1148-1152
• 8 Gardner DK, Rodriegez-Martinez H, Lane M. Fetal development after transfer is increased by replacing protein with the glycosaminoglycan hyaluronan for mouse embryo culture and transfer. Hum Reprod 1999; 14 (10) 2575-2580
• 9 Stojkovic M, Kölle S, Peinl S. et al. Effects of high concentrations of hyaluronan in culture medium on development and survival rates of fresh and frozen-thawed bovine embryos produced in vitro. Reproduction 2002; 124 (01) 141-153
• 10 Schoolcraft W, Lane M, Stevens J, Gardner D. Increased hyaluronan concentration in the embryo transfer medium results in a significant increase in human embryo implantation rate. Fertil Steril 2002; 78: S5
• 11 Simon A, Safran A, Revel A. et al. Hyaluronic acid can successfully replace albumin as the sole macromolecule in a human embryo transfer medium. Fertil Steril 2003; 79 (06) 1434-1438
• 12 Babayan A, Neuer A, Dieterle S, Bongiovanni AM, Witkin SS. Hyaluronan in follicular fluid and embryo implantation following in vitro fertilization and embryo transfer. J Assist Reprod Genet 2008; 25 (9-10): 473-476
• 13 Zhu R, Wang SC, Sun C. et al. Hyaluronan-CD44 interaction promotes growth of decidual stromal cells in human first-trimester pregnancy. PLoS One 2013; 8 (09) e74812
• 14 Berneau S, Ruane P, Brison D, Kimber S, Westwood M, Aplin J. Investigating the role of CD44 and hyaluronate in embryo-epithelial interaction using an in vitro model. Mol Hum Reprod 2019; 25 (05) 265-273
• 15 Valojerdi MR, Karimian L, Yazdi PE, Gilani MA, Madani T, Baghestani AR. Efficacy of a human embryo transfer medium: a prospective, randomized clinical trial study. J Assist Reprod Genet 2006; 23 (05) 207-212
• 16 Menezo YJ, Guerin JF, Czyba JC. Improvement of human early embryo development in vitro by coculture on monolayers of Vero cells. Biol Reprod 1990; 42 (02) 301-306
• 17 Singh N, Gupta M, Kriplani A, Vanamail P. Role of Embryo Glue as a transfer medium in the outcome of fresh non-donor in-vitro fertilization cycles. J Hum Reprod Sci 2015; 8 (04) 214-217
• 18 Safari S, Razi MH, Safari S, Razi Y. Routine use of EmbryoGlue(®) as embryo transfer medium does not improve the ART outcomes. Arch Gynecol Obstet 2015; 291 (02) 433-437
• 19 Urman B, Yakin K, Ata B, Isiklar A, Balaban B. Effect of hyaluronan-enriched transfer medium on implantation and pregnancy rates after day 3 and day 5 embryo transfers: a prospective randomized study. Fertil Steril 2008; 90 (03) 604-612
• 20 Fu W, Yu M, Zhang XJ. Effect of hyaluronic acid-enriched transfer medium on frozen-thawed embryo transfer outcomes. J Obstet Gynaecol Res 2018; 44 (04) 747-755
• 21 Thornton M, Ghaemi S, Keskintepe L. Does the utilization of embryo glue give promise in donor embryo fets?. Fertil Steril 2018; 109 (03) e32
• 22 Vitrolife.com. EmbryoGlue Short Protocols – Embryo Transfer. 2020 . Accessed December 3, 2020 at: https://www.vitrolife.com/globalassets/support-documents/short-protocols/short-protocols-g-series_embryo-transfer.pdf
• 23 Perez O, Adriaanse H, Tilley B. et al. The effect of extended blastocyst exposure of hyaluronan enriched transfer media on implantation rate in frozen embryo transfers. ASRM Abstracts 2019; 112 (03) E438
• 24 Heymann D, Vidal L, Or Y, Shoham Z. Hyaluronic acid in embryo transfer media for assisted reproductive technologies. (Review) Cochrane Database Syst Rev 2020; 9: CD007421
• 25 HFEA. Treatment add-ons. Hfea.gov.uk. Accessed March 21, 2019 Published at: https://www.hfea.gov.uk/media/2563/hfea-fertility-trends-and-figures-2017-v2.pdf 2019
• 26 Marei WFA, Raheem KA, Salavati M, Tremaine T, Khalid M, Fouladi-Nashta AA. Hyaluronan and hyaluronidase, which is better for embryo development?. Theriogenology 2016; 86 (04) 940-948
• 27 Nishihara T, Morimoto Y. Evaluation of transfer media containing different concentrations of hyaluronan for human in vitro fertilization. Reprod Med Biol 2017; 16 (04) 349-353