EmbryoGlue®

Proven to increase clinical pregnancy rate and live birth rate when used for embryo transfer1

Description Bicarbonate buffered medium containing hyaluronan and recombinant human albumin.

Purpose Medium for embryo transfer.

Application For use after pre-equilibration at +37ºC and 6 % CO2.

Storage Store dark at +2 to +8°C

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EmbryoGlue®

1 x 10 mL

EmbryoGlue®

5 x 1.5 mL

Disclaimer: Not for sale in US

EmbryoGlue for successful transfer

Embryo transfer is one of the most sensitive and critical procedures in IVF treatment. EmbryoGlue®, a hyaluronan-rich transfer medium, is designed to promote embryo implantation. Few interventions in embryo transfer have improved the success rate as significantly as EmbryoGlue according to the clinical evidence2. EmbryoGlue has been shown to promote successful implantation and increase the pregnancy and live birth rate without increasing the risk of adverse events1.

What is EmbryoGlue?

EmbryoGlue is a medium developed exclusively for embryo transfer and is the only existing transfer medium with a proven implantationenhancing effect1. EmbryoGlue has the basic composition of a rich blastocyst culture medium and contains recombinant albumin and a high concentration of hyaluronan. It can be used for transfer of all embryo developmental stages, including cleavage embryos, blastocysts after assisted hatching, biopsied embryos and cryopreservation. The use of EmbryoGlue for embryo transfer can increase the clinical pregnancy rate and live birth rate1.

How to optimise transfer

A meta-analysis from 2022 on transfer interventions showed that three methods stand out with positive outcomes in terms of clinical pregnancy rate and with significant clinical evidence for their effectiveness2.

  1. Hyaluronic acid-enriched media (EmbryoGlue)
  2. Ultrasound guidance
  3. Soft transfer catheter

Optimised implantation with EmbryoGlue® and ERA®

As a global leader in reproductive health and by combining Igenomix’s portfolio of reproductive genetic testing services with Vitrolife’s best-in-class IVF device portfolio, the Vitrolife Group supports clinics and patients across the fertility journey. We offer our customers and patients ground-breaking solutions to create the best conditions for an embryo to implant, with one single goal: to fulfil the dream of having a healthy baby.

Learn more about optimised implantation

The proven effectiveness of EmbryoGlue
- How successful is EmbryoGlue?

Since the market introduction of EmbryoGlue in 2003, multiple studies have been published regarding its effectiveness.
Three reviews on the effect of hyaluronan in transfer media have been published by the Cochrane Library in 2010, 2014, and 2020.

The Cochrane Review in 2020 on “Hyaluronic acid in embryo transfer media for assisted reproductive technologies” by Heymann et al. concludes:

"Moderate‐quality evidence shows improved clinical pregnancy and live birth rates with the addition of hyaluronic acid as an adherence compound in embryo transfer media in ART"

The miscarriage rate was reduced in some studies but did not reach statistical significance in the total data set. The review includes a total of 26 randomized, prospective, controlled trials including a total of 6704 patients undergoing IVF/ICSI treatment. The embryo transfers were performed in either a transfer medium containing no or a low concentration of hyaluronan or EmbryoGlue with a high concentration of hyaluronan.

What is the clinical outcome of using EmbryoGlue?

The live birth rate increased from 33.3% to 40.2% with the use of EmbryoGlue. According to a number needed to treat (NNT) calculation, based on the Cochrane Review, one additional live birth was achieved for every 14 transfers. For a clinic with 700 cycles annually, this is one additional baby born per week, or a 20% increase in live births1.

 

 

The number needed to treat varies between patient groups, and the strongest benefit is seen in women ≥35 years of age and women with Previous Implantation Failures (PIF)3.

EmbryoGlue – Summaries of selected studies

The effectiveness of EmbryoGlue has been proven in many clinical studies, performed 2002-2022. In this document we have gathered and summarised the strongest clinical evidence of EmbryoGlue which demonstrate its effect and safety.

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How does EmbryoGlue work?

EmbryoGlue is a transfer medium containing a high concentration of an implantationpromoting macromolecule, hyaluronan.

Hylauronan is the main glycosaminoglycan present in follicular, oviductal, and uterine fluids and can significantly contribute to the high-viscosity environment of the female reproductive tract4,5,6,7.

The synthesis of hyaluronan increases dramatically on the day upon which implantation is initiated, and it decreases to near basal levels by the next day, indicating its importance for the implantation event. Other types of glycosaminoglycans do not show elevated synthesis at the time of implantation8,9.

Possible mechanisms for the implantation-
promoting effect of hyaluronan

Improved adhesion

Hyaluronan is known to increase cell adhesion, and thus it can support the initial attachment of the blastocyst to the endometrium10.

Rapid mixing with uterine secretions

Hyaluronan facilitates the rapid diffusion of the contents of the transfer medium into the viscous secretion of the uterus. An aqueous medium containing an appropriate concentration of hyaluronan produces a medium with a far higher viscosity in comparison to a solution only containing proteins. EmbryoGlue has the highest viscosity compared to other common transfer media11,12.

Receptor cross-linking

The hyaluronan surface-adhesion receptor CD44 is present throughout development from the oocyte to the blastocyst stage12. The CD44 receptor is also expressed on human endometrial cells at the time of implantation13,14. Another type of hyaluronan receptor, RHAMM/IHABP, is also expressed on the embryo surface at the implantation stage, suggesting a possible receptor-mediated process where hyaluronan cross-links the receptors on the embryo and endometrial cells15.

The inclusion of hyaluronan is not only associated with increased embryo development and viability, and there is also a distinct benefit of having hyaluronan in the transfer medium. From every perspective, the inclusion of hyaluronan in both culture and transfer media makes physiological sense, and the data clearly support multiple benefits to the embryo.

Professor David Gardner, Distinguished Professor, School of BioSciences, University of Melbourne and Scientific Director, Melbourne IVF and the inventor of EmbryoGlue

EmbryoGlue is as safe as standard of care

When using an implantation-promoting medium, one may be concerned that embryos without the potential to become a healthy baby may implant; however, no increase in adverse events, such as early or late miscarriage, has been shown1,17,18. Due to the increase in implantation with EmbryoGlue, it is recommended to be used with a single embryo transfer policy1,17.

Increased live birth rate in all development stages

In 2011 Balaban et al. performed a follow up study on pregnancies obtained by Urman et al. (2008), with the use of EmbryoGlue. The study included almost 1300 embryo transfers.

The results showed a significantly increased delivery rate with the use of EmbryoGlue independent of day of transfer3,19.

Outcomes of PCOS patients after fresh SET in EmbryoGlue

According to Kandari et al. (2019), the use of EmbryoGlue for time-lapse SET in women with PCOS significantly increases the implantation rate and live birth rate with lower miscarriage rates compared with conventional embryo transfer medium18.

No increase in pregnancy loss

Adeniyi et al. (2021) investigated a total of 3391 fresh embryo transfers in a study between 2011 and 2015 using three different protocols – low hyaluronic acid (G-2 PLUS), short (10-30 min) EmbryoGlue exposure, and long (2-4h) EmbryoGlue exposure. The purpose of the study was to assess the safety and efficacy of implementing EmbryoGlue as a transfer medium. The results showed no increase in pregnancy loss or miscarriage and an overall improvement in live birth events17.

PGT patients and EmbryoGlue - a perfect match

PGT (Preimplantation genetic testing) treatment requires a lot of time, effort, and resources in your clinic. The increased complexity is estimated to add six hours of working time for every cycle that includes genetic testing, which is the reason why you want to give your embryos the best chance of implantation.

Data indicates that PGT embryos benefits from being transferred in EmbryoGlue. A retrospective study showed the clinical outcomes from 830 transferred embryos (557 in the control group with no hyaluronan added and 273 transferred with EmbryoGlue). The data showed an increase in both implantation rate and clinical pregnancy rate20.

Patient groups offered
PGT21,22

  • Older patients >35
  • Patients with previous implantation failure
  • Blastocyst transfer
  • Patients with recurrent miscarriage

Patients groups benefiting most from EmbryoGlue3,23,24

  • Older patients >35
  • Patients with previous implantation failure
  • Blastocyst transfer
  • Transfer of cryopreserved embryos/ blastocysts

The reintroduction of EmbryoGlue as the embryo transfer medium unexpectedly coincided with statistically significant improvements in clinical outcome metrics – chemical, clinical, and ongoing pregnancy - specifically for frozen embryo transfers in PGT cycles. Using EmbryoGlue as the transfer medium instead of buffered media proved to be simple, cost-effective, and clinically efficacious.

Dr Mike Reed, Laboratory Director at the Fertility Center of New Mexico, USA

EmbryoGlue is easy to use

It is important to pay attention to the lab and transfer workflow in the clinic when using EmbryoGlue. Being a well-studied transfer medium, EmbryoGlue has more data on transfer optimisation than other products17,25. For transfer protocols, the preparation of dishes, embryo equilibration time, and catheter loading are important factors that can affect the results.

3 things to remember

Follow the instructions for use to ensure stable osmolality, pH and temperature. Below are three important lab procedural steps to follow. Please contact your Vitrolife representative for clincal support.

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Dish volumes

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Embryo equilibration

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Catheter loading

EmbryoGlue - Tips & Tricks

This guide highlights practical tips and tricks when using EmbryoGlue for a successful embryo transfer.

Download now

The benefit of extended exposure to EmbryoGlue when transferring cryopreserved blastocysts

New data supporting treatment benefits with EmbryoGlue is being presented at ASRM. The study is looking at the benefit of extended exposure to EmbryoGlue when transferring cryopreserved blastocysts. Listen to Dr. Oscar Perez, lab director of Dallas Fertility Center, explaining the research and result.

New study evaluating the benefit of EmbryoGlue in PCOS patients

A study by Sayali Kandari, MS PhD, Cellsure Biotech And Research Centre, Mumbai, India, has evaluated the benefit of EmbryoGlue in PCOS patients. The use of EmbryoGlue for time-lapse selected sET in PCOS shows significant increase in implantation and live birth rates with lower miscarriage rates compared with conventional embryo transfer medium.

EmbryoGlue improves the chance of having a baby

See this movie where Laboratory Director Basak Balaban from American Hospital of Istanbul in Turkey explains how using EmbryoGlue for transfer can increase the chance to have a baby.

References

1. Heymann et al. (2020) Cochrane Database of Systematic Reviews 9.
2. Tyler et al. (2022) Hum Reprod Update 28.
3. Urman et al. (2008) Fertil Steril (90):3.
4. Lee and Ax. (1984). J Dairy Science 67.
5. Suchanek et al. (1994). Fertil Steril 62.
6. Rodiguez-Martinez et al. (1998). In Gametes: Development and Function, Serono symposia.
7. Kano et al (1998). Biol of Reprod 58.
8. Carson et al. (1987). Dev Biol 120.
9. Zorn et al.( 1995). Cell Mol Biol 41.
10. Turley and Moore. (1984). Biochem Biophys Res Commun 121.
11. Reed and Said (2019) Reprod Biomed Online 39.
12. Stojkovic et al. (2002). Reprod 124.
13. Campbell et al. (1995). Hum Reprod 14 (Suppl 6).
14. Behzad et al. (1994). Biol Reprod 51.
15. Yaegashi et al. (1995). Hum Pathol 26.
16. Stojkovic et al. (2003). Biol Reprod 68.
17. Adeniyi T et al. (2021) Hum Rerpod Open 1.
18. Kandari S (2019) Fertil Steril 112.
19. Balaban et al. (2011). ESHRE oral presentation.
20. Reed (2022) Poster PCRS.
21. Survey about PGS. http://www.ivf-worldwide.com
22. Vitrolife global survey data on file (2016).
23. Hashimoto et al. PP-009. ALPHA 2014.
24. Friedler et al. (2007) Hum Reprod, Vol 22, Issue 9.
25. Perez (2019) Fertil Steril 112.

Support Documents

Documents Language

EmbryoGlue®

Package inserts

English

Package insert EmbryoGlue 10085 - Multi-language

Document and Ref: REF 20441, version 12

EmbryoGlue®

Package inserts

English

Package insert EmbryoGlue 10168 - Multi-language

Document and Ref: REF 28232, version 03

EmbryoGlue®

Short protocols

English

G-Series™ Embryo transfer - EmbryoGlue® 1x10 ml

Document and Ref: REF 19182. Version 03. Date of issue 221216 This short protocol describes how to perform embryo transfer using EmbryoGlue® 1x10 ml.

EmbryoGlue®

Short protocols

English

G-Series™ Embryo transfer - EmbryoGlue® 5x1.5 ml

Document and Ref: REF 19187. Version 3. Date of issue 220923. This short protocol describes how to perform embryo transfer using EmbryoGlue® 5x1.5 ml.

EmbryoGlue®

Safety data sheets (SDS)

English

SDS EmbryoGlue

Document and Ref: Date Revised : 06/01/2023. Revision No : 6. Safety data sheet for EmbryoGlue

EmbryoGlue®

Scientific summaries

English

EmbryoGlue improves pregnancy and implantation rates. Results from a meta-analysis on almost 10,000 embryo transfers

Document and Ref: A meta-analysis of Japanese studies, including almost 10,000 cycles shows that EmbryoGlue improves implantation resulting in increased pregnancy rates confirming findings from the Cochrane reports.

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