What is EmbryoGlue, and does a hyaluronan transfer medium raise pregnancy chances? ESHRE, Cochrane and HFEA assessments, multiple pregnancy risk.
EmbryoGlue is the commercial name of a transfer medium containing hyaluronan (hyaluronic acid) in which the embryo is held for a short time just before the transfer; in everyday speech it is also called "embryo glue". A current guideline in Europe classifies this addition in the "recommended" category; the same guideline reports an increase in multiple pregnancy and states that no benefit was found in studies in which only frozen transfer was done. The regulator in the United Kingdom, on the other hand, takes the view that effectiveness is not clear and that the evidence remains contradictory. The evidence assessments differ from one another; you can talk with your doctor about whether the practice is meaningful for you.
What is an embryo culture medium?
In the IVF laboratory your embryos are kept in a liquid culture medium during the days from fertilisation to transfer or freezing. These media are prepared by different manufacturers and their contents can vary. From your side this medium is an invisible detail; but some products, such as a transfer medium with added hyaluronan, may be recommended separately as an add-on practice.
What is a transfer medium containing hyaluronan?
Hyaluronan is a component added to the medium in which the embryo is held before the embryo transfer. A review looked in particular at media containing a high concentration of hyaluronan.
What changes in the transfer procedure?
What changes is the laboratory environment in which the embryo is held before the transfer. The product is applied to the embryo in the laboratory; it requires no separate procedure for you. The transfer procedure itself continues in its usual course.
For what purpose is hyaluronan thought to be used?
The product is thought to be able to help attachment by making the interaction between the embryo and the lining of the uterus easier. This is a biological assumption; it does not mean that the mechanism has been proven. Claims of benefit rest not on this mechanism but on studies looking at outcomes such as live birth. The name "glue" can therefore be misleading: the embryo being glued to the uterus is not a proven process.
What do studies show about live birth and pregnancy?
A review team brought together under one roof the controlled studies examining the method of enriching the transfer medium with hyaluronan. It was reported that live birth and clinical pregnancy were probably more common with high-concentration media, while the reliability of these results remained moderate. It was added that multiple pregnancy also probably increased. It was thought that there might be a small decrease in pregnancy loss, but the reliability of this finding is low; there is no clear result on adverse events. The results rest mainly on fresh transfer studies.
Why do the assessments of expert bodies differ?
In a current good practice guideline prepared for Europe, adding hyaluronan to the transfer medium is in the "recommended" class; that is, it is among the recommended add-on practices. The same guideline finds it appropriate that the multiple pregnancy rate continue to be monitored. A note is also seen pointing out that use should be considered together with a single embryo transfer policy. The word "recommended" does not mean that it must be applied to every patient or that it guarantees an outcome.
The regulator in the United Kingdom, on the other hand, classifies this medium as amber for most patients: whether it is effective is not clear, and the findings of medium- and high-quality studies do not agree with each other. These different classifications appear to arise from the same evidence being interpreted within different frameworks.
Can the same benefit be expected in fresh and frozen transfer?
The assessment texts on this subject report that no benefit was seen in studies in which only frozen-thawed embryo transfer was done. For this reason the favourable findings in fresh transfer studies cannot automatically be applied to frozen transfer.
Why is the evidence debated?
The hyaluronan concentrations used in the studies and the numbers of embryos transferred differ from one another. The assessment text on this subject states that the benefit was seen in transfers both at the cleavage stage and at the blastocyst stage; however, the reliability of this evidence is moderate. Because many factors, such as your age and the number and quality of the embryos, also affect success, it is hard to tell to what extent a single product changes the outcome.
Why should the risk of multiple pregnancy be discussed separately?
It is written in both the review and the current guideline text that the multiple pregnancy rate has increased. The review summary states that this increase may have arisen together with the transfer of more than one embryo; it adds that it needs to be tested separately in single embryo transfer studies. In multiple pregnancy, problems such as preterm birth can also be seen more often.
Is there a known additional risk for the embryo and the baby to be born?
The regulator in the United Kingdom states that there is no known additional risk for the patient or the child to be born. This is not an assurance carrying certainty for every individual.
How can you assess the product's cost and its possible benefit?
Some centres may ask for an extra charge for this product; you should ask the centre about the amount and scope. You can talk openly with your doctor about whether you will pay for a product whose benefit is debated. After an unsuccessful cycle, the thought "if I do not use it, my chance will fall" is a common anxiety; in such periods getting psychological support is also an option.
For whom is it considered?
The assessment text on this subject reports that the benefit was seen in both good- and poor-prognosis groups of patients; for this reason it is hard to reach a separate conclusion for particular groups such as age or previous failure. Whether the practice is used routinely or in selected situations may vary with the centre's approach. You can ask your doctor about the reasoning for the recommendation and its relationship with your fresh or frozen transfer plan.
What can you ask your doctor about the transfer medium?
- Why is the addition of hyaluronan to the transfer medium in my plan?
- Will my transfer be fresh or frozen, and does this change the meaning of the product?
- How many embryos will be transferred, and how is the possibility of multiple pregnancy taken into account in this decision?
- Is there a separate fee for this product?
- In what words does the product appear in the consent text?
Frequently Asked Questions
What is a culture medium with added growth factor for?
The current assessment on this subject states that an embryo culture medium with added growth factor is not recommended. The reasons given are that a meta-analysis found no difference in live birth and miscarriage, and that evidence is insufficient for both effectiveness and safety.
Which is more suitable, a single-step or a sequential culture medium?
In systematic reviews comparing these two types of medium in blastocyst culture, there is not enough evidence to say that one is superior to the other. One review reported a difference in blastocyst formation with the single-step medium, but no difference was seen in the formation of high-quality blastocysts, and the quality of the evidence was found to be very low. Another review found no difference in clinical pregnancy, ongoing pregnancy and miscarriage.
What is the effect in donor egg cycles?
The assessment text on this subject reports that in a study done in donor egg cycles the effect was small and the reliability of this evidence remained low. For this reason no clear benefit can be spoken of for donor egg cycles.
Is it worth paying an extra fee?
For those who fund their treatment themselves, repeating the standard cycle can also be considered as an alternative to an add-on whose evidence is not settled.
Does "embryo glue" mean the embryo is glued to the uterus?
No. This name can be misleading. The idea that it may make the interaction easier is a biological assumption; the embryo being glued to the uterus is not a proven mechanism.
If a medium containing hyaluronan is used, is an additional procedure done on me?
No. What changes is the laboratory environment in which the embryo is held before the transfer. The product is applied to the embryo in the laboratory; the transfer continues in its usual course.
Does the "recommended" classification show that it must be applied to everyone?
No. Although it is among the recommended add-on practices in the European guideline, this classification does not mean that it must be applied to every patient or that the outcome is assured.
Are the assessments of the bodies the same?
No. While the European guideline assesses the addition of hyaluronan in the recommended class, the regulator in the United Kingdom states that effectiveness is not clear and that the evidence remains contradictory.
Are the favourable results in fresh transfer also valid for frozen transfer?
They cannot automatically be regarded as valid. No benefit was seen in studies in which only frozen-thawed transfer was done. The favourable review results rest mainly on fresh transfer studies.
Should the risk of multiple pregnancy also be discussed?
Yes. An increase in multiple pregnancy is reported in the review and the guideline. The effect of transferring more than one embryo should also be taken into account; it is stated that it should be assessed separately in single embryo transfer studies.
Is the absence of a known additional risk an assurance for everyone?
No. The regulator states that there is no known additional risk for the patient or the child to be born; this does not mean a definite assurance for every individual.
Does my age or my previous failure show that I will particularly benefit from this medium?
It is hard to reach a separate and definite conclusion for these groups. You can ask your doctor about the reasoning for the recommendation and its relationship with your fresh or frozen transfer plan.
Get Your Free Consultation
Fill out the form below and our team will contact you
