Role of Embryo Glue as a transfer medium in IVF treatment
What is EmbryoGlue? When is it used in the process of treatment? Does it improve the chances of implantation? Are there any risks? What about the evidence the EmbryoGlue?
Watch and listen experts explaining all of it in 3on1 #IVFANSWERS:
- Dr Marcin Trzeciak, Obstetrician/ Gynaecologist at InviMed
- Dr Harry Karpouzis – Scientific Director and Founder of IVF Pelargos Fertility Group
- Dr Stavros Natsis – Obstetrician/ Gynaecologist, Fertility Expert – Gennima IVF
Answer from Dr Trzeciak
Assisted hatching is a conflicting issue in the field of IVF. It has been used for many years now. There is a lot of research behind it but no conclusive evidence that it can really help. Just to explain a bit about assisted hatching: an oocyte has a protein membrane around itself, called zona pellucida. After the fertilisation with the sperm, this goes harder and goes around the embryo. It happens so as not to allow more sperm to intrude the embryo. Another reason is to protect the embryo from implanting in the tubes, before reaching the uterine cavity, and giving an ectopic pregnancy. When the embryo moves from the cavity into the inside of the womb, the zona pellucida is thinner and this helps in the opposition attachment and invasion of the embryo to the lining of the womb.
Scientists observed that day 3 embryos, with a thinner zona pellucida, had better implantation rates. Besides, when a blastocyst had some natural holes around it, the implantation rates were better, too. That’s why they thought of perforating the membrane artificially and manipulating with it. This is called assisted hatching. It can
Hyaluronan-containing mediums, like EmbryoGlue, are quite commonly applied in IVF procedures. These are physiological solutions containing hyaluronan, which is normally secreted in large quantities by the endometrial cells during the preimplantation phase.
Scientific research shows that more hyaluronan increases the viscosity of secretions, which makes them more adhesive. Thus, it stabilises the interaction of the endometrium with the embryo, helping to implant the embryo into the endometrium.
EmbryoGlue therefore mimics the action of the uterine secretions from the pre-implantation period and makes endometrium more receptive to embryo implantation, helping to initiate the process.
In addition to enhanced viscosity, hyaluronan acts as a medium between embryo and endometrium at the beginning of the implantation process by binding itself to specific receptors, mainly CD44. These are present in both: the embryo trophoblast cells and endometrium.
The application of EmbryoGlue during embryo transfer increases the success rate of IVFtreatments. However, our findings show that significant differences are only observed when
EmbryoGlue is used in the embryo transfer at the blastocyst stage, i.e. on the 5th or 6th day of the development.
It is particularly advisable to use the medium in transfers of fresh and frozen blastocysts, if the previous transfers failed and the women is over 35 years of age be done in many ways. The best and the safest one is the laser.
Generally, in many studies it has been shown that assisted hatching can improve the clinical pregnancy rate. But in a large meta-analysis and Cochrane data, it has been shown that it doesn’t really change the live birth rate.
Given that, it would not be recommended for any IVF. Actually, there is some evidence that when we talk about a good quality embryo, it can make things worse rather than better. But there is some evidence for using it in repeated unexplained IVF failures in older women with poor quality embryos.
Answer from Dr Karpouzis
EmbryoGlue is not actually glue. EmbryoGlue is a culture material which includes hyaluronan. Hyaluronan is a substance that naturally exists in the endometrium and it has been proved that it helps in the attachment and invasion of the embryo inside it. The idea is to put embryos into this material before we transfer them inside the womb. In this way, we mimic the natural environment. According to some research, it has been shown that it increases the chances of implantation.
Is there any conclusive evidence behind it? Well, there is a research that shows a small increase in clinical pregnancy rates. Most of the research shows that it is not statistically significant. So definitely we need more randomised evidence behind it. It hasn’t been really associated with an increase in the live birth rate.
But we can use it in a specific group of patients. This means patients that had unexplained failures before, with normal womb lining thickness, good quality embryos and no other factors that could possibly affect the implantation. It is a cheap product that only slightly adds to the cost of IVF. It hasn’t been associated with any risks. But I wouldn’t be using it in all IVF cases.
Dr Stavros Natsis, GENNIMA IVF, Greece
Answer from Dr Natsis
EmbryoGlue is very new in IVF. At the moment, a lot of laboratories are looking into it. It is actually a medium that we use when we transfer the embryos. They stay there for some time. This medium usually contains high concentration of proteins. It is a protein called albumin. It has been shown in some studies that if an embryo develops in this fluid culture, it creates a very thick sticky matrix that can help it attach better to the lining of the womb. So actually it was a very clever idea.
Initially, we were very skeptical about how safe it could be for an embryo to stay in this medium before we transfer it into the uterus. The initial studies have shown that it is completely safe for the embryo, it doesn’t have any adverse effects on it. Now there is a lot of study going on whether it has some benefit or not.
Recently there was a study which, in medical terms, we call a Cochrane study. These are doctors who are gathering all the data from smaller studies related to this topic and trying to see whether this helps or not. In general, it has been shown that it has no benefit in the success rates.
But there is a very small group of patients that it actually has shown some benefit in. These patients are usually 42 years old and they had 2 IVF attempts with the implantation failure. They created good quality blastocysts that were not able to implant. In this patients, EmbryoGlue could have some benefit. For this reason, in our lab we are considering to start using this technology. Our lab director is trying to find appropriate funds so we can get this medium and start using it in a very well selected population of patients.
Unfortunately, this medium is a little bit expensive. It costs about 600 euros. You have to be very sure where to put it and whether you have a clear indication to put it. So we are looking into it. There could be a potential benefit for some people to use it. So the answer is: yes, we consider using it. However, only in a very well selected population group – not in all cases, as it hasn’t shown any clear benefit for all patients doing IVF.