What is Embryo Glue, and do I need it for IVF?

What is Embryo Glue, and do I need it for IVF?

Ever since Rachel and I had IVF we have been thinking about what next, it’s likely that we will need to have a private cycle, so I have been researching many of the addons and realised most of the information is from clinics themselves which don’t offer an unbiased review of them. Here is a distilled version of all that we have learned.

Embryo glue contains a fairly high concentration of hyaluronan (hyaluronic acid), which is naturally occurring compound found within soft tissues including the endometrium. Some studies have found that hyaluronan increases soft tissue ‘stickiness’. An embryo is prepared in this embryo glue before transfer with the intention of giving a greater chance of implantation.

The Science bit

This bit might get a little bit technical, but we will try to keep it as reader friendly as possible. Understanding the chemistry doesn’t prevent you from making a more informed decision. Hyaluronan or hyaluronic acid (HA) is the ingredient in embryo glue which reportedly improves the chances of implantation.

Hyaluronan isn’t the same as hyaluronic acid, although in everyday language they are often used interchangeably. The reason for this is that the polysaccharide (a combination of smaller molecules) synthesised in the cells is a salt rather than an acid. Specifically, it is a polymer (a large combination) of disaccharides (double sugar molecules). The polymer can have up to 25,000 disaccharides making it a very large molecule. HA is used in cosmetics and is approved in the US for treatment of osteoarthritis of the knee via direct injection.

 

Does Embryo Glue help with implantation and IVF overall?

As a note the HFEA (Human Fertilisation Embryo Authority) still have this treatment rated as amber. They believe that there is some evidence to support the treatment, but it is currently not strong enough to make it as part of evidence-based practice. So let’s take a look at some of the research. This treatment took a major blow in 2012  “Embryo glue” does not seem to improve chances of subsequent pregnancy in refractory in vitro fertilization cases with the conclusion stating:

“Embryo glue does not improve pregnancy outcome in women failing in previous IVF cycles.”

However in 2017 the research Adherence compounds in embryo transfer media for assisted reproductive technologies (a Cochrane review which are generally the gold standard in healthcare) which looked at a number of studies found 2 key points of note. An increase of live births of 450 vs 367 per 1000 through use of embryo glue however, on a negative it found that the chance of riskier multiples was also increased 282 vs 175 per 1000. Now in its study it stated that not all of the analysis showed improvement of HA containing outcomes which means that some studies didn’t show an increase in live birth rates, but over the whole meta data that it was identified that there was a significant (10%) increase in chance of birth rates. It also states that the makeup of the studies was 1 high quality and the others were of moderate quality data and that further research is needed. The video to the right is it being discussed – A disclaimer, the company presenting make embryo glues, however what they are saying about the study was found so it still has some merit.

In theory the embryo glue helps with 3 stages of implantation.

  1. Contact – it’s high viscosity (thick, sticky fluid texture), should allow for easy mixing with the intrauterine fluids which should minimise unnecessary movement
  2. Adhesion – CD44 is an antigen specifically important in cell adhesion and migration. It is expressed by the embryo; the endometrial cell walls have a receptor for CD44 which is Hyaluronan. Imagine CD44 is a key and that the receptor is the lock so the two fit together. The embryo glue has more of these receptors, so in theory means that the two are more likely to bind.
  3. Implantation – It is supposed to help with the cohesion between the embryo and the endometrial cells allowing for the invasive part of implantation to start.

So, where does this lead you. Having read both papers, I am currently airing on the side of caution but have some hope that embryo glue is a treatment option which may show some benefit for those going through IVF treatment. There is currently a major trial going on through the University of Oxford on the effectiveness of embryo glue and soon as the results are released, I will be sure to update the article.

How is Embryo Glue used in IVF?

Embryo glues are products which are used at the embryo transfer stage of IVF. The day before transfer the well dishes (those that contain the embryo before transfer) are prepared. Approximately 1ml will be added to the well and 1-2ml added to the moat of the dish, this is then left to pre-equilibrate (means to bring it to the same temperature) at about 37centigrade for 4-18 hours.

On the day of transfer the embryos are placed within the embryo glue in the well and left for a minimum of 10 minutes and a maximum of 4 hours at 37 centigrade. This is to ensure the embryo is well coated around the zona with embryo glue. The transfer syringe then draws up and out the embryo glue from the moat until no trapped air bubbles are observed.

 

The catheter is then attached to the syringe and some of the embryo glue is expelled. Under a microscope the embryo is gently and carefully drawn into the transfer catheter.

This like other normal embryo transfers is inserted through the cervical canal into the uterine cavity where all the fluid is transferred in the uterus. Carefully remove the catheter and the embryologist will ensure the embryo has been transferred under the microscope.

Are there any specific risks associated with embryo glue?

At this current point in time the only identified potential risk is the increased risk of multiple pregnancies, which hasn’t had any additional specific research performed so can’t be guaranteed. At this present time there are no other specific risks identified, however, again just keep in the back of your mind no major studies have been performed about this use of Hyaluronan although it has been used medically for a few years.

Should I pay for the Embryo glue add-on?

I am personally very upset with the regulation and situations couples find themselves in the UK. With the IVF postcode lottery and long waiting times often couples are forced to private clinics. Which ultimately are businesses, often their treatment options read like a ‘how much do you REALLY want a child menu’ you might find in some perverted restaurant!

However, with most clinics offering embryo glue as a relatively low cost (in fertility treatment terms), often around £120 – £180, I think it is not a bad choice on the menu. With current evidence leaning slightly towards it has positive impacts for a very minimal risk increase; the 2014 study showing improvements of possibly up to 10% improved chance (I personally think this will be significantly lower as more research is generated) it is worth the additional cost, even if it is just for peace of mind. But ultimately the choice is yours and I wish you the best of luck with and fertility treatment you may be having or had.

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