The “Glue” in Embryo Transfer

It is an appealing idea. It creates a wonderfully simple picture: a tiny embryo, placed inside the uterus in a slightly sticky medium, somehow held more securely against the endometrium until it implants.

EmbryoGlue — and other commercially available media designed to enhance implantation — is not actually a glue. Its key ingredient is hyaluronan, or hyaluronic acid, a molecule naturally present in the female reproductive tract and the endometrium. Because hyaluronan is involved in cell adhesion, it seemed reasonable to think that adding more of it to the transfer medium might help the embryo “stick” to the uterine lining.

But implantation is not that simple. The embryo does not simply land on the endometrium and stick. Implantation happens in stages: first the blastocyst makes loose contact with the endometrial surface, then attaches more firmly, and finally begins to invade the maternal tissue. And hyaluronan may play different roles at different stages.

Laboratory experiments suggest that it may help with the embryo’s first contact — its initial “docking” — but, surprisingly, removing hyaluronan from endometrial cells can actually make the next stage of attachment happen faster. That is already rather different from glue.

Even more interestingly, when researchers exposed human blastocysts to a hyaluronan-rich transfer medium and then studied how they attached to endometrial cells, the embryos did not attach better!

So, if hyaluronan-enriched transfer medium improves IVF outcomes, simply making the embryo “stick” to the uterus is unlikely to be the whole explanation.

Then why did we start using it?

Because for many years the clinical data looked quite promising.

A large Cochrane review published in 2020 concluded that embryo-transfer media containing a high concentration of hyaluronan probably increased live birth rates. Based on the studies available at the time, the estimated live birth rate increased from approximately 33% to around 37–44%. A subsequent analysis also suggested a benefit in IVF cycles using a woman’s own eggs.

In 2023, ESHRE therefore recommended the use of hyaluronic acid-enriched embryo-transfer medium, preferably together with a single-embryo-transfer policy.

But fortunately, science does not stop when a recommendation is written. More recent and methodologically stronger studies have made the picture much less certain. A 2026 systematic review found no statistically significant improvement in live birth. A large multicentre randomized trial of 865 women also found no significant difference: live birth rates were 51.5% with the high-hyaluronan medium and 47.7% with the comparison medium. For someone going through IVF, that difference may feel anything but small. Statistics, however, was not convinced — the difference was not statistically significant.

And another major evidence review published in 2026 — this time deliberately excluding randomized trials with concerns about their trustworthiness — again found no robust evidence that hyaluronan-enriched transfer medium increases the chance of live birth.

This does not mean that hyaluronan has no biological role in implantation. There is good evidence that it does. Nor does it rule out the possibility that some patients might benefit. But, as so many times before, we are reminded that a biologically plausible idea is not automatically an effective treatment.

It is reassuring that there is currently no convincing clinical evidence that exposing an embryo to a hyaluronan-enriched transfer medium causes harm to the embryo, the pregnancy, or the child. But we are still not sure whether adding more hyaluronan actually improves the chance of taking a healthy baby home.

And this is where I have to admit that my clinical intuition and the evidence are not entirely in the same place.

But, as far as I know, “doctor’s gut feeling” has yet to earn its place at any level of the evidence-based medicine hierarchy — if it ever does. :)