EmbryoGlue in IVF: What the Evidence Shows and When It Is Not Needed
Key Takeaways
EmbryoGlue is a transfer medium with a high concentration of hyaluronan (hyaluronic acid); it does not glue the embryo in place. The 2020 Cochrane review found that it probably raises the live birth rate modestly, from about 33% to between 37% and 44%, but a 2026 meta-analysis found no clear benefit, and the estimate shrank further once weaker trials were set aside. In frozen embryo transfers, a randomised trial found no difference. ESHRE recommends it, noting a benefit only after fresh transfers and pairing it with single embryo transfer; the HFEA rates it amber.
Key evidence: Cochrane review: hyaluronic acid in embryo transfer media (2020) Randomised trial in frozen embryo transfer (Fertil Steril 2021) Meta-analysis of randomised trials (JBRA Assist Reprod 2026)
On this page
- EmbryoGlue in IVF
- What EmbryoGlue Is
- How It Is Thought to Work
- What the Evidence Shows
- Fresh and Frozen Transfers
- What ESHRE and the HFEA Say
- Safety and Twins
- What EmbryoGlue Cannot Do
- Frequently Asked Questions for Dr. Aksoy
- Sources
EmbryoGlue in IVF
EmbryoGlue is one of the better-known IVF add-ons, and the name does a lot of the selling. It is not a glue. It is a transfer medium with a high concentration of hyaluronic acid, in which the embryo is placed shortly before transfer.
Does it increase the chance of a baby? The honest answer: perhaps a little, in some cycles, and the evidence is less settled than the name suggests. The 2020 Cochrane review found a probable modest rise in the live birth rate.[1] A 2026 meta-analysis found no clear benefit, and the estimate shrank further once trials at high risk of bias were set aside.[3] A randomised trial in frozen transfers found no difference.[4]
Dr. Aksoy’s Approach: EmbryoGlue is neither a miracle cure nor a marketing gimmick.
I view high-concentration hyaluronan transfer media as a complementary option with a possible, modest benefit. Its use can be discussed individually in situations such as unexplained recurrent implantation failure or a complex transfer cycle.
It is not a proven requirement for a specific subgroup or a substitute for embryo quality.
What EmbryoGlue Is
EmbryoGlue is a transfer medium made by Vitrolife. The manufacturer describes it as a bicarbonate-buffered medium containing hyaluronan (also called hyaluronic acid) at 0.5 mg/mL and recombinant human albumin at 2.5 mg/mL.[9] It also contains the antibiotic gentamicin. The manufacturer states that it must not be used in anyone with a known allergy to any of its components.[11] If you are allergic to gentamicin, tell the team before transfer. In the trials, the comparison media contained less hyaluronan (0.125 mg/mL) or none.[1]
Hyaluronan occurs naturally in the body. In the endometrium, hyaluronan deposition has two peaks: one in the mid-proliferative phase (days 5 to 10) and one in the mid-secretory phase (days 19 to 23), around the time an embryo would implant.[6]
For you, nothing changes during the transfer itself. The embryo is placed in the medium in the laboratory beforehand, following the product instructions.
How It Is Thought to Work
Two explanations are usually proposed. Both are plausible. Neither has been proven in women.
- Viscosity. The medium is thicker than standard media, and it has been suggested that this helps keep the embryo from being expelled after transfer.[5]
- Receptor binding. A receptor called CD44, which binds hyaluronan, is present on human embryos throughout development before implantation.[7] The theory is that hyaluronan helps the embryo attach to the lining of the uterus. In a laboratory model, however, a hyaluronan-containing medium did not help human blastocysts attach to endometrial cells.[8]
The mechanism remains unproven, so clinical trials, not theory, have to answer the question.
What the Evidence Shows
The 2020 Cochrane review included 26 randomised trials with 6,704 women. It compared media with a high concentration of hyaluronan (0.5 mg/mL) with media containing little or none.[1] Only 10 of these trials, with 4,066 women, reported live birth.[1]
| Outcome | Trials (women) | Risk ratio, RR (95% confidence interval) | What it means | Certainty |
|---|---|---|---|---|
| Live birth | 10 (4,066) | RR 1.21 (1.10 to 1.31) | If 33% have a live birth without it, about 37% to 44% would with it | Moderate |
| Clinical pregnancy | 17 (5,247) | RR 1.16 (1.09 to 1.23) | Probably a small increase | Moderate |
| Miscarriage | 7 (3,091) | RR 0.82 (0.67 to 1.00) | Possibly fewer; no clear difference in trials at low risk of bias | Low |
| Multiple pregnancy | 7 (3,337) | RR 1.45 (1.24 to 1.70) | Probably more multiple pregnancies; this may relate to transferring more than one embryo | Moderate |
| Adverse events | 3 (1,487) | RR 0.86 (0.40 to 1.84) | Effect uncertain | Low |
A 2022 analysis by the same group found a benefit in cycles using the woman’s own eggs: the live birth rate rose from 32% to 39%, which means about 14 women would need to be treated for one additional live birth. That is an average across the trial populations, not a figure that applies to each patient. In donor-egg cycles, where only two small trials were available, there was little effect.[2]
Newer data are less encouraging. A 2026 meta-analysis of randomised trials, with searches up to December 2024, found an RR for live birth of 1.14 (95% CI 0.99 to 1.31). When trials at high risk of bias were removed, it fell to 1.06 (0.85 to 1.31). The authors rated the certainty of the evidence as very low and concluded that current evidence does not show a clear benefit.[3] The Cochrane review and the 2026 meta-analysis are likely to share many of the same older trials, so they are not independent confirmations of each other.
What this means in practice: if there is a benefit, it is modest, and it is not certain.
Fresh and Frozen Transfers
The distinction between fresh and frozen transfers is central to this debate.
Fresh transfers. ESHRE (2023) concludes that hyaluronan increases the live birth rate after fresh transfers.[5] That conclusion predates the 2026 meta-analysis, which found no clear overall benefit.[3]
Frozen transfers. Here the evidence does not support a benefit. A double-blind randomised trial in 550 women having a frozen embryo transfer compared EmbryoGlue with a standard medium. The live birth rate was 25.5% with EmbryoGlue and 25.8% without (RR 0.99; 95% CI 0.74 to 1.31).[4] ESHRE also notes that the three trials done only in frozen cycles, with 713 participants, showed no evidence of benefit.[5]
What ESHRE and the HFEA Say
The two main bodies read the same evidence a little differently.
- ESHRE add-ons (2023) recommends adding hyaluronan to transfer media and advises monitoring the multiple-pregnancy rate. It states that the benefit was seen after fresh transfers, that no effect was seen after frozen transfers, and that hyaluronan should be combined with a single embryo transfer policy.[5]
- ESHRE IVF laboratory (2026) repeats the same distinction: a benefit for live birth in fresh transfers and none shown in frozen transfers, although study results vary and multiple pregnancies are more frequent.[12]
- HFEA (2023), the UK fertility regulator, rates hyaluronan-enriched transfer medium (which it calls hyaluronate-enriched) amber for most fertility patients: on balance, it is not clear whether it improves the chance of having a baby, because moderate- to high-quality studies conflict. Its expert committee reviewed the evidence in July 2023.[10]
Safety and Twins
No clear additional risk to the woman or the baby has been shown. The HFEA states that the add-on carries no known additional risks.[10] The Cochrane review, however, rates the certainty of the adverse-event data as low and the effect as uncertain.[1]
The main signal is an increase in multiple pregnancies. The Cochrane review suggests this may come from combining hyaluronan with the transfer of more than one embryo.[1] For identical (monozygotic) twins after a single embryo transfer, there is no sign of an increase. In one retrospective study of 1,619 pregnancies after a single frozen transfer, hyaluronan medium was associated with fewer identical twins, although a study of this kind cannot prove cause.[13] Single embryo transfer remains the most reliable way to reduce the risk of twins, whatever medium is used.[5] Twin pregnancies carry higher risks for both mother and babies.
What EmbryoGlue Cannot Do
EmbryoGlue cannot:
- correct a chromosomal abnormality in the embryo
- replace embryo selection, whether by appearance or by genetic testing
- overcome a significant problem in the uterine cavity, such as a submucosal fibroid or adhesions
- guarantee implantation.
Related Reading
- Embryo Transfer in IVF: What Matters Most for Success
- Fresh vs Frozen Embryo Transfer: Which Fits Your IVF Cycle?
- Can You Have Twins With IVF? Risks and Safer Transfer Plans
- Endometrial Scratching Before IVF: Why It Is No Longer a Routine Add-On
Frequently Asked Questions for Dr. Aksoy
Who do you use EmbryoGlue for, and when do you consider it unnecessary?
First, I explain to the patient that EmbryoGlue is not a substance that sticks the embryo to the uterus. It is a special transfer medium with a higher hyaluronic acid content. Some studies have reported higher pregnancy and live-birth rates, but the results are not consistent. It can be discussed as an additional option, particularly for patients with repeated implantation failure, although even in this group its benefit has not been proven. For a patient having her first transfer, with a good-quality embryo and a suitable endometrium, I do not see it as necessary. I do not want a patient to feel she has lost an important chance of success because EmbryoGlue was not used.
Does EmbryoGlue help in a frozen embryo transfer?
In frozen embryo transfers, the evidence is weaker. In particular, a randomised trial of 550 women found no difference in live birth between those who had EmbryoGlue and those who had a standard transfer medium: 25.5% and 25.8%. So we cannot say that using EmbryoGlue in a frozen transfer increases success. For me, the quality of the embryo, the preparation of the endometrium, the timing of progesterone and the transfer technique matter much more.
Does EmbryoGlue have risks, and does it increase the chance of twins?
So far, studies have not shown a clear additional safety risk from EmbryoGlue for the mother or the baby. However, some studies found a higher multiple-pregnancy rate. This is thought to be linked mainly to transferring more than one embryo. It is not correct to say that EmbryoGlue by itself splits an embryo and creates twins. The most effective way to reduce the risk of twins is single embryo transfer for suitable patients. That is why I would never consider it right to transfer more embryos just because EmbryoGlue is being used.
Sources
- Heymann D, Vidal L, Or Y, Shoham Z. Hyaluronic acid in embryo transfer media for assisted reproductive technologies. Cochrane Database Syst Rev 2020;9:CD007421.
- Heymann D, Vidal L, Shoham Z, Kostova E, Showell M, Or Y. The effect of hyaluronic acid in embryo transfer media in donor oocyte cycles and autologous oocyte cycles: a systematic review and meta-analysis. Hum Reprod 2022;37(7):1451–1469.
- Rocha RM, Andrade MCR, Barcelos IDES, Viana IGR, Martins WP. Hyaluronic acid enriched medium for embryo transfer: a systematic review and meta-analysis. JBRA Assist Reprod 2026;30(2):382–395.
- Yung SSF, Lai SF, Lam MT, et al. Hyaluronic acid-enriched transfer medium for frozen embryo transfer: a randomized, double-blind, controlled trial. Fertil Steril 2021;116(4):1001–1009.
- ESHRE Add-ons working group; Lundin K, Bentzen JG, Bozdag G, et al. Good practice recommendations on add-ons in reproductive medicine. Hum Reprod 2023;38(11):2062–2104.
- Salamonsen LA, Shuster S, Stern R. Distribution of hyaluronan in human endometrium across the menstrual cycle. Implications for implantation and menstruation. Cell Tissue Res 2001;306(2):335–340.
- Campbell S, Swann HR, Aplin JD, et al. CD44 is expressed throughout pre-implantation human embryo development. Hum Reprod 1995;10(2):425–430.
- Ruane PT, Buck CJ, Babbington PA, et al. The effects of hyaluronate-containing medium on human embryo attachment to endometrial epithelial cells in vitro. Hum Reprod Open 2020;2020(2):hoz033.
- Vitrolife. EmbryoGlue: product information.
- Human Fertilisation and Embryology Authority. Hyaluronate enriched pre-transfer culture medium (e.g. EmbryoGlue). Rated amber; evidence reviewed July 2023.
- Vitrolife. EmbryoGlue: summary of safety and clinical performance (contraindications).
- ESHRE Good Practice in the IVF Lab Working Group; Arroyo G, et al. ESHRE recommendations on Good Practice in the IVF laboratory. Hum Reprod 2026;41(8):1245–1269.
- Kelly AG, Blakemore JK, McCaffrey C, Grifo JA. Evaluation of clinical parameters as predictors of monozygotic twins after single frozen embryo transfer. F S Rep 2021;2(4):428–432.
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The content has been created by Dr. Senai Aksoy and medically approved.