Embryo glue treatment

Last updated date: 17-Aug-2023

Originally Written in English

Embryo Glue Treatment

Embryo transfer is an integral part of an In Vitro Fertilization (IVF) cycle. The embryo goes toward the uterine wall or the endometrium after being transferred, interacts with it, and adheres to it for continued growth. Implantation is the name of this process. When the uterine environment is suitable, free of uterine abnormalities, and the uterine receptivity is supportive, a high-quality embryo will implant itself. Even under ideal uterine receptivity and embryo quality conditions, the embryo may occasionally fail to implant.

Researchers have discovered an embryo development medium termed the embryo glue for such instances of implantation failure. Hyaluronan medium with recombinant human albumin makes up the embryo glue. According to studies, the uterine layer produces hyaluronic acid or hyaluronan at the time of implantation, which helps the embryo and endometrium interact. A protein complex called hyaluronan is produced by the body and helps to lubricate and hydrate the tissues. Hyaluronan serves as a binding agent between the endometrium and the embryo.

The embryo glue method involves dipping the IVF/ICSI-produced embryos into a hyaluronan solution. As a result, the embryo is placed in an environment resembling the uterus, and the embryos coated with hyaluronan adhere to the uterine lining to continue developing.


What is Embryo Glue?

What is Embryo Glue?

There are several assisted reproductive technology (ART) extensions that support in-vitro fertilization that use more advanced technologies to increase treatment success rates during IVF-ET. The most crucial stage of ART is embryo transfer, in which the most capable embryo is implanted in the female uterus. Numerous innovative methods have been developed to increase the success rate of IVF treatments, including sperm selection procedures, time-lapse embryo monitoring, preimplantation genetic screening, assisted hatching endometrial injury, and embryo glue, which are adjuvants used in embryology to increase implantation and turn the ratio of fertilization. The IVF professional will use the techniques stated above in the best IVF facilities to address the rising infertility rate.

In IVF-ET cycles, embryo glue works as an adhesive culture medium that is substantially enriched in hyaluronan (hyaluronic acid), which is employed during embryo implantation and increases the likelihood of pregnancy. By enclosing media over the embryo and directing the embryo's bonding activity to the uterus with sticky properties that have a consistency similar to the mucosal membrane, these media help the embryo's adhesion to the mucous membrane in the uterus. The IVF specialist at the IVF clinic offers embryo transfer and embryo glue to assist couples to boost their chances of getting pregnant.

Although widely distributed throughout the human body, HA is particularly abundant in the female reproductive tract's oviduct and uterine fluid. It is a key component of the extracellular matrix necessary for the expansion of cumulus cells. It aids in the implantation process, encourages cell growth, and speeds up apposition and adhesion. Additionally, hyaluronan improves pregnancy and implantation in IVF treatment by increasing viscosity in the surroundings of the oviduct and uterus.


What is the Evidence for Embryo Glue?

Embryo Glue Evidence

The Human Fertilization and Embryology Authority (HFEA), an independent regulator of fertility treatment, has created a red-amber-green rating system and offers information on their website concerning treatments that are offered as add-ons to your regular reproductive treatment. They believe that conducting a randomized controlled trial (RCT) is the only method to be certain that treatment is efficient enough to be used frequently. In an RCT, patients are divided into two groups at random: a treatment group that receives the novel therapy and a control group that receives a tried-and-true therapy or a placebo (empty tablet or treatment).

The use of hyaluronan-enriched medium increases live birth rates, but there is only one high-quality study that supports this claim; other studies are only of moderate quality, and additional high-quality studies are required to support the efficacy of the treatment. For this reason, the HFEA has given EmbryoGlue an amber rating. EmbryoGlue has not been demonstrated to offer any benefits, according to CARE's own experience. Concerns regarding the safety of EmbryoGlue are not expressed by the HFEA. Researchers consider it essential that you are fully informed before deciding to use EmbryoGlue for treatment. Before making a choice, they also advise you to review the information on the HFEA website.


Ingredients of Embryo Glue

Ingredients of Embryo Glue

A rich blastocyst culture medium is used to make embryo glue. Hyaluronan and a significant amount of recombinant human albumin make up this substance. This mixture aids in the implantation of the embryo by warming and conditioning the female uterus for it. Our bodies naturally contain a chemical called hyaluronan. During the implantation of the embryo, its proportion increases. The embryo's internal movement is slowed down by this viscous fluid. It is jam-packed with carbohydrates that actively participate in the early phases of embryo implantation.

The substance's purpose is to shield the embryo from any injury that might result from the environment of the operating room or the instruments used in the procedure. The application of embryo glue has increased pregnancy success rates and is therefore a technique that embryologists and fertility specialists prefer. After the use of embryo glue during IVF, the overall success rate of pregnancies has been observed to increase. Patients over the age of 35 benefit the most from this since they experience unexplained infertility and failed implantation at higher rates than other age groups. By keeping the temperature and other necessary factors constant, this glue mimics the uterine environment during implantation. As a result, the embryos are implanted successfully and remain in their optimum health.


Embryo Glue Benefits

  • For people who experience recurrent implantation failure, embryo glue is helpful.
  • When a patient has an ectopic pregnancy, embryo glue helps to increase embryo implantation.
  • Embryo glue helps the embryo better appoint and connect to the uterine cavity for implantation.
  • HA-enriched mediums, such as embryo glue, are advantageous for older females.
  • Because embryo glue contains a lot of HA, it helps with physiological processes such as cell differentiation, proliferation, adhesion, migration, and development of the embryo during implantation.


Indications of Embryo Glue

Indications of Embryo Glue

One of the main indications of embryo glue is implant failure. The following are further indications of the hyaluronic glue technique:

  • Advanced maternal age.
  • Failure of the implant even during the most probable donor cycle.
  • Women who have fallopian tubes that are obstructed, damaged, or distorted.
  • Couples who have had implantation problems, particularly when the uterine environment and embryo quality were both favorable.
  • Patients who have experienced repeated implant failure.
  • Couples who have experienced two or more failed IVF cycles.
  • Women who have experienced implantation failure but who have healthy uterine lining and receptivity.
  • Unexplained infertile couples
  • Couples whose IVF attempts have failed but for which the cause is unknown.
  • Couples who have experienced implantation failure in the absence of uterine problems including uterine distortion, polyps, or fibroids.

These novel and recently developed technologies are employed in the well-equipped laboratories of many reproductive facilities. The embryos are grown by fertility specialists in a medium supplemented with hyaluronan. The receptors on the hyaluronan-coated embryos resemble those on the uterine lining. These embryos are securely implanted into the uterus.


Preparing for Embryo Transfer

An embryologist makes a dish with the medium in the center the day before an embryo transfer. The dish is then modified in an incubator for up to 18 hours. The embryologist transfers the embryo from the culture plate to the pre-equilibrated dish containing the medium the following day, between 10 and 30 minutes before the transfer. The embryo is injected into the catheter that will be utilized for the transfer using a syringe. The reproductive endocrinologist introduces the catheter through the cervix and implants the embryo, which is surrounded by the medium, into the uterus under the guidance of ultrasound and the patient's full bladder. The utilization of an embryo transfer medium holds great potential, but additional research is required.


How is Embryo Glue Used in Treatment?

Embryo Glue Treatment

The ingredient used to create EmbryoGlue, hyaluronan, increases the embryo's propensity to adhere to the lining of the uterus. It is not true glue in the traditional sense. Everywhere in the body is a form of carbohydrate called hyaluronan. It helps to thicken the EmbryoGlue, which lessens how much the embryo can move and is a good source of the carbs, amino acids, and protein the embryo needs to grow properly. If you choose to use EmbryoGlue during your therapy, it will take the place of the regular culture medium that doctors employ for embryo transfer after ICSI or IVF. The embryo(s) chosen for transfer are put into EmbryoGlue and cultivated there for a brief period before being transferred. Despite the embryo being put in EmbryoGlue, the embryo transfer process is the same.


What Does Embryo Glue Do?

Embryo glue

Embryo glue is made to resemble uterine secretions in composition. The enhanced implantation rates are partially explained by the compositional similarity of the viscous embryo glue solution and uterine secretions, but the embryo glue's high levels of hyaluronan are what allow its components to mix with uterine secretions. It also has a significant impact on the embryo's ability to stick to the endometrium, which facilitates implantation. There are three stages of the implantation process:

  • Contact stage. The embryo can remain inside the uterine lumen due to the high viscosity of the glue, which makes the contents of the transfer medium mixable with uterine fluid. It reduces unintended embryo movement by allowing the embryo to remain in the uterine lumen. The embryo is brought into close contact with the endometrium by the viscous embryo glue solution, which quickly diffuses with the viscid uterine secretions.
  • Adhesion stage. The cell surface glycoprotein CD44 is expressed in the embryo. Hyaluronan has a receptor called CD44. Only during the receptive phase can CD44 receptors be detected in the cell wall of endometrial cells. These CD44 receptors can dock on the Hyaluronan thanks to pods on its surface that serve as receptacles. To link the CD44 receptors on the embryo and CD44 receptors in the endometrium and to strengthen the contact between them, hyaluronan molecules successfully perform their intended function. The uterine secretions naturally include hyaluronan, and embryo glue also provides it externally. By working on specific specialized enzymes produced by the uterus that improve the adhesion rate, the glue aids in adhesion at this point.
  • Implantation stage. Embryo glue aids in implantation and promotes cohesiveness between the endometrial lining of the endometrium and the embryonic cells. The invasive phase of implantation can start as soon as the embryo can find a suitable site to settle into.


Embryo Glue Results

Embryo Glue Results

In actuality, Embryo Glue is a development of Vitrolife culture media. However, more hyaluronan is needed for it to work. At the time of transfer, embryo glue is very helpful since it improves the mixing of the embryo with uterine secretions. This serves as a binding substance between the uterine lining and the embryo. Contrary to other substances that may hurt embryos, embryo glue results in higher pregnancy rates after the transfer of frozen embryos.

An effective transfer medium for promoting implantation is embryo glue. Hyaluronic acid, which is present in the human uterus, is present in it. As a result, it provides a natural setting for the development of the embryo. Hyaluronic acid, which can be employed at any stage of embryo transfer, is delivered into the uterus at a high concentration along with the embryo.

Comparing the clinical pregnancy rate when EmbryoGlue was utilized for embryo transfer to a typical culture medium with low or no hyaluronan, the clinical pregnancy rate increased considerably from 40% to 50%. More than 3200 patients were included in the meta-analysis of the 13 publications that were part of the Cochrane review article. It's important to note that the analysis did not reveal a rise in miscarriages or other unfavorable outcomes. A clear favorable effect (of having large amounts of hyaluronan in the transfer medium) was detected, the Cochrane authors concluded. The number of births using EmbryoGlue increased by 11.5 percent, according to the findings of a study conducted by Dr. Basak Balabanov and presented in 2011 at the ESHRE (European Society of Human Reproduction and Embryology).



EmbryoGlue is a tissue adhesive that mimics the microenvironment in the uterus during the embryo's natural settling process. EmbryoGlue, to put it simply, aids in gluing the fertilized egg to the uterine wall. Hyaluronic acid, which is included in EmbryoGlue, forms a link between the uterus and the embryo and essentially glues them together. The substances it contains are essential for the embryo's growth. EmbryoGlue enhances the likelihood of becoming pregnant. The number of babies born utilizing EmbryoGlue increased by 10%, according to the results of a study conducted by doctor Basak Balaban and presented in 2011 at the ESHRE International Medical Conference.