Treatment Add-Ons

When going through IVF you may be offered a treatment add-on to improve your chances of having a baby. For most patients, having a routine cycle of fertility treatment is effective without using any treatment add-ons. As treatment add-ons come at an additional cost you are not only a patient, you also become a consumer paying for parts of your treatment. This can be really difficult to navigate, so we’ve put together this guide to help you. 

What are treatment add-ons?

Treatment-add ons are supplementary treatments that can be performed during your IVF cycle1. They are often offered at an additional cost to the patient. There is varying evidence for the different treatment add-ons and your doctor should guide you through if you’ve been advised to have any particular add-on.

Which treatment add-ons are available?

The Human Fertilisation and Embryology Authority (HFEA) regulates fertility clinics through licensing, inspecting and setting standards for operating processes2. They have published a guide with all of the treatment add-ons available with a traffic light rating to indicate if the add-on is effective at improving the chances of having a baby for someone undergoing fertility treatment3. However it’s important to remember that they look at most fertility patients in general and there may be evidence base for your personal circumstances. Therefore, your clinic should provide you with the evidence of effectiveness of any treatment they offer you4. The rating system has three levels:

Green rating – a green rated add-on has more than one high quality study which shows that the procedure is effective at improving the chances of having a baby for most fertility patients. If they are rated green, they may be used routinely and are not included in the HFEAs review list. We’ve added a few treatments that would be considered green.

Amber rating – an amber rating is given for an add-on where there is conflicting evidence from studies to show that an add-on is effective at improving the chances of having a baby for most fertility patients. This means that the evidence is not conclusive and further research is required, and the add-on should not be recommended for routine use. 

Red rating – a red symbol is given for an add-on where there is currently no evidence from studies to show that it is effective at improving the chances of having a baby for most fertility patients. The HFEA have stated that treatments that have no strong evidence of their safety or effectiveness should not be recommended for routine use. 

Green rated treatment add-ons

Intracytoplasmic sperm injection (ICSI) 

ICSI is a fertilisation method where sperm are injected individually into eggs. More than one high quality study has shown that the procedure is effective at improving the chances of having a baby if the cause of infertility is sperm related. It may be routinely used and would be considered to have a rating of green3

Blastocyst culture

Blastocysts are embryos that have been able to develop for longer in the laboratory. It can be easier for the embryologist to select the embryos that are most likely to implant in the uterus when they reach the blastocyst stage. This means that blastocyst transfers tend to have higher birth rates5. However, not all embryos that are left to the blastocyst stage will survive and in some cases a couple could have no embryos available to transfer. Blastocyst culture may be routinely used.

Embryo freezing

Often when an IVF treatment is completed, there may be surplus good quality embryos available after the embryo transfer. Instead of discarding them, there is the option to freeze them in order to use them at a later date (for example if the treatment isn’t successful or to try for a sibling). Using frozen embryos is just as safe as fresh embryos and success rates from frozen embryos are comparable with fresh6. Embryo freezing may be routinely used. 

Amber rated treatment add-ons

Elective freeze all

An elective freeze all cycle is a cycle of IVF where an embryo transfer does not take place, instead all good quality embryos are frozen and an embryo transfer is planned for a different cycle. The procedure is safe but there is always a risk involved with freezing and thawing embryos that they may not survive. This add-on has a traffic light rating of amber as there is conflicting evidence to support efficacy in improving pregnancy rates for patients7

Endometrial scratch

Endometrial scratching is a procedure performed by your doctor where the lining of the uterus is scratched using a small sterile plastic tube. The theory is that this procedure triggers the body to repair the site of the scratch, releasing chemicals and hormones that make the womb lining more receptive to an embryo implanting. There is a small risk of infection as it is an invasive procedure, but it is otherwise considered safe. It has a traffic light rating of amber as there is not enough evidence to support whether it is effective in improving pregnancy rates for most fertility patients8

EmbryoGlue

EmbryoGlue is a hyaluronate enriched medium that is used at the time of embryo transfer. It contains hyaluronan, a component which is usually present during implantation and the theory is that the enriched medium promotes implantation, to improve chances of having a baby. EmbryoGlue is a safe fertility treatment add-on that currently has a traffic light rating of amber but the HFEA acknowledges that there is a high quality study which shows that it may improve chances of having a baby9

Time-lapse imaging 

Time-lapse imaging is available through an incubator with a built-in camera that takes thousands of images of embryos while they’re growing. It allows for uninterrupted culture, the embryos do not have to be removed from the incubator and it gives a continuous view of each embryo as it develops, rather than just viewing them once a day. The embryologist can then choose a specific embryo for implantation based on criteria such as rate of development and the number and appearance of cells. Time-lapse incubation and imaging does not carry any additional risks to the embryos in culture or children born from them. Initial research has shown promise however there’s not enough evidence to show efficacy in improving pregnancy rates for most fertility patients and time-lapse has therefore been given a rating of amber10

Red rated treatment add-ons

Artificial egg activation

Artificial egg activation is a laboratory process where embryologists use a chemical called calcium ionophore in order to attempt to improve fertilisation rates. This method may be offered if there has been a previous cycle where fertilisation has failed with ICSI. There’s not enough information to show if the procedure carries a risk of abnormal embryo development. The HFEA have given this treatment add-on the rating amber as there is conflicting evidence to show if it is effective in improving chances of having a baby11

Assisted hatching

Assisted hatching is a laboratory process where embryologists use a laser, chemicals or a needle to create a hole in the zona, the outer layer of the embryo. During implantation, the embryo must hatch out of the zona to successfully implant. Assisted hatching is meant to encourage that process. This may be offered if there’s an indication of the embryos having thick zonas or in cases where multiple embryo transfers have taken place without implantation. While safe to perform on the embryos, this currently has a traffic light rating of red as it has not shown that it is effective at improving chances of having a baby12

Endometrial receptivity assay (ERA)

ERA is a test that is meant to find the optimal time for an embryo to be transferred into a woman’s uterus for the embryo to implant, known as the window of implantation. ERA involves taking a biopsy of the endometrial lining of the uterus and testing the tissue to determine the optimal window. In subsequent cycles of treatment, the patient will then have a personalised embryo transfer, taking place during her specific window of implantation to hopefully improve chances of a successful implantation. This currently has a traffic light rating of red as there is currently no evidence to show that it will in fact improve chances of success13.

Immunological tests and treatments

For many patients experiencing fertility problems, no underlying causes are found. Due to this inability to explain why a successful pregnancy does not occur, one theory widely shared is that the cause may be the patient’s immune system. A range of tests may be offered to assess if that’s the case. The fertility treatments that may be offered could have a profound and serious impact on the patient’s immune system. Because there is no evidence that any immune cells ever do prevent a pregnancy, there is no reason for any patient without an immunological disease to take these therapies. None of these treatments are harmless and some of their side-effects are serious. For example, they can give rise to severe allergic reactions or make patients susceptible to infections that could also affect the baby.All the good evidence to date shows that there is a risk of considerable harm without any increase in the chances of a live birth. Therefore these tests and treatments have been given a traffic light rating of red14

Intracytoplasmic morphologic sperm injection (IMSI)

IMSI is a sperm selection method used in ICSI. The technique involves using a microscope to view sperm under very high magnification, over x6000, compared to standard ICSI which uses x200 and x400. This is a safe add-on that allows embryologists to view detailed images of sperm. Systematic reviews suggest that IMSI could be beneficial in specific situations such as previously failed ICSI attempts, however for most fertility patients it has not shown to be effective at improving pregnancy rates and therefore has a rating of red15

Intrauterine culture

Intrauterine culture is a fertility treatment add-on which utilises a device that allows the patient to carry their embryos in the uterus for several hours during early development before the embryos can be transferred or frozen. The theory is that the embryos will develop better in a more natural environment as opposed to an incubator in the laboratory. There are no known risks to the treatment but as early stages of development take place in the fallopian tube and not the uterus, the science is conflicting and there is no evidence to show that it may improve chances of success. This add-on has been given the traffic light rating of red16

Physiological intracytoplasmic sperm injection (PICSI)

PICSI is a technique used to select sperm to use for ICSI treatment. It involves placing sperm with hyaluronic acid, a natural compound found in the body. PICSI identifies sperm that can bind to HA and these sperm are selected to be injected. It is a non-invasive test used on sperm prior to ICSI and considered to be safe. A large study showed that there is not enough evidence to show that it improves pregnancy rates17

Pre-implantation genetic testing for aneuploidy (PGT-A)

PGT-A involves checking embryos for abnormalities in the number of chromosomes. Embryos with an abnormal number of chromosomes have less chance of developing into a baby or, increased risk of miscarriage. PGT-A identifies embryos that are unsuitable for fertility treatment. Embryologists perform a biopsy on the embryos to remove cells that can be tested for any chromosomal abnormalities. In some cases the cells may not yield a result, or have a mix of both normal and abnormal chromosomes. The biopsy can cause damage to the embryo, which could impact how it survives the freezing and thawing process. There is no evidence to suggest that PGT-A improves chances of having a baby in most fertility treatment patients, however some studies show that it can reduce the risk of miscarriage in older patients. It currently has a traffic light rating of red18.

Additional tests

Sperm DNA fragmentation

Testing for sperm DNA fragmentation is an additional diagnostic test and not necessarily considered a treatment add-on, and therefore has no traffic light rating. That being said the HFEA have published information about it as it’s widely available at fertility clinics. It has been suggested that during sperm cell maturation the DNA is susceptible to factors which may cause the DNA strands to break or fragment, furthermore that this may cause failed IVF cycles or miscarriage. The results of a sperm DNA damage test are unlikely to impact on the management of your fertility treatments as there is no known effective treatment for repairing the DNA damage. There are no risks to the diagnostic test as it uses a small sample of sperm that will not be used for treatment19

Speak with your doctor

If you’ve been offered a treatment add-on or are considering one, please speak with your doctor about why it may be recommended and how it may improve your chances of having a baby. 

Learn more

References

This information is accurate as of the publishing date but it’s important to note the HFEA reviews these add-ons annually and changes may occur.