It is important to keep in mind that for most patients, having routine cycles of proven fertility treatment are effective without using any treatment add-ons. If you are paying for your own treatment, you may want to think about whether it might be better to pay for multiple cycles of IVF or IUI, rather than spending large sums of money on a single treatment cycle with treatment add-ons that haven’t been proven to be effective.
Share your experiences by joining our Patient Engagement Forum.Treatment add-ons with limited evidence
For some treatment add-ons there is not enough evidence to show that they are effective at improving treatment outcomes. This page explains what some of these treatment add-ons are.
What are treatment add-ons?
In vitro fertilisation (IVF) and intrauterine insemination (IUI) are established treatments that have been proven effective for most patients. Treatment add-ons are optional non-essential treatments that may be offered in addition to such proven fertility treatment. The HFEA provides information on add-ons that meet the following criteria:
- Additional treatments (to the core treatment e.g. IVF or IUI), that are being offered to the general patient population in licensed fertility clinics in the UK,
- where there are published scientific studies which claim to demonstrate that the treatment add-on improves the chances of having a baby or other treatment outcomes rated by the HFEA; but
- where evidence of effectiveness for the use of the treatment in a clinical setting is lacking or absent; and
- where patients need unbiased information about the effectiveness and risks of this treatment.
The treatment add-ons named on this page are not a complete list of all treatment add-ons that patients may be offered and other add-ons may be rated in future.
Complementary and alternative therapies may be suggested to patients undergoing fertility treatment to help with relaxation or general wellbeing. We do not regulate any complementary therapies and they are not usually offered in an HFEA licensed fertility clinic.
When is it appropriate to use a treatment add-on?
Treatment add-ons may be offered for reasons other than to improve the chances of having a baby. In some circumstances there may be a justifiable medical reason for using the treatment add-on as part of fertility treatment. Some treatment add-ons show benefits in certain groups of patients for outcomes other than improving your chances of having a baby. For example, there may be evidence that a treatment add-on could reduce the chance of having a miscarriage or reduce the risk of ovarian hyperstimulation syndrome (OHSS). Some treatment add-ons on our list may also have additional ratings for specific treatment outcomes. Please see the individual webpages for each treatment add-on for their ratings
Your clinic will be able to discuss with you whether a treatment add-on would be appropriate given your personal circumstances.
An agreement between the HFEA and other professional and patient bodies (the 19th October 2023 consensus statement) states that treatments that have no strong evidence of their safety and/or effectiveness should only be offered in a research setting. Patients should not be charged extra to take part in research, including clinical trials.
If a treatment add-on is offered, you should question why it is being offered and ask if it may be of benefit for you specifically. Questions about treatment to ask your fertility clinic can be found here.
What do the ratings mean?
There are five ratings that indicate whether a treatment add-on is effective at improving treatment outcomes for someone undergoing fertility treatment, according to evidence from studies. To make it easier to understand the scientific evidence for each treatment add-on we have a range of symbols and colours for each rated add-on below.
Green traffic light
On balance, findings from high quality evidence shows this add-on is effective at improving the treatment outcome.
Yellow traffic light
On balance, it is not clear whether this add-on is effective at improving the treatment outcome. This is because there is conflicting moderate/high quality evidence – in some studies the add-on has been found to be effective, but in other studies it has not.
Grey traffic light
We cannot rate the effectiveness of this add-on at improving the treatment outcome as there is insufficient moderate/high quality evidence.
Black traffic light
On balance, the findings from moderate/high quality evidence shows that this add-on has no effect on the treatment outcome.
Red traffic light
There are potential safety concerns and/or, on balance, the findings from moderate/high quality evidence shows that this add-on may reduce treatment effectiveness.
Most treatment add-ons on our list will have a rating to indicate whether the evidence shows that the treatment add-on is effective at improving the chances of having a baby for most fertility patients. Some treatment add-ons on our list may also have additional ratings for specific treatment outcomes. For example, whether the evidence shows that the treatment add-on reduces miscarriage. There may also be further ratings for specific patient groups, for example whether the evidence shows that the treatment add-on is effective for those who are aged over 40. Please see the individual webpages for each treatment add-on for their ratings.
Treatment add-ons
The treatment add-ons below have been rated by the Scientific and Clinical Advances Advisory Committee (SCAAC). The ratings on this page indicate whether the treatment add-on is effective at improving the chances of having a baby for most fertility patients. You can click on each treatment add-on to find out if it has also been rated by the HFEA for other treatment outcomes.
Grey traffic light
Yellow traffic light
Red traffic light
Yellow traffic light
Yellow traffic light
Hyaluronate enriched pre-transfer culture medium (e.g. EmbryoGlue)
Grey traffic light
Immunological tests and treatments for fertility - Intralipids
Red traffic light
Immunological tests and treatments for fertility - Intravenous immunoglobulin (IVIG)
Grey traffic light
Grey traffic light
Black traffic light
Physiological intracytoplasmic sperm injection (PICSI) – in use for patients having ICSI treatment for male factor infertility
Red traffic light
Black traffic light
Additional information
Artificial egg activation calcium ionophore
When a sperm meets an egg (oocyte), it triggers a process called ‘egg activation’ which starts off the process of embryo development, while at the same time allowing only one sperm to fertilise the egg. If the egg doesn’t activate, then it won’t develop. Egg (or oocyte) activation may be stimulated by chemicals called calcium ionophores which are added to the liquid (culture media) that the egg is placed into. Egg activation using calcium ionophore theoretically could cause embryos to have abnormal numbers of chromosomes, which may cause the pregnancy to miscarry. Currently, there’s not enough evidence to decide whether these risks are a serious concern.
Artificial egg activation using calcium ionophore is an HFEA authorised process for use in selected patients only given the possible risks. Clinics offering this treatment should only do so for selected patients, such as those with Phospholipase C zeta (PLCzeta) deficiency, in line with published best practice guidelines.
In August 2023, the Association of Reproductive and Clinical Scientists (ARCS) and British Fertility Society (BFS) published professional guidelines on best practice use of artificial egg activation which states that:
- Artificial oocyte activation (AOA) should not be used routinely with ICSI as its safety, in terms of the potential developmental consequences and birth outcomes, has yet to be established.
- ICSI with AOA may be used where two previous routine ICSI cycle(s) have resulted in <30% or no fertilisation.
- Where AOA is used, patients should be advised that safety, in terms of the potential developmental consequences and birth outcomes, has not been established.
- Patients should be provided with safety data relating to the specific AOA technique used.
In October 2023, artificial egg activation using calcium ionophore was removed from our rated list of treatment add-ons as it should only be offered in specific circumstances.
If you have any questions about the safety and risks, your clinic will be able to discuss whether a treatment would be safe for you to use considering your specific medical history and circumstances.
How do I know if a treatment add-on is safe?
Our ratings indicate the effectiveness of a treatment add-on at improving treatment outcomes. If there are specific safety concerns about a treatment add-on they will be given a red safety rating and relating information will be included on the webpage for that treatment add-on, under the dedicated section ‘Is this treatment add-on safe?’.
A red safety rating highlights a potential concern, it does not automatically mean the treatment add-on is unsafe or unsuitable for you. Your medical history and personal circumstances may influence the safety and risks of a treatment add-on. If you have any questions about the safety and risks of an add-on, your clinic will be able to discuss whether a treatment add-on would be safe for you to use considering your specific medical history and circumstances.
While we do our best to identify potential safety concerns, some of the studies that we use to decide the ratings may have been designed to report on the effectiveness of a treatment add-on and not to report on safety or risk factors.
How are ratings decided?
There are five ratings that indicate whether the evidence from studies shows that a treatment add-on is effective at improving treatment outcomes. Ratings are determined by the Scientific and Clinical Advances Advisory Committee (SCAAC), which is a subcommittee of the Authority. Ratings are reviewed when new evidence comes to light or at least every five years. More information about the process for allocating and reviewing ratings can be found in the SCAAC meeting papers. The minutes of this decision-making process, and the specific evidence used to inform these decisions, can be found in the description for each treatment add-on.
Your clinic should provide you with the evidence of effectiveness of any treatment they offer you.
How are treatment add-ons introduced to this list?
If you feel that there is a treatment that should be included on our rated list of add-ons due to a lack of evidence supporting its use for improving treatment outcomes, then you are able to make an application to the HFEA. We will use this application form, and any supporting evidence submitted with it, to determine whether the treatment is suitable to be part of our rated list of add-ons.
Review date: 23 September 2026
