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Treatment add-ons with limited evidence

For some treatment add-ons there is not enough evidence to show that they are effective at improving the chances of having a baby for most fertility patients. This page explains what some of these treatment add-ons are.

We would like to thank everyone who completed our recent survey on their understanding of this webpage. We have used this feedback to make further improvements to the text below. You can find a summary of the results of this survey in Annex A of the Treatment add-ons progress report 2020 (PDF), presented at our November 2020 Authority meeting. 

On this page

What are treatment add-ons?

  • optional additional treatments, also referred to as ‘supplementary’, ‘adjuvants’ or ‘embryology treatments’.
  • often claim to be effective at improving the chances of having a baby (live birth rate) but the evidence to support this for most fertility patients is usually missing or not very reliable.
  • likely to involve an additional cost on top of the cost of a routine cycle of proven fertility treatment. Some treatment add-ons can cost hundreds or thousands of pounds each.

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 directly for your own treatment, you may want to think about whether it might be more effective and/or affordable to pay for multiple routine proven treatment cycles, rather than spending large sums of money on a single treatment cycle with treatment add-ons that haven’t been proven to be effective at increasing the likelihood of you having a baby.

We aim to publish clear and reliable information about some of the treatment add-ons that don’t have enough evidence, from high-quality randomised control trials (RCTs), to show that they improve your chances of having a baby.

To make it easier to understand the scientific evidence for each treatment add-on we have developed our traffic-light rated list of add-ons, available below. The treatment add-ons included on this page are not a complete list of all the add-ons that patients may be offered. Additional treatment add-ons are likely to be rated by us over time.

What do the traffic light ratings mean?

Our traffic-light rated list of add-ons consists of three colours that indicate whether the evidence, in the form of high-quality RCTs, shows that a treatment add-on is effective at improving the chances of having a baby for someone undergoing fertility treatment. You can read more about RCTs further down this page.

green traffic light

Green - A green rated add-on has more than one high quality RCT which shows that the procedure is effective at improving the chances of having a baby for most fertility patients. These treatment add-ons may be routinely used in fertility treatments and information on these can be found elsewhere on our website, for example the use of intracytoplasmic sperm injection (ICSI) if the cause of infertility is sperm related. Therefore, green rated add-ons will not be included in this review list.

amber traffic light

Amber - We give an amber symbol for an add-on where there is conflicting evidence from RCTs 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 traffic light

Red - We give a red symbol for an add-on where there is no evidence from RCTs to show that it is effective at improving the chances of having a baby for most fertility patients.

An agreement between the HFEA and 10 other professional and patient bodies (the January 2019 consensus statement - PDF) stated 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.

For specific patient groups there may be reasons for the use of a treatment add-on other than improving your chances of having a baby. In these situations, it may be appropriate for you to be offered a treatment add-on as part of your treatment and not in a research setting.

 

Treatment add-ons

Artificial egg activation calcium ionophore

Traffic light rating: Amberamber traffic light

Assisted hatching

Traffic light rating: Red amber traffic light

Elective freeze all cycles

Traffic light rating: Amberamber traffic light

Endometrial scratching

Traffic light rating: Amberamber traffic light

Hyaluronate enriched medium (e.g. EmbryoGlue)

Traffic light rating: Amberamber traffic light

Immunological tests and treatments for fertility

Traffic light rating: Redamber traffic light

Intracytoplasmic morphologic sperm injection (IMSI)

Traffic light rating: Redamber traffic light

Intrauterine culture

Traffic light rating: Redamber traffic light

Physiological intracytoplasmic sperm injection (PICSI)

Traffic light rating: Redamber traffic light

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

Traffic light rating: Red amber traffic light

Time-lapse imaging

Traffic light rating: Amberamber traffic light

Additional information

Sperm DNA damage

When is it appropriate to use an add-on?

Treatment add-ons listed on this page are allocated their rating based on whether there is enough evidence from RCTs that they improve the chance of a live birth for most fertility patients. Our traffic-light rated list of add-ons consists of three colours that indicate whether the evidence, in the form of high-quality RCTs, shows that a treatment add-on is effective at improving the chances of having a baby for someone undergoing fertility treatment. This provides useful information to patients and allows them to question the use of add-ons.

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 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). Therefore, it may be that a red or amber rated add-on could be used appropriately for specific clinical cases after careful discussion with a clinician. 

The add-ons such as PICSI and PGT-A while remaining red for overall or routine use in fertility patients, could be considered appropriate to use in certain circumstances as there is either some or emerging evidence that there may be a benefit for some patients specifically. For example, PICSI could be used to reduce the chance of miscarriage or PGT-A may improve the chance of pregnancy for women over 35.

The evidence that supports the use of add-ons in specific cases might not be as high quality as that used to decide the traffic light ratings. Often the findings have been reported in a subgroup analysis of RCT’s and not studied independently. The studies may also be of poorer quality, for example because they include low numbers of patients or have bias.

If an add-on is offered, a patient should question why it is being offered and ask if it may be of benefit for them specifically. Your clinic will be able to discuss with you whether a treatment add-on would be appropriate given your personal circumstances.

How do I know if a treatment add-on is safe?

Our traffic light ratings only indicate the effectiveness of a treatment add-on at improving your chances of having a baby. Specific safety concerns about a treatment add-on are included in the information on the webpage for that treatment add-on, under the dedicated section ‘Is this treatment add-on safe?’. This will set out the evidence we have used.

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.

Before January 2021, our traffic light ratings indicated both the effectiveness and safety of each treatment add-on. After considering survey feedback from patients and recommendations made at the Scientific and Clinical Advances Advisory Committee (SCAAC), we felt it would be clearer to use the traffic light rating to indicate effectiveness only.

There are a few reasons for this:

  • The safety of undergoing medical treatments can be specific to a person’s medical history; traffic light ratings may not be relevant or helpful in considering that person’s risks.
  • Safety could include the risks for the person undergoing fertility treatment, the eggs, sperm or embryo and the child born as a result of fertility treatment so cannot easily be communicated under one rating.
  • The evidence base used to decide the traffic light ratings, RCTs, may not set out to report on safety or risk factors if they were designed to report on the effectiveness of a treatment add-on.

How are traffic light ratings decided?

The Scientific and Clinical Advances Advisory Committee (SCAAC) is a subcommittee of the Authority. Every 12 months, the SCAAC and an independent expert reviewer of the quality of evidence, review the available research for each treatment add-on in our traffic-light rated list to determine whether the evidence base has changed. 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.

The SCAAC view is that the best way to be confident that a treatment add-on is effective enough to be used routinely is to look at its use within the setting of an RCT. The traffic light rating for each treatment add-on is based on our review of RCT evidence.

It may be the case that there is evidence from other studies which are not RCTs that suggests some benefit for the use of an add-on, either to improve your chances of having a baby or other outcomes such as a reduced rate of miscarriage. This may include cross sectional studies, case-control studies or cohort studies. These studies use less rigorous approaches to investigate the effectiveness of treatments, so the results are less reliable than RCTs. Therefore the SCAAC only consider RCT evidence in the traffic light assessment of a 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 traffic-light rated list of add-ons due to a lack of evidence supporting its use for increasing the chances of having a baby for most fertility patients, 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 traffic-light rated list of add-ons. We will consider the following questions:

  • whether the treatment is an additional, non-essential treatment
  • if patients undergoing fertility treatment in the UK are currently being offered, or requesting, the treatment on a regular basis and/or are being charged for its use in their treatment;
  • whether the safety of the procedure, for both patients and children born as a result of treatment, cannot be demonstrated;
  • the likelihood that treatment doesn’t produce the desired outcome compared to using established fertility techniques without the treatment add-on; and
  • whether there is a lack of standardised procedure between different laboratories and the lack of potential for this treatment to be implemented by other centres.

Find out more about the application process

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Review date: 21 April 2023

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