Artificial egg activation calcium ionophore
Treatment add-on with limited evidence.
For most patients, having a routine cycle of proven fertility treatment is effective without using any treatment add-ons.

Amber
Artificial egg activation calcium ionophore is rated amber because there is conflicting evidence from randomised controlled trials (RCTs) to show that it is effective at improving the chances of having a baby for patients that are eligible to undergo this treatment.
What does this traffic light rating 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 most fertility patients.
Generally, 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.
However, due to the theoretical risk of artificial egg activation using calcium ionophore related to embryo viability, centres are expected to only use this treatment in selected patients, such as those with PLCz deficiency. For this reason, the traffic light rating for calcium ionophore reflects the evidence base for increasing the chances of having a baby for patients who are eligible to undergo this treatment, as it is not authorised to be used in most fertility patients.
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, including those discussed above, are included under the dedicated section ‘Is this treatment add-on safe?’.
What is egg activation?
When a sperm meets an egg, 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. These chemicals can be added to the liquid that the egg is placed into (culture media) in the lab.
What’s the evidence for egg activation?
In the few studies done to date, egg activation using calcium ionophores may be effective at improving fertilisation rates in ICSI cycles where the egg and sperm have failed to activate in previous treatment cycles. However, there are no RCTs to show that it is effective and there are no follow up studies on the safety of this technique.
At the October 2019 Scientific and Clinical Advances Advisory Committee (SCAAC) meeting the Committee evaluated the evidence base for egg activation. Minutes of this discussion and the evidence used to inform this discussion are available on the SCAAC webpage.
Is this treatment add-on safe?
Egg activation theoretically could cause embryos to have abnormal numbers of chromosomes, which would cause the pregnancy to miscarry. Currently, there’s not enough evidence to decide whether these risks are a serious concern.
Given the possible risks, clinics offering this treatment should only do so for selected patients who have had failed fertilisation and should be able to justify their reasons for doing so.
If you have any questions about the safety and risks, 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.
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 a routine cycle of proven fertility treatment is 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 are effective at improving 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.
Review date: 30 December 2023