Artificial Oocyte Activation (AOA) with Calcium Ionophore

What is artificial oocyte (egg) activation?

Artificial oocyte activation (AOA) is used to help improve the fertilisation rates for patients who have experienced failed or low (<33%) fertilisation in a previous ICSI cycle. It involves the use of a substance called calcium ionophore which can artificially activate a human egg by increasing the amount of calcium within it and therefore improve fertilisation rates.

AOA is classed by the HFEA as a “treatment add-on” since it is not used routinely for fertility treatment: HFEA.gov (opens in a new tab)

AOA is rated as amber on the HFEA’s treatment add-on traffic light system. This means there is conflicting evidence to show whether or not an add-on can improve live birth rates, or that the add-on is safe for patients to use. This means that the evidence is not conclusive and further research is required to determine how effective, if at all, the procedure is and who will benefit from it.

How is an egg activated naturally?

Studies have shown that 80% of total failure to fertilise is due to a failure of activation of the egg by the sperm. During normal oocyte activation there is a dramatic rise in calcium within the egg which is triggered by a protein contained within the sperms head (Phospholipase C zeta). This ‘activates’ the egg to release calcium from its internal stores and this calcium increase facilitates fertilisation. Without this the egg will remain unfertilised.

Who may benefit from AOA?

Not everyone needs or will benefit from AOA, the technique is intended to be of benefit for a relatively small and very specific group of patients.

Although ICSI has significantly improved fertility rates in patients with male factor infertility, total fertilisation failure is still seen in 2-3% of all cases. This may be due to a defect in the sperm, where the sperm factor cannot be released and so the egg cannot be activated and fertilised.

Failure to fertilise can occur for patients who appear to have normal sperm parameters however there is a much higher risk of this in the very small population of men who only produce ‘round headed sperm’, a condition known as ‘Globozoospermia’ as their sperm completely lack the protein needed for oocyte activation.

How successful is it?

Many scientific studies have shown that activating human eggs with calcium ionophore is successful in improving ICSI fertilisation rates, particularly where patients have a history of no fertilisation or a low fertilisation rate of <30%. In the case of globozoospermic patients, fertilisation rates are reported to be restored to normal after AOA. Although AOA can improve outcomes there is no guarantee that it will do so for every patient choosing to use it as part of their treatment.

How do we perform AOA in an assisted conception cycle?

AOA is a very simple, non-invasive procedure. Following routine ICSI, the eggs are incubated in a solution of calcium ionophore for a short period of time (15 minutes). The eggs are then washed and returned to normal culture conditions, to await fertilisation as they would in any other ICSI treatment cycle.

There is currently no commercially available calcium ionophore product that is specifically designed and certified for use in IVF. It is however CE marked as an in vitro diagnostic device for use with human eggs but not as a medical device for clinical treatment, although an application for this purpose is pending. We have chosen to use the product most widely used within the fertility sector that has a wealth of supporting data regarding its use clinically and its safety. The Human Fertilisation and Embryology Authority who regulate the UK fertility sector expect us to only use this technique in selected patients who show clear indications for its use.

Is it safe?

There are a number of small studies that show AOA does not adversely affect the health and growth of babies born. Studies have shown no difference in birth defect rates, birth weight, neonatal and neurodevelopmental outcome after using AOA. Data is reassuring however it is preliminary and therefore AOA should be used with caution and after careful consideration and discussion with a clinician and embryologist.

Comment on Witnessing

We are all very aware there have been IVF mix-ups in other clinics in the UK and across the world. Cambridge IVF has taken every step possible to minimise the risk of mix up occurring here and we are very proud that since we opened in 2011 we have never had a mix up event occur.

In addition to stringent checking and procedural controls being in place, we have invested in an electronic system called RI Witness which provides a further layer of transparent and auditable protection against the mixing of incorrect sperm and eggs or transfer of the incorrect embryos in your cycle. We are not saying we are likely to have made a mistake without it, this could not be further from the truth but we do believe in making our processes as safe and risk free as possible and we believe that RI Witness ensures this. We also believe it is right to inform you that such risks exist and we do everything possible to reduce them.

We hope you have found this booklet informative and interesting. We realise we may not have covered all of your questions so if you do have any other queries we are here to help so please contact us via any of the means below;

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Cambridge
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