What is assisted Hatching - should I get this IVF addon?

What is assisted Hatching – should I get this IVF addon?

Assisted hatching is an assisted reproductive technique which either thins or makes an opening in the outside layer of the embryo known as the zona pellucida. This can be done mechanically, chemically, using laser or electric pulses (piezo technology).

The rationale was that it could aid implantation of embryo’s with thicker zona as it had been found that microsurgical fertilised embryos with artificial gaps in their zona appear to have high rates of implantation. However, at this time no high-quality studies have demonstrated that it improves pregnancy rates in IVF.

An overview of assisted hatching 

If you don’t know much about IVF, then start with our article how does IVF work.. The first live pregnancy from an embryo having had assisted hatching performed was born in 1988, so it is old technology in assisted reproduction terms. It was thought that it would improve the rates of implantation of those going through IVF which over the whole sample set is around 15% implantation. In theory it is supposed to thin or make a small hole in the zona allowing for a greater chance of implantation, let’s look at this in more detail.

The Science bit of assisted hatching

The zona pellucida surrounds the oocyte (immature ovum or egg cell) and the blastocyst. In the stage post fertilisation, it is around 13 -15µm (read micrometre), it is a two-layer acellular (no cells) construct, with a thick outer layer and thin but resilient inner layer. It is composed of proteins, carbohydrates and glycoproteins. It has important functions from fertilisation through to implantation, however after compaction (this is the formation links between cells formed through cleavage known as a blastomeres) it has minimal importance.

The zona pellucida has an important function in fertilisation as it promotes sperm binding, acrosome reaction (in simple terms the fusing with the membrane allowing the acrosome to be exposed from the sperm head which have the antigen for binding and enzymes to allow penetration of the membrane). After fertilisation it is vital to prevent the blastomeres from dispersing, prevents multiple sperm fertilising an egg, the movement of the embryo and finally prevents undesired contact with other cells.

As the egg turns into an embryo then finally a blastocyst the zona thins out, becomes harder as you can see in the differences between the first and second image. Once at the blastocyst stage the cleaved cells shown as the trophoblast on the second image and the uterus release lysins proteases which break down the zona by cleaving the proteins specifically at the carboxyl side of lysine. This is further supported by the expanding mass of the embryo which exerts pressure from the inside. This all reduces the thickness to allow the trophectoderm cells and the endometrial cells to interact and leads to implantation.

 

If you’re more of a visual person then chck out out what is assisted hatching video below.

Simple version of the science of Assisted Hatching

The egg has a outer membrane that allows only sperm in and prevents the interior of the cell from escaping. After the egg is fertilised and turns intoa  blastocyst this layer becomes thinner, which allows the embryo push out with the help of some chemicals and then attach into the endometrial lining of your womb.

What role does assisted hatching possibly have in the IVF process?

When the original concept of assisted hatching was being explored, it was thought that the reason an embryo didn’t implant was due to the fact that the zona was either thicker than normal or harder than normal. This was assumed because microsurgery performed on fertilised embryos which had artificial gaps appeared to have a higher rate of implantation.

It is thought that one of the reasons for low rates of implantation within assisted reproduction specifically IVF is a lack of zonal rupture and subsequent non-hatching of the embryo. This is thought because it is has been observed embryos have a varying zona thicknesses and hardness which may be partly attributed to age and also those with an intrinsically thick zona of greater than 15µm or secondary hardening could be due to the culture used in IVF and also if they are cryogenically preserved.(

The way in which assisted hatching helps with implantation is still unclear and undefined. However, one key idea is that what is clearly evidenced is that the timing of implantation is critical. If the endometrial layer is in its most receptive stage and the embryo implants early in this it leads to higher number of viable pregnancies, if it’s later in this window then it has been linked with a higher rate of early pregnancy loss. Therefore, it has been inferred that assisted hatching allows the embryo to implant earlier in this receptive phase in increase pregnancy rates.

What are the assisted hatching techniques?

There are several techniques used in the assisted hatching all of them need to be performed quickly to minimse time out of the incubator and have minimal impact on pH we will take brief look at each of them below: –

  • Chemical Assisted Hatching Techniques – In simple terms an acid called ‘acid Tyrode’s is put on to the zona using a microneedle. This process is controlled through mouth suction. It is a highly skilled technique which requires quick reactions, as you don’t want excess acid exposure to the embryo. The embryo is then washed to reduce long term exposure and implanted into the woman’s uterine cavity as usual. An interesting video of the technique in action shown to the right.
  • Mechanical Assisted Hatching Techniques – This is a highly skilled procedure, that uses a pipette to hold the embryo in place and a microneedle is used to pierce through the zona. This technique can lead to suboptimal size holes and thinning’s within the zona which can allow the blastomeres loss and invasion by unwanted immune and infectious substances.
  • Laser based  assisted hatching techniques – Lasers allow for hyper-focused targeting of energy and as such are highly applicable to microsurgery. Currently non-contact methods are used to minimise the risk of UV radiation causing harmful mutations within the cells. Historically the laser was used to create a hole, however further experiments determined that laser thinning of the zona was enough to assist in hatching which can seen on this you tube video to the left. This reduces the risk of blastomere loss and invasion by other cells and infections.
  • Piezo assisted hatching techniques – This technique is the newest and involves the use of a piezo-micromanipulator. In simple terms the embryo is held in place using a pipette and a high frequency vibration is created using electrical pulses. This is then used to carve out cone shaped holes within the zona, creating 5-8 of these next to each other can lead to complete hatching.

What evidence is there for assisted hatching in IVF?

If you have read this far, I’m sure you’ll agree the arguments seem logical and the process by which it should help seem sound. However, the evidence of this procedure improving live pregnancy rates is minimal. Cochrane who are considered the gold standard did a review of key studies into assisted hatching, they reviewed 31 trials of varying quality mainly what they deem moderate quality trials. The review captured 1992 pregnancies from 5728 woman on the trials. Its key finding was this:

There was no significant difference in the odds of live birth in the AH group compared with the control group “

It goes onto further clarify that the overall data showed a tiny increase in pregnancy rates that is barely statistically significant. What it does suggest is that the spread of results in the collection of this data indicated that factors outside of those considered where impacting the results.

One specific subgroup (those with previously failed attempts at IVF) of the analysis did indicate that there was a statistically significant result that those women who had previously failed IVF cycles did have an improved clinical pregnancy rate. However, as this was not a specific study more trials of higher quality are required before this is proven.

Finally, the study looks at miscarriage rates, however it clearly notes that the data for this comes from low quality studies and as such this means that it cannot be firmly established. But this data showed there was no significant change in miscarriage rates for those that had assisted hatching.

Looking further into this a 2016 study called Assisted hatching and live births in first-cycle frozen embryo transfers looked at frozen embryo transfer (FET) cycles from 2004-2013 and looked at 151,533 frozen embryo transfers over this time frame. It is clear in its weaknesses as a study but found that assisted hatching reduced live birth rates by 3.8% from 35.4% in non-assisted hatching cycles to 34.2% in assisted hatching cycles. It also highlights that it is even more prominent in older women which it deems over 42 years old. It goes on to state that further trials are required to more rigorously explore the impacts of assisted hatching on frozen embryo transfers.

Are there any specific risks associated with Assisted Hatching?

As we have highlighted in certain points of this article, the risks are mainly to the embryo. These techniques can cause damage to the embryo. This can be physical damage to the embryo and the blastomeres. It can be that a full hole is created, this can lead to loss of blastomeres as they are able to escape the confines created by the zona before they are ready to implant. This can also mean that infections and immune cells can gain access directly to the embryo which would have been blocked by the membrane. This can cause a non-viable embryo. At this current point in time, there is not enough evidence to say for certain whether there are additional risks to the mother, however research at this point indicates the additional risks are minimal – one risk which has been highlighted is that these procedures do seem to come with an increased risk of identical twins -with which comes the normal risks associated with multiple pregnancies – but a note that identical twins can share the same sack and blood supply which increases the risks further.

Should I choose assisted hatching as an optional addon for my IVF treatment?

The average cost of adding an assisted hatching technique to an IVF treatment in a licenced private clinic in the UK is around £600. Whether you choose this and think its value for money is an entirely personal choice. However, our opinion at I Need IVF is that with the current research not showing an improvement in general populations chances of a successful pregnancy, we would not recommend this and your hard earned money can be used more effectively.

2 slight caveats to that is that it may be worth considering this treatment addon for older women going through fresh embryo transfers where the zona is thickened or harder than normal. Also, those who have had multiple failed IVF treatments may benefit – – although the evidence for both of these is still not robust to prove this yet and as such there may be no improved chance of pregnancy with these assisted reproduction techniques.

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