Does assisted hatching (AH) on fresh embryos have an impact on IVF success rates?

Assisted hatching is where we try to either make a small hole in the wall around the egg that has been fertilized or the embryo or it’s thinning of that zona or the wall around it so, the shell basically that holds initially the egg and later on the embryo. The reason this is done sometimes is because, for example, we visually can see that this zona or this shell is relatively big to what we see in a normal embryo or egg. If we have seen that then, we usually suggest that we use laser technology, we either thin this zone or shell to help the embryo to be able to hatch out later or we may actually make a complete hole in it and then allow the embryo to be able to hatch out later. So this is the process of assisted hatching. Who is it used for it it depends as mentioned whether it is some structural defect we already see that needs to be dealt with or we know, for example, when we freeze and thaw embryos or eggs that we get hardening of this zona or this shell and therefore it is suggested sometimes that when we’re freezing, for example, embryos for use in another treatment later on, that we collapse the the blastocyst which is a Day 5 embryo by making a small hole in it and allowing the embryo to then later after being thawed or warmed, to be able to expand again and this hole opens and allows the embryo to be able to hatch up. So, this is the process that is done once the embryos are then frozen and thawed in order to assist the embryo to hatch.

Assisted Hatching is a quite controversial technique. It’s been around for a long time. One of the previous Cochrane reviews found a significant increase in pregnancy and implantation rate if you did Assisted Hatching but it was quite poor quality evidence that didn’t report a live birth rate and once you sort of removed those studies, there was no significance. It’s red lighted by the UK regulator the HFEA to say that there’s no evidence that it improves efficiency or improves outcomes. There is some evidence that it might improve frozen embryo implantation because the way that the embryos are frozen and in a process called vitrification, there is a theory that hard shell left over from your eggs can harden during the freezing process and there by doing assisted hatching, you sort of bypass that reaction but again we’ve done studies here and which have shown no difference so we don’t feel it will necessarily increase your chances of implantation or success.

Most studies support the hypothesis that the assisted hatching significantly improves the clinical pregnancy rate in patients with a poor prognosis, especially in those with repeated IVF failure, also in the group of patients with 37 years old or more, and this depends of the quality of the oocyte and embryo, for example cases with a very thick zona pellucida that prevents the implantation of the embryo, the assisted hatching can be helpful. Furthermore, assisted hatching is associated with an increase in the multiple pregnancy rate, although there is insufficient evidence to associate it with an increase of twin pregnancy. In patients with a good prognosis, no significant difference is seen, so it should be performed in special cases.

Assisted hatching is a conflicting issue in the field of IVF. It has been used for many years now. There is a lot of research behind it but no conclusive evidence that it can help. Just to explain a bit about assisted hatching: an oocyte has a protein membrane around itself, called zona pellucida. After the fertilization with the sperm, this goes harder and goes around the embryo. It happens so as not to allow more sperm to intrude on the embryo. Another reason is to protect the embryo from implanting in the tubes before reaching the uterine cavity and giving an ectopic pregnancy. When the embryo moves from the cavity into the inside of the womb, the zona pellucida is thinner, and this helps in the opposition of attachment and invasion of the embryo to the lining of the womb.

Scientists observed that day 3 embryos, with a thinner zona pellucida, had better implantation rates. Besides, when a blastocyst had some natural holes around it, the implantation rates were better, too. That’s why they thought of perforating the membrane artificially and manipulating it. This is called assisted hatching. It can be done in many ways. The best and the safest one is the laser.
Generally, in many studies, it has been shown that assisted hatching can improve the clinical pregnancy rate. But in a large meta-analysis and Cochrane data, it has been shown that it doesn’t change the live birth rate.

Given that, it would not be recommended for any IVF. There is some evidence that when we talk about the good quality embryo, it can make things worse rather than better. But there is some evidence for using it in repeated unexplained IVF failures in older women with poor quality embryos.

Assisted Hatching was not invented yesterday. That’s about 30 years in circulation. All the credible evidence out there just says that it adds no value. So I would hesitate to put additional money for a technique that has not shown to be worthwhile.

Assisted hatching is a micromanipulation method performed on fresh embryos before the transfer. It should help the embryo in hatching or leaving the zona pellucida before implantation. We think it has an impact on a decision whether an embryologist should perform hatching or not. So, most of the time when we perform a transfer we do assisted hatching; it’s recommended only by the embryologist because he or she is closely following the fertilization, the development of the embryo and the embryologists know the quality of the embryos from the microscope at the day of the embryo transfer, and they should decide whether to perform or not to perform the hatching.

We use in our center for all the embryos that undergo PGD or in case there is an embryo in early stage of blastocyst that is going to be transferred but present thick zona pellucida. In this case we advise to perform this technique in order to allow the embryo to go out of the zona and implant in the endometrium of the woman.

Assisted hatching is a technique where usually with a laser we create a tiny hole at the shell that surrounds the embryo to help the embryo to escape that shell in order for the embryo to implant in the uterus. Does it improve implantation and live birth? I am not sure. The studies so far show that it doesn’t improve the success rate but some clinics do use that tool and usually to group of patients that have a series of failed IVF cycles.

Assisted Hatching is a procedure where a laser is used in order to thin or make a hole in the zona pellucida that is arounds the embryo in order to help it break out and implant in the womb. However, HFEA has given a red symbol for Assisted Hatching and that means that there is no evidence from randomized control trials to show that it is effective at improving chances of having a baby for most fertility patients. Right now, until further research is available, Assisted Hatching is actually not recommended as it has not been shown to improve a pregnancy rate.

It has been a very big debate on whether assisted hatching (AH) could help couples having IV treatment a lot. To be honest, this is the idea that started back in 1998. Someone thought that creating tiny holes in the embryo zona, the layer that protects the embryo when it enters the uterine cavity might help the embryo attach better. To do that, they used either mechanical ways with tiny needles that were creating tiny holes in the zona, or they used some chemical acids that would make the outer lining of the embryo thin to help conduct its implantation better.

Initially, there was a big acceptance of this method. Some studies showed that there could be some benefit if couples were selected well. Usually, those were the couples above the age of 42 who created good quality embryos that were not implanted successfully. The reason is that women who are above 42 create embryos with a big and hard outer surface. That’s why it is very difficult for embryos to implant.

In the last years, many IVF centres are using laser technology to create tiny holes that can help the embryo attach better to the lining of the womb. In our centre, we do not use this method because later studies have shown that it’s not actually helpful. If people want to read about it further, they can look for NICE (National Institute for Health and Care Excellence) guidelines. Most of the centres are using these recommendations. It is clearly suggested that there is no benefit of doing assisted hatching to the embryos. Actually, you can impair the potential of the embryo to grow. It is a surgical procedure, and you can create even lethal complications when trying to punch a hole in the embryo.

It was also shown that sometimes you can create a monochorionic twin pregnancy. The rate of monochorionic twin pregnancies is higher after the hatching. And as we know, twin pregnancies, especially the monochorionic ones, are very difficult and have a lot of risks for the mother and also for her babies.
We do not use assisted hatching in our lab because we think it has no clear benefit, and it creates more complications than actual advantages. We think there are better ways to help with better implantation. We use e.g., time-lapse technology that can help us identify embryos with bigger implantation potential in a completely non-invasive way.

Zona pellucida (called the egg coat) is the outer layer formed by the oocyte. Its proper structure determines the fertilization process and proper development of the embryo. On the 6th or 7th day of normal embryo development, that is at the blastocyst stage, the process of hatching from the egg coat occurs. This allows the embryo to interact with the endometrium lining of the uterus. In the absence of this phenomenon, the initiation of the embryo implantation or its growth is impossible. One of the causes of hatching problems is the egg coat defect, which, in the course of the IVF process, led to the development of the Assisted Zona Hatching (AZH) method.

AZH involves a mechanical or laser partial zona dissection (PZD) of the embryo’s egg coat (zona pellucida), which theoretically supports the embryo hatching at the blastocyst stage. AH is a procedure used primarily in the embryo transfer on the third day of its development, if such a transfer strategy is applied by a fertility clinic. The use of AH statistically does not improve the results of the transfer. However, the use of the method can bring positive effects in the following groups of patients:

1. the ones whose growing embryos show significant anomalies in the structure of the egg coat;
2. the ones who have a medical history of repeated implantation failure;
3. the ones whose eggs are of poor quality.

The use of AZH in blastocysts is not commonly practised. However, the use of the method is justified in cases of blastocysts with low potential for development, containing numerous cytoplasmic fragments as a result of abnormal cell division. Here, in turn, it prevents the growth and expansion of those blastocysts.

To sum up, specific medical and embryological indications are required for AZH treatments.