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

Assisted hatching. Pros & Cons. For or rather against?

Is assisted hatching beneficial? What are the effects of AH on IVF success rates and pregnancy outcomes? Why is it controversial and should this technique be recommended at all?

We have all the answers for you from our experts presenting 3on1 #IVFANSWERS:

  • Dr Harry Karpouzis Scientific Director and Founder of IVF Pelargos Fertility Group
  • Dr Stavros Natsis – Obstetrician/ Gynaecologist, Fertility Expert – Gennima IVF
  • Dr Agnieszka Popow-Woźniak, Embryologist at InviMed
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Dr Harry Karpouzis, IVF Pelargos Fertility Group, Greece

Answer from Dr Karpouzis

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 really help. Just to explain a bit about assisted hatching: an oocyte has a protein membrane around itself, called zona pellucida. After the fertilisation with the sperm, this goes harder and goes around the embryo. It happens so as not to allow more sperm to intrude 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 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 with 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 really change the live birth rate.
Given that, it would not be recommended for any IVF. Actually, there is some evidence that when we talk about a 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.

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Dr Stavros Natsis, GENNIMA IVF, Greece

Answer from Dr Natsis

It has been a very big debate 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 creating tiny holes in the zona, or they used some chemical acids that would thin the outer lining of the embryo 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 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

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Dr Agnieszka Popow-Woźniak,  InviMed, Poland

Answer from Embryologist Popow-Woźniak

Zona pellucida (called the egg coat) is the outer layer formed by the oocyte. Its proper structure determines the fertilisation 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 are 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 practiced. However, the use of the method is justified in cases of blastocysts with low potential for development, containing a large number of cytoplasmic fragments as a result of abnormal cell division. Here, in turn, it prevents growth and expansion of those blastocysts.
To sum up, specific medical and embryological indications are required for AZH treatments.

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