The aim of in vitro fertilisation (IVF) treatment is to obtain embryos that are able to implant in the uterus and lead to the birth of a healthy child. Unfortunately, this is not always the case and some couples go through the process unsuccessfully time and time again and these cases are catalogued as implantation failure. When this happens, we need to reflect and look for alternative routes for solving such complex cases.

Instituto Bernabeu has set up an interdisciplinary unit including doctors, embryologists and molecular biologists for treating implantation failure. They work together to provide an answer to the question of why a patient is not getting pregnant.

There are many areas that need to be worked on, but the IVF laboratory concentrates on one of them: the embryo.

A large number of international research projects are currently being carried out in order to increase an embryo’s chances of implanting in the woman’s uterus. Amongst other measures, culture mediums are optimised; embryos are kept under observation until blastocyst stage so that those with the best quality (morphology) can be selected; the embryo karyotype is analysed before it is transferred (comparative genomic hybridisation); and the embryo is aided in breaking through the zona pellucida (assisted hatching).

Given that it is a controversial issue, we will take a look at assisted hatching. The zona pellucida (ZP) plays a crucial role: it is necessary for spermatozoa-oocyte recognition during fertilisation; it stops more than one spermatozoa entering into the ovule, thus avoiding abnormal fertilisation; it protects the embryo during the initial phase of development and division; and, when the embryo reaches blastocyst phase, its thickness reduces so that it can rupture, travel and implant in the mother’s uterus. Sometimes, rupture of the zona pellucida does not take place and this has a direct impact on embryo implantation.

Since the aforementioned unit was set up at Instituto Bernabeu, assisted hatching in patients with a history of implantation failure has been carried out and promising results have been obtained. It would appear that fracturing the zona pellucida of the embryo by applying laser pulse improves implantation in some very specific cases. It has been observed that it is advantageous for couples who have gone through several unsuccessful cycles and/or embryos with a particularly thick zona pellucida due to the mother’s advanced age or as a result of cryopreservation. It is important to point out that there are no advantages to using this technique when there is no reason to do so. What’s more, excessive handling of the embryo can have a harmful impact on development and subsequent implantation.

The zona pellucida fracture technique can vary from laboratory to laboratory, but it is fundamentally a matter of carrying out the procedure whilst interfering as little as possible in correct development of the embryo.

We have recently acquired and implemented a new state-of-the-art technique called array CGH that is far more sensitive and efficient than the conventional karyotype (it enables identification of duplications or absences of small chromosome regions that are not detected in the karyotype). That is, diagnosis levels that are better 10-fold. This technique is a huge step forward for cases of sterility with an unknown cause, and for repeated implantation failure (get to know more about array CGH).

Dr Dori Rodríguez, biologist at Instituto Bernabeu.

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The work of in vitro fertilisation laboratories in cases of implantation failure: the embryo
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