PGD yes or no

There is not a simple reply to the question of PGD yes or no. Preimplantation genetic diagnosis (PGD) is useful in patients with recurrent miscarriages, failure of implantation and altered FISH analysis in sperm. Outside of these scenarios, its utility is more controversial. A proper analysis of each case is essential to be able to recommend the technique and to know who will really benefit from it.

PGD to analyze the number of chromosomes in embryos, is known as PGS, and it consists in analyzing one or more cells of the embryo and study if they have the correct number of chromosomes (euploid embryo), or missing or extra chromosomes (aneuploid embryo). To perform a PGD, it is necessary to undergo in vitro fertilization (IVF) treatment. Normal embryos are transferred, or will remain frozen, and the rest of the embryos are discarded.

It is very logical to think that PGD is useful for all patients as it discriminates chromosomally normal and abnormal embryos and, therefore, it should be a technique to be proposed to all the couples that go through an IVF cycle. However, analyzing the scientific reviews in this regard, we realize that the reality is not so simple.

DGP Yes or no: arguments in favor

Those who are in favor, argue that PGD could be useful in reducing the time until pregnancy, since it reduces the number of embryo transfers by selecting the chromosomally sound embryos. There are couples where it is expected to have a higher than normal percentage of embryos with chromosomal alterations. In these couples, the benefit may be clearer. This circumstance occurs in couples with recurrent miscarriage and failure of implantation, where a significant number of non-pregnancy and miscarriages are due to chromosomal abnormalities in their embryos.

PGD could be useful also in other two circumstances: in advanced maternal age, since as women age, the percentage of oocytes with chromosomal abnormalities increases and this reflects in the embryos; and if the FISH analysis on sperm is altered, as having embryos with chromosomal alterations is more likely.

DGP Yes or no: arguments against

There are several arguments against PGD of biological and technical origin.

Embryos without diagnosis: around 10% of the embryos biopsied will have no diagnosis, or diagnosis will not be conclusive, due to problems in the biopsy and fixation processes, or the complexity of the techniques used. Paulson et al., in 2017, accounts for up to 40% of normal embryos lost for these reasons.

Embryo Mosaicism: sometimes the results of PGD are contradictory. This happens when we are faced with a « mosaic embryo », i.e. when in a same embryo there is normal and abnormal cells at the same time. Mosaicism in a natural process that affects 10-30% of human embryos. Mosaic embryos are considered non-transferable unless there are no available healthy embryos. However, there are pregnancies to term of healthy children with mosaic embryos. In these cases, to transfer the mosaic embryos, the consent of the couple and a genetic counseling is necessary. Although prenatal diagnosis is necessary, there is no demonstrated higher risk of illnesses or malformations in born children; however, there is a higher risk of no pregnancy or miscarriage.

Mandatory use of the ICSI technique: to do PGD is necessary to use the ICSI technique, which consists in microinjecting a sperm inside the oocyte. The reason is that, for the result of the genetic analysis to be reliable, there should be no DNA from other cells different from the embryo (something that happens with conventional IVF because there are remnants of the DNA of the sperm around the embryo). The ICSI technique has very good results and is essential when there is a male factor. However, the fact of being an invasive technique on the oocyte, makes ICSI not be suitable for all patients.

Need to vitrify (freeze) embryos: Although PGD can be done on the third day of embryonic development and transfer two days later (day + 5), the current trend is to perform the biopsy in day +5 since it allows the analysis of a larger number of cells. However, this implies having to vitrify the embryos, since the results are not in time to be able to do a fresh embryo transfer. The possible pregnancy will be postponed for a month and the embryo will be submitted to a vitrification and thawing. Although today, the embryo vitrification produces very good results, the SEF Registry in 2015 reported that 7.1% of frozen embryos did not survive the process of thawing.

A normal PGD is no guarantee of pregnancy: Although the pregnancy rate is higher when we transfer an embryo characterized as normal with PGD, it is essential to inform patients that this is no guarantee of pregnancy. The implantation process involves multiple factors aside from the chromosomal endowment of the embryo.

Economic reasons: It is true that doing PGD will reduce the number of embryo transfers, and therefore reduce that part of the IVF cost. However, the price of the PGD technique, the ICSI, the long culture to blastocyst, the embryo vitrification and the frozen embryo transfer is high. Additionally, in many cases, when women are above 37, they are asked to accumulate embryos from several IVF cycles to increase the number of embryos to be biopsied at the same time.

In assisted reproduction, it is essential to perform the tests needed without falling into the overdiagnosis or overtreatment. Before considering that PGD is useful for all patients, we should analyze each case and evaluate the pros and cons of each technique. In URH García del Real, according to this premise, we evaluate individually each couple with the aim of offering the best possible advice.

If you are interested in finding out whether PDG could be useful for you, do not hesitate to request an appointment  for a free consultation with us, or call 917401690. We will be happy to help you!

 

Dr. Laura Blasco Gastón – Gynecologist specialized in Assisted Reproduction

Dr. Sylvia Fernández-Shaw Zulueta – Director of URH García del Real 

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