Controversias del Diagnóstico Genético Implantacional

Written by: Dra. Sylvia Fernández-Shaw Zulueta
Edited by: Anna Raventós Rodríguez


The dr. Fernández-Shaw, who has more than 20 years of experience in Assisted Reproduction, directs the Unit of Assisted Reproduction of URH García del Real. It has different publications and conferences of the specialty, especially on endometriosis, protocols of ovarian stimulation, prevention of multiple pregnancy, embryo transfer in blastocysts and the impact of Assisted Reproduction techniques on the health of the children born of the same ones. This article explains what the preimplantation genetic diagnosis consists of and what controversies it has.


To perform a PGD the woman must undergo an IVF cycle


Preimplantation Genetic Diagnosis (PGD) is a technique developed in the 1990s to evaluate the chromosomal condition of embryos before transferring them to the maternal uterus. There are many published studies on PGD.


While there is no doubt about its utility in the case of serious hereditary diseases, there is controversy when used in cases of implantation failures, advanced maternal age or repetitive abortions. Some studies find an improvement in the results of In Vitro Fertilization and others do not.


What is preimplantation genetic diagnosis?

In order to carry out a preimplantation genetic diagnosis (PGD), the woman must undergo an In Vitro Fertilization (IVF). This consists of stimulating the woman's ovaries to produce several eggs, to inseminate them with spermatozoa and to get embryos.


To perform the DGP it is necessary to extract (biopsy) from each embryo a cell on its third day of development (usually have about 8 cells), or extract a larger number if the extraction occurs on the fifth day of development (in the blastocyst stage ).


The biopsy consists of making a small hole in the zona pellucida of the embryo (membrane surrounding it) to access the cells. This can be done with a laser, mechanically or with acid tyrodes (which "digests" the zona pellucida). Depending on the day of the biopsy and the technique used, the embryos can be transferred fresh (in the same IVF cycle), or the embryos must be frozen, waiting for the results and transferring the embryos without alterations in a cycle defrost and cryotransfer .


The PGD is to stimulate the female ovaries to produce several eggs, to inseminate them with spermatozoa and to get embryos.


Preimplantation genetic diagnosis for monogenic diseases

PGD ​​is indicated when there are monogenic diseases, to avoid transmitting to the offspring a specific disease that has a parent (or both). For example, Duchenne muscular dystrophy, Marfan syndrome, Fragile X syndrome, hereditary cancer syndromes, hemophilia A and B. That is, "serious hereditary diseases of early onset and not susceptible to postnatal treatment or for the detection of other alterations that may compromise the viability of the pre-embryo". Other inherited diseases that do not fall under this definition require special permission from the National Commission for Assisted Human Reproduction (CNRHA), which is the advisory body responsible for authorizing DGP cycles on a case-by-case basis.


It is estimated that there are more than 6000 monogenic diseases. Individually they are usually rare, but as a whole they are a serious medical problem because in addition many of them cause important disorders to those who suffer them. Nowadays, this DGP can be applied for any monogenic disease from which the causative gene is known.


Preimplantation genetic diagnosis for aneuploidy screening (PGS)

The PGS is performed to see if the chromosomes of the embryo are in the correct number, or if they are left over or missing genetic material. The goal is to avoid transferring embryos to the uterus that will not lead to pregnancy or produce abortions. Nowadays, the most frequent cases in which this test is recommended are repetitive abortions, advanced maternal age, previous IVF cycles without pregnancy, or knowledge of any possible chromosomal alteration in the eggs or spermatozoa.


Controversies of preimplantation genetic diagnosis

  • It is estimated that there are more than 6000 monogenic diseases.
    It is not possible to biopsy all the embryos: for the PGD only biopsies of good morphological quality can be biopsied; that is, not all embryos obtained after IVF can be biopsied since it is usual that not all are of good quality. This decision may leave out the DGP embryos that are not of good morphological quality, however, and although with a low probability, lead to a pregnancy.
  • Decreased likelihood of implantation; the DGP makes it necessary to extract one or more cells from the embryo to diagnose them. The manipulation of the embryos with any of the techniques used may lead to good quality and chromosomally normal embryos morphologically not giving rise to pregnancy due to the damage caused by the biopsy.
  • Embryos without diagnosis. Occasionally there may be some technical problem when performing PGD making it impossible to have a reliable diagnosis of the embryo. In these cases embryos are discarded without knowing whether or not they are chromosomally normal.
  • False positives and negatives. In the DGP a few cells of the embryo are analyzed, but not the embryo in its entirety. It is demonstrated that embryos can coexist chromosomally normal and abnormal cells within the same embryo, so there are cases in which an embryo is diagnosed as healthy when it has abnormal cells and vice versa. It is also described that the human embryo is able to leave out of development the abnormal cells, leading to a healthy pregnancy.


Several authors argue that PGS increases the probability of pregnancy by embryo transfer, and decreases the time until pregnancy, because it makes a pre-selection of the embryos before their transfer to the uterus. However, to date, the PGS has not been shown to increase the probability of child at home per patient or per cycle of IVF started. In the last register of the Spanish Fertility Society , in 2015, less than half (41%) of the PGD cycles started reached embryo transfer. It is possible that the transfer would not be performed because all the embryos are anomalous, but it is also possible that embryos were discarded for transfer because of the above problems. Embryos that, without such analysis, could have led to a healthy pregnancy.


Although DGP is a widely established technique in Assisted Reproduction, it is necessary to carefully evaluate the cases that could benefit from it, especially PGS, since it is still an expensive and invasive technique, and not all patients will improve their pregnancy with it.

*Translated with Google translator. We apologize for any imperfection

By Dra. Sylvia Fernández-Shaw Zulueta
Fertility Specialty

Directs the Assisted Reproduction Unit of URH García del Real. He has more than 20 years of experience in the field of Assisted Reproduction. She is also a doctor from the University of Oxford with a work on endometriosis. He has several publications and lectures on Assisted Reproduction, especially on endometriosis, ovarian stimulation protocols, prevention of multiple pregnancy, embryo transfer in blastocysts and the impact of Assisted Reproduction techniques on the health of children born from them.

He is a member of the Embryonic Health Interest Group of the Spanish Fertility Society since 2005.

*Translated with Google translator. We apologize for any imperfection

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