Preimplantation Genetic Diagnosis Does Not Prevent Early Spontaneous Abortions
Preimplantation Genetic Diagnosis Does Not Prevent Early Spontaneous Abortions
Preimplantation Genetic Diagnosis Does Not Prevent Early Spontaneous Abortions
Preimplantation genetic diagnosis (PGD) may not be effective in preventing early spontaneous abortions, according to the results of a study conducted by a group of Italian researchers and doctors (University of Messina, University "Sapienza" of Rome, Clinica GENERA de Rome) and Americans (Yale University, New Haven), published in the latest issue of the journal Reproductive Biomedicine Online.
The study included 803 embryos, diagnosed as "chromosomally normal" by PGD and transferred in 789 women, and 1259 embryos not analyzed by PGD and transferred in 1021 women. According to the conclusions, there are no relevant differences between the frequency of spontaneous abortions between both groups.
All interventions were performed with frozen embryos in the blastocyst stage (day 5-6 after fertilization) for a period of 6 years. Considering that the main cause of spontaneous abortions are embryo chromosomal abnormalities, it could be expected that the analysis of the chromosomes by DGP would have to significantly reduce their risk, which could not be demonstrated in the Italian-American study.
The study, conducted with relatively high numbers of embryos, adds to other observations that confirm the doubts about the efficacy of PGD to detect chromosomal abnormalities. According to Dr. Jan Tesarik, author of one of these works, the current way to perform PGD has several weaknesses "the first and most important, is the impossibility of evaluating the chromosomal composition of the future fetus from the analysis of the sampled cells "
Chromosomes of a cell about to divide (in blue) organized in the equatorial line of the mitotic spindle (in green), waiting for the permission of regulatory mechanisms of the cell to separate to the two poles of the spindle and form nuclei of 2 cells daughters (Photo: MARGEN)
Tesarik indicates that the PGD procedure is performed on the fifth day after fertilization, when the embryo reaches the "blastocyst" stage, which has the form of a vesicle delimited by a layer of external cells, called trophoblast, and a mass of internal cells called embryoblast (Image 1). The trophoblast will be part of the future placenta, while the embryoblast will originate the embryo's own body. "To carry out the PGD," says Tesarik, "a group of 5-6 trophoblast cells is usually removed for genetic analysis. However, the chromosomal content in the trophoblast cells does not necessarily correspond to that of the embryoblast and, therefore, to the future fetus. Hence the majority of erroneous results, both false positives and false negatives of the current PGD technique. "
In this sense, a group of American scientists have created a mathematical model, based on the distribution of cells in human embryos at the blastocyst stage, and have concluded that it is necessary to analyze at least 27 cells of the trophoblast so that the margin of error is acceptable, something that would be difficult to reconcile with the survival of the embryo analyzed.
According to an article recently published by Dr. Jan Tesarik in the journal Reproductive Biomedicine Online, human embryos affected by chromosomal abnormalities have self-defense mechanisms that allow them to detect and block abnormal cells. When these mechanisms detect a chromosomal anomaly, the division of the chromosomes, located in the equatorial line of the mitotic spindle (Image 2) does not progress, the cell does not divide, it deactivates its genomic expression and finally disintegrates and disappears. Thus an embryo initially carrying chromosomal anomalies can spontaneously become a normal embryo.
Beyond the cost and lack of efficacy of PGD, Dr. Tesarik points out the risk of the "voluntary" destruction of normal embryos, mistakenly diagnosed as abnormal, especially in patients with low ovarian reserve "who may lose one of his last chances to procreate with his own eggs. " In this sense, the Tesarik team works on the development of more reliable DGP techniques. "And before its introduction into clinical practice," he concludes, "it is advisable to use indirect indices of chromosomal normality of embryos, such as those published in 2004." (Source: MARGEN)
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