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Preimplantation genetic diagnosis of numerical and structural chromosome abnormalities.

Abstract
The causes of the decline in implantation rates observed with increasing maternal age are still a matter for debate. Data from oocyte donation strongly suggest that in women of advanced reproductive age, the ability to become pregnant is largely unaffected while oocyte quality is compromised. The incidence of chromosomal abnormalities in embryos is considerably higher than that reported in spontaneous abortions, suggesting that a sizable percentage of chromosomally abnormal embryos are eliminated before any prenatal diagnosis. Such loss may partly account for the decline in implantation in older women. Because of the correlation between aneuploidy and reduced implantation, it has been postulated that selection of chromosomally normal embryos could reverse this trend. Preimplantation genetic diagnosis (PGD) for aneuploidy had three objectives relevant to the present paper: (i) to increase rates of implantation, (ii) to reduce risks of spontaneous abortion, and (iii) to avoid chromosomally abnormal births. Implantation rates did not increase when only five chromosomes were analysed in blastomeres. With eight chromosomes, a significant increase in implantation was achieved. PGD can significantly reduce the incidence of spontaneous abortion. In our clinic, a significant decrease in spontaneous abortions was found, from 23 to 11% after PGD. Currently in cases diagnosed at Saint Barnabas, 0.8% chromosomally abnormal conceptions have been observed after PGD versus an expected 3.2% in a control age-matched group. It seems clear that PGD reduces the possibility of trisomic conceptions under all conditions. If a couple's main interest is to improve their chances of conceiving (improve implantation), then one should consider maternal age and number of available embryos. Improvements in conception after PGD again increase after 37 years of age with eight or nine probes. Carriers of translocations are at a high risk of miscarriage or chromosomally unbalanced offspring, and a high proportion have secondary infertility. PGD of translocations has been approached through a variety of methods, here reviewed, and has resulted in a significant reduction in spontaneous abortions. However, implantation rates in translocation carriers are directly correlated with the proportion of normal gametes, and male patients with 70% or more unbalanced spermatozoa have great difficulty in achieving pregnancy with PGD.
AuthorsSantiago Munné
JournalReproductive biomedicine online (Reprod Biomed Online) 2002 Mar-Apr Vol. 4 Issue 2 Pg. 183-96 ISSN: 1472-6483 [Print] Netherlands
PMID12470583 (Publication Type: Journal Article, Review)
Chemical References
  • Membrane Glycoproteins
  • translocating chain-associating membrane protein (TRAM)
Topics
  • Abortion, Spontaneous (genetics)
  • Aneuploidy
  • Chromosome Aberrations
  • Chromosome Segregation
  • Embryo Implantation (genetics)
  • False Negative Reactions
  • False Positive Reactions
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Membrane Glycoproteins
  • Mosaicism
  • Preimplantation Diagnosis
  • Trisomy

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