PMID- 19633308
OWN - NLM
STAT- MEDLINE
DCOM- 20100218
LR  - 20211020
IS  - 1460-2350 (Electronic)
IS  - 0268-1161 (Print)
IS  - 0268-1161 (Linking)
VI  - 24
IP  - 11
DP  - 2009 Nov
TI  - What next for preimplantation genetic screening? High mitotic chromosome 
      instability rate provides the biological basis for the low success rate.
PG  - 2679-82
LID - 10.1093/humrep/dep266 [doi]
AB  - Preimplantation genetic screening is being scrutinized, as recent randomized 
      clinical trials failed to observe the expected significant increase in live birth 
      rates following fluorescence in situ hybridization (FISH)-based screening. 
      Although these randomized clinical trials are criticized on their design, skills 
      or premature stop, it is generally believed that well-designed and well-executed 
      randomized clinical trials would resolve the debate about the potential benefit 
      of preimplantation genetic screening. Since FISH can analyze only a limited 
      number of chromosomal loci, some of the embryos transferred might be diagnosed as 
      'normal' but in fact be aneuploid for one or more chromosomes not tested. Hence, 
      genome-wide array comparative genome hybridization screening enabling aneuploidy 
      detection of all chromosomes was thought to be a first step toward a better 
      design. We recently showed array screening indeed enables accurate determination 
      of the copy number state of all chromosomes in a single cell. Surprisingly, 
      however, this genome-wide array screening revealed a much higher frequency and 
      complexity of chromosomal aberrations in early embryos than anticipated, with 
      imbalances in a staggering 90% of all embryos. The mitotic error rate in cleavage 
      stage embryos was proven to be higher than the meiotic aneuploidy rate and as a 
      consequence, the genome of a single blastomere is not representative for the 
      genome of the other cells of the embryo. Hence, potentially viable embryos will 
      be discarded upon screening a single blastomere. This observation provides a 
      biological basis for the failure of the randomized clinical trials to increase 
      baby-take-home rates using FISH on cleavage stage embryos.
FAU - Vanneste, Evelyne
AU  - Vanneste E
AD  - Center for Human Genetics, University Hospital Gasthuisberg, Catholic University 
      of Leuven, Leuven, Belgium.
FAU - Voet, Thierry
AU  - Voet T
FAU - Melotte, Cindy
AU  - Melotte C
FAU - Debrock, Sophie
AU  - Debrock S
FAU - Sermon, Karen
AU  - Sermon K
FAU - Staessen, Catherine
AU  - Staessen C
FAU - Liebaers, Inge
AU  - Liebaers I
FAU - Fryns, Jean-Pierre
AU  - Fryns JP
FAU - D'Hooghe, Thomas
AU  - D'Hooghe T
FAU - Vermeesch, Joris R
AU  - Vermeesch JR
LA  - eng
PT  - Journal Article
DEP - 20090724
PL  - England
TA  - Hum Reprod
JT  - Human reproduction (Oxford, England)
JID - 8701199
SB  - IM
MH  - Aneuploidy
MH  - Birth Rate
MH  - Blastocyst
MH  - *Chromosomes, Human
MH  - Female
MH  - Genetic Testing
MH  - *Genomic Instability
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Mitosis
MH  - Pregnancy
MH  - *Preimplantation Diagnosis
MH  - Randomized Controlled Trials as Topic
PMC - PMC2763130
EDAT- 2009/07/28 09:00
MHDA- 2010/02/19 06:00
PMCR- 2009/07/24
CRDT- 2009/07/28 09:00
PHST- 2009/07/28 09:00 [entrez]
PHST- 2009/07/28 09:00 [pubmed]
PHST- 2010/02/19 06:00 [medline]
PHST- 2009/07/24 00:00 [pmc-release]
AID - dep266 [pii]
AID - 10.1093/humrep/dep266 [doi]
PST - ppublish
SO  - Hum Reprod. 2009 Nov;24(11):2679-82. doi: 10.1093/humrep/dep266. Epub 2009 Jul 
      24.