PMID- 21447693
OWN - NLM
STAT- MEDLINE
DCOM- 20110912
LR  - 20110518
IS  - 1460-2350 (Electronic)
IS  - 0268-1161 (Linking)
VI  - 26
IP  - 6
DP  - 2011 Jun
TI  - First births after preimplantation genetic diagnosis of structural chromosome 
      abnormalities using comparative genomic hybridization and microarray analysis.
PG  - 1560-74
LID - 10.1093/humrep/der068 [doi]
AB  - BACKGROUND: Balanced chromosomal rearrangements represent one of the most 
      frequent indications for preimplantation genetic diagnosis (PGD). Although 
      fluorescence in situ hybridization (FISH) has been successfully employed for 
      diagnosis in such cases, this approach usually restricts assessment of the 
      chromosomes involved in the rearrangement. Furthermore, with FISH-based 
      strategies, it is sometimes necessary to create patient-specific protocols, 
      increasing the waiting time and costs. In the current study, we explored the use 
      of two comprehensive chromosome screening methods, conventional metaphase 
      comparative genomic hybridization (CGH) and microarray-CGH (aCGH), as 
      alternatives for PGD of chromosome rearrangements. METHODS: The study included 16 
      patients who underwent 20 cycles of PGD for a variety of chromosome 
      rearrangements (reciprocal or Robertsonian translocations or inversions). Testing 
      was performed at various embryonic stages using CGH (9 cases) or aCGH (11 cases). 
      RESULTS: Results were obtained for 121 out of 132 samples (91.7%). Of the 
      diagnosed samples, 48.8% were found to carry abnormalities associated with the 
      rearrangement, either alone or in combination with other chromosomal 
      abnormalities. A further 28.9% of samples were normal/balanced for the rearranged 
      chromosomes, but affected by aneuploidy for other chromosomes. Only 22.3% of 
      samples were chromosomally normal. Of the 15 patients who completed their 
      treatment cycles, 5 became pregnant after one or two cycles resulting in four 
      healthy births. The delivery rate per cycle was 21% (27% per embryo transfer). 
      CONCLUSIONS: This is the first study to describe the clinical application of 
      comprehensive chromosome screening applied to polar bodies, blastomeres or 
      trophectoderm cells from patients carrying inversions and translocations. Using 
      these techniques, most patients requesting PGD for a chromosome rearrangement can 
      be treated using a single protocol. Additionally, the detection of abnormalities 
      affecting chromosomes unrelated to the rearrangement may assist in the selection 
      of viable embryos for transfer.
FAU - Alfarawati, S
AU  - Alfarawati S
AD  - Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, 
      University of Oxford, Oxford OX3 9DU, UK.
FAU - Fragouli, E
AU  - Fragouli E
FAU - Colls, P
AU  - Colls P
FAU - Wells, D
AU  - Wells D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110329
PL  - England
TA  - Hum Reprod
JT  - Human reproduction (Oxford, England)
JID - 8701199
SB  - IM
MH  - Birth Order
MH  - *Chromosome Aberrations
MH  - Chromosome Inversion/genetics
MH  - *Comparative Genomic Hybridization
MH  - Female
MH  - Genetic Diseases, Inborn/*diagnosis
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Microarray Analysis
MH  - Pregnancy
MH  - *Preimplantation Diagnosis/methods
MH  - Translocation, Genetic/genetics
EDAT- 2011/03/31 06:00
MHDA- 2011/09/13 06:00
CRDT- 2011/03/31 06:00
PHST- 2011/03/31 06:00 [entrez]
PHST- 2011/03/31 06:00 [pubmed]
PHST- 2011/09/13 06:00 [medline]
AID - der068 [pii]
AID - 10.1093/humrep/der068 [doi]
PST - ppublish
SO  - Hum Reprod. 2011 Jun;26(6):1560-74. doi: 10.1093/humrep/der068. Epub 2011 Mar 29.