Title
Chromosome constitution of human embryos generated after in vitro maturation including 3-isobutyl-1-methylxanthine in the oocyte collection medium
Date Issued
01 March 2015
Access level
open access
Resource Type
journal article
Author(s)
Spits C.
Mertzanidou A.
Jacobs K.
Ortega-Hrepich C.
Gilchrist R.B.
Thompson J.G.
De Vos M.
Smitz J.
Sermon K.
Vrije Universiteit Brussel
Publisher(s)
Oxford University Press
Abstract
Do cleavage-stage embryos obtained from oocytes matured in vitro after pre-incubation with a phosphodiesterase inhibitor (IBMX) carry more chromosomal abnormalities than those generated from oocytes matured in vivo? summary answer: The rate and type of chromosomal abnormalities in normally developing cleavage-stage embryos generated with an in vitro maturation (IVM) system including pre-incubation with IBMX are not different from those observed in supernumerary embryos obtained from oocytes matured in vivo. what is known already: Very limited information is available about the chromosomal constitution of IVM embryos. Previous studies were carried out using FISH on single biopsied blastomeres or arrested whole embryos and only provided fragmentary information on chromosomal abnormalities in IVM embryos. There is no systematic study of chromosomal abnormalities in all blastomeres of human Day 3 embryos with good morphology. study design, size, duration: BetweenJuly 2012 and December2012, 16 young (age,35 years old) egg donors underwent 18IVM cycles for the generation of research embryos. Eighteen embryos developed to Day 3 and were analysed using array comparative genomic hybridization (aCGH). participants/materials, setting, methods: Immature oocytes were retrieved from 2 to 10 mmfollicles after mild ovarian stimulation with gonadotrophins but without hCG ovulation trigger. At collection, oocyteswere pre-incubated with 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor and matured in vitro. After IVMculture,mature oocyteswere microinjected with sperm froma single donor. Embryos were cultured to Day 3 after ICSI and all blastomeres of 18 good-morphology embryos were collected individually for aCGH. main results and the role of chance: Oocyte maturation rate in vitro was 50.2% (120/239). The mean fertilization rate was 68.3% (82/120) and 30.5% (25/82) of fertilized oocytes developed into a morphologically good quality embryo on Day 3 after ICSI. Of these, 18 embryos that developed well up to Day3 were analysed usingaCGH.Eighty of the 123 blastomeres analysed showedat least one chromosomal abnormality. Three out of eighteen embryos had completely normal cells.Asingle embryocarried a meiotic abnormality, 11 embryoswere mosaic and three were chaotic. Although the aneuploidy data of this study are too limited to allow statistical analysis, these data are comparable to our own published data on the chromosome constitution of whole day 3 and day 4 embryos after conventional ART. limitations, reasons for caution: ArrayCGHtechnology determines relative quantification of chromosomal domains but does not allow for the visualization of chromosomal rearrangements, assessment of ploidy or detection of uniparental isodisomy.Conclusions drawnon segmental abnormalities should be treated with caution. Although the limited number of embryos analysed here precludes firm conclusions, they provide valuable data on possible causes of the reduced potential of IVM embryos. wider implications of the findings: This is the first study to describe the complete chromosome complement of all single blastomeres of good-morphology day 3 embryos obtained with IVM (including the presence of IBMX in a pre-incubation medium). The results demonstrate that a high proportion of good-morphology embryos are aneuploid and that there is no obvious increase in aneuploidies as a result of IVM which seems to suggest that the reduced efficiency of IVM technology compared with standard IVF may be accounted for by factors other than aneuploidy, such as cytoplasmic defects or reduced endometrial receptivity. study funding/competing interest(s): This studywasfunded by theTBM(Applied Biomedical Research with Societal Finality) programme of the IWT (Agency for Innovation through Science and Technology - Flanders, 110680) and by a Methusalem grant of the Vrije Universiteit Brussel. C.S. is a post-doctoral fellow of the Fund for Scientific Research Flanders (FWO - Vlaanderen). K.J. is a PhD student funded by the FWO. The University of Adelaide owns a patent family associated with IVM technologies that is licensed to Cook Medical. R.B.G. and J.G.T. are inventors. The remaining authors have no conflict of interest to declare.
Start page
653
End page
663
Volume
30
Issue
3
Language
English
OCDE Knowledge area
Tecnologías que implican la manipulación de células, tejidos, órganos o todo el organismo Genética humana
Scopus EID
2-s2.0-84935078452
PubMed ID
Source
Human Reproduction
ISSN of the container
02681161
Sponsor(s)
Programme of the IWT (Agency for Innovation through Science and Technology – Flanders, 110680) and by a Methusalem grant of the Vrije Universiteit Brussel. C.S. is a post-doctoral fellow of the Fund for Scientific Research Flanders (FWO – Vlaanderen). K.J. is a PhD student funded by the FWO. The University of Adelaide owns a patent family associated with IVM technologies that is licensed to Cook Medical. R.B.G. and J.G.T. are inventors. The remaining authors have no conflict of interest to declare. The authors thank the clinical embryologists, laboratory technicians and nurses of the Centre for Reproductive Medicine. In vitro maturation research at the Vrije Universiteit Brussel has been granted by the Institute for the Promotion of Innovation by Science and Technology in Flanders, Project number IWT 110680 (Principle investigator: J. Smitz). The authors greatly acknowledge the support by Cook Medical. CS is a postdoctoral fellow of the Fonds voor Wetenschappelijk Onderzoek Vlaan-deren.
Sources of information: Directorio de Producción Científica Scopus