O-064 Genome-wide analysis of meiotic recombination reveals a subset of oocytes with reduced frequency of recombination and increased risk of aneuploidy.

Abstract Study question Are there differences in recombination rates between male and female embryos, is the frequency of associated with risk aneuploidy? Summary answer There more meiosis than males. Aneuploidy fewer events. Genome-wide reduction predisposes oocytes to aneuploidy. What known already believed be primary explanation for embryo implantation failure miscarriage is, therefore, great relevance IVF. Despite high clinical importance aneuploidy, mechanisms causing a gamete become chromosomally abnormal are only partially understood. One factor influence aneuploidy meiotic recombination. An absence or atypical positioning chiasmata chromosomal malsegregation. Most data on subject comes from miscarriages aneuploid births, but this provides an incomplete view since most aneuploidies lethal at earlier developmental stages. design, size, duration ∼300,000 polymorphisms scattered across genome were genotyped DNA 125 couples 543 blastocysts that they produced. The inheritance individual alleles was tracked parents allowing parental origin each chromosome determined. This strategy also permitted detection numbers chromosomes, allowed deduction which division had arisen in, revealed sites embryos analysed. Participants/materials, setting, methods Embryo analysis involved trophectoderm biopsy, followed by multiple displacement amplification. Parental amplified samples then tested using microarray. 22,133 events 14,561 chromatids evaluated. relationship considered. average distance calculated dividing size autosome (in Mega bases – Mb) number detected unpaired t-test conducted statistical analysis. Main results role chance A quarter all found carry one abnormalities (altogether, 221 detected). Of these, 82% maternal (oocyte) origin, while 18% paternal. Chromosomes 16 22 frequently affected together accounting 33% abnormalities. Analysis maternally paternally inherited chromosomes confirmed significantly higher (41.4 ±7.7 compared 24.4±4 paternal origin). 21 showed lowest events, consistent their small (average 0.6 0.7 per chromosome, respectively). As expected, complete occurred lower Interestingly, evidence produced them general (not restricted chromosomes) those producing euploid (P = 0.01). Across genome, distances ∼10% (72.4 +/-14 Mb versus 81+-18 0.0004). Limitations, reasons caution It possible pattern exist sperm might show some during study, considering half either fail fertilise produce arrest before blastocyst stage. Wider implications findings rate seen meiosis. levels whole not suggesting unusually low activity Trial registration applicable