Genetic analysis of human egg cells (oocytes) has long been an area of interest in relation to in vitro fertilisation (IVF) – partly as a means of testing for inherited forms of disease, and also for testing for chromosomal abnormalities. These become much more common as a woman ages and play a major part in the corresponding decline in fertility.
Oocytes are formed following a process of specialised cell division called meiosis, which produces an associated structure called the first polar body (PB1). On fertilisation, the oocyte produces a similar structure called the second polar body (PB2).
A new paper in Cell sets out a novel method using single-cell whole genome sequencing to examine human oocytes at high resolution. The approach uses multiple annealingand looping-based amplification cycle (MALBAC)-based sequencing technology to examine not only the oocyte genome but also those from the first and second polar bodies. The researchers show that this provides insight into the processes of genetic recombination that have taken place during oocyte maturation, and that the genomes of PB1 and PB2 can be used to deduce that of the mature oocyte.
The authors propose that MALBAC-based preimplantation genomic screening could provide ‘accurate and cost-effective selection of normal fertilized eggs for embryo transfer’ in IVF. The advantage of this approach is that it allows deduction of the genetic composition of the oocyte using the polar bodies alone, without manipulation of the fertilised oocyte or resulting embryo, and also permits more in-depth analysis of the genome for the presence of disease-associated genetic variants or aneuploidy (abnormal chromosomal number) than current approaches, such as array CGH (see previous news).
Comment: These results are exciting for experts interested in the genetic processes underlying oocyte formation and fertilisation, but it is the potential application of the techniques demonstrated for IVF screening that are of more general interest.
Given the very small sample sizes in the study (a total of eight Asian women and 70 oocytes) it is too early to be sure whether this approach will prove robust enough for use in routine IVF, but it could offer significant advantages – more accurate genomic analysis and at an earlier stage in the IVF cycle (simultaneous with egg retrieval as opposed to following fertilisation and growth).
It would not, however, allow the identification of any abnormalities inherited from the father, and so would have limited utility for pre-implantation genetic diagnosis (PGD) in families known to be affected by inherited diseases. It would also fail to detect any genetic abnormalities that can arise in the initial stages of embryonic cell division.