PGDIS Newsletter, May 24, 2017

Dear Colleague,

The 16th International conference on Preimplantation Genetics concentrated as usual on the areas of PGD progress with considerable impact on the evolving PGD standards and its wider application to the ART and genetic practices ( For the first time the approaches to the prospective identification of at-risk PGD couples were addressed, demonstrating an obvious value of the extended gene testing panels for the sperm and egg donors, and potentially for all the IVF patients. This can be seen from the progress in identification of couples at risk for common disorders, which has already resulted in the extended application of PGD for such reported borderline indications, as PGD for predisposition to cancer and heart disease, representing over 10% of the overall PGD experience for single gene disorders in some major references PGD centers.

As approximately three quarters of PGD are still done for chromosomal aneuploidies (PGD-A), one of the major emphasis was on the emerging problems in detection and interpretation of chromosomal variations with the use of the next generation technologies, and the progress in understanding the intrinsic and extrinsic factors in the origin of these abnormalities. Having reviewed these factors, the first evidence of specific genetic polymorphisms predisposing to aneuploidy was presented. No sufficient proof of the impact of controlled ovarian stimulation modalities, embryo culture conditions, lifestyle and environment were proven obvious, but their influence on epigenetic transgenerational inheritance cannot be excluded, representing a non-genetic form of inheritance, the role of which in embryo development and disease etiology has now become better understood.

New data were presented regarding the biological significance and reproductive impact of mosacism and segmental aneuploidy detected by next generation sequencing (NGS). As stressed in the PGDIS recommendations (, the transfer of mosaic embryos should be avoided, although limited data are being collected on the outcome following replacement of the mosaic embryos, which may provide useful information for proper counseling of these patients when mosaicism and segmental anomalies are detected. On the other hand, comparison of types and frequency of these abnormalities in preimplantation embryos and spontaneous abortions showed comparable rate for mosaicism, and five-fold lower rate of segmental imbalances in spontaneous abortions. This may suggest that the majority of segmental aneuploidies are not compatible with implantation, but at least some proportion of them as well mosaic abnormalities still survive implantation and contribute to fetal loss, which may explain the unexplained miscarriages following PGD-A, using low resolution methods. For particular interest in this respect was a reported mouse model of mosaicism, which could be of a great potential for understanding the nature and biological significance of this phenomenon in preimplantation development.

Further data were presented on the potential factors contributing to the outcome of euploid embryo transfer, such as the influence of cytoplasmic DNA contents, follicular environment and genetic expression related to euploid oocyte competence, as well as by endometrial receptivity. Randomized Controlled Trial (RCT) on the latter is still underway to make conclusion, while contradictory results were obtained regarding the impact of mt-DNA copy number. On the other hand, novel information on a possible selection against mtDNA mutations in human oocytes was reported. It was suggested that it occurs through the extrusion of the first polar body, while the contents of the second polar body represents the exact genetic status of the oocyte. However, there seems to be no known mechanism of how this purification process is controlled in oogenesis.

Finally, the results of a well designed RCT on the reproductive impact of PGD-A performed by array-CGH at the cleavage stage was reported, demonstrating significantly improved implantation and delivery rates, with an extraordinary high reduction of spontaneous abortions. However, despite the lack of any detectable damage of the applied invasive procedure in this study, and considerable improvement of biopsy techniques at the present time, particularly with the shift from cleavage to blastocyst stage, the potential negative effect of embryo biopsy cannot be excluded. So a number of attempts for non-invasive PGD were reviewed, showing that the currently applied approaches with the use of spent media have still considerable limitations, not allowing their possible application for practical purposes. On the other hand a great progress was achieved in the development of non-invasive prenatal tests (NIPT), suggesting the future prospect for PGD follow up by NIPT.

The next PGD Conference will be held in Singapore, April 29-May 2, 2018 (see the preparations for the Conference program at the PGDIS website - (

Anver Kuliev, MD, PhD
Svetlana Rechitsky, PhD
Executive Director of PGDIS President of PGDIS