Dear Colleague,

The 12th International PGD conference, held in Istanbul, May 8-11, 2013 (see PGDIS website www.pgdis.org) was devoted to clinical aspects of PGD and the accuracy of the expanded application of microarray-based technology for testing of oocytes and embryo. The focus was on the controversial issues, involving the application of PGD to improve pregnancy rates in assisted reproductive technology (ART), and the growing application of PGD approaches for improving reproductive outcome in poor prognosis ART patients.

The special emphasis was on the clinical challenges with the application of technological developments in PGD practice, as well as on those clinical issues which have not previously been explored in relation to PGD, such as the effect of controlled ovarian stimulation (COS) on aneuploidy rates and endomential receptivity, choice of appropriate stimulating protocols and efficacy and appropriateness of biopsy procedures.

Having reviewed available experience on COS for different PGD indications, requirement for specific COS regiments was demonstrated for a number of conditions, such as FMR1 and myotonic dystrophy. While there was no evidence reported on the impact of COS on aneuploidy rates, it was demonstrated that COS does significantly affect endometrial receptivity, which coupled with cleavage stage biopsy that may alter the embryo development, significantly affects implantation rate. This may explain the less than expected or even no improvement of implantation rate following the cleavage stage aneuploidy testing, previously reported but especially evident in the centers with insufficient experience in embryo biopsy procedures. This is in contrast to significantly improved implantation and pregnancy rates following blastocyst biopsy testing, vitrification and frozen transfer now reported in many centers around the world. It was noted however that good results were also achievable with other biopsy procedures, including polar body or blastomere sampling. This could be seen to suggest that any center doing PGD may require expertise in a variety of biopsy approaches. The decision as to which procedure to use, if any, may be determined by the patient’s own requirements and expectations regarding transfer and nature of testing..

The other major area was the review of the advantages and disadvantages of the recent technological breakthroughs for genetic testing, including microarray-based testing and the next-generation sequencing (NGS) application to PGD. Following the analysis of biological evidence for positive impact of aneuploidy testing, and the reasons why such benefit was undetected in the previous randomized controlled trials (RCT), the data were presented on the clinical evaluation of the aneuploidy testing outcome, based on microarray-based technology, depending on the biopsy procedures and microarray technology application.

Although more data are still needed to better tabulate the expected microarray error rates, a comprehensive aneuploidy testing for 24 chromosomes is steadily and quickly replacing FISH. The available data already provide strong evidence on the improved implantation rates and reproductive outcome after microarray-based aneuploidy testing. In combination with appropriate biopsy, these improvements are particularly evident in patients of advanced reproductive age. The data are also in agreement with the reported preliminary results of the ongoing RCT on the clinical outcomes of 24 chromosome aneuploidy testing.

Microarray-based technology is currently looking to be universal for PGD of chromosomal rearrangements, with almost no need for initial work-up prior to PGD. However, sufficient band level (650) on parental karyotypes is required for proper consideration on the choice of FISH or microarray-based approach, which sometimes may not be sufficiently accurate for testing smaller rearrangements, or a small fragments at a particular position- at least with the most common array platform now in use. New array processes may overcome some of these limits and offer a broader scope for chromosome and genetic testing.

There was also a dramatic progress in NGS, showing that it may currently be applied to single cells, which provides the basis for a comprehensive PGD for both single gene and chromosomal disorders in one test and same biopsy material. However, the technique still has significant technical considerations and limitations in detecting ADO, testing for dynamic mutations and avoiding misdiagnosis due to pseudogenes, which can presently be done reliably by traditional methods.

A large body of data was reviewed, showing the expanding PGD application to common late-onset conditions, already impacting the preventive strategy for common diseases of public health importance, such as inherited cancers and cardiac disease. The proportion of these cases in the overall practice of PGD for monogenic disorders is already exceeding 10% in the leading PGD centers at the present time. The other area of the recent PGD expansion is its use for HLA typing, as an approach for at risk couples to produce an unaffected progeny that is HLA matched to their affected sibling, requiring stem cell transplantation treatment. Hundreds of HLA matched children have recently been born and the follow up data of the HLA identical stem cells transplantation treatment show an extremely high success rate of radical treatment of congenital disorders and immunodeficiencies. The first such follow up data were presented for the largest series of HLA-identical stem cells transplantation treatments in Turkey, showing the success of engraftment and full recovery of as many as 44 of a total 48 affected siblings with 10 different conditions. While still considered controversial in some countries, this approach provides the basis for further applications of this valuable cell therapy for congenital disorders and immunodeficiencies, and for which there is still no alternative general treatment available.

To support the growing demand for blastocyst biopsy, which steadily is replacing cleavage stage embryo biopsy, the Post-Congress Hands-on Workshop on the procedure, combined with novel methods for genetic testing, was organized for the fifth time. The next, 13th International PGD Conference will be organized in Canterbury, UK, April 29-May 2, followed by another Post-Congress Hands-on Workshop on PGD by Blastocyst Biopsy in Istanbul, May 3-5, 2014 (see the program of the Workshop on PGDIS website www.pgdis.org), and then International PGD Conference will be held in Chicago, USA, in 2015, where the 1st International PGD Conference was organized in 1990, to celebrate 25th anniversary of PGD.

Sincerely,