Abstract
Pre-implantation genetic diagnosis for aneuploidy testing (PGD-A) is a tool to identify euploid embryos during IVF. The suggested populations of patients that can benefit from it are infertile women of advanced maternal age, with a history of recurrent miscarriages and/or IVF failures. However, a general consensus has not yet been reached.After the clinical failure of its first version based on cleavage stage biopsy and 9 chromosome-FISH analysis, PGD-A is currently performed by 24 chromosome screening techniques on trophectoderm (TE) biopsies. This approach has been clearly demonstrated to involve a higher clinical efficiency with respect to the standard care, in terms of sustained pregnancy rate per transfer and lower miscarriage rate. However, data about PGD-A efficacy calculated on a per intention-to-treat basis, as well as an analysis of its cost-effectiveness, are still missing.TE biopsy is a safe and extensively validated approach with low biological and technical margin of error. Firstly, the prevalence of mosaic diploid/aneuploid blastocysts is estimated to be between 0 and 16 %, thus largely tolerable. Secondly, all the comprehensive chromosome screening (CCS) technologies adapted to, or designed to conduct PGD-A are highly concordant, and qPCR in particular has been proven to show the lowest false positive error rate (0.5 %) and a clinically recognizable error rate per blastocyst of just 0.21 %.In conclusion, there is a sufficient body of evidence to support the clinical application of CCS-based PGD-A on TE biopsies. The main limiting factor is the need for a high-standard laboratory to conduct blastocyst culture, biopsy and vitrification without impacting embryo viability.
Highlights
Pre-implantation genetic diagnosis (PGD) in assisted reproductive technologies (ART) is suited to many inheritable genetic disorders caused by a known mutation and chromosome structural abnormalities, in order to increase the chance of delivering a healthy baby
Real mosaicism and methodological aspects can impact the reliability of the diagnosis due to false positive errors, up to date, there has been no evidence at all from well-designed pre-clinical studies that this is a major issue in the application of PGD-A as long as validated technologies are used for comprehensive chromosome screening (CCS)
Nowadays and ever since PGD-A was introduced in the clinical practice, the counselling given to a couple has changed dramatically
Summary
Pre-implantation genetic diagnosis (PGD) in assisted reproductive technologies (ART) is suited to many inheritable genetic disorders caused by a known mutation and chromosome structural abnormalities, in order to increase the chance of delivering a healthy baby. In a review published in 2015 [15], Lee and colleagues summarized all the RCTs, observational and prospective studies that approached CCS-based PGD-A in comparison to the standard care They were able to show that in both young and AMA patient populations, PGD-A results in a higher delivery rate per embryo transferred. It should be acknowledged though that the efficacy of PGD-A, namely the possibility to obtain the same delivery rate per intention to treat with respect to the standard care, is still to be demonstrated This is a critical aspect since it would prove that by extending the culture to the blastocyst stage, by performing TE biopsy and CCS, and by adopting a freeze-all and SET strategy, we are not causing any harm to the intrinsic reproductive potential of the embryo itself. Regardless, it is of critical importance to provide comparative data about the cost-effectiveness of PGD-A in all the different settings in the future
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