First systematic experience of preimplantation genetic diagnosis for single gene disorders and or preimplantation human leukocyte antigen typing combined with 24 chromosome aneuploidy testing
Increased pregnancy and reduced 3-fold spontaneous abortion rates were observed in a series of 317 PGD cycles with combined single-gene, and/or HLA typing, and 24-chromosome aneuploidy testing.
Svetlana Rechitsky, Ph.D., Tatiana Pakhalchuk, M.S., Geraldine San Ramos, M.S., Adam Goodman, B.S., Zev Zlatopolsky, M.S., Anver Kuliev, M.D., Ph.D.
Volume 103, Issue 2, Pages 503-512
To study the feasibility, accuracy, and reproductive outcome of 24-chromosome aneuploidy testing (24-AT), combined with preimplantation genetic diagnosis (PGD) for single-gene disorders (SGDs) or human leukocyte antigen (HLA) typing in the same biopsy sample.
Preimplantation genetic diagnosis center.
A total of 238 PGD patients, average age 36.8 years, for whom 317 combined PGD cycles were performed, involving 105 different conditions, with or without HLA typing.
Whole-genome amplification product, obtained in 24-AT, was used for PGD and/or HLA typing in the same blastomere or blastocyst biopsy samples.
Main Outcome Measure(s):
Proportion of the embryos suitable for transfer detected in these blastomere or blastocyst samples, and the resulting pregnancy and spontaneous abortion rates.
Embryos suitable for transfer were detected in 42% blastocyst and 25.1% blastomere samples, with a total of 280 unaffected, HLA-matched euploid embryos detected for transfer in 212 cycles (1.3 embryos per transfer), resulting in 145 (68.4%) unaffected pregnancies and birth of 149 healthy, HLA-matched children. This outcome is significantly different from that of our 2,064 PGD cycle series without concomitant 24-AT, including improved pregnancy (68.4% vs. 45.4%) and 3-fold spontaneous abortion reduction (5.5% vs. 15%) rates.
The introduced combined approach is a potential universal PGD test, which in addition to achieving extremely high diagnostic accuracy, significantly improves reproductive outcomes of PGD for SGDs and HLA typing in patients of advanced reproductive age.