Preimplantation genetic screening for aneuploidy
- Glenn L Schattman, MD
Glenn L Schattman, MD
- Associate Professor of Reproductive Medicine
- The Ronald O Perelman and Claudia Cohen Center for Reproductive Medicine
- The Weill Medical College of Cornell University
- Kangpu Xu, PhD, HCLD
Kangpu Xu, PhD, HCLD
- Associate Professor
- Director, Laboratory of Preimplantation Genetics
- Center for Reproductive Medicine
- Weill Cornell Medical College of Cornell University
There are two types of genetic testing of an embryo prior to transfer: preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). Both procedures require in vitro fertilization even if the couple is not subfertile, biopsy of in vitro embryos for genetic testing, and transfer of embryos based on the results of genetic testing. Genetic testing can also be performed on the first and second polar bodies obtained from mature oocytes prior to and after fertilization.
This topic will discuss issues related to PGS. PGD is reviewed separately. (See "Preimplantation genetic diagnosis".)
ROLE OF PGS VERSUS PGD
●Preimplantation genetic screening (PGS) – The goal of PGS is to identify de-novo aneuploidy, including subchromosomal deletions and additions, in embryos of couples known (or presumed) to be euploid. Forty to 60 percent of preimplantation embryos are aneuploid, which is one potential etiology for the relatively low implantation efficiency of both natural conceptions and in vitro fertilization (IVF) . Theoretically, performing IVF, determining the genetic status (chromosomal copy numbers) of the preimplantation embryos, and then selecting only euploid embryos for embryo transfer should increase the frequency of successful implantation, pregnancy, and live birth. This process should also reduce multiple pregnancy rates by allowing efficient single embryo transfers. Examination of embryo morphology and rate of development under the microscope or with a time-lapse system is routinely performed for this purpose, but is an inexact method for selecting embryos with the highest implantation potential or distinguishing euploid embryos from aneuploid embryos.
●Preimplantation genetic diagnosis (PGD) – The goal of PGD is to establish a pregnancy that is unaffected by a specific gene mutation(s) when one or both biologic parents is a known carrier of a specific gene mutation(s). Additionally, PGD can be used to identify an unbalanced chromosomal complement when one parent is a carrier of a balanced translocation or chromosomal rearrangement. It is also used to select embryos for transfer that have a specific genetic complement, such as particular sex chromosomes or human leukocyte antigen (HLA) type. For example, if a child has Fanconi anemia, a sibling with a compatible HLA type and absence of Fanconi anemia could become a donor for hematopoietic cell transplantation. (See "Preimplantation genetic diagnosis", section on 'Reasons couples choose to undergo PGD'.)
Advantages versus alternative procedures — Trophectoderm biopsy of embryos at the blastocyst stage rather than the cleavage stage (day 3 of development) is becoming more common. This is mainly due to improvements in culture conditions, resulting in more consistent survival of cultured embryos to the blastocyst stage; improvements in biopsy techniques; improvements in cryopreservation of blastocysts, mainly vitrification; and evidence that cleavage stage biopsy reduces the take-home baby rate compared with not performing the biopsy .
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- ROLE OF PGS VERSUS PGD
- BLASTOCYST BIOPSY
- Advantages versus alternative procedures
- Array comparative genomic hybridization and single nucleotide polymorphism arrays
- - Karyomapping
- - Fluorescence in situ hybridization
- Alternative procedures
- - Polar body biopsy
- - Cleavage stage biopsy
- LIMITATIONS OF PGS
- CLINICAL USE
- Settings where PGS has potential clinical utility
- - Planned single embryo transfer
- Settings where clinical utility of PGS is unproven
- - Recurrent in vitro fertilization implantation failure
- - Advanced maternal age
- - Recurrent early pregnancy loss
- NEONATAL AND EARLY CHILDHOOD OUTCOMES
- SUMMARY AND RECOMMENDATIONS