TOPIC
• Preimplantation genetic diagnosis
CLINICAL BOTTOM LINE
• Preimplantation genetic diagnosis (PGD) is an assisted reproductive technology (ART) that evaluates embryos for genetic conditions prior to implantation. It is a highly accurate method of selecting unaffected embryos for implantation and pregnancy.1
• PGD requires in vitro fertilization (IVF) combined with genetic testing of one or two cells removed from the embryos. Based on the test results, unaffected embryos are then selected and transferred to the uterus before day 6. Prenatal diagnosis by chorionic villus sampling (CVS) or amniocentesis is recommended, but not required, to confirm the genetic status of any resulting pregnancy.
• Couples who utilize this technology significantly reduce their risk of having an affected child, help to eliminate an undesirable genetic condition from future generations, and avoid facing the decision of terminating a planned and desired pregnancy. Indications for PGD are described in Table: Indications for PGD and PGS (in the online version of this article).
• Primary care management pearls
– Before PGD, referral to genetic counseling is crucial to ensure patients fully understand the risk of having an affected child, the potential impact of disease on an affected child, and the benefits and limitations of all available options for PGD and prenatal diagnosis.2
– Patients should be informed of the full scope of the procedure and counseled regarding the financial costs, risks, and success rates.
– During counseling, patients considering PGD should be informed that no embryos will be transferred if they are all predicted to be affected. A plan for unused embryos (cryopreservation, donation, research, discard) and all possible options to avoid genetic disease, including gamete donation, should also be discussed.3
– When selecting a PGD provider, patients and clinicians should consider several factors, including the following: the laboratory's experience with the type of testing requested, biopsy and molecular methodology, the center's error and success rates, and cost.
WHAT IS PGD?
• Preimplantation genetic diagnosis was developed in the early 1990s as a method of reducing the risk of genetic disease in families with known X-linked recessive disorders by applying molecular genetics to test embryos derived from IVF for gender. This technology has greatly expanded, making it possible for molecular diagnostic techniques to evaluate a single cell for cytogenetic abnormalities or one of hundreds of single-gene disorders.
• Currently, PGD is proposed for couples at risk of having a child with a genetic condition who wish to avoid pregnancy termination. PGD is a lengthy process that can be emotionally taxing and stressful. Couples work closely with a team of genetic counselors, genetic specialists, and reproductive specialists to coordinate the procedure.
• Although PGD can significantly reduce the chance of the birth of a child with a genetic disorder, inconclusive or incorrect results are possible. Prenatal diagnosis by CVS or amniocentesis is recommended to confirm the genetic status of any pregnancy resulting from PGD.
• Preimplantation genetic screening (PGS) is currently proposed for
– Couples with repeated implantation failure following assisted reproduction treatments that transfer normal karyotypic embryos to enhance pregnancy success
– Couples with repeated unexplained early miscarriages
– Women of advanced maternal age, in order to avoid chromosomally abnormal offspring and to improve the success of IVF procedures
– Severe male factor infertility4
• Common applications for PGD and PGS with examples are available in Table: Indications for PGD and PGS in the online version of this article.