The Ronald O. Perelman and Claudia Cohen "Center for Reproductive Medicine" - of Weill Cornell Medical College

Cornell’s Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS) Program

First in Preimplantation Genetic Diagnosis in the United States

In 1993, the United States’ first PGD baby was born to a CRM patient. Led by Dr. Kangpu Xu, Cornell’s Preimplantation Genetic Diagnosis Laboratory has since produced many other PGD “firsts,” and hundreds of CRM patients have become parents to healthy babies following PGD/PGS over the last two decades.

As one of the few New York State Department of Health-certified PGD labs, we provide patients top-quality, comprehensive PGD and PGS clinical services.

What are PGD and PGS?

Performed as part of an in vitro fertilization (IVF) cycle, PGS and PGD diagnostic services are an option for patients whose oocytes or embryos are at risk for chromosomal abnormality or genetic disease. Since PGD and PGS are performed prior to embryo transfer and pregnancy, they lessen the chance of a disease or chromosomal problem being found using amniocentesis, chorionic villous sampling (CVS) or other prenatal tests. Thus, PGD and PGS increase the chances of establishing a pregnancy with an unaffected embryo(s).

Quick glance: Who might benefit from PGD or PGS?

PGD/PGS may benefit prospective parents in these situations:

  • Women or couples with a family history of genetic disorders such as cystic fibrosis
  • Women of advanced maternal age, whose eggs have a greater chance of chromosomal abnormalities
  • Couples who carry a gene for a sex-linked disease such as hemophilia
  • Women with two or more miscarriages (recurrent miscarriage)
  • Couples where one or both partners has a chromosomal translocation
  • Couples in need of  human leukocyte antigen (HLA) testing
  • Patients interested in using PGS to help select an optimal single embryo for transfer


Preimplantation Genetic Diagnosis (PGD)

PGD can identify an embryo unaffected by heritable genetic disease before transfer to the uterus, the last step of IVF. Embryos or oocytes are biopsied with a microscopic needle. The removed cell or cells are then analyzed to detect genetic mutations that cause diseases. Almost any single-gene disease for which mutations have been identified can be diagnosed in an oocyte or embryo using PGD.

Patients who have a question about specific conditions are encouraged to contact CRM to set up an initial consultation with a physician to discuss IVF with PGD. PGD can greatly increase parents' chances of having a child that is unaffected by heritable genetic disease, including sex-linked diseases, cystic fibrosis and hundreds of other disorders.

               Polar body biopsy of oocyte.jpgBlastomere biopsy.jpgTrophectoderm biopsy.png

Above, L-R: Biopsy of oocyte (egg), blastomere (3-day-old embryo) and trophectoderm biopsy of a 5-day-old embryo

CRM frequently tests embryos for the following diseases using PGD:

  • Beta-thalassemia
  • Cancer predisposition genes (BRCA1 and others)
  • Cystic fibrosis
  • Duchenne muscular dystrophy
  • Fragile X syndrome
  • Huntington’s disease
  • Multiple endocrine neoplasia
  • Retinoblastoma
  • Sickle cell anemia
  • Tay-Sach’s disease

Nearly any patient carrying a common or rare disorder due to a genetic mutation is a candidate for PGD. In order to test patients’ embryos, CRM’s PGD Laboratory may apply existing in-house diagnostic protocols, develop a new protocol specific to the patient or arrange for the oocytes or embryos to be tested at an accredited referral laboratory. Patients interested in PGD discuss its benefits and limitations with the Center’s genetic counselor as well as their physician to determine if they are appropriate candidates for PGD.

The PGD Process: Genetic Counseling and Protocol Design

Patients who are interested in PGD make an appointment with one of Cornell’s physicians. After an initial consultation, patients meet with the genetic counselor to discuss patient and family history and evaluate the risk of having a child with an inherited disorder. Blood may be drawn for genetic testing to confirm genetic mutations or chromosomal abnormalities. Depending on the condition, the PGD lab may need six weeks to two months to design a protocol that can be used to test a specific patient's embryos. Once the PGD protocol is ready, the patient proceeds to IVF, including ovarian stimulation and oocyte retrieval.

PGD/PGS is performed at specific embryonic developmental stages as deemed best for the condition in question at either CRM's PGD laboratory or at a specialized referral laboratory. Unaffected embryo(s) may be transferred to the patient immediately, while any remaining unaffected embryos may be cryopreserved for a future pregnancy.   

Preimplantation Genetic Screening (PGS)

The gain or loss of an entire chromosome or chromosome segment occurs frequently during the maturation of eggs and sperm as well as during early embryonic (post-fertilization) development. Chromosomal abnormality, or aneuploidy, in eggs also increases significantly as women age. Such abnormalities may cause a pregnancy to be miscarried or severe health problems in the child if the pregnancy goes to term.

PGS identifies chromosomally normal embryos ("euploid" embryos) for transfer to the uterus in the last step of an IVF cycle. Patients with a history of recurrent miscarriage or failed IVF cycles, which can be linked to chromosomal abnormality, may benefit from PGS. In addition, patients may also undergo PGS with the goal of transferring a single embryo.

Like PGD, PGS includes the biopsy and analysis of cell material from oocytes or embryos.

CRM uses array comparative genomic hybridization (aCGH) microarray technology, which allows for the testing of all 23 chromosomes. Earlier forms of PGS utilized a sensitive single-cell FISH (fluorescence in-situ hybridization) technology on cells taken from embryos to screen 9-12 chromosomes. FISH is still available at CRM, as it is useful for the detection of chromosome translocation in cases when microarray may not be used. 

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PGS using array CGH of a normal 46,XY male embryo.

Trisomy 18 PGS.png

Array CGH reveals an extra chromosome 18 (elevation at chromosome 18 in the figure, circled), a condition known as trisomy 18. 

PGS image.png

PGS using FISH to detect chromosome translocation. Two red and two green signals indicate a normal embryo with balanced chromosomes.

PGD Research at CRM

PGD and PGS are evolving technologies whose potentials are yet to be realized. CRM’s PGD team is currently developing a next-generation DNA-sequencing platform that will combine PGD and PGS in a single test intended to detect nearly all disorder-causing mutations as well as screen all 23 pairs of chromosomes.