Preimplantation Genetic Diagnosis (PGD)

Preimplantation Genetic Diagnosis and Preimplantation Genetic Screening by: Edward Marut, MD (Reproductive Endocrinologist)

Preimplantation Genetic Diagnosis or PGD is a technique used with In Vitro Fertilization- Embryo Transfer (IVF-ET). It deals with the analysis of chromosomal number, chromosomal structure or individual genes of an embryo resulting from IVF. The goal is to transfer embryos that have been screened for abnormalities, so that the resulting pregnancy has the greatest chance of being normal. Both IVF Centers of Fertility Centers of Illinois, Highland Park IVF and River North IVF, offer this service.

The three major uses of PGD are diagnoses of single gene defects, either recessive (like cystic fibrosis), dominant (like polycystic kidney) or X-linked (like hemophilia, where only males are affected), detection of carriers of unbalanced chromosomal structural abnormalities (like translocations or inversions, which usually result in miscarriages) and most commonly, Aneuploidy screening (commonly called Preimplantation Genetic Screening or PGS) looking for either polyploidy (too many copies of all the chromosomes), extra copies (trisomy, such as trisomy 21, which causes Down Syndrome) or missing copies (monosomy) of individual chromosomes. Any of these chromosomal abnormalities may cause Infertility, miscarriages, or the delivery of an abnormal baby.

The reason a couple use PGD is obviously the personal or family history of someone affected by the disease caused by a single gene defect. It could be the known existence of a balanced translocation or inversion in one of the partners attempting pregnancy, determined from previous pregnancy losses or infertility. Advanced maternal age, which increases the chances of infertility, miscarriage and an ongoing pregnancy with an abnormal Fetus, would be another reason. Recurrent miscarriage at any age, where either a chromosomal cause has been determined, or after elimination of non-genetic causes, justifies the use of PGD or PGS. A previously chromosomally abnormal fetus or offspring or family history of the same would be a reason to use PGD. For patients going through infertility treatment, maximizing the chance of a normal pregnancy could justify PGD or PGS, and recurrent IVF failure can often be explained by PGD  or PGS findings. PGS may also help in the selection of normal embryos when testicular or highly abnormal sperm are used. Even fertile couples, who may be reluctant to do invasive prenatal genetic testing, or would refuse to abort an abnormal fetus might find PGS helpful. The incidence of an abnormal fetus in a pregnancy arising from IVF with PGS is not eliminated, but markedly reduced. In general, aneuploid screening detects abnormalities of chromosomes that are responsible for up to 90% of pregnancy losses and ongoing aneuploidy. The error in the testing is around 5%, largely due to mosaicism, where both normal and abnormal cells co-exist in one embryo. 9 chromosomes are usually tested; testing for more chromosomes or specific chromosomal abnormalities can also be tailored to fit a couple's needs. Newer techniques, such as Comparative Genomic Hybridization or Microarray Analysis may improve the accuracy of PGS and PGD and the clinical usefulness. Selection of one of these techniques by the physician and embryologist may be advisable in certain situations.

To perform standard PGD or PGS during an IVF Cycle, the embryo biopsy (removal of one, or rarely, two cells) on the day 3 embryo (4-8 cell stage) is performed and the cell sent to a reference laboratory while the embryo continues to develop in our IVF lab. The results take 1-2 days, and the transfer of any embryo is determined first by genetic information, and then by the developmental quality, or microscopic appearance of the embryos. PGD might not be useful in the patient who has embryos that are poorer quality or fewer in number than desirable; other alternatives would be better. The use of PGD in IVF has become more common and more successful, and can provide critical information for a couple, even more than the achievement of a normal pregnancy in the treatment cycle. It can explain fertility treatment failures, recurrent miscarriages, and either provide closure for the older patient in attempting pregnancy using her own eggs or encourage further tries.