Preimplantation Genetic Diagnosis (PGD)

Preimplantation genetic diagnosis (PGD) is a laboratory technique that permits genetic analysis of embryos prior to embryo transfer. This allows for embryo transfer of only those embryos which are free of specific genetic disorders or chromosomal abnormalities. Couples with a family history of specific genetic diseases or recurrent pregnancy loss due to a chromosomal abnormality, who are found to be carriers of the defective genes or chromosomes, can have PGD performed on their embryos in order to avoid transfer of affected embryos.

Prior to the advent of PGD, couples who were carriers for a genetic disease had to resort to prenatal testing in the first trimester (chorionic villus sampling = CVS), or in the second trimester (amniocentesis), to determine whether their fetus was affected with the disease. This meant that a definitive diagnosis would not be obtained prior to 11-13 weeks gestation (in the case of CVS), or 16-18 weeks gestation (in the case of amniocentesis), before the couple had the option of terminating an affected fetus. Moreover, many couples who consider such a therapeutic abortion unacceptable would have no option but to continue carrying the pregnancy and thus deliver an affected child. The anxiety associated with not knowing whether the fetus is affected, along with the devastation of having to terminate or deliver an affected child, is immense. PGD gives couples the reassurance that they would not have to face such anxiety as they plan their next pregnancy.

In order for PGD to be performed, couples must undergo IVF to allow for the formation of early embryos in the laboratory. When embryos are three days old (typically containing 6-8 cells), a biopsy is performed by inserting a small needle into each embryo and removing 1 or 2 cells (called blastomeres). Various techniques of gene amplification and chromosomal analysis are next applied in order to analyze removed blastomeres for their genetic make-up. Embryos determined to be abnormal are discarded and normal embryos are transferred into the uterus within 48 hours of the procedure. The safety of PGD has been documented in numerous animal and human studies.

PGD Indications:

• Autosomal Recessive Disorders
  PGD may be performed for detection of specific autosomal recessive disorders. If a man and woman are found to be carriers of an autosomal recessive genetic disorder (Cystic Fibrosis, Tay-Sachs, Thalassemia, Gaucher's...), their offspring has a 25% risk of being affected by the disease. This means that out of every four embryos created with in vitro fertilization (IVF), one embryo will be affected with the disease and three embryos will be unaffected. PGD would allow identification of the unaffected embryos so that they may be transferred into the uterus safely.



• Autosomal Dominant Disorders
  PGD may also be performed for autosomal dominant genetic diseases (Achondroplasia, Huntington's Chorea, Adult Polycystic Kidney Disease...). In such diseases, one parent is typically affected with the disorder and has a 50% chance of transmitting the disorder to their offspring. This means that out of every four embryos created with IVF, two embryos will be affected with the disease and two embryos will be unaffected. Again, PGD would allow identification of the unaffected embryos for transfer.
  


• Sex-Linked Disorders
  PGD is further performed for the detection of sex-linked genetic disorders (Duchenne Muscular Dystrophy, Hemophilia...). In such diseases, one of the parents is a carrier of a specific mutation on one of their sex chromosomes (typically the X chromosome). In the case of an X-linked disease, if the female partner is a carrier, there is a 50% chance that if the couple has a male offspring, the boy will be affected with the disease (50% of males are affected). Female offspring have a 50% chance of being carriers, however they typically do not manifest the disease. Therefore, if the disorder of concern is an X-linked disease, PGD may be employed to determine the gender of each embryo conceived with IVF (out of every 4 embryos conceived, two will be male and two will be female). Then, couples have the option of transferring only female embryos, which are not affected with the disease. If gender selection is not desired, PGD can be performed to determine if an embryo is affected with the disease, and transfer of that embryo can be avoided.
  


• Recurrent Pregnancy Loss (Habitual Abortion)
  Couples who have experienced two or more miscarriages may have an underlying problem predisposing them to such miscarriages. One possible cause for recurrent miscarriages may be a chromosomal abnormality in one of the parents. Although various chromosomal abnormalities may lead to miscarriages, the most common abnormality is termed a chromosomal translocation (Robertsonian or reciprocal translocation). Having a translocation in one of the parents predisposes to the formation of abnormal gametes (eggs or sperm), which then leads to chromosomally abnormal embryos. Such embryos are prone to miscarriage. Occasionally, such embryos may develop into anomalous fetuses with a chromosomal aberration (like Down syndrome). When a chromosomal abnormality such as a translocation is identified in one of the parents, a specific chromosomal probe can be developed, which may then detect such abnormality in embryos conceived with IVF. Using a technique called preimplantation genetic screening (PGS) (see below) embryos affected with a chromosomal abnormality can be excluded from transfer, thereby reducing the likelihood of carrying an anomalous fetus and of miscarriage.
  

Virtually every genetic disease can be tested for and diagnosed with PGD. The California Center for Reproductive Health is proud to offer PGD to couples in need.