Pre – Implantation Genetic Testing – PGD

Preimplantation genetic diagnosis (PGD) offers the possibility of a genetic diagnosis during an IVF cycle in order to increase the potential of a successful embryo transfer and implantation. It is a genetic test on the embryo cells that helps the embryologists select the best embryo(s) that are free of a genetic disease. Preimplantation genetic diagnosis (PGD) was developed due to the need to provide an alternative to prenatal diagnosis for couples that face the risk of transmitting a genetic disease to their children. Preimplantation Genetic Diagnosis and Screening (PGD/PGS) for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aiming at identifying non affected and/or euploid embryos in a cohort produced during an IVF cycle. It is recognized as an important alternative to pre-natal diagnosis. Re-implantation embryo diagnosis requires in vitro fertilization, embryo biopsy with either using fluorescent in situ hybridization or polymerase chain reaction at the single cell level. In the late 1980s, many teams worldwide were attempting clinical PGD, including the Hammersmith team in London. In synthesis, PGD/PGS is a powerful tool to reach the goal of a pregnancy and attenuate its adverse events. In order to achieve this goal, it is mandatory not to significantly harm the embryo during the biopsy and to preserve its viability and reproductive potential.


Who should consider PGD?

PGD could be considered as an option in cases of:

  • Couples with an increased risk for chromosome abnormalities or specific genetic diseases. This includes women who have had several miscarriages, or who have had a prior pregnancy with a chromosome abnormality.

Women over the age of 38 and men with some types of sperm abnormalities may also produce embryos with higher rates of chromosome abnormalities. In addition, if a person carries a rearrangement of the chromosomes, PGD can identify which embryos have a normal amount of chromosomal material. When there is a 25% or 50% chance to have a child affected with a specific genetic disease, PGD can be designed to identify which embryos are affected, unaffected, or a carrier (if applicable) for that disease. Then, only embryos without the disease are transferred to the uterus to attempt pregnancy.


Assisted reproduction and fetal genetic material in PGD

In the majority of the reported cycles, intracytoplasmic sperm injection (ICSI) is used instead of IVF. The main reasons are to prevent contamination with residual sperm adhered to the zona pellucida and to avoid unexpected fertilization failure. The ICSI procedure is carried out on mature metaphase-II oocytes and fertilization is assessed 16–18 hours after. The embryo development is further evaluated every day prior to biopsy and until transfer to the woman’s uterus. During the cleavage stage, embryo evaluation is performed daily on the basis of the number, size, cell-shape and fragmentation rate of the blastomeres. On day 4, embryos were scored in function of their degree of compaction and blastocysts were evaluated according to the quality of the throphectoderm and inner cell mass, and their degree of expansion.


Clinical practice

The experience of Medical Genetics Laboratory has been practiced in PGD for monogenic diseases over the last 13 years, in the Medical laboratory of the National and Kapodistrian University of Athens, such as:

  • Mediterranean hemopathic syndromes
  • Cystic fibrosis(CF)
  • Superior mesenteric arterysyndrome(SMA)
  • X-linked recessive inheritance as Duchenne muscular dystrophy
  • The fragile X syndrome
  • (Congenital Lipoid Adrenal Hyperplasia – CLAH).

Also we examined and dealt with rare diseases such as:

  • Glycogen Storage Disease – GSD
  • Spastic paraplegia 3A (SPG3A)
  • Leber’s Congenital   Amaurosis   –   LCA
  • Marfan syndrome(MFS)
  • Autosomal recessive polycystic kidney disease(ARPKD)
  • Neurofibromatosis type I(NF-1)
  • Myotonin-protein kinase(DM1)

All the above diseases are having conspicuous signs and symptoms, but instead all that CF relates with males infertility. The Greek population of men, reaches the 70% of congenital absence of vans deference and the remaining 30% suffers by obstructive azoospermia. Mediterranean syndromes and CF are two of the most common diseases in the Greek population. 10% of the population are carriers of   β-thalassemia,  (Mediterranean anemia or Cooley anemia), hemoglobin pathologies, such as sickle cell anemia or drepanocytosis  and 5% are carriers of CF. More than 80 mutation have been detected into CFTR gene , which is responsible for CF and hemoglobin beta gene. Based on the data the 85% of the CFTR gene mutations are located in 7 of the 27 gene exons and 97% in the hemoglobin beta gene are located in the first half of the gene, we designed and improved two flexible and easily adopted protocols.


Ethical, Legal and Social Issues Relating to PGD

Considerable differences in the regulatory oversight of PGD exist among countries, ranging from total bans on any embryo manipulation to the almost complete absence of any regulations or authority. The high cost of practice, low pregnancy rate, problems with patient access and insurance coverage appear to be the biggest drawbacks to universal acceptance in societal terms. Ethical discussions considering the moral status of the human embryo and what constitutes severe genetic disease have been debated elsewhere but such discussions are clearly outside of the purview of this methodological review. Somewhat reassuring for those centers currently offering PGD is the acknowledgment from professional organizations that PGD can now be considered a “standard of care” rather than an experimental treatment


Who can benefit from PGD?

Preimplantation genetic diagnosis can benefit any couple at risk for passing on a genetic disease or condition.


The following is a list of the type of individuals who are possible candidates for PGD/PGS:

  • Carriers of sex-linked genetic disorders
  • Carriers of single gene disorders
  • Those with chromosomal disorders
  • Women aged 35 and over
  • Women experiencing recurrent miscarriages
  • Women with more than one failed fertility treatment

PGD has also been used for the purpose of gender selection. However, discarding embryos based only on gender considerations is an ethical concern for many people.

The following are considered benefits of PGD/PGS:

  • PGD can test for more than 100 different genetic conditions.
  • The procedure is performed before implantation thus allowing the couple to decide if they wish to continue with the pregnancy.
  • The procedure enables couples to pursue biological children who might not have done so otherwise.


The following are considered concerns or disadvantages associated with the use of PGD/PGS:

  • Many people believe that because life begins at conception, the destruction of an embryo is the destruction of a person.
  • While PGD helps reduce the chances of conceiving a child with a genetic disorder, it cannot completely eliminate this risk. In some cases, further testing is needed during pregnancy to ascertain if a genetic factor is still possible.
  • Although genetically present, some diseases only generate symptoms when carriers reach middle age. The probability of disorder development should be a topic of discussion with the healthcare provider.
  • Keep in mind that preimplantation genetic diagnosis does not replace the recommendation for prenatal testing.