Preimplantation Genetic Diagnosis

Early diagnosis of hereditary genetic diseases before pregnancy

Preimplantation genetic diagnosis is a technique which can be used during in vitro fertilization in order to screen embryos for genetic abnormalities before they are placed in the uterus. With this method, couples who are carriers of hereditary genetic diseases have a choice to implant only disease-free embryos. The methodology of PGD was developed in the late 1980s and was first applied in 1989 by a team of Hammersmith Hospital in London.

The first pregnancy following the application of preimplantation diagnosis published in 1990 and since then hundreds of children have been born across the world, free from hereditary genetic diseases. The PGD laboratory in the Center for Human Reproduction was founded in 2001 and until today more than 250 healthy children have been born . Our laboratory is represented on the board of PGD Consortium at the European Society of Preimplantation Genetic Diagnosis (ESHRE PGD Consortium).
In our country , the application of preimplantation diagnosis is allowed by the law 3305/2005 .


Hereditary genetic diseases

Preimplantation diagnosis is the method of choice for most couples carrying hereditary diseases and have high chances to pass them on to their children. At the Center for Human Reproduction we apply the method of preimplantation genetic diagnosis in couples carriers of hereditary genetic diseases in order to identify the disease-free embryos and transfer them to the uterus in order to begin the pregnancy safely.

Preimplantation genetic diagnosis can be applied for all genetic diseases, if the genetic disorder is known (mutation identified). At the Center for Human Reproduction we apply the method of preimplantation genetic diagnosis for the most common genetic diseases such as thalassemia and cystic fibrosis, but also for many other rare gene diseases (see Table 1), including Mediterranean syndromes and related hemoglobinopathies, chronic granulomatous disease, tuberous sclerosis, congenital adrenal hyperplasia,'s Huntington's disease, Cadasil, X-linked agammaglobulinemia of Bruton type and neuromuscular disorders.

With PGD it is also possible to block the transmission of genes in the next generation that affect the quality of life, such as diabetes and cancer. We have already implemented successful preimplantation genetic diagnosis to exclude genes associated with tumors such as neurofibromatosis, multiple endocrine neoplasia type II and retinoblastoma and as a result, healthy children have been born.


Screening for histocompatibility (HLA typing)

In recent years, the application of preimplantation genetic diagnosis has extended beyond preventing transmission of hereditary diseases in the next generation and to third parties who are already in the family. The method of preimplantation genetic diagnosis with parallel screening for histocompatibility (HLA typing) applies to couples who wish to have healthy children to serve as donors for transplantation of multipotent hematopoietic cells in siblings suffering from serious diseases.

In 2005 we were the first center in Greece to implement preimplantation genetic diagnosis with histocompatibility screening in a family who had a sick child from chronic granulomatous disease and our success has been published in international scientific journal. Also, for the first time in Greece we implemented preimplantation genetic diagnosis with histocompatibility screening for a family with a sick child with sickle cell anemia, resulting in the birth of twins.

To date, we have implemented in our laboratory, preimplantation genetic diagnosis and analysis of histocompatibility in 49 families with the following indications: thalassemia, sickle cell anemia, anemia Fanconi, sex-linked Bruton, total acute immunodeficiency syndrome, Wiskot-Aldrich syndrome etc. In addition preimplantation diagnosis with HLA typing has become a valuable therapeutic tool for families who have children suffering from serious diseases, such as leukemia.


Structural chromosomal abnormalities

Chromosomal rearrangements carriers, such as chromosomal translocations, inversions, etc., are at high risk of conceiving a chromosomally abnormal embryos leading to recurrent miscarriages or at risk to conceive children with congenital anomalies and mental retardation. Preimplantation genetic diagnosis may reduce the risk of these adverse outcomes. With preimplantation genetic diagnosis we are able identify the embryo with normal chromosomal number or with balanced chromosomal translocation and select it for transfer to the uterus.

Numerical chromosomal abnormalities

(Preimplantation Genetic Screening)

Preimplantation genetic screening (P.G.S.) has been reported to be applied for women of advanced reproductive age or with a clinical history of recurrent miscarriages or a clinical history of repeated IVF failures, in order to screen embryos for aneuploidies before their
26 transfer to the uterus.

Many studies have shown that in the above cases, approximately 60% of cleavage stage embryos (3 days after fertilization) and 40% of the blastocysts (5-6 days after fertilization) in vitro have aneuploidies. Morphological criteria used currently for embryo selection to the uterus, fail to reveal chromosomal abnormalities. Thus, in couples where women are of advance reproductive age or have a history of recurrent miscarriage or a history of repeated IVF failures, preimplantation genetic screening for aneuploidies may be beneficial to facilitate the selection of the appropriate embryo to the uterus.

Biopsy methods

Preimplantation genetic d iagnosis is performed in the time frame between fertilization and embryo transfer. As for each cycle of IVF, ovarian stimulation of women is followed by transvaginal oocyte retrieval with ultrasound guidance, followed by oocyte collection, fertilization with ICSI and in vitro culture methods.

Biopsy is applied at various stages during the preimplantation embryo development in the laboratory:

  1. First and second polar bodies from the fertilised egg (oocyte retrieval day)
  2. Cleavage stage biopsy (third day after fertilization), and
  3. Blastocyst stage biopsy

Biopsy methods

Polar body biopsy is applied to screen for diseases or chromosomal abnormalities of maternal origin only. Blastomere biopsy from an embryo is the most widespread and popular method of biopsy in all centers in the world.

Biopsy at the blastocyst stage was the firstly applied in our center in 2003, with very good clinical outcomes. Blastocyst biopsy has advantages over other biopsy methods because it allows the removal of a larger number of cells (up to 20) allowing enough material for the application of complex genetic analyses, without compromising the implantation potential of the embryo. The first successful blastocyst biopsy application was performed for the preimplentation genetic diagnosis of beta-thalassaemia and was sealed with the birth of the first healthy child , world wide. This innovative application was published in international scientific Journals and our center has been included in the pages of world history of IVF (

Methods for genetic analysis

At the Center for Human Reproduction we collaborate with genetic centers that widely apply molecular analyses techniques and methods for the preimplantation genetic d iagnosis of hered itary monogenic d iseases, chromosomal rearrangements and aneuploidies.
For the diagnosis of hereditary diseases, gene mutations are screened by molecular biology techniques based on the polymerase chain reaction (PCR).
For the screening of chromosomal abnormalities the method of Comparative Genomic Hybridization microarray DNA (CGH-Array), is used where all 23 pairs of chromosomes are analysed. The first children born following the application of this new technique in Greece was in June 2011 by our Center.
At Genesis Athens Clinic, we face each year a large number of cases and the experience of working with our collaborating genetic laboratories, enabled us to develop new methods and innovative applications in the field of preimplantation genetic diagnosis, allowing us to offer comprehensive support to couples seeking solutions to their genetic problems.

IVF enables millions of infertile couples to have children. Preimplantation diagnosis ensures the birth of healthy children.