Preimplantation Diagnostics

Nicole Wendler holds a PhD in biology in the field of oncology and immunology. As a medical editor, author and proofreader, she works for various publishers, for whom she presents complex and extensive medical issues in a simple, concise and logical manner.

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Pre-implantation diagnosis (PGD) is used by doctors to look for serious genetic diseases in artificially fertilized egg cells. If they find what they are looking for, the egg cell is not even inserted into the uterus.Here you can find out how PGD works, which couples can use it and the advantages and disadvantages of pre-implantation diagnosis.

Preimplantation Diagnostics - Definition: What is PGD?

The pre-implantation diagnosis is a genetic test method. Reproductive medicine does this at a very early stage of development on the genome of an artificially created embryo.

PGD is used to identify serious hereditary diseases or genetic diseases and chromosome damage, which, among other things, would prevent the cells from developing successfully. The diagnosis takes place outside of the maternal body, even before (pre) the embryo is inserted (implanted) in the uterus. In English usage, the term "preimplantation genetic diagnosis" (PGD) is used.

PGD can be used if there is a suspicion of ...

... a severe monogenic hereditary disease (mutation in a gene)
... a chromosomal disorder: structural (translocation) or numerical (aneuploidy screening: mono-, zero- or trisomy)
... a sex-linked, serious hereditary disease

Preimplantation Diagnostics in Germany

PGD is actually forbidden in Germany. Only since 2011 has a law existed that allows pre-implantation diagnostics in Germany under very specific conditions and requirements.

For example, pre-implantation diagnostics are only approved if there are serious hereditary diseases in the family and severe damage is considered likely. Even if you already have a child with a hereditary disease, have suffered a death or miscarriage in the past, or have a fertility disorder, you are one of the high-risk couples who are eligible for pre-implantation diagnosis.

Which hereditary disease is considered serious is not firmly regulated by law. The ethics committee of the respective federal state determines for which individual case a pre-implantation diagnosis is actually possible. Decisive for this is an expected, particularly severe clinical picture, hardly any / no therapy options or a short life expectancy. However, each individual case is decided individually. Therefore - and also for ethical reasons - a general list of PGD diseases is not possible.

Requirements for pre-implantation diagnosis:

Application and approval of the ethics committee
medical / human genetic and psychological counseling
Implementation in a specialized, certified center

PGD may not be used for so-called "rescuer siblings" in Germany. This is different in Great Britain, for example. There, doctors can use pre-implantation diagnostics to select genetically matching embryos that can later help an older, sick sibling with their umbilical cord blood or bone marrow donation.

How does PGD work?

Before pre-implantation diagnostics can start on the embryo, human geneticists have to develop their own genetic test procedure for each couple. For this, blood and DNA samples from the man and woman and possibly from the couple's children are required.

It can take up to six months for the special test systems for your family to be ready. Only then does hormonal stimulation begin, followed by egg retrieval and artificial insemination using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). If the artificial insemination is successful, the doctor can remove an embryonic cell for pre-implantation diagnosis. Depending on when this happens, a distinction is made between blastomer and blast cyst biopsy and polar body diagnosis.

Blastomer biopsy

After four days in the Petri dish, the fertilized egg cell has reached the so-called eight-cell stage. These eight cells (blastomeres) are toti / omnipotent cells. This means that in principle each of these cells could develop its own embryo. According to the Embryo Protection Act, this early biopsy is forbidden for PGD in Germany - but it is used in other countries.

Blastocyst biopsy

From the fifth day after artificial insemination, the fertilized egg cell reaches the blastocyst stage. The embryo now consists of pluripotent cells, which means that these cells can still develop into different types of tissue, but can no longer produce a complete embryo on their own.

The cells of the blastocyst are arranged in an outer and an inner cell layer. One or two pieces of the outer cells (trophoblasts) are removed for pre-implantation diagnosis.

Despite improved culture media, only about 50 percent of artificially fertilized egg cells reach the blastocyst stage.

Polar body examination

Actually, this method, which is supposed to improve the success rate of IVF, is more a part of prefertilization diagnosis than pre-implantation diagnosis:

Shortly after the sperm has penetrated the egg cell shell, the egg cell forms the two so-called polar bodies as it divides into maturity. They are no longer needed later and die off.

Strictly speaking, since the egg and sperm cells have not yet fused at the time of the polar bodies, fertilization has not yet taken place. With the removal of the polar bodies, the polar body diagnosis bypasses the Embryo Protection Act and does not require the approval of the ethics committee.

At best, both polar bodies are removed for the examination. Their genetic material allows indirect conclusions to be drawn about the genetic makeup of the egg cell. Therefore, polar body diagnostics can only determine hereditary diseases in women as well as genetic disorders, genetic defects and structural chromosomal disorders of the egg cell (e.g. distribution of chromosomes 13, 16, 18, 21 and 22). A gender determination or an analysis of the male genetic material is not possible.

Preimplantation Diagnostics: Procedure for Genetic Examination

For pre-implantation diagnostics, the genetic information (DNA) must be taken from the embryonic cell nucleus and examined. The following techniques can be used to identify changes in chromosomes and genes:

Polymerase chain reaction (PCR): duplication of individual genes / gene segments
Fluorescence in situ hybridization (FISH): Marking of several selected genes of a chromosome
Comparative genomic hybridization (CGH): comparison of pattern / number of all chromosomes

PGD: Pros and Cons

For years, opponents and supporters have been discussing the advantages and disadvantages as well as ethical concerns in the use of pre-implantation diagnostics.

Per PID

Fulfillment of the desire for children for high-risk couples
Preimplantation diagnosis is physically and mentally less stressful than an abortion in a severely damaged embryo / fetus.
Pre-implantation diagnostics remains a well-controlled exception for high-risk couples (as regulated by law).

Against PID

Artificial insemination is imperative, with all the associated risks
PGD has a high error rate: sorting out potentially healthy embryos, additional careful prenatal diagnosis (e.g. amniocentesis) required
Great ethical responsibility: Which diseases are serious (life worth living vs. life unworthy of living)? Risk of abuse and first step towards a "designer baby"
Discrimination against people with disabilities

PGD: Risks and Complications

Couples who want to use pre-implantation diagnostics must undergo artificial insemination (IVF, ICSI). That means hormonal stimulation of the woman, egg retrieval, sperm preparation and implantation of the fertilized egg cell examined by PGD and found to be good. Every step is physically demanding. Hormone stimulation in particular harbors risks. It can result in ovarian hyperstimulation syndrome (OHSS), which in the worst case can be life-threatening.

The probability of becoming pregnant after artificial insemination is also lower than with natural conception. If pregnancy has set in, couples are nevertheless advised to undergo careful prenatal diagnostics (ultrasound, amniotic fluid examination, umbilical cord puncture) due to the relatively high error rate in pre-implantation diagnostics, with all the associated risks and consequences.

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