9. IVF and Genetics

Preimplantation genetic diagnosis (PGD)

What is preimplantation genetic diagnosis (PGD)?

Preimplantation genetic diagnosis (PGD) is series of techniques used to diagnose and exclude genetic abnormalities of embryos, egg or sperm, prior to their use or transfer to the body.

Genetics, chromosomes and DNA

Just about every cell in your body contains a central area called the nucleus. Within the nucleus are 23 pairs of chromosomes. In humans there are 22 similar pairs in both sexes. Women have one more pair of "X-chromosomes whereas men have one "X" and one "Y" chromosome, in addition to the 22 other pairs.

At certain points in the life of a cell, the chromosomes shorten and condense upon themselves, like an uncoiled spring being compressed and wound to its smallest shape. At this point, the chromosomes are visible under a normal (light) microscope and can be assessed to determine the chromosome count, abnormal chromosome joints and large missing pieces of chromosomes can all be determined.

Each chromosome is a very long stand of a molecule of deoxyribonucleated acid (DNA). Along each chromosome there are thousands of tiny sections of DNA that provide the cell with information on how to function and how to make proteins for function. These small regions on each chromosome are called genes. We use the tecnique of DNA analysis to look for missing or abnormal genes, with procedures such as polymerase chain reaction (PCR).

Types of genetic disease

People with genetic disease can have an abnormality on the number or structure of their chromosomes, as would be shown in an abnormal karyotype. An example of such an anomaly is Down's syndrome, where the affected individual carries an extra chromosome number 21.Other people with genetic disease are missing only one single tiny gene (a gene deletion) or have an abnormal gene (called gene mutation). An example is cystic fibrosis.

Some couples are carriers of genetic disease. Even though they have no apparent illness, they carry a defective gene that can be passed on to their children, which in severe cases results in birth abnormalities or early childhood death. In some situations one parent carries an abnormal gene on his X chromosome, so that, for example, baby boys are seriously affected, as they have only one X-chromosome but girls not so, since they have an extra "backup"X-chromosome. Diseases that result from abnormal genes on the X chromosome are called X linked diseases. Haemophilia is an example of an X linked disease.

Couples who are carriers of genetic disease formerly had no option but to rely on luck that a baby might escape the problem, or sometimes they could have a test during pregnancy and then consider the option of terminating the pregnancy if an abnormality of the fetus was revealed. Now, with PGD, they can avoid these unhappy events if their genetic abnormality can be detected on their embryos (or possibly in their eggs or sperm) prior to pregnancy.

How is PGD done?

Following ovarian stimulation, multiple egg collection and fertilization, early embryos are watched in the laboratory, just as they are for couples with infertility having IVF. However with PGD each embryo is tested for the abnormality their parents carry, resulting in transfer of only unaffected embryos.

Three days after egg collection, embryos usually consist of six to eight cells. Each of these cells has complete genetic information, and each cell has the potential to continue growth to establish pregnancy. Therefore, one or two cells can be removed from an eight-cell embryo (embryo biopsy), and the embryo will usually continue to develop normally. The removed cells can then be analyzed for specific genetic problems. See our photo gallery for a picture of an embryo biopsy.

The kind of test, which is performed on the cells, depends on the underlying genetic problem. For X linked disorders, the cells are analyzed to determine whether each embryo is male or female using a technique called fluorescent in situ hybridization (FISH). The FISH technique tells us whether an embryo cell has two X chromosomes (female) or an X and a Y chromosome (male). Testing an embryo cell using FISH takes only a few hours, so that the correctly diagnosed embryos can be transferred to the uterus later that day. FISH can also be used to look for other specific whole chromosome problems.

For gene deletion and mutation, PCR can be used to look for the problem in embryo cells after embryo biopsy, if the exact structure of the abnormal or missing gene is known.

Can all genetic problems be found using PGD?

Unfortunately not. In many cases of genetic mutations, the exact gene structure and location on a particular chromosome is not known. However, new information is always being obtained on gene mutations as the entire DNA structure of every human chromosome is gradually being mapped in centers all around the world.

Also, whilst we can use FISH to determine the presence or absence of whole chromosomes, the analysis of a single cell is not enough to analyze all 23 pairs of chromosomes. At present, therefore, a complete karyotype cannot be carried out on each embryo, but it may be possible to perform this testing in the future.

Other PGD procedures

FISH can be used to look for specific chromosome abnormalities in sperm, and in men with a high percentage of sperm abnormalities it might be possible to separate normal from abnormal sperm using the MicroSoft technique.

Removing and assessing the polar body of the egg with FISH can also assess chromosome abnormalities of eggs. The polar body is a condensed second copy of the egg's chromosomes that is expelled by the egg during the maturation process.

New methods of PGD are constantly emerging and in the future it is likely that genetic testing of embryos will be used more routinely to improve IVF success rates. With the transfer of genetically normal embryos, a higher percentage of implantation and reduced miscarriage rates can be expected.