An individual's genetic information is packaged into strings of genes called chromosomes. Normal human cells contain 46 chromosomes, or 23 pairs. These include chromosomes 1 to 22 (the autosomes) and chromosomes X and Y (the sex chromosomes).

What is a translocation?
An individual's genetic information is packaged into strings of DNA called chromosomes.  Normal human cells contain 46 chromosomes, or 23 pairs.  These include chromosomes 1 to 22 (the autosomes) and chromosomes X and Y (the sex chromosomes). 
A translocation is a rearrangement of chromosome segments between two different chromosomes.  These translocations may be either reciprocal translocations, with reciprocal exchange of segments between chromosomes, or Robertsonian translocations, involving a whole arm exchange between chromosomes (Figure 1).   Carriers of these translocations are considered "balanced" because all their genetic information is present.  However, they are at risk of producing sperm or eggs with an "unbalanced" form of their translocation.  This may result in difficulty to conceive, recurrent miscarriages or the birth of a child with developmental abnormalities. 

Figure 1: Different types of translocations.

Preimplantation Genetic Diagnosis for translocations
Preimplantation genetic diagnosis (PGD) is an option for couples that carry a balanced translocation.  PGD utilises assisted reproductive technology to stimulate the woman's ovaries to produce a number of eggs.  These eggs are collected and fertilised using the male partner's sperm.  Resulting embryos are cultured in the laboratory and embryo biopsy is performed on Day 3 after egg collection.  Embryos that have developed to at least 5 cells are suitable for biopsy.  A hole is drilled in the zona (the outer shell) of the embryo and 1 or 2 cells are removed from the embryo (Figure 2).

Figure 2: Embryo Culture and Biopsy

The biopsied cells are tested using a technique called Fluorescent In Situ Hybridisation (FISH).  Fluorescent dyes are used to tag the specific translocation chromosomes and these show as fluorescent "dots".  By counting these dots it is possible to determine whether the embryo is "normal" or "balanced" for the translocation or carries an "unbalanced" form of the translocation (Figure 3).  Embryos identified as "normal" or "balanced" can then be transferred into the female's uterus.  This should increase the chance of a successful pregnancy and significantly reduce the risk of miscarriage.  Chromosomally "normal" or "balanced" embryos in excess of those transferred will be grown in culture to Day 5 or Day 6.  If they reach an appropriate stage of development (ie: form a blastocyst), they will be frozen.  These embryos may be used in a subsequent IVF cycle if you do not achieve a pregnancy with the fresh embryos.

Figure 3: Examples of FISH analysis for a reciprocal translocation. Normal or balanced cells should have two red signals, two green signals and two aqua signals.

Feasibility Testing
Prior to commencement of a PGD cycle, it is necessary for all carriers of a Robertsonian or reciprocal translocation and their partners to undergo genetic counselling at our PGD clinic and a feasibility test on a small sample of their blood.  This allows preliminary analyses to be performed to determine if PGD is possible for their particular translocation.  Most carriers of reciprocal translocations have unique chromosome rearrangements and therefore a new FISH test must be developed for every couple.  In some instances, due to the particular translocation, the FISH procedure may not be capable of identifying all potential unbalanced products of conception, and in this situation PGD will not be an option.  If feasibility has been confirmed, PGD may proceed. 

What are the costs?
There is a fee for the feasibility test and a separate fee for a PGD cycle.  Information relating to the cost of feasibility testing and embryo biopsy and chromosome testing is available from Monash IVF.  Please note that additional costs will be incurred for IVF services.  Please contact Monash IVF for a list of current prices.

What else do I need to know?

1. Embryo biopsy has been used extensively at Monash IVF and other major IVF clinics throughout the world and follow up studies have shown that the procedure is safe and does not appear to have any adverse affect on the embryo's potential to implant and develop normally. 
2. It may not be possible to obtain a FISH result from some or all of the biopsied embryos.  Some embryos may not be of sufficient quality to biopsy, or in some embryos the test results may not be conclusive.
3. PGD cannot distinguish between normal or balanced embryos, but can identify unbalanced embryos.
4. PGD for a translocation only tests for the chromosomes involved in the translocation.  In some instances it may also be possible to identify aneuploidy of other chromosomes (ie: chromosomes X, Y, 13, 18, 21).  This additional testing will only be performed upon request.

Worldwide data indicates that the PGD-FISH procedure has approximately 90% accuracy.  In some instances, however, the biopsied cell may not be representative of the whole of the embryo.  It is therefore considered that this test is only a screening test and not a diagnostic test, and consequently prenatal diagnosis is highly recommended in an ensuing pregnancy.

Quality Systems
Monash IVF employs a very high standard of quality assurance. The laboratories are NATA accredited.  Through the application of quality systems we monitor and provide standards of excellence in quality service, care and advice.