PGS/PGD in action: a single cell is being removed from the embryo so it can be sent off and biopsied. Note that this image shows a biopsy of a day 3 embryo. We now only biopsy day 5/6 embryos.
I get a lot of questions from both current and prospective patients about PGD, or Preimplantation Genetic Diagnosis. With good reason too. PGD is a complex procedure that can greatly affect the outcome of a patient’s IVF cycle. In order to potentially answer some of these questions I wanted to write up a more detailed piece about the procedure. So without further ado…
[2016 update: There are now two types of genetic screening techniques available to patients. PGS or Preimplantation Genetic Screening and PGD. PGS looks at the whole set of chromosomes for structural issues, such as an extra set of chromosomes (Down Syndrome or Trisomy 21), or for transcriptions or deletions in the individual chromosomes. PGS is now routinely done in all fresh IVF retrieval cycles at ORH. PGD is a more specific technology that looks for individual genetic defects that are associated with a targeted condition. This is usually done to make sure that the embryos do not contain one or more hereditary conditions that are present in one of the parents. ]
What is PGS/PGD again?
It is possible to remove genetic information from embryos during certain phases of their development and carry out testing on that cellular material. One stage that this can be done is on day 3 when an embryo should be between the 6-8 cell stage, and taking this cell from a developing embryo during treatment has been shown to be ‘completely safe’, according to the largest study of babies born following this particular technique. PGD done at this stage is often preferred as it allows for the results to be obtained by day 5 and a fresh transfer to occur. This technique is outdated and we no longer use this methodology. We now only perform blastocyst biopsies and also do not do fresh transfers with the patient’s own eggs. Transferring embryos back on the same cycle as they were retrieved has been shown to result in lower pregnancy rates. This effect is thought to be the result of the stimulation medications used to hyperstimulate follicle production. We now transfer all embryos back into an unstimulated uterus which means a subsequent FET (frozen embryo transfer) will be required.
It is also possible to remove multiple cells from the trophectoderm of a day 5 blastocyst. If the results are going to be back the next day (can vary depending on what we are testing for) we can transfer fresh embryos to the uterus on day 6. If the results are not going to be back in time for a fresh transfer we would then vitrify (a method of freezing) them and possibly transfer them on a subsequent FET (frozen embryo transfer) cycle if the results came back as desired. As mentioned above, we no longer transfer embryo obtained from a fresh cycle as that particular practice results in lower pregnancy rates. All embryos obtained in fresh cycles are now routinely frozen and transferred at a later FET. I kept the description of the older practice because many practices still perform PGS/PGD this way.
PGS/PGD can help doctor’s spot diseases, chromosomal abnormalities and even gender before deciding which embryos to transfer during fertility treatment. However, there have been concerns about the safety of the technology, but recent studies have reassured people in the field.
It has suggested the risks of low birth weight, premature birth, major malformations and the perinatal death rate is the same as for other forms of IVF. This would suggest that embryo biopsy does not adversely affect the health of newborn PGS/PGD children.
So, what can we test for as far as PGD is concerned? There are a huge number of diseases and conditions that can be tested for, including many forms of translocations and other genetic errors. To some degree as long as it is a test that can be found by doing any form of post pregnancy testing, such as an amniocentesis, then that same test can be applied to PGD. It is also possible to build a specific test using cheek swab samples taken from a couple, so total customization is possible. We currently work with a number of different testing laboratories and if you have concerns about whether the condition you wish to be tested for is available we can direct you to the appropriate genetic counselor to discuss it further with them.
What do I do if I want PGS/PGD?
PGS is now routinely done for all patients undergoing IVF at ORH. We made this switch late in 2015 due to mounting evidence that the technique of only transferring genetically normal embryos results in markedly increased implantation rates and lower incidence of miscarriage.
PGD is a little different as it calls for a probe specific to you and the condition(s) you want tested to be built. This process can be very involved, and can expect to take at least 12 weeks. It is important to make sure that the probe can be reliably used to identify the condition and that there are specific markers that can be used to check this. The best advice is to initiate the probe preparation step as soon as possible and then work on the rest of your IVF work-up. We generally wait until the probe is finished before we start your IVF cycle. However, freezing technology for eggs/embryos has become robust enough that exceptions to this rule can be made in certain situations.
There are risks associated with this treatment, as there are with all forms of medical treatment and these will have to be weighed up against the benefits that you might gain. These are really best done on a case by case basis with the medical staff here and the genetic counselors at the PGD testing laboratory.
The next step after you have met the doctor and made the decision to undergo PGD for any reason is to meet with one of the nursing staff to go over the paper work and consent forms that are required. During that meeting someone will be able to go over all the finer details of the treatment that will happen in the laboratory and the time frame for getting results.
During the actual laboratory procedures great care is taken to make sure that the embryos themselves are allocated a totally unique number to identify them and that this number is assigned to each cell that is removed from it. During the biopsy and each and every time that an embryo is moved after the biopsy is taken place this procedure is witnessed by an additional staff member to assure that the integrity of the numbering system is maintained. That way you can be assured that the PGS/PGD results obtained actually relate to the correct embryo.
What else should I know about PGD?
There are limitations to the procedure and various hurdles that have to be gotten over on the way to undertaking a PGD cycle. We currently recommend that the minimum number of embryos to proceed with the case is 6-8, but this is very case specific and the final decision is left to you. The reason for having a minimum is the fact that there is a damage rate associated with the biopsy and that as well as getting an appropriate PGD result the associated embryo has got to be suitably developed in order to be used for a transfer. Taking this into consideration the risk of not having anything to transfer is greater with a lower number of embryos to biopsy.
It is also possible to carry out PGS/PGD on embryos that have been previously frozen, whether they were frozen at the 2PN, cleavage or blastocyst stage of development. The procedures for the biopsy are the same, and the timing of all the different aspects of the treatment are going to be dependant on the stage at which they were frozen.
This is an exciting new field that has a lot of possibilities for improving outcomes for patients, and we are very happy to be keeping at the cutting edge of treatment. For the latest developments and treatment options relevant to you please contact the clinic directly.
Cheers!
