Trends in Pre-implantation Genetic Diagnosis

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So what are the new developments increasing interest in PGD?

The first is that there is more laboratory expertise on growing the embryos to blastocysts (see blog on blastocyst). These are embryos that have grown not 3, but 5 days in the lab.  As the embryo grows with time, the total number of cells increases from 6-8 to 30-60. Because the cell number is much higher, we can more safely remove more than on cell, maybe 3-5 cells. All of that extra DNA helps us reach much more accurate results.


The second has to do with the way we test the DNA.  The DNA amplification techniques have improved, as have the techniques for identifying important areas in the DNA.


An advantage of blastocyst biopsy is that in a good blastocyst, we can tell by looking which cells will be the embryo (the inner cell mass) and which will be the placenta (the trophectoderm- thus the term trophectoderm biopsy, also called TE biopsy for short).  Naturally, at the time of the biopsy, it is the placental cells we take as not to interfere with the fetal cells. Taking a few extra cells from the placenta is much less harmful than taking cells needed for the fetus.


Another advantage of performing the biopsy on day 5 is that mosaicism is much less of a problem in a blastocyst. (The last blog explains mosacism), The cells we get on day 5 more accurately reflect the DNA status of the embryo as a whole.   We are not sure why mosacisism is less of a problem on day 5, it may be that it’s common for an embryo to start off with some abnormal cells, but with time the normal cells outgrow the bad ones.


One downside to TE biopsy is that in most cases, the results of the biopsy take 1-3 days to process. We do not want a day 5 embryo growing extra days in the lab waiting for the results. Therefore, we usually freeze the blastocysts just after the biopsy, get the results a few days later, and then have the patient come back the next month for a thaw cycle.  This gives the patient a one month delay, which may or not be an important factor, depending on the expectations of the patient.  There are some programs that offer same cycle PGD biopsy and transfer, but usually those women with only the fastest growing and best looking are candidates for the same cycle process.


Patients are naturally concerned about embryo freezing, as is it is mostly true that embryos in a frozen cycle have lower pregnancy rates than when the embryos are transferred when fresh.  However, there may be some very explainable reasons why freezing normal blastocysts may not be problematic.  In a standard fresh cycle, the best embryos are transferred. While the extra embryos may look very good, the best ones go back originally, leaving the left overs for the frozen cycle, and this could explain the lower rates.  In a PGD cycle, even the best embryos are frozen, upping the odds for a successful cycle after the thaw.  Also, at least from what I have seen, normal embryos seem to thaw and freeze very well. So if you know you have a good one in the freezer odds are good that it will survive the freeze and thaw and have good potential for success.


In addition, freezing techniques have really blossomed in the past few years.  Most programs have moved to vitrification (the fast freezing method), and embryos do have better outcomes when preserved this way.


On top of all of this, there are some doctors who believe that all embryos, even without biopsy, should be frozen. There is the revival of an old theory that the endometrium of an IVF cycle is not ideal for implantation, possibly due to excessive estrogen levels caused by the fertility drugs. Others feel that the relationship between the timing of ovulation and embryo transfer is altered with IVF, lowering the ability of the embryo to implant.  I’m not so sure about theses theories, but I am raising the point here to say that a frozen embryo cycle is not necessarily a bad thing.


There are still a few more points about PGD that I will go over next time.


Thanks for reading, and don’t forget the disclaimer 5.17.06


Dr. Licciardi



  • Braude P. Preimplantation diagnosis for genetic susceptibility. N Engl J Med 2006; 355(6):541-3.
  • Gutiérrez-Mateo C., Colls P., Sánchez-García J., Escudero T., Prates R., Wells D., Munné S. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011; 95: 953-958.
  • Twisk M, Mastenbroek S, van Wely M, Heineman MJ, Van der Veen F, Repping S. Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilization or intracytoplasmic sperm injection. Cochrane Database Syst Rev 2006; 25(1):CD005291.
  • Munne S, Fischer J, Warner A, Chen S, Zouves C, Cohen J, Referring Centers PGD Group. Preimplantation genetic diagnosis significantly reduces pregnancy loss in infertile couples: a multicenter study. Fertil Steril. 2006; 85(2):326-32.


2 responses to “Trends in Pre-implantation Genetic Diagnosis”

  1. Sharon D. says:

    We shall be using the frozen (vitrified) donor eggs of a woman in her early twenties. Because of a miscarriage that occurred with my own eggs due to a problem PGD likely would’ve caught, I want microarray PGD done on the embryos.

    However, I developed second thoughts when my nurse mentioned it involves freezing the embryo. I assumed this would be harmful though I have not yet discussed that concern with my RE. So, if as you indicate, freezing a biopsied embryo in fact may not diminish the viability of an embryo, are there any reasons that in your opinion would weigh against PGD where the embryo transfer is being done on a donor recipient?

    Also, of the 9 oocytes, I only want 2 or 3 fertilized to avoid the possible outcome of having 6 additional embryos remaining following a successful pregnancy and delivery. Given the fertilization, PGD & transfer process, is that a good plan?

  2. Sharon D. says:

    …and when I ask about reasons that possibly weigh against PGD (where the embryos are being transferred to an egg donor recipient), I mean any other reason in addition to the obvious one of additional financial cost.

    Thanks for any thoughts you’d care to offer on my 2 questions!

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