The state of PGD—an update from ASH

At the 53rd meeting of the American Society of Hematology (ASH), held from December 10-13 in San Diego, there was an “education spotlight” session entitled, “Preimplantation Genetics: The Science, The Medicine, The Bioethics.” The speakers were Joyce Harper, PhD, from the University College London Centre for Preimplantation Genetics and Diagnosis (PGD), and Mark Hughes, MD, PhD, from Genesis Genetics Institute in Detroit. I’m hardly a PGD expert, so I attended to hear perspectives from people who are practicing it. The session was long on science and medicine but too short on the discussion of ethics. This was a shame because the speakers clearly have ethical worries, even though they are clearly not congruent with the concerns of most TIU bioethicists. Still, I found the session thoughtful and informative.
There was far too much for a brief blog post, but here are some highlights, first on the medical/scientific side:
1) PGD can be made on a single cell (typically 1-5), taken at any of several stages of early embryonic development. Dr. Hughes showed how he takes a single cell at the blastocyst stage (5-6 days after fertilization). Results in 24 hours, with a stated diagnostic error rate of 0.7%, and an attendant 1% post-PGD risk of a genetic-recessive disease (compared with 25% by standard Mendelian genetics).
2) PGD is most commonly used by fertile couples to try to avoid a severe genetic disease after a first affected birth or known risk based on parental genetics.
3) Genetic analysis is moving toward genome-wide arrays that can read the entire genome quickly, and at ever lower cost (currently about $2500 per genome). Dr. Hughes: “The technology now has no limitations [diagnostically]…so the question is not ‘can we?’ but ‘should we?’” [diagnose].
4) Biopsied embryos generally—but not always—do well, so the success rate of the (necessary) IVF pregnancies is reduced. The number of implantations is also reduced—e.g., 12 eggs to get 10 fertilizations, 8 embryos biopsied, 7 successfully diagnosed, 5 abnormal and 2 normal, one of those two judged viable for implantation.
5) Dr. Hughes said there were 47,164 PGD babies in the US in 2010. I thought he said born in 2010 but that number sounds high for a single year. Still, it’s a lot.
6) The most prominent “savior sibling” examples are for a disease that is curable with bone marrow transplant (BMT), e.g., sickle cell anemia (SCA). The PGD baby’s umbilical cord blood (UCB) becomes the donor blood. An example is sickle cell anemia (SCA). Dr. Hughes told the story of the family of NBA player Carlos Boozer, whose first child was cured of SCA after receiving a UCB transplant after the birth of his baby brother. Dr. Hughes is working to take this approach to SCA to West Africa at low cost.
7) For a Mendelian-recessive disease, one needs an unaffected embryo that is also an HLA (immunologic) match, with the probabilities being ¾ x ¼=3/16. In other words, 16 embryos to get 3 genetically appropriate “saviors.”
As I said, the ethical discussion was compressed, and must also be here. Clearly one worries about all the other embryos created in this process—and at least one questioner at ASH raised this by mentioning the value of all people despite disease or disability. As someone who considers himself a strong pro-lifer, I do find PGD for the most severe genetic disorders a “hard case,” and I have to admit that I am reluctant to condemn the Boozers. The speakers were most concerned about how to limit the use of PGD, medically. They are clearly uncomfortable with drawing premature conclusions or taking action on the often-uninterpretable results of a genome-wide analysis. They also raised hard cases of using PGD for otherwise treatable disease (e.g., polycystic kidney, or to obtain UCB to transplant a sibling with leukemia), using PGD to get an Rh-negative baby when mom has sensitized to Rh in a prior pregnancy, or using PGD to eliminate a cancer-susceptibility gene like BRCA-1 from the family tree (Dr. Hughes would accept, but he had debated Francis Collins, who would not permit this). Bottom line: these two professionals do seem to agree that defending the “therapeutic boundary” is important. If I read that correctly, I find it at least a bit reassuring and perhaps a contact point for engagement.
Space does not permit more here. I’m happy to try to field questions or carry on discussion through comments.

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ProgenesisJon HolmlundMark Hughes, MD, PhDJon Holmlund, M.D.John Kilner Recent comment authors
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John Kilner
John Kilner

Thanks for the interesting update! To give readers a sense of what is happening to human embryos here, would you please clarify #4? In the typical case you describe, where 10 embryos are produced, are the 8 biopsied the only ones with a chance of living–i.e., are the other 2 clearly unable to remain viable if implanted? Is the one of the 8 that is not diagnosed, still viable if implanted (i.e., is it simply unknown what it’s genetic make-up will be)? Of the remaining 7, 5 are abnormal, but presumably any of those 5 could remain viable if implanted,… Read more »

Jon Holmlund, M.D.
Jon Holmlund, M.D.

As I understood the presentation, for some reason (not clear to me), biopsy either could (technically) or would be done on only 8 of the 10 embryos produced. I inferred at the time of the presentation that the limitation was technical. A diagnosis would be made on only 7 of the 8–again, for technical reasons. The 5 “abnormal” would be affected in some way, but would indeed be potentially viable if implanted. Of the two normal (unaffected with the disease), only one would be judged fit (likely to survive to term birth) if implanted, but I imagine there might be… Read more »

Mark Hughes, MD, PhD

This is an attempt to answer Dr. Holmlund’s question and clarify the question by Mr. Kilner. 1)In any IVF cycle, regardless of whether genetic testing is performed, some of the collected eggs do not fertilize and some of those that do, fail to develop at the clinic. It is believed that this mimics what occurs in the uterus in that mother nature recognizes that some fertilized eggs simply are not biologically capable of producing a baby. 2) Couples at high risk for an inherited genetic disease have multiple choices: a) they can elect not to have any (more) children; b)… Read more »


I really appreciate your articles about the state of PGD. I am also engaged to related industry and working as a genetic researcher in La Jolla leading genetic testing center Progenesis.