October 23, 2005
IVF Embryo Genetic Defect Rate For Young Women Has Ethical Implications

Studies using Pre-Implantation Genetic Diagnosis (PGD or PGID) on embryos created using In Vitro Fertilization (IVF) found that most embryos formed from eggs donated from young healthy women have errors in chromosome count.

Paulette Browne, at the Shady Grove Center for Preimplantation Genetics in Rockville, Maryland, US, and her colleagues, examined 275 embryos created from the donated eggs of women aged between 21 and 31. All the donors were ostensibly healthy. The researchers removed cells three days after conception and examined them for aneuploidies. They found that 137 – half – of the embryos had at least one error.

Aneuploidy is the state of having too many or too few chromosomes. So either the embryo cells had extra chromosomes or missing chromosomes from each chromosome pair. Note that aneuploidy is just one type of genetic abnormality and testing for aneuploidy by itself leads to an underestimate of the incidence of genetic abnormalities.

Another study found a high rate of chromosome damage.

In research presented at the American Society for Reproductive Medicine in Montreal yesterday, Jeffrey Nelson of the Huntingdon Reproductive Centre in California used a technique called preimplantation genetic diagnosis (PGD) to screen 289 embryos created from healthy egg donors, all of whom were under 30. He found that 42% had damaged chromosomes, the strands of DNA that together hold the entire complement of human genes. The extent of damage ranged from 28% to as high as 83% in some women. "We had always assumed that embryos created from eggs donated by younger women would not have these defects," Dr Nelson said. "But just the fact that we are seeing this high rate of abnormality suggests that we should be using [PGD] more."

The spelling for that center is really "Huntington Reproductive Center".

A third study by Peter Nagy of Reproductive Biology Associates in Atlanta found similar results.

At Reproductive Biology Associates in Atlanta, GA, researchers investigated the differing incidence of aneuploidy in young infertility patients as compared with older patients and found that the frequency of chromosomally abnormal embryos is unexpectedly high in those of young reproductive age. In a prospective on-going study, 36 infertile patients (average age 32.5, all under 35), with no prior treatment and representing all diagnoses of infertility proportionally, had IVF with PGD. Their PGD results were compared with a control population of women over 38 (average age 40.7) who were undergoing IVF at the same time. Young patients in the study population had an average of 17.6 eggs retrieved, of which 70% fertilized; the older control patients had 13.5 eggs on average, of which 69% fertilized. The younger women in total had 103 embryos identified as normal and 198 abnormal embryos. The older women had, as expected, a higher proportion of abnormal embryos: 323 abnormal to 116 normal. Of the younger patients, 56% became pregnant, while 33% of the older patients became pregnant.

Eric Surrey, MD, President of SART, remarked, “PGD may become a very useful technique for maximizing the chances of success of a particular cycle of IVF. And these results do shed light on some of the reasons why a particular young donor or patient might produce many eggs, which fertilize and develop as embryos of normal appearance, but do not result in pregnancy. However, PGD, especially using a single cell, is not fail-safe. Mosaicism, the presence of normal and abnormal cells in the same embryo can confound the results of single-cell PGD.”

Nagy says that the extent of genetic abnormalities was even greater than his test showed.

These findings overturn long-held assumptions that reproductive problems are primarily age-related, Nagy said.

"This is new information," he said, adding that the genetic-defect rate could turn out to be even higher once pre-implantation genetic diagnosis extends to the entire genome.

"We tested 11 chromosomes, not the whole genome," he said.

Even if he'd tested all the chromosomes that would only have detected larger scale abnormalities. Smaller scale genetic damage would not show up with current testing techniques.

Most pregnancies fail before women even know they are pregnant.

Researchers also suggested the rate of genetic problems seen in IVF embryos mirrors the real world.

There's a "baseline of abnormal" in the general population that increases with age, Nelson said.

An estimated 60 to 70 per cent of pregnancies are lost before a woman recognizes she'd been pregnant, he added.

The human reproductive system produces a lot of genetically damaged embryos. Think about that. Two thirds of pregnancies end before women even know they are pregnant. Some additional percentage miscarry after a woman knows she's pregnant. Consider these facts in light of religious beliefs held by some that at the moment of conception a spirit is somehow attached to the fertilized egg. Does God attach spirits to all these fertilized eggs that are doomed to never attach to the uterus or that initially attach but fail due to genetic damage?

Consider this result in light of the recent work by Rudolf Jaenisch and Alexander Meissner at MIT's Whitehead Institute to create mouse embryos that can can not grow a placenta. This results in embryos that can not develop very far. Their goal is to find ways to develop embryonic stem cells that will not elicit as many objections from some religious folks. Nature (or God if you prefer) already generates lots of embryos that can not develop into humans. Likely most embryos created naturally lack that capacity. Doesn't that fact make the Jaenisch and Meissner approach more ethically acceptable?

Genetic deactivation and/or genetic deletion using genetic engineering techniques essentially mirrors what happens naturally. What happens naturally, if done by human will, would be considered highly morally objectionable by some. Natural selection produced an outcome where the most efficient way to make viable humans is to allow large numbers of fertilizations to fail to develop all the way to birth.

If an embryo lacks genes needed to develop a complete human but has most of the genes needed to produce a human it is not even a potential human. It lacks the potential to become a human. Should we consider a thing that lacks even the potential to become a human as possessing the rights of a human?

Share |      Randall Parker, 2005 October 23 11:47 AM  Bioethics Reproduction


Comments
Brett Bellmore said at October 24, 2005 3:58 AM:

Any idea how this percentage compares to other species? It *may* be a feature, but given that the human race has gone through some evolutionary bottlenecks, and been subject to heavy selective pressure on all sorts of fronts, it may just be a bug that we overcome by starting a lot of pregnancies.

Certainly, it's another diagnostic that could be applied in fertility problems; Do the chromosomal errors go back to the egg and sperm, so that they could be detected without a pregnancy?

Engineer-Poet said at October 24, 2005 4:00 PM:

Testing gametes for genetic defects is like testing fuses.

"That one was good.  That one was good.  That one was good...."

Brett Bellmore said at October 24, 2005 5:51 PM:

Yes, but if you open a box of fuses, and test half of them, and they all come up bad, you might suspect that the reason the lights don't come on is, oh, maybe bad fuses. And it's not like you're going to run short of *male* gametes to test for chromosomal abnormalities. ;)

Fly said at October 24, 2005 9:13 PM:

“Natural selection produced an outcome where the most efficient way to make viable humans is to allow large numbers of fertilizations to fail to develop all the way to birth.”

Yes, sperm competition, competition for which cells become mature eggs, and successful fetal development act as selection filters to maintain genome quality.

Engineer-Poet said at October 25, 2005 5:43 AM:

Getting back to ethical and theological implications, I think this removes the last shred of support for the "life begins at fertilization" school.  We learned long ago that most fertilized ova don't come to term, and now we've learned that a great many of those have no capability to do so.  Those claiming that the cells sitting in liquid nitrogen in fertility clinics are "babies" are now arguing purely for faith, not facts.

Francesco said at May 11, 2008 9:45 PM:

I always thought it would be unethical to nuke a densely populated area, but after reading this great statement of yours, I changed my mind:

"Genetic deactivation and/or genetic deletion using genetic engineering techniques essentially mirrors what happens naturally. What happens naturally, if done by human will, would be considered highly morally objectionable by some"

Then it's Ok to drop an atom bomb over Southeast Asia. For the sake of science. You know, a big experiment about the effects of radioactivity.
You're just doing what the tsunami did. It happens naturally!

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