Search for tag: "embryos"

Dr. Jones: We have so many choices in our lives now, but some things we don't have choices about and that's when is it time to have a baby and when is it too late? But there are some choices.

Today in the studio we're with Dr. Joe Letourneau, who is a reproductive endocrinologist at the Utah Center for Reproductive Medicine and director of our oncofertility program and also for fertility preservation.

Well, you've planned everything in your life just right and you kind of didn't have kids because you were looking to find the right person to have kids with or you were looking at your job, and now you're older and you find out that you don't have many eggs left. What are your choices then?

Dr. Letourneau: This is the circumstance in which having frozen eggs can be quite helpful. At that point, it would be possible to consider thawing some or all of those eggs to try to create embryos and use them for fertility treatment.

In the last 10 or 15 years, we have developed a new type of technology called vitrification. And with this process we use a safe sugar type of solution to dehydrate the egg as we freeze it. This takes the water out of it and prevents the ice crystal injury. When we then use the egg in the future, we warm it back up and we allow it to refill with water, and it's a very healthy egg. So the survival rate of eggs currently is very high. It's in the 80% to 90% range. Whereas in our own field with our best technology 20 years ago, it was probably only 1% or 2% survival rate.

Dr. Jones: That's been the biggest change in IVF. So if a woman then decides she wants to use her eggs, some of them are thawed, and then sperm are added and then the embryo grows in the labs. So they go through an IVF process once they're finally ready to make a baby?

Dr. Letourneau: That's correct. After five or six days of growth, we would put the embryo into the uterus the same way it would sort of roll out of the fallopian tube, but we actually place it through a natural opening in the cervix.

Dr. Jones: So if a woman is lucky and maybe she has 20 eggs, they'll go into the freezer. She might have more than one chance at IVF, maybe more than one chance at having more than one kid perhaps?

Dr. Letourneau: Absolutely.

Dr. Jones: And how successful is it? And that probably is a function of how many eggs you get and how old the patient is, but what's the ballpark?

Dr. Letourneau: You've intuited there that age and the number of eggs has a big impact. So one egg for any woman could make a baby. But it really comes down to a probability. So one egg in one's early 40s has a much lower chance of one egg in one's early 20s. And as such, it helps to have many eggs. So likely getting as many eggs as we can safely achieve is probably the best method to preserve fertility. But probably each egg has somewhere between a 5% to 10% chance of making a single baby.

Dr. Jones: So what happens for now a woman's 42 or 43 and she's tried a couple of times with her own eggs and IVF hasn't worked? What are her next options?

Dr. Letourneau: It's important to think of the frozen eggs as one method of helping one conceive, and it's not 100% success rate as we spoke about earlier. Not every egg makes a baby, but coupled with the idea that some people their circumstances in life may change where they're ready to try to conceive their first baby at 38 or 39, they may be able to do that.

It may be that the frozen eggs are most helpful for the second baby or some other aspect of their family building. So some people may conceive on their own, some people may require some fertility treatment, and some people may even consider fertility treatment to have that first baby if they've been trying to conceive at 42 using their eggs at that time for new IVF and then saving the eggs from age 34 for, you know, their second baby. So it's a pretty dynamic process, but in general, having the frozen eggs does involve sometimes revisiting kind of the IVF process in order to use the frozen eggs.

Dr. Jones: And then the option if for some reason none of those things are working, we have donor eggs from young women that can be an option for people who find that appealing or they're willing to think about that choice.

Dr. Letourneau: Absolutely. We've been using donor eggs for 30 years or so in our field, and it's a very normal thing to do and it's an excellent way to build a family. A common concern that patients have about the relatedness, you know, I won't be related and my partner will or I won't pass on my genes. The reality is that most of us humans have most of our genes that are exactly the same, just about and so there is certainly a uniqueness to us. Part of that comes in our genetic code and then part of it comes in the way we use our genetic code.

And what we've found in research in big studies of human populations and in other mammals is that the maternal environment during pregnancy impacts the way the baby and then even their babies and their grandchildren after that use their DNA. And so there is a big impact on genetics. There's a big biological relationship that's created between the mom who carries the pregnancy from the donated egg, and I think it's a really excellent way to build a family if that should be needed.

Dr. Jones: Well, I think that knowing that you have options, whether you can exercise those options or not, for women who are trying to think about making a family someday is important for us as providers and for women who have the questions it's good that we actually have those options here. Thank you for talking to us about it, Dr. Letourneau, and thanks for joining us on The Scope.

Dr. Jones: The mammalian miracle of growing babies inside you is amazing. Yeah, that's a lot of M's in one sentence, but what do we know and what don't we know about implantation? And what do couples do and doctors do to try to make it work better?

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Dr. Jones: In humans, eggs are sort of squished out of the follicle, and that's the cyst that has the egg in it in the ovary when ovulation occurs. Okay. It usually works. It's not too hard to understand, and we can study it in other mammals like lab mice. The fallopian tube picks up the egg, which is surrounded by a cloud of sticky cells, and moves the egg and its cells into the tube. Okay. I got that.

Sperm, which were deposited in the vagina, swim up the cervix, uterus, and out the tube and meet the egg. Okay. That seems hard and a long way for the tiny guys, but there are so many of them. The egg and sperm recognize each other as human, and only one sperm gets in the egg. Now, that's amazing, and there are so many of them. And the egg gets fertilized.

Okay. We understand that mostly, and we can watch it happen in the IVF lab with human eggs and sperm. We do know that a lot of eggs and sperm and a lot of fertilized eggs are not normal, so there are lots of time that the process doesn't go much farther than this. But if things are normal enough, the fertilized egg starts to divide, wanders down the fallopian tube with a little help of tiny little fingers on the cells of the fallopian tube and arrives in the uterus at the time that the embryo has developed enough to have over 100 cells and specialized cells that can settle into the uterus lining and start to burrow under the lining. And, after that, we really don't have a clue as to what happens at all.

The human process of implantation is not necessarily like mice or cows. We actually are much less efficient. Removing the uterus of women at various stages of implantation to study what's going on is not going to be done. The primates that we share our genes and our reproductive biology with are increasingly rare and are protected from this kind of research. Implantation, the process of the embryo burrowing under the uterus lining, capturing some of the blood supply of the uterus lining, and growing enough to make a placenta, which then grows to feed the embryo and fetus, is mostly a mystery.

It is thought that about one in five fertilized eggs goes on to make a baby to viability in fertile couples. In infertile couples, it doesn't happen that often, and sometimes we don't know why or what to do about it. So many couples who are not getting pregnant move to in vitro fertilization. It is thought about 1% of all the babies born in the U.S. were conceived with IVF, and that makes about a million babies in the U.S. over the years. Hundreds of thousands of cycles of IVF are done each year in the U.S. But you can put lovely looking embryos into the uterus of a woman and not get pregnant for no good reason.

This leads doctors and patients to try to come up with strategies to increase the chance of implantation. In the old days, we had a woman in bed tipped upside down for a day after putting the embryo in her uterus with hopes that it wouldn't fall out. Then we had women rest for hours, then an hour, then 15 minutes, and then not at all because randomized trials showed that laying down flat after an embryo transfer didn't seem to make a difference in implantation. Some people have tried acupuncture with the hope that it might help implantation through some ancient wisdom that we understand about as well as we understand implantation. Randomized trials showed that acupuncture didn't work better than fake acupuncture and implantation, but doctors and patients were desperate to make this very expensive and life-consuming process work.

Some years ago, someone came up with the idea that if you disrupted the uterus lining the month before IVF, maybe it would cause a reaction in healing that might increase the chance of implantation. Given that we have no clue about implantation, it seemed like an idea. And some early studies suggested it might have a small effect, increasing the likelihood that the embryo would successfully implant and grow. Now, this isn't like gardening where you scratch the earth and then put the seeds down in hopes that they will grow better than just dropping the seeds on the ground, although it sort of sounds like that.

The endometrial disruption called endometrial scratching actually happens the month before the IVF cycle. It can be done in several ways, but the most common is to put a small tube with a sharp edge at the tip into the uterus, through the cervix, and move it around back and forth, sort of scuffing up or scratching the uterus lining. So does it work? Some people thought it did. Some studies suggested it might, and patients and doctors were desperate.

In a widely read medical journal, the "New England Journal of Medicine," a large randomized trial of endometrial scratching versus no scratching before an IVF cycle reported that it didn't help. There was no difference. Not exactly a surprise. At least it didn't hurt. Well, actually, it did hurt. Putting a tube in the uterus and swirling it around is uncomfortable to most women. And for doctors who charge for this procedure, it could be 200 to 600 bucks, so scratch that. Well, no, don't scratch that.

Lots of things have been tried. Word gets out on the web, and patients request some intervention or another that might increase the chance of getting pregnant. I will admit to some magical thinking of my own that I did after putting embryos back in the uterus of patients undergoing IVF in my years as an IVF doctor. There are a couple of minutes between putting a tiny drop of fluid with embryos, or better one embryo, into the top of the uterus. And when the embryologist in the lab checks the tube and makes sure that the embryos are gone, it's a couple of minutes. I would practice deep breathing and imagine the embryo in the uterus happy and implanting, and growing, and seeing children at our IVF picnic. I didn't tell patients that I did this little exercise, but it seemed like a good use of a few quiet minutes. Magical thinking. What I really wanted was some kind of tissue super glue, but somebody actually tried that, and it didn't work.

So what do we do when we don't know what to do? The world of infertility and early pregnancy loss has been filled with well-meaning therapies to try to help people have the children that they hope for. Most, at least, haven't been harmful -- acupuncture to increase IVF implantation, aspirin to prevent miscarriage, and many others. But before we suggest it or offer it to patients who want it, we should at least know that it won't hurt physically, emotionally, or financially. Large, well-done randomized trials are very expensive, and in the IVF world, usually not funded by our government, but they need to be done. As patients and consumers of reproductive health care, we should try to get the best information from our physicians and take a deep breath and do the best we can. And thanks for joining us on The Scope.

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Interviewer: A group of concerned scientists have raised the question: Should we be able to genetically engineer people? We'll talk about that next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: Scientists have called for a moratorium on genetically engineering human embryos until the safety and ethics have been worked out. I'm talking with Dr. Dana Carroll, a distinguished professor of biochemistry at the University of Utah. He and his colleagues have made their voices heard in a commentary that was just published in the journal Science. Dr. Carroll, why is this topic coming under scrutiny now?

Dr. Carroll: The CRISPR technology is very, very simple in its design and application and it's turned out to be extremely effective. More and more laboratories are now using this technology for a variety of purposes for research, even for agriculture. Because it's so easy and so many people are using it, the issues, which were sort of in the background for a number of years, have now moved to the front and amongst them is this issue of potentially engineering the human germ line.

Interviewer: One of the points under discussion right now is germ line modification. Can you explain what the germ line is and what that means?
Dr. Carroll: The thing that makes the germ line changes more serious than things you might do to somatic cells is that the changes are permanent and heritable. So if mom and dad are carrying mutations that could cause disease in their offspring, the idea is that the genome engineering would allow the correction back to what we would call the normal DNA sequence of that potential disease gene.

Interviewer: Yes, well exactly, and that's why this technology is so exciting is that we may be able to eliminate inherited diseases within a family. Correct?

Dr. Carroll: That's right.

Interviewer: So you told us about the promise of this technology, but what are people worried about? Why is this under discussion right now?

Dr. Carroll: There are a few things to be concerned about. One, from a scientific perspective is that, although I said we can make very specific targeted changes in the genome, the reagents that we are using, these nucleases, are not 100.00% specific. There may be other changes that occur, not just at the gene we're trying to target, but elsewhere in the genome. So we need to perfect the technology to a point where we can be quite confident that we aren't making things worse at the same time we're making things better.
There is some concern that because the technology is easy, that it will begin to be used for what you might call trivial purposes, like a couple trying to endow their children with what they consider favorable characteristics: blonde hair, blue eyes, athletic prowess.

Interviewer: How close are scientists to being able to do these types of experiments?

Dr. Carroll: In humans . . .

Interviewer: In humans, yes.

Dr. Carroll: This sort of manipulation has been done in a lot of different organisms, including mice and rats and pigs and cows and even monkeys. So the technology is ready to be applied to humans.

Interviewer: I think one thing that is interesting is that there is not even consensus among informed scientists. I think you're in the camp that can see a future where this technology is permissible, under the right control, but there are others who think that we shouldn't go forward with this technology at all.

Dr. Carroll: The commentary that was published in Nature basically said, the authors stated that they could never envision a situation where germ line genome modifications should be allowed or would be necessary. I think that's a little bit short-sighted. Like I said, I don't know what the best candidate genetic diseases are for this kind of genome engineering, but I'd love to hear from physicians and other biologists who are sort of closer to the human disease arena to see what they have to say about it.
The other thing is that we don't want to get into a situation where the public in general, individuals around the country and around the world, think that scientists are just trying to make monsters. We want to engage the public to see what the public thinks about it. If it turns out that there's, at this stage, close to zero public acceptance of going forward, then I think scientists should be governed by that.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences radio.