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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