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What Do We Know About the Embryo Implantation Process?

When an embryo is not able to properly implant into the uterine wall, this is called implantation failure. In this video, Dr. Gleicher explains the process of implantation and what this knowledge means for infertility treatment.

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Hi, today I want to talk to you a little bit about the implantation an embryo has to undergo if a pregnancy is to be established.

And let me use my body to explain a few things. If this is the uterus and this is my right fallopian tube, then during sexual intercourse, the man deposits sperm in the vagina. That sperm, through its own motility, marches up in through the uterus into the fallopian tube, where in the distal third of the fallopian tube the sperm meets the egg which has entered the tube from the other side. Once egg and sperm meet, fertilization takes place and the fertilized egg then has to march all the way back down the fallopian tube into the endometrial cavity of the uterus. And interestingly there, it doesn’t immediately implant (meaning dig into the uterine wall), it actually swims around (symbolically speaking) for about 48 hours. Now, it doesn’t really swim because the cavity doesn’t contain fluid. It contains mucus, a very thick fluid, but the embryo spends 48 hours in the endometrial cavity before it implants and it usually implants only on the top of the uterus or this quote the fundal area.

And how that process works is still, to a large degree, a black box because we obviously cannot watch it while it’s happening (at least not in humans). And so we are very dependent on animal data and on some in-vitro laboratory experimentations that we can do. And some of the most important laboratory investigations were actually recently performed (to be exact) in 2016 in two laboratories– two very famous laboratories– one in Cambridge and one in New York at Rockefeller University. And both of these laboratories built an artificial implantation model. In other words, they succeeded in establishing a model where human blastocyst stage embryos, which is the stage in which an embryo usually implants (usually day 5/6 after fertilization), where those embryos could implant on an artificial surface.

And both of these prominent laboratories demonstrated independently that these embryos had the capacity to grow and develop up to day 14 after fertilization without any contribution from a mother. And that was an amazing discovery because it suggests that all that the ability to develop, to divide, to develop all the characteristic features of a human being, are really programmed fully in that embryo in that embryos own cells without any need for help from the mother at least in those early stages. And if one really thinks about this discovery, it is very very remarkable because even though it’s obviously in-vitro (meaning in the laboratory) and that means that in-vivo (in the body) things may happen differently. But it suggests something about the implantation process that we previously did not know and that was this total independence of the early human embryo. And that is very important to understand when we are trying to get a little light into this black box of early implantation.

So, the embryo spends 48 hours in the cavity and then implants and we think the reason why that is happening is because the embryo needs those hours to send a message to the mother that says, “Hey, I’m here. Let me in!” Because in principle the endometrium is hostile and it must be hostile because think about it. If the endometrium wasn’t hostile to invaders like the embryo (and the embryo is really a parasite), then the mother would constantly be invaded through that opening by bacteria, viruses, parasites, and God knows what else. So the endometrium must be hostile to invasion, yet a normal embryo has the ability to send messages to the mother and the maternal immune system that says, “Hey, you can safely let me in!” And what those messages are, we don’t know yet. But that is currently the subject of very intensive investigations.

Implantation therefore is a process which is much more driven by the embryo than we used to believe. Though not obviously maternal influences also play a role. And like anything in nature, processes can malfunction and so there’s no question that those malfunctions may be existing on the embryo side or on the maternal side. And the research that is currently going on is trying to figure that out because there’s no question that a lot of cases of female infertility are clearly caused by failures in this implantation process.