By Mo Bahrami
Recently we have been asked to provide some information about embryo implantation. It is an exciting area of research that that we as a group are pursuing. However, as is the case with all things in research – answering one question leads to more questions.
Before I start, I’d like to apologise in advance – this blog entry is a little more “wordy”. I’ve tried to keep it as short, and as simple as I can. However, it is important to understand that the process of embryo implantation is multifactorial, and to suggest that a short blog is sufficient to cover all of the key aspects is disingenuous to say the least. One more piece of housekeeping; due to time constraints, we have had to use diagrams from other resources. All diagrams used in this blog are done so with permission from the original authors, and in the event that the authors could not be contacted, links will be provided.
Ok, so you have gone through a stimulation cycle and have had multiple oocytes collected. Thankfully a number have been successfully fertilised and cultured to the blastocyst stage of development (bear in mind some clinics will transfer cleavage stage embryos) and are ready for transfer (whether that is on a fresh or frozen cycle is decided by your specialist team). Finally the day comes for your embryo to be transferred – no doubt there will be optimism and excitement (especially if it is your first time), or stress, anxiety and fear if you’ve had a previous transfers that did not lead to a pregnancy. Once the transfer procedure is completed, it may feel somewhat anticlimactic – after all, you’ve had multiple injections, gone through a pick up procedure and had to wait while the embryos developed in culture. Now it is up to the biology of implantation. Whilst it may feel like nothing is happening, this is arguably the most complex process.
The day of embryo transfer will coincide with what is commonly referred to as the Secretory phase. That is why your doctor will give you drugs such as progynova if you are going through a frozen embryo transfer – they’re timing the transfer so it coincides with the phase most receptive to an embryo, otherwise referred to as the “window of implantation”. There is a general consensus that the window of implantation is a period of approximately 4 days. At this stage, the follicle undergoes physical and biochemical changes to become the corpus luteum (CL). The CL will secrete the hormone progesterone, which is critical for maintaining pregnancy in the early stages of implantation.
This diagram has been taken from Understanding Human Sexuality, and is the property of the McGraw-Hill Companies.
The changes that occur to the uterus are quite dramatic; the endometrium thickens, and becomes highly vascularised, with increased secretions from uterine glands; furthermore, during the secretory phase, the endometrium is covered with rounded cells called decidual cells. The changes to the uterus are very complex; to give you an idea, the images below demonstrate just how drastic the changes to the endometrium are!
These images are taken from a lecture provided given by Professor Lois Salamonsen, of the Hudson Institute.
Assuming the uterus is receptive, and the embryo has been transferred, what happens next? The first step requires the embryo to hatch from its shell (Zona Pellucida). Sometimes, the “best” embryos will not lead to a pregnancy because they are unable to hatch from the zona. In the event where the embryo hatches, it will bind loosely to the endometrium; a process referred to as apposition. Embryo attachment (some texts will call this embryo adhesion) follows apposition – this is a stronger attachment of the embryo to the uterine wall. At this stage, microvilli (very tiny protrusions) on the surface of the trophoblast cells will bind to the epithelial cells of the uterus. This binding is facilitated by many factors, such as surface glycoproteins (keep in mind glycoproteins are one class of proteins – there are many more that are involved in implantation!).
This diagram is from the following website: https://courses.washington.edu/conj/bess/implantation/implantation.htm. The inner cell mass is what gives rise to the foetus, whilst the placenta develops from the trophoblast cells.
After the embryo has attached; the following series of events is collectively referred to as invasion. This is where the trophoblast cells will penetrate through the uterine wall. As they penetrate, these cells will change into a new cell type – and are now referred to as the syncytiotrophoblast. The syncytiotrophoblast cells will continue to penetrate through the decidual cells (remember, those rounded cells I mentioned earlier) until the embryo is entirely embedded into the endometrium. From this point, the syncytiotrophoblast will make contact with the maternal blood – and initiate the formation of the placenta.
The above image is the property of La Trobe University, and has been modified from the following website: http://www.latrobe.edu.au/biochemistry-and-genetics/research/greening/exosomes-and-their-role-in-regulating-embryo-implantation.
So that my friends is embryo implantation at its simplest. For the trained scientists amongst you, you’d most likely read this any say, you’ve missed out on X, Y and Z!! But in reality, I’ve missed a lot. And the reason for that (as I mentioned earlier) is that there are multiple, complex events that constitute implantation. I’ve tried to familiarise you with some of the key steps, and in future blogs, my colleague and I will attempt to explain specific examples of embryo implantation failure. As is often the case, the cause of implantation failure in one patient is most likely completely different to another.
If your require us to simplify anything in this blog, please don’t hesitate to get in contact with us through our website.
As always, please ensure that you seek medical advice from your fertility specialist.
Best of luck!
Mo
