It can be the option and it cannot. It’s difficult to say how a pregnancy is progressing. I can tell you from my experience: when you put a top quality day 5 blastocyst into a healthy uterus, then the implantation will happen 100% because the embryo will hatch in a few hours: one, two, three, five hours and will implant. I’m saying that because when the embryo has progressed outside very well for five days, I cannot find any reason why it will stop for the next two, three, five hours. This actually is very important before I will assess the immunological problem. When you have a bad embryo at the beginning then, it’s not nice to think, it’s not sensible to think that the problem is with the house that you put this embryo to live in but you have first of all to be sure that this embryo can live as long as you want in order to have a successful pregnancy.
There’s no real way of discerning what a perfect embryo is or how many compounding factors that can impact on the day how an embryo will behave or grow, adapt in vitro like in the little plastic dish or as a transplanted back and there are many reasons as to why a really good quality ambient has been graded as a high quality embryo and fails to produce a pregnancy. That can be down to the receptivity of the endometrium that means that the lining of the womb doesn’t pick the embryo and attach the embryo well enough; it could be down to if the embryo itself, the outer cells of the embryo that are implanted to endometrium may not be functioning properly either. So, there are many factors but because this whole happens inside into uterus, is very little is known as to why that may be caused but there are lots of research using mouse embryos and using other different animal models and human embryo models in vitro to be able to kind of find out the causes of these. There’s lots of interesting research going on.
Maybe in such cases we can have a perfect embryo, euploid blastocyst 5AA or 6AA for example and there is no implantation in the uterus. So in this case it might be that the endometrium, thickness of the endometrium is an important thing, the age of the patient, the previous failed cycles and the medical history of the patient can impact outcome.
A difficult one and in some ways it’s the million dollar question and the way I think of it is there’s like a funnel with IVF treatment and if you think of everyone going into the top of the funnel starting off treatment most of them, some 90% of them will go on and have a 90% plus or go on and have an egg collection, of those 95% and nearly all of them will have embryos to transfer. So most people who start out on IVF will have an embryo transfer. The next step is when you get this funnel and essentially from an embryo transfer, only about 30 to 40% of women will become pregnant. So there’s this huge kind of drop off after the transfer and then after a positive pregnancy test about 70 to 80% of women will go on and have a baby. So really IVF fails the most between embryo transfer and pregnancy test.
Now the reason behind that you can probably put into one of four categories, as part of a jigsaw puzzle, so the first thing is: it a problem with the embryo and we you’d ask the questions about good quality embryos and embryos is quite difficult to grade and even the conventional grading looking down a microscope, is not that reliable. Even putting back the best quality embryo probably only has about a 50% chance of a pregnancy and that’s putting them the best quality back. Some people will do genetic testing of embryos and even putting back a perfect embryo doesn’t alter those statistics still, so it’s probably something more than just the embryo but perhaps the embryo perhaps accounts for at least a third of those failures. The other three things to think about: is it the transfer process itself that has been difficult or tricky and you can use ultrasound to put an embryo back inside the womb but we still know embryos are not sticky and move around. You can put it back, you can see it’s back in the uterus and still end up with an ectopic pregnancy, so ultrasound isn’t always that reliable. Is it to do with immunology? Is it the immune system that’s attacking the embryo or doesn’t allow it to implant? There’s lots of research happening in that area but we’re still not really much further to understanding that and then finally it is about the endometrium, the womb lining itself. Is the problem with the receptivity or not? Selecting a good embryo or even there’s some thought perhaps if there’s a problem with the endometrium you accept an embryo that’s abnormal then that leads to miscarriages.
These are still areas that are very much the focus of research. There are some supplementary tests that can be added on to look at endometrial receptivity but the science backing them up at the moment is a bit unhelpful in that it is not very easy and sort of affects how you do the treatment. So many places don’t necessarily offer those tests at all. So ultimately you don’t really know the honest answer is no one can tell you why that failed in your circumstances but they’re the four factors that probably have some influence on why it doesn’t work.
They used to think aneuploidy and poor quality of embryos are the most frequent reasons for IVF failures so if we transfer good quality, euploid embryos, the pregnancy rate is much higher and it reaches about 60, 65% but this is not a 100 %. All these transformations occurring in the zygote’s falling fertilisation are monitored by all assisted reproductive clinics to determine embryo quality, morphological embryo quality. Embryo quality is assessed on the basis of several parameters: morphological, developmental, genetic and metabolic. The quality of an embryo is dependent on the quality of the oocyte that created it and while many studies have described the relationship between oocyte and embryo quality. Several of the embryo quality parameters have also been influenced by paternal factors.
Clinically it has been observed that the transfer of euploid embryos results in an implantation rate about 60% while almost 40% of embryos remain unaccounted for. Although some losses can be accounted for by endometrial factors so the residual loss could be partly accounted for by paternal factors. Those factors like obesity, alcohol consumption, stress, severe male factor of infertility, advanced paternal age and some gynaecological problems itself may have influence on IVF outcomes. What counts and among these factors we need to especially pay attention are gynaecological diseases. We need to work with our female patients and it is well known that several types of uterine fibroids, endometriosis, pelvic inflammation may influence IVF outcome so once a person has any of these diseases, we need to prepare her for the embryo transfer just to optimise chances for success.
One of the most important factors for the embryo to implant is the window of implantation. Embryo needs to be completely synchronised with the uterus which is hard to do as an embryo is made outside of the body and then brought inside of the body. Second reason why it is not always easy is that even with good embryos there is a failure. is that not every embryo that is made in the lab is normal. Recent studies proved that most of the embryos that are made are abnormal. Could be sometimes 40 % of embryos that are abnormal and by abnormal I mean that they don’t have the right number of the DNA that an embryo should have. In most of the cases, the embryo will just not implant.
We must take into account that we transfer embryos in accordance to the morphological characteristics and that we have certain pregnancy rates per transfer. Nevertheless when we transfer two or three good quality embryos and there is no pregnancy, we are talking about implantation failure and this is when we must review the study to identify the reason for implantation failure.
This is an extremely difficult question to answer. In fact, I don’t really have an answer. But what I can say is that there are different factors in achieving a pregnancy. And one of them is the embryo, and the quality, the good quality. And even good quality or good looking embryo doesn’t mean that the embryo is actually competent or able to implant.
So we have to think that even if we transfer a perfectly looking blastocyst, perfectly developed, then we don’t really know the actual inside of the embryo. We know that around 30-40%, it depends on the age of the patient. 40% of the embryos are actually not able to implant despite them looking fine, so that could be already a reason.
Then other factors affecting implantations are the importance of the lining of the womb to be coordinated or synchronized with the stage of the embryo. There has to be what we call the window of implantation. It is a time frame where the embryo is most likely to implant. If we get that window implantation wrong, then the embryo is at a certain stage, and the lining is at the stage that could be either bit behind the embryo or a little bit forward compared to the embryo. If that happens, there is no perfect synchronization, and the embryo is not going implant, and so that’s another important factor. That leads to the hormonal environment, which again has to be perfectly precise, and the thickness that we already discussed. We take into account the endometrium thickness, the whole environment, the glands, the substances, and the stuff inside the uterus, the receptors. So there is a micro world or microenvironment which is all in that thickness, in that lining and that is what has to be perfect for the embryo implant.
Why doesn’t a very good-quality embryo implant? There are two reasons. It can be a low-quality embryo with bad genetic information inside. It may look like a very nice embryo, morphologically nice. But it may contain the incorrect number of chromosomes. The embryo development stops. The other reason is the implantation window, the best timing for embryo transfer. 20% of women are not receptive 5 days after the first intake of progesterone. If we have, for example, two or three embryo transfers without implantation with negative HCG, it is necessary to think about the implantation window and about testing it. So it depends from case to case.
In women after 45, it is necessary to think about chromosomal abnormality inside of the embryo. In younger women, very often, the reason is the bad timing of embryo transfer. But individually, it’s not possible to say why it did not work. It’s only a general answer, but there is no individual answer. It is necessary to do many tests, and sometimes we can’t find the reason.
