Blastocyst and implantation
In nature fertilisation occurs within the fallopian tube and the embryo does not come into the uterus until it is at the blastocyst stage.
Embryos at the blastocyst stage are essentially at the immediate preimplantation phase and the next stage in embryo development is hatching and implantation into the endometrium. By continuing development there may be better synchronisation with the endometrium.
Extended embryo culture is the practice of prolonging embryos in culture for more than three days. Embryos that satisfactorily progress beyond this stage are of higher quality and have the greatest potential for implantation. There is no doubt now that the pregnancy rate and implantation rate following a blastocyst transfer is significantly higher than with cleavage stage embryos. This is supported by validated HFEA data.
This means that a high pregnancy rate can be maintained and the concomitant risk of multiple pregnancy is reduced by replacing fewer embryos each time.
Replacing a single blastocyst, freezing any other available blastocyst with a view to later replacement results in more live births than replacing two blastocysts together especially in younger women.
There is a certain wastage in trying to produce a blastocyst. Some embryos that look fine on day three do not go on to achieve blastocysts. It is possible that these embryos are of lesser quality but it is also possible some embryos do not form a blastocyst due to the imperfections of the culture system of the clinic. Usually around about half of the embryos do not progress to blastocyst.
In a small proportion of people none of the embryos progressed to blastocyst and the pregnancy rate is undoubtedly lower in embryos that slow down and are still pre-blastocyst on day five. It is still worth considering replacing these embryos as there is a chance of pregnancy although it is generally not thought appropriate to cryopreserved them.
There are a number of competing technologies that attempt to predict which embryos will become blastocysts including Eeva and embryoscope. These take time lapse photographs in an attempt to identify embryos that are likely to form blastocysts and replace them earlier reducing laboratory cost and time.
When choosing a program to have treatment a successful, mature and well used blastocyst programme is likely to give you a better chance of pregnancy.
The uterus and uterine receptivity
In implantation, the embryo first approaches the endometrium, it then sticks to the endometrium and then it invades the endometrium. For this to happen the embryo must be competent to perform these functions but the uterus must also be able to respond appropriately to the embryo. There are a large number of substances that appear to inter-react to cause these phenomena to happen. As yet no reliable test appears to exist for recurrent implantation failure although it is known that if the endometrium appears thin when measured by ultrasound the results are less good.
In recurrent miscarriage unusual populations of natural killer cells may be present in the uterus however in this case miscarriage is occurring after implantation has happened. If the natural killer cells are responsible it is possible that suppression in this group of people using steroids might help them. There may be a risk however to the pregnancy and they should not be used without clear reasoning suggesting the benefit outweighs the risk. This process is still under intensive research.
The embryo may participate in this process partly through HCG secretion. It is also likely that abnormal embryos secrete substances which indicate to the endometrium its adverse state. The endometrium is therefore able to identify poor quality and abnormal embryos by these substances and actively discourage their implantation. In order to prevent the abnormal embryo implanting the endometrium as a whole reduces its receptivity. If more than one embryo is transferred into the uterus it will not be able to identify the good from the bad embryo. The effect is that the endometrium effectively rejects both embryos by hindering implantation.
This may be the reason why pregnancy rates from single blastocyst embryo transfers where the second embryo is frozen and replaced at a later time give more pregnancies overall than a double transfer (two blastocysts).
Abnormalities affecting implantation
Implantation may be of course affected by infection which leads to a hostile environment, by adhesions from past surgery or infection which disrupts the endometrium by inflammation . Polyps or fibroids that distort the womb internal surface (endometrium), and a thin septum dividing the uterine cavity can adversely affect implantation. This is either by causing inflammation of the endometrium or by being an area of poor implantation potential probably due to poor blood supply. These can all be investigated by ultrasound and Hysteroscopy.
Adhesions, polyps and fibroids can be treated by removal through hysteroscopy surgery.
How can we assess the endometrium?
Any physical assessment or biopsy in the treatment cycle will disrupt the endometrium so cannot be advised. Assessment outside the treatment cycle may not replicate the events in a stimulated cycle. It may be appropriate for a natural cycle but this is an area for research and development. Gene array assessment has been tried and is under development. At present there are concerns that the results may vary from cycle to cycle and this would seriously limit its value.
The main method of assessment is by ultrasound which is highly imperfect. An endometrium of 7mm or less is associated with a lower implantation rate. A trilaminar appearance during stimulation is associated with a higher pregnancy rate. This applies to IVF/ICSI cycles and egg donation cycles.
Blood flow has given variable results. Uterine artery flow measures the blood flow throughout the uterus and not just the endometrium and other methods are imprecise. Attempts to increase blood flow using Viagra have met with inconsistent results.
Hycosy and hysterosalpingography tests may identify abnormalities of uterine shape as well as assessing tubal patency.