This may be one of the most common questions that we gynaecologists and embryologists face in our daily practice. This very reasonable question – posed just before the much-desired transfer, and after all that our patients have gone through during the assisted reproduction treatment – is, however, one of the most difficult to answer.
According to the studies published and our clinical experience, we can indicate a percentage of success in general, but that percentage will always vary according to the case at hand. It is this that prevents us from giving a specific and individualised answer.
So, what can cause the implantation rate vary from case to case?
The simple fact is that embryo implantation is a very complex event that is conditioned by many factors. The implantation occurs when the embryo in the blastocyst stage (Day 5 or Day 6 of development) and attaches to the endometrium (a mucous layer that covers the inside of the uterus), penetrating it in order to continue developing inside the uterus.
This whole event has to take place in the correct uterine environment, thus obtaining synchronisation between the development of the embryo and that of the endometrium.
The definition of embryo implantation already clearly identifies two of the most important factors that will influence the implantation rate: embryo and endometrium.
The embryology laboratory is tasked with assessing and selecting the optimal embryo to transfer. The assessment of embryo quality ranges from the gametes (oocytes and sperm) to the last day of cultivation, and it includes its morphological and kinetic characteristics.
Therefore, during these days of development, we will be studying the factors related to the embryo that will influence the implantation rate.
The oocyte has the most important role in the early days of embryo development. The patient’s age will determine the oocyte quality and will be one of the main factors that affect embryo quality and, thus, the implantation rate.
The latest results published by the Spanish Fertility Society (SEF) show that the pregnancy rate with the mother’s own oocytes decreases as the patient’s age increases: 45% (<35 years), 35.9% (35-39 years) and 22.5% (≥40 years).
The ICSI technique has made it possible for us to solve cases with a serious male factor, in addition to allowing us to make a better sperm selection by choosing the sperm with the best motility and morphology. We also have other, complementary, techniques that help us make a better sperm selection when there are alterations in the sperm’s genetic material that will affect the correct fertilisation of the oocyte or the subsequent development of the embryo.
Due to the new time-lapse incubation system and the advances and improvements in embryo culture media, the trend in laboratories is to bring the embryo to the blastocyst stage (Day 5 or Day 6 of cultivation). The best quality embryos are the ones that will reach the blastocyst stage, while those of lesser quality will not develop correctly or will simply cease to develop. Thus, we will obtain more information on embryo development, meaning that we will do a better embryo selection in order to transfer the best quality embryo.
Being considered a good quality embryo does not mean it is genetically normal. This is something we have to remind people of continuously. An embryo with chromosome alterations that are not compatible with life will result in implantation failures or a subsequent miscarriage. To do this, the PGD (Preimplantation Genetic Diagnosis) will allow us to select “healthy” – that is, normal – embryos. This tool, along with the morphological evaluation of the embryo, will allow us to select the healthy embryo with the greatest implantation potential.
As we have already commented, synchronisation between embryo and endometrium development is crucial for implantation. If the endometrium is not prepared on the day of the transfer – regardless of however good the embryo quality may be – it will never be implanted correctly. Therefore, a receptive endometrium is another crucial factor for implantation to occur.
The main factors related to the endometrium that may influence the implantation rate are:
Most research concludes that implantation rates are better when a trilaminar endometrium is achieved that is at least 7 mm thick. This thickness will be attained by administering external hormones such as oestrogens and progesterones.
This is the time period that the endometrium is receptive and allows the embryo to be implanted. This window may change, which results in the transfer of the embryo and the implantation window not being synchronised. This factor is the most difficult to control, although there are currently molecular diagnostic tests that can study it.
In addition to the quality of the embryo and the endometrium, there are other factors that may affect the implantation rate:
Infections, polyps, myomas, and uterine malformations will affect the implantation and development of the embryo in the endometrium.
Immune system disorders that cause the mother’s immune system to damage the embryo by identifying it as a foreign body. This causes a failure in implantation or a subsequent miscarriage.
These are blood clotting disorders related to implantation failures and repeated miscarriages. Treatment with aspirin and heparin is indicated for these cases.
This heterogeneous illness may – in addition to affecting the ovarian reserve – cause pelvic adhesions and changes in hormone production. This may lead to ovulatory dysfunction and changes in endometrial receptivity, thereby reducing the rate of embryo implantation.
Polycystic ovary syndrome (POS)
This may make implantation difficult due to a change in the production of sex hormones that may affect endometrial receptivity, including oestrogens and progesterone.
Other factors that will also influence the implantation process include:
Tobacco use affecting the quality of the gametes; changes in the BMI (obesity and low weight) or stress that will influence the woman’s normal hormonal function. As we can see, the implantation is a complex event involving a multitude of variables. We must take these variables into account when determining an individualised implantation rate. The entire team will try to study and control the maximum possible variables and attain the best possible implantation rate based on the case.
We must always remember that the success that really matters is not implantation or pregnancy in our patients, but the birth of a healthy baby.
We cannot ignore the fact that there is a considerable percentage of spontaneous miscarriages. That is why we will always try to explain the rates as clearly as possible, so that we can help our patients to reconcile the hopes provided by statistics with the emotional cost of the whole process.