This question is always posed following a failed treatment cycle.
One of the factors contributing to this failure is the failure of implantation.
Implantation is the process by which the embryo is fixed to the endometrium at a certain stage and within a period of time known as the implantation window, and then continues its intrauterine development. This process is regulated and conditioned by many factors, both endometrial and at embryonic level, systemic and / or localised, and most cases yet unknown.
The vast majority of treatments produce an acceptable number of embryos with four to eight cells, however, only a few are able to survive after being transferred into the uterine cavity.
Classically implantation failure is considered as “the situation in which we have not achieved pregnancy after transferring in at least two or three attempts, depending on factors such as age, embryo quality in a cycle of IVF or egg donation”.
Throughout all these years of treatment for recurrent miscarriage, the knowledge base has been improving and expanding in many aspects involved in these treatments; both in the drugs used for ovarian stimulation as well as the research into the nutritional needs in gametogenesis and the embryonic development taking place in the laboratory. With regards to implantation, it has not yet been possible to further expand knowledge to the extent which enables us to improve results, when what fails is this link, key to the whole process.
It should be noted that in humans only 30% of embryos, achieve successful implantation.
Given this, there are a number of widely accepted diagnostic recommendations which should be implemented.
There are three groups of factors:
1. Endometrial receptivity
The study of the endometrium is still assuming a challenge in the field of reproduction, since its development is regulated by complex mechanisms. It tries to look for a gene pattern that favours receptivity, looking at the activation or repression of a gene pool. The causes that lead to a decrease in endometrial receptivity are:
- Environmental endocrine disruptors: we know that in controlled ovarian stimulation cycles, responsiveness is decreased compared to the natural cycle, especially in cases of high responders and high estradiol levels. To minimize this effect we use moderate stimulation processes.
- Inadequate endometrium development it is in dispute what should be considered the minimum thickness of the endometrium to consider it as appropriate. It should be greater than 7 mm. If necessary, we can promote its development with substances such as sildenafil, aspirin, transvaginal oestrogen, and others)
- Organic uterine pathology: in these cases, we recommend performing a hysteroscopy to rule out polyps, endometriosis, myoma, and other diseases that are diagnosed in most cases with modern ultrasound equipment.
2. Embryonic Factors
- Chromosomal abnormalities: embryogenesis can be altered by abnormal paternal chromosomes, hence the recommendation to conduct a study of the karyotype on both partners. Highlight the implantation failure associated with sperm chromosomal abnormalities, assessed by FISH, as shown in some of our Works which have been published in the prestigious journal Human Reproduction ” Fertility and Sterility ” .
Also mention the controversy over the implementation of the PGD in the study of aneuploidy in order to select the chromosomally correct embryos. In most cases, their benefits are not shown, thus reducing their strict use in implantation failure, where there could be an increase in these anomalies.
- Embryonic fragmentation and the hardening of the pellucid zone: An over fragmented embryo or thickened pellucid zone, have a negative impact on implantation. In these cases, we can carry out aspiration of the degenerate fragments, which hinder the intercellular signals that promote embryo splitting and “assisted hatching “. The latter technique is used to create an opening in the embryo to facilitate its emergence and implantation, either by chemical methods, laser, or others.
- Embryo-endometrium Asynchrony: to try to improve synchronization, we perform the so – called long culture, transferring the blastocyst stage embryo. It is the moment when it breaks the pellucid zone and the endometrium is prepared for the embryo to adhere. The tendency in selected cases, is the transfer of a single blastocyst stage embryo, even though it is necessary to have a large number of good quality embryos and this is not always the case.
Perhaps in the future we can detect the presence of other genetic, chromosomal or biochemical markers in embryos, which would allow us to better select and therefore increase the chances of implantation.
3. Maternal factors
- Narrow titled cervical canal: this hinders the process of embryo transfer. In these cases it is advisable to perform a test of cervical permeability prior to stimulation cycle. Always it advised that such transfer is always under ultrasound control.
- Hydrosalpinx: no doubt that this disease reduces rates of implantation and removal or ligation is recommended even prior to implantation failure.
- Endometriosis affects both egg quality as embryonic, and can be helped with prior medical or surgical treatments.
- Thrombophilia: In the most recent studies have shown a higher prevalence of thrombophilia in patients with implantation failure. They are characterised by an imbalance between coagulation and fibrinolysis.
In Segrelles IVF we give special attention to these factors, which in our opinion, are underestimated. Our personal experience confirms that this delivers great benefit to a certain group of patients.
Despite the above, the failure of implantation remains a challenge for clinicians. It is important to visit a Unit like Segrelles IVF who has extensive experience in these types of diagnosed cases and in performing the prescribed treatment for each case and thereby increasing the chances of embryo implantation.