Along the IVF road there are many twists & turns. As much as you might want to, you can not always predict what might happen next including future IVF failure.As with all tough and challenging experiences, failed IVF entails a lot of tough questions that need to be answered – mainly in order to spare ourselves similar challenges in the future. In this webinar, Dr Laura García de Miguel [Medical Director at Clinica Tambre] tells us more about what to do if our IVF cycle fails.
Dr Laura García de Miguel starts with reminding us what we mean by in vitro fertilisation (IVF). By definition, it is a reproductive treatment that creates embryos in a laboratory to maximise the chances of implantation. It is generally differentiated into a few types, such as own eggs and partner’s sperm, own eggs and donor’s sperm and egg donation (with partner’s or donor’s sperm). Additionally, there is also the ROPA method for lesbian couples – called ‘shared motherhood’- in which one partner is the egg donor and the other carries the pregnancy. Each of this treatment types can be conducted with so-called ‘normal IVF’ (when the egg and the sperm are left in the laboratory dish to fertilise on their own) and the ICSI (intracytoplasmic sperm injection) procedure when one sperm is injected directly into the egg. Dr García de Miguel also talks about the various stages that the IVF cycle takes including ovarian stimulation, egg retrieval, sperm retrieval, fertilisation, embryo culture and embryo transfer.
If IVF is done with egg donation, it requires the selection of an egg donor. Generally, such a person is younger than 30 years old and she has to undergo complex psychological, medical and genetical tests. In Spain, egg donation is anonymous – however, the selection is always done on the basis of recipient’s physical characteristics. The donor and the recipient have their cycles synchronised with hormonal treatment – the donor undergoes ovarian stimulation and egg retrieval whilst the recipient has the embryo transferred to her uterus and – as a result – gets pregnant and gives birth to a baby.
At least, this is the desired scenario. But as we all know, life isn’t always this way and IVF treatments can be unsuccessful. Dr García de Miguel reminds us that the 50% of unsuccessful IVF is due to embryo abnormality. It is caused by different factors, such as poor ovarian reserve, male factor, poor embryo morphology or chromosomal disorders. Apart from that, the outcome of IVF may be negatively affected by endometrial receptivity and uterine abnormalities as well as coagulation and immunological disorders.
Fortunately, there are some potential solutions for IVF failure that include cutting-edge technology and treatment techniques. If IVF failure is caused by a male factor, sperm diagnostics may be an answer. There are some diagnostic tests to be performed, such as Comet (to detect simple and double sperm fragmentation), Chromosperm (to confirm if sperm chromosomes are balanced or not) and FISH (to assess if all chromosomes in sperm are absolutely normal). Depending on the detected abnormality, there are different fertilisation techniques which can be used – e.g. Fertile Chip, MACS or SpermSlow.
Dr Laura García de Miguel goes on to explain IVF failures caused by eggs. In such cases, there are two options possible: doctors may decide to go for another round of IVF with own eggs or turn to egg donation. In case of the former, it is possible to use melatonin, change a stimulation protocol, do a dual trigger shot or go for dual stimulation. If egg donation is a second choice, then the recommendation is to go for a fertility proven donor, do donors’ immunological selection if necessary and always do a day 5 embryo (blastocyst) transfer.
Dr García de Miguel reminds us that the blastocyst culture is of great importance for the success of IVF as well. As 50% of human embryos cease to develop on day 3, transferring the ones that outgrew the rest on day 5 significantly maximises the pregnancy rates and assures a better embryo-endometrium ‘dialogue’. When conducting embryo culture, it is recommended to use time lapse incubators that enable uninterrupted embryo development along with real-time monitoring and recording.
In the case of previous implantation failures, it is very important to confirm that karyotypes of both partners are normal. Dr García de Miguel advises to always use PGS (preimplantation genetic screening) in order to select chromosomally normal embryos. PGS is said to increase the chances of a healthy baby by reducing the risk of miscarriage and increasing the chance of pregnancy per transfer.
Another very important issue to confirm is endometrial receptivity. Dr García de Miguel says that 30% of patients have changes in the window of implantation. Doctors may evaluate the receptivity of the endometrium by conducting the ERA test. Apart from that, there is also the ALICE test, that makes it possible to exclude endometrial infection, and the EMMA test that studies microbiome in a patient’s uterus. All three tests (ERA, ALICE and EMMA) are included in the EndomeTRIO test. According to Dr García de Miguel, undergoing this test before another round of IVF will help to exclude all endometrial problems. Additionally, it is necessary to confirm progesterone levels before the embryo transfer.
Another reason for IVF failure may be uterine abnormalities. This is why it is important to use a scan to exclude uterine malformations (septum, double uterus) and pathological conditions, such as polyps or fibroids. Hysteroscopy allows to view uterine cavity while 3D scan helps to confirm if adenomyosis is present and if particular pre-treatment is necessary before the embryo transfer.
Finally, Dr Laura García de Miguel talks about coagulation and immunological disorders. There are women who have potential blood-clotting problems, such as thrombophilia or antiphospholipid syndrome. They could be decreased by using the treatment with heparin which modulates coagulation and improves implantation. When it comes to immunological disorders, it is necessary to conduct thyroid test (TSH + antibodies) to check if pre-treatment with thyroid hormones is needed. It is also common to check vitamins (D, B and folic acid) and study natural killer (NK) cells. Doctors may also want to confirm if the patient has a type of celiac disease she may not even be aware of as well as KIR (killer cell immunoglobulin-like receptors) + HLA (human leukocyte antigens) system to know if there is a negative prognosis that requires a specific pre-treatment or immunological selection of the donor.