Failure after IVF can be devastating for many couple. A cycle of IVF requires work, effort, money and most of all… generate hope. Hope for success that results in having a healthy beautiful baby in your arms.

So, when IVF fails, it raises the question of why? Why did not work with me? What I did wrong? Sometimes there will be a clear reason but often there is no direct answer. And this again can be very frustrating for the couple and for the team as well.

Let’s try to make things clear. First of all, it’s NOT your fault and you did not do anything wrong. A successful pregnancy requires 3 main things: a capable embryo, a capable uterus and immune acceptance. And most probable a myriads of small things in between that unfortunately we are not able yet to fully understand.

There are though still many factors that we can identify and in most of the case treat.

In this your fertility specialist’s experience is critical when faced with a failed IVF, to try to determine the reasons. Approaching the answer to this question requires evaluating all the multiple aspects of the IVF process in an attempt to define where something went wrong and how to correct it and personalise a further cycle enhancing the chances of success. An IVF cycle it is obviously a treatment plan but it is also, and that is what most of the couple do not appreciate, a very potent diagnostic tool from which the doctor can gain a variety of data very useful in the process that will lead to a precise diagnosis and finally to a successful cycle.

And then of course, there will also be those sad cases of multiple failed attempts, when the couple but especially the doctor will need to face reality and say “it is time to close the door”.

Dividing the world of IVF into the world of the embryo, the uterus and the immune acceptance offers a starting point and an easy way to approach the problem.

Don’t Judge the embryo by its Cover.

The world of the embryo requires a normal sperm and a normal egg to meet, to mix and then equally separate the genetic material (chromosomes) and then start dividing into a new embryo. These embryos will continue to develop and on day 3 or day 5 will be selected for embryo transfer.

Many human embryos can appear perfectly normal under the light microscope on day five and yet have the wrong number of chromosomes. For example, as many as 90% of all normal looking embryos from a women in her 40s will have the wrong number of chromosomes, while the abnormal embryos will be only 25-30% in a women in her early thirties. The most common cause of this problem is age.

Repeated attempts at IVF will not correct this problem but of course multiple cycles and embryo transfers will increase the chance to find the “good one”. Fortunately, recent advances in technology can be used to reduce the number of embryos transferred with the wrong number of chromosomes. The use of preimplantation genetic screening (PGS) allows us to determine with very high reliability the actual chromosome number of an embryo which has developed to the stage of blastocyst.

Using data from the literature, we see that transferring an embryo with the correct number of chromosomes result in delivery rates as high as 60%, and may actually go higher. However, still not all transfers result in a live birth. So the question remains – WHY?

The problem must be then somewhere else, although it is important to understand that is possible that there are other genetic issues with the embryo that are not detected by PGS, and for the time being, these abnormalities will remain undetectable.

The Uterus and Recurrent Implantation Failure

The uterus is the place where the pregnancy start and is kept until the delivery. It is therefore  fundamental that the uterus is functioning properly so that the embryos could implant and develop. Uterine malformation, presence of fibroids in the muscle of the uterus or presence of fibroids and or polyps in the endometrial cavity can affect uterine functionality and impair implantation. For the same reasons implantation may occur but the pregnancy may end in miscarriage. A full evaluation of the uterus and the uterine cavity by SIS, HyCoSy orHSG is mandatory before proceeding to IVF. And in case of failure a diagnostic hysteroscopy (looking inside the uterus with a scope) may be indicated.

The endometrium is the tissue lining the uterus, which gets thicker during the cycle until it reaches the optimum thickness for implantation following ovulation. While shape and thickness are very important, the receptivity of the endometrium is a crucial factor in determining the success of IVF treatment.

The endometrial receptivity is the status in which the endometrium is ready for embryo implantation to take place and it is also called window of implantation. This occurs normally around days 19-21 in each menstrual cycle of a fertile woman.

In some couples who have recurrent implantation failure, it may be that the window of implantation is displaced either back or forward a few days.

Again advancement of science can help us to diagnose a receptivity problem thanks to the development of a specific test called ERA (Endometrial Receptivity Array). The ERA test involves taking a biopsy of the womb-lining and analysing the genes of this tissue taken on the day of “normal” receptivity”. The biopsy procedure is simple, fast and performed in clinic in a similar procedure to an embryo transfer.

“My uterus is perfect and the embryos are genetically normal, so WHY am I not pregnant yet?”

When recurrent miscarriage occurs after natural conception, or for patients who undergo IVF with a capable uterus and repeated excellent quality embryos transferred and yet have no success, other factors must play a part.

Reproductive immunology is a field of medicine which studies the interaction between the immune system and reproductive organs. Research has suggested that during a normal pregnancy, a unique type of immunity occurs that stops the body rejecting an embryo as a foreign body and aids the growth and development of the foetus. If this immunity does not work properly, embryos may not implant or may be rejected early after implantation. A number of important components of the immune system have been recognised as key players to successful pregnancy.

Those women at high risk of more profound immune factors such as women who have an autoimmune disease or who have a history of repeated failed IVF, recurrent implantation failure or pregnancy loss, should undergo to a comprehensive investigation panel including antibodies, cytokines and Immunophenotype assay. The results of the immunological panel are careful analysed and interpreted to choose a personalised therapeutic protocol that more efficiently targets the underlying immune component.

In conclusion…

Infertility is not a curse but a disease and many times, a cause can be determined. A failed cycle, that it seems a tragedy at first can sometimes be the key to understand the real problem. Based upon the findings, recommendations can be made as to how best approach the diagnosed problem and reach our goal.

DO NOT GIVE UP!