In this webinar, Dr Luca Gianaroli, Scientific Director of S.I.S.Me.R. located in Bologna, Italy, has been talking about reasons for failed IVF attempts and how to turn them into a successful outcome.
If we look at the factors causing infertility, they range from genetic factors, and congenital factors to acquired factors, like infections or diseases. BMI, diabetes and other disorders, as well as ageing, can also impair your fertility. Different causes require different solutions. Prevention is better than cure. The first step is not to wait too long before seeking medical advice if you are ready for a baby. A comprehensive diagnostic workout for a woman and her partner is required to be sure that the ART and related techniques are the options we need to use for the best treatment. On the other hand, if you are not ready for a baby yet, think about fertility preservation (social freezing), mainly for females, it’s probably the most effective way to avoid failed IVF treatment.
Fertility preservation is oocyte cryopreservation for medical or nonmedical reasons, it is performed for future use within an IVF treatment with a higher success rate because your age is the age at the time of oocyte collection. For better outcomes, it’s recommended to do it before you turn 35, you can do it after 35 but then you have to realize that maybe more than 1 oocyte retrieval would be necessary to collect a suitable amount of oocytes. You also need to remember that the success rate of a subsequent IVF treatment may be lower than expected.
If we look at the age of female patients below 34 up to 40 and so on, you’ll see the proportion of oocytes that are impaired, they are carriers of an incorrect number of chromosomes. When you have an oocyte that has an incorrect number of chromosomes, the chance to deliver a baby is dramatically lower. At the age of 41-43, 1 out of 8 oocytes is still suitable for delivering a healthy baby. If the age is more advanced, 96% of oocytes are going to be aneuploid at the age of 44 and over.
The more oocytes you cryopreserve, the higher chance you have to deliver a baby. If cryopreservation is no longer an option for you, then some other ways can be managed to overcome IVF failure.
Implantation failure
If you had a failed cycle, you need to seek medical advice and try to realize that your choice of medical advice is the right one. You may consider doing another treatment, perhaps PGT might be a solution for you, or Endometrial Receptivity Test (BeReady) and finally, gametes donation.
Having an unsuccessful IVF means to have a failure of implantation. You can have a failure of implantation because your embryos went into arrest, you had an early miscarriage, or your embryos did not implant even though your embryos were euploid. There are a lot of reasons why recurrent implantation failures happen. RIF (recurrent implantation failure) is characterized by the specific need of a group of patients. The major problem is that this group of patients is a heterogeneous population. Many factors are involved in repeated IVF failures, starting from immunological reactions to karyotypes that are altered in one of the partners, not necessarily the female. There could be endometrial anomalies, so the uterus looks normal, but the endometrium has anomalies, there is an important factor related to sperm contribution, so even the male factor plays a role, and it doesn’t matter if the parameters of the analysis of sperm look normal, there could be something more subtle. Genetic factors can affect the competence of the oocyte and the competence of the male gamete.
The development of a full-time pregnancy has 2 phases. The endometrium must be receptive, which means there shouldn’t be any uterine anomalies, coagulation defects, no endometrial anomalies, or immunological reactions, even if they are rare, should not happen in that specific individual. On the other hand, there is an embryo, which has to be viable, which means that gametes have to be healthy because their contribution is very important to the formation of a normal embryo, the embryo must be able to develop normally. Then if IVF is performed, the conditions of the lab as in vitro culture are crucial to generate a healthy embryo. Furthermore, the procedure itself of embryo transfer can also play an important role.
Data show how the repetition of treatment is crucial. Looking at the percentage of patients who deliver after the first transfer, we can see it is 36%, all the remaining non-pregnant patients came back, and another percentage of them became pregnant. Of the remaining patients, less than 50% came back again for their 3rd transfer, and again some were able to achieve pregnancy. What’s important is that almost 3 patients out of 4 achieved pregnancy, which is why it’s so important not to give up.
If you have at least 3 failed IVF attempts, the concept of selecting embryos for aneuploid screening might be beneficial. Avoiding the transfer of abnormal embryos can reduce implantation failure and miscarriage but also the cost of treatment and what is more important reduce the time to a full-term pregnancy.
Endometrial Receptivity Test (BeReady test)
If you have a few failed attempts, you should look into your window of implantation. One of the tests called the BeReady test helps to find the best time for embryo transfer. They’ve selected 67 genes and the accuracy is quite good because it goes down to a single molecule, and it is cost-effective. The biopsy is done during a monthly cycle and then the full sequencing is done to select 67 genes that are involved in implantation you end up with information, and you can detect the receptivity of your uterus that is expressed as a score called a receptometer. There can be three scenarios, it can be pre-receptive, receptive and post-receptive. According to this data, the transfer can be done at a certain point in time or can be postponed.
Sperm donation & egg donation – indications
If the gametes of both oocytes and sperm are so limited that it is almost unadaptable to reach pregnancy with these gametes, then you should think about egg or sperm donation or both. Sperm donation is usually indicated in azoospermia, which is quite rare or when there is a congenital factor or medical causes like chemotherapy, or surgery. It is also indicated in the case of sperm chromosomal abnormalities or genetic disease in the male partner occur when we have an infectious disease that has destroyed the potentiality of the individual sperm.
Egg (oocyte) donation is an option when the quality of the oocytes is very low because there is a primary ovarian insufficiency or there is no chance to get more oocytes, like in premature ovarian failure or menopause. It is also an option when the female partner has a chromosomal or genetic disease, they can still produce oocytes, but their quality is extremely low. It is advised for poor responders or with previous IVF failures using their own gametes, or in cases of recurrent miscarriages. If you have impaired ovarian function due to chemotherapy or surgery, endometriosis is another reason to look at egg donation.