Why in-vitro fertilisation is not always successful (2) by Prof. Oladapo Ashiru
We are still on the most common reasons why in-vitro fertilisation is not always a successful option in the treatment of infertility. The following factors have also been identified as part of the problem:
The age factor
Age has often been regarded as the major cause of an IVF cycle failure for many years. Doctors used to believe that a woman’s age determined it, but now we know that the man’s age is as important.
There is little we can do or change about the age of our patients undergoing an IVF cycle. What you can do is take care of yourself. Before you receive treatment, you should spend between two and three months looking after yourself, with exercise, diet and lifestyle changes. There is so much you can do to improve your chances.
This is possibly the most controversial of all reasons. Today, we have a 50-50 split with fertility experts as to whether this is a cause. Some doctors will say it is not an issue, while the others will oppose their views. However, more tests are being developed to establish if it is a cause.
It is basically where the immune system destroys an embryo before it can build implantation, all the way up to the eighth week of a positive pregnancy.
There are immune therapy approaches that will help implantation to occur, but again, there is a 50-50 split as to whether they are a viable approach. Nevertheless, it is something you should consider talking to your doctor about if you have had three or more failed IVF cycles or have experienced two or three miscarriages in a row.
The sperm performs an intricate role in the fertilisation of the female egg. To do so, they must be healthy, motile and sufficient in quantity.
The sperm and eggs have specific receptors on their surface that allow for their interaction and when that happens, enzymes produced from the sperm head that cause a hole in the outer membranes of the egg, allowing it to penetrate through.
A good number of recurrent IVF failures are due to the male factor. Recent studies have linked sperm DNA fragmentation to frequent IVF failure, although few authors doubt this concept it is better to ear on the side of caution by the male avoiding things that can alter the sperm DNA.
There are some etiologic factors associated with sperm DNA fragmentation and impaired internal cell integrity of the sperm (Chromatin). These causes are many and they range from environmental conditions, such as cigarette smoking, petrochemicals in oil and gas industries, pesticides, irradiation, excessive consumption of alcoholic beverages and chemotherapy to pathophysiologic conditions, such as the presence of white blood cells in the sperm, varicoceles, and cancer. Even iatrogenic causes such as sperm cryopreservation associated with sperm DNA damage
Genetic and chromosomal causes
The rate of chromosomal abnormality in human embryos is one of the significant factors for IVF failure.
Various studies have shown that the rate of chromosomal abnormalities in human eggs (and therefore in human embryos) start to increase significantly after the mid-30s.
IVF with self-eggs in women over 40 years of age is known to result in poor quality embryos, almost 75 per cent of which are chromosomally abnormal. Hence, the low rate of IVF success in older women.
We now know that older eggs have an inefficient spindle apparatus that is unable to line up the chromosome pairs correctly. Pairs of chromosomes are not appropriately split, leading to an alteration in the required balance of 23 chromosomes per egg.
Chromosomal anomalies in the sperm can also lead to chromosomally abnormal embryos, but that incidence is reported to be small at 1 per cent to 2 per cent of cases as compared to about 20 per cent to 90 per cent of human eggs.
The pre-implantation genetic screening (PGS) testing determines the chromosomal competence of an embryo.
The way forward
Moving forward from a negative cycle is difficult and trying to figure out your next steps can be even more confusing. By understanding the leading causes of IVF failure and how you can prevent these is a motivating way to begin another cycle.
There are three fundamental reasons why IVF fails. The first is that embryos transferred to the uterus were ‘incompetent’ or abnormal and thus, unable to propagate a viable pregnancy. In most cases, this is due to an irregular number of chromosomes in the embryo (aneuploidy).
The second reason is an underlying implantation dysfunction that prevents the embryo from properly attaching to the uterine lining. The most typical causes for this include:
A thin endometrium (measuring less than 8 mm) at the peak of estradiol stimulation. (That is, at the time of the hCG trigger or the initiation of progesterone administration)
Surface lesions that protrude into the uterine cavity (scarring, polyps, and uterine fibroids), which creates a local adverse environment that prevents implantation.
The immunologic dysfunction results in implantation failure.
The third reason relates to the technical difficulty in the performance of embryo transfer, which is a rate-limiting factor. It is an undeniable fact that not all doctors are equally skilled at the execution of this critical step of the IVF process. The use of Transabdominal Ultrasound Guided Embryo Transfer should minimise this issue and increase pregnancy rate.
IVF failed – what next?
Summary for a second trial with IVF:
Get an honest estimate from your IVF doctor on your chances for success rates with a second IVF trial.
If there were difficulties with the ovarian stimulation or low numbers of eggs – consider modifications to the drug protocol
If there were average or good-looking embryos for transfer, but none implanted, try IVF a second time at the same or a different IVF clinic
If there are significant egg and embryo quality issues, it is most likely due to an egg problem or an IVF laboratory quality control problem. Therefore, consider changing the IVF clinic to a program with higher in vitro fertilisation success rates to see if these issues were due to egg quality – or a problem with the ovarian stimulation, or a challenge in the IVF lab
Donor sperm, donor eggs or donor embryos could be future considerations, but those are usually further down the road than after one failed IVF cycle.
The uterus can be the problem. The new factors causing implantation failure must be evaluated and removed. The uterus is not always receptive for embryo implantation.
Overall, IVF success rates are only slightly lower for second attempts as compared to the first IVF attempt. Couples with the best egg quality are more likely to get pregnant on their first attempt, but this is balanced out to some extent by potentially learning from the first failed cycle and making adjustments to maximise success for the second in vitro fertilisation attempt.