For many patients, IVF is often considered the last resort on their way to parenthood. It’s what they turn to once all other options fail, and it’s often the method they put all of their hopes and faith in. What if it doesn’t work, however? As much as we don’t want to admit that, there is a possibility the first, second, or even the third IVF attempt will simply fail. What then?
Reproductive science is steadily marching progress, and modern genetic diagnostics allow us to observe, analyse and understand the process of fertility at every step of the way; following a failed IVF cycle, doctors and other specialists are able to pinpoint the precise reason for failure in most cases.
To explain modern analysis methods, we invited Dr Jon Aizpurua, founder and president of the IVF Spain group. His presentation will describe modern techniques and procedures which are employed to determine the genetic reasons behind IVF failures.
Parenthood has changed severely from what it used to be even a hundred years ago. In the 1960s, a social revolution took place, which made women postpone parenthood and instead focus on their education, careers and social life. The problem lies in the fact that biologically speaking, women are designed to become mothers in their twenties – the longer they wait, the less fertile they get. There exists a proven link between age and the increasing probability of aneuploidy in oocytes; aneuploid eggs result in aneuploid embryos, which often lead to miscarriages or don’t implant outright.
Due to this cultural shift, fertility rates are dropping in all of Europe. It’s simple enough to understand – it’s harder to achieve pregnancy at an older age, so women are having less children. This is true even in IVF scenarios – due to egg quality dropping with age, embryo transfers in own egg IVF have lower birth rates the older the patient is, dropping to below 10% by the age of 44.
Several solutions to this problem exist – younger patients, for instance, have access to egg banking. They can freeze their eggs now and use them whenever they’re ready. Egg donation is also available for older patients who didn’t freeze their eggs earlier. Success rates for embryo transfers do not drop with age, making it an attractive option for those past the age of 40.
The number of eggs – and their quality – for each woman drops with age. The precise reason for that has to do with genetics – the older an egg, the higher the probability of genetic errors appearing during its maturation process. If the eggs are fertilised, these errors are inherited by the embryo. These errors are the main reason for implantation failures, miscarriages, and congenital diseases such as Down syndrome in newborns. The precise term is “aneuploidy” – the condition of having an incorrect number of chromosomes.
What about sperm, however? Does it also have an age-dependent impact on the health of the embryo? Well, men are designed completely differently to women – their fertility does not go down with age as dramatically as it does for women. Despite this, the male factor accounts for around 40% of all infertility cases. This is mainly due to DNA defects in the sperm. These can be caused by urogenital infections, vascular diseases or lifestyle factors – smoking, excessive consumption of alcohol and a poor diet can all impact the quality of the sperm. As such, not only should basic sperm tests be mandatory – DNA fragmentation testing should also be performed.
At the end of the day, however, the male factor simply does not have as much of an impact on the success of IVF as the female factor does. Age, however, still plays a role in sperm quality. There is evidence suggesting that sperm from older men can cause pregnancy loss and genetic defects. However, because there are millions of cells available in each sample, diagnostic technology can be used to always pick out the healthiest ones to use. The same luxury, unfortunately, isn’t afforded to women and their oocytes. In the end, the female factor has more of an impact on the embryo’s health – and the older they are, the harder it is to produce several healthy embryos per stimulation cycle. There is about an 11% chance of a woman over the age of 42 producing a chromosomally normal embryo.
Thankfully, this is another area in which technology comes into play. Genetic screening allows us to select genetically healthy embryos for transfer, which drastically improves treatment success rates. PGT-A testing (previously known as PGS) is a widely used technique to determine embryo euploidy. Although it doesn’t actually “fix” embryos, it allows patients to save time (and money) by preventing them from wasting time by transferring defective embryos.
Egg quality isn’t the only factor to keep in mind – quantity also matters. Only certain eggs manage to generate strong embryos which reach the blastocyst stage in time. Only a certain portion of those blastocysts will be chromosomally normal. If there are twenty eggs, which result in five blastocysts, a certain portion of them being genetically normal – let’s say three of them. That’s three potential transfers – three potential children, in the best case scenario. The number of eggs produced through stimulation cycles drops with age, however – what if we only have five eggs to work with? What if we only manage to produce two blastocysts and neither of them is chromosomally normal? That’s when we resort to egg donation. This is why time is a major factor in the whole process of treating fertility.
Modern diagnostics and analysis methods allow doctors to evaluate the patient’s reproductive health based on certain parameters. These parameters can then be used to reliably calculate the amount of time and effort needed to produce a euploid blastocyst for the patient. Because of this possibility, the patient knows how many cycles will be needed to provide a reasonable chance of success, allowing them to decide whether they want to commit to treatment using their own eggs or not.
If they decide that the effort would be too much – or if the chances of success are too slim to even attempt treatment – egg donation remains as the last viable option. As we all know, success rates of egg donation programs are age-independent. Compared to conventional IVF treatments, egg donation seems like a very pragmatic solution: it’s efficient, safe, and well-regulated in most European countries. Genetic donor matching techniques are becoming increasingly popular – compared to traditional matching protocols, they allow for much more accuracy.
In conclusion, current technologies allow tailoring the treatment to the individual needs of the patient. The improvements in genetic diagnostics over the last 10-20 years have made reproductive medicine much more precise and efficient.