In this session, Dr Elias Tsakos, FRCOG, Medical Director at EmbryoClinic, Thessaloniki, Greece, has talked about advanced maternal age groups and explained multiple factors that can prevent such patients to achieve pregnancy but also provided best practices that can help to get a positive outcome.
There are two main types of IVF that we discuss with patients of advanced maternal age. The first is IVF with own eggs, and the other is the egg donation IVF. Maternal age is a huge factor of success in that age group
, and it’s even more important when we’re talking about IVF, egg donation is there as an option that has been available quite for a few decades. Nowadays, it’s becoming more and more used in the last maybe 10-15 years.
Dr Tsakos started by explaining that the quality and the quantity of oocytes are reduced with advancing age, and this reduction starts in the mid-20s. Therefore, for females, it becomes even more profound after the age of 30. After the age of 35, it diminishes even more, and after 40, it diminishes to a great extent, as a result, the success rate of IVF has a lot of denominators, a lot of main factors and maternal age when we’re using own eggs is perhaps the most significant factor regardless of what method we use the stimulation protocol, the drugs we use and the methods in the lab and so forth. Female age of 38 plus by itself is an adverse factor of success, and not only for IVF success but also for pregnancy outcome in terms of either a miscarriage or complications in pregnancy.
Advanced female age is considered perhaps 38, but so is 40, 42, and so is 45, so the huge question is where do we draw the line? The answer is, it depends. According to Dr Tsakos, we can divide advanced female age between 38 and 42, from 43 to 46, and from 47 to 50. In most countries, including Greece, the upper age limit for performing IVF treatment for females is 50. In Greece, there’s a new law that has extended this limit to 52 in the light of the COVID-19 pandemia, which prevented lots of women from having IVF. At the moment, we can treat women until the age limit of 52 under certain conditions and under a special licence that is required. A woman between 50 and 52 will require a special licence from the health authorities to perform IVF.
Age group 38-42
We always need to assess and evaluate every patient as carefully as possible. We can’t afford to waste a lot of time on these patients, and the patients also need to understand that time is precious, sometimes, 6 or 8 months may make a big difference in regard to the outcome, the quantity, and the quality of their eggs. Therefore, for those patients, it’s very important to ensure that the team at the clinic will give them the best possible chance based on their individual characteristics.
We need to evaluate the AMH, the ultrasound characteristics, the hormonal profile, the history, some individual details in the particular case, and the male assessment is also significant to provide them with the best possible option. In this age group, we always aim for an adequate amount of eggs and embryos that would give us the best possible chance. For someone at 38-39, it would be good to have 4 or 5 oocytes and get 2-3 healthy embryos. How many will implant? That depends on the embryo quality, the wishes of the patients and the characteristics they have. Invariably some of those patients would have had already IVF cycles, they would have had perhaps failures in the past or even successes, so we take their history into account and try to aim at giving them the best possible chance we use all the proven tools of success in stimulation protocols, in terms of choosing the best-suited protocol, trying not to overstimulate them, but trying to stimulate them adequately with FSH hormones, sometimes with the add-on of LH and sometimes with the add-on of tablets like Clomiphene and so forth.
We’re fairly optimistic for this age group. In the age group of 38 to 42, the success is roughly 25% in terms of pregnancy, and we would like to offer our patients that opportunity.
Age group 43-46
For the age group beyond 43 to 46, things are getting more complex. The patients need to understand that the success rate is very low, perhaps less than 10%, in some cases less than 5% depending on the individual characteristics. Some pregnancy complications are much higher, pregnancy loss, miscarriages, and abnormalities limit the healthy take-home baby rate to very small numbers, perhaps in the region of 2 to 3%.
Many patients are not discouraged by that, it’s only logical for the majority of the patients wishing to try with their own eggs in this age group, although they understand that the odds are against them, and some lucky ones do succeed and do take home a healthy baby.
Age group 47-50
There’s only one report of a successful IVF pregnancy with a healthy birth in this age group, and the patients need to be aware of that. Sometimes, it’s very difficult to get to terms with this fact, but the scientific team has to be very realistic, but also be psychologically very close to the patients and help them understand the odds and make sure that any complications are minimized.
When we talk about egg donation, the success rate is different. Maternal age is still important both for the success of IVF and for the outcome of pregnancy, however, with the use of younger genetic material, we can be more confident about success. We still need to evaluate the couples, and the patients still need to be very careful in selecting the program, and the protocol before starting any treatments.
First, we should do no harm, and we should ensure that our treatment is safe before it is successful. I do insist on screening tests, I’m well aware that screening criteria differ from country to country, but I do insist that we don’t cut coordinates in safety, so the advanced maternal age, we need to ensure that it’s safe before they embark on IVF. Proper health screening, also general screening for standard conditions like thyroid disease, heart disease, lung disease, etc., should be evaluated.
Egg donation negates the adverse effect of genetic inadequacy associated with advanced maternal age, however, it’s not always successful, it’s not always safe to perform, and we need to be very careful in the pre-IVF phase, which is very significant, even more significant for the advanced maternal age patients.
We need to ensure single embryo transfers for those patients, although we are under a lot of pressure to perform double embryo transfers in the egg donation cycles to maximize success, and so forth. There’s a lot of understanding, a lot of counselling, and a lot of discussions to build the trusted relationship that is of paramount importance before we move on.
I don’t think scientifically there’s an age limit, however, we need to obey our guidelines and the legal scenarios, and we need to ensure that all our patients are screened adequately, and we stick to this age limit. Finally, I think we should not forget that apart from the effect on the oocyte quality associated with advanced maternal age, the uterus quality, the quality of the implantation environment is altered with advanced maternal age. The chance of developing fibroids, polyps or even cancer in the uterus is increased with maternal age, and we should be very much aware of that.’