This #IVFWEBINARS with Dr Elena Santiago explains solutions for Advanced Maternal Age focusing on:
Late motherhood is on the rise, but it has its downsides. Can ART (assisted reproductive technology) be helpful in this case?
During this event, Dr. Elena Santiago [Fertility Specialist at Clinica Tambre] tells us more about IVF & women over 38 – what limitations there are and what treatment options and prospects patients can make use of.
Although ovarian reserve is one of the most frequent subjects discussed in relation to IVF treatment, not many patients know what it really means – or how to calculate it correctly. Dr Elena Santiago says that it is very important for us to understand the concept that women are born with a finite number of eggs in their ovaries. This number is reduced as women age – which means that it is impossible to produce new eggs over time. This is in contrast to men who produce new sperm every 3 months.
Of course, ovarian reserve is not the same in every woman. Dr Elena mentions a few important factors that influence it the most. Apart from a woman’s age, these are toxics, lifestyle, the environment we live in, gynaecological pathologies (e.g. endometriosis), ovarian surgeries or oncological therapies. Additionally, we have to take the family background into account. Dr Elena admits that sometimes premature menopause (resulting in ovarian failure) may run in the family.
When it comes to calculating ovarian reserve there are two basic tests that each fertility patient should undergo: an ultrasound (or a scan) with AFC (antral follicle count) and AMH (anti-Müllerian hormone) test. The former is conducted vaginally and it allows us to see the follicles – small liquid sacks that should contain one egg each. The normal ovarian reserve is when we have 10-20 follicles in both ovaries (less than 10 follicles is a low ovarian reserve and over 20 – a high ovarian reserve). Only one of these follicles is going to grow in a cycle to produce ovulation – the rest will disappear. It means that each cycle, women are losing many eggs – that’s why the minimum of 10 eggs is necessary to ensure good pregnancy chances.
The anti-Müllerian hormone test on the other hand, is very specific. AMH is produced in the follicles and it can be measured by a simple blood test (done at any time of women’s cycle – with no need to be fasting). The results are being compared with the scan to see whether there is a normal (1-3.5 ng/ml), high (>3.5-4 ng/ml) or low (< 1ng/ml) ovarian reserve.
Dr Elena Santiago highlights that ovarian reserve is always dependant on the woman’s age. What is more, ovarian quality is also related to one’s age. However, the problem is that the latter cannot be tested – it can only be predicted on the basis of how old a particular patient is. Unfortunately, ovarian quality has very little to do with ovarian reserve itself. Even if a 40- year old patient has a high ovarian reserve, it is likely that its quality is not going to be as equally good.
Ovarian reserve, ovarian quality, AFC and AMH all decrease as a woman ages. Dr Santiago mentions another hormone that is often used in testing ovarian reserve – FSH (follicle-stimulating hormone). It can be used to indicate the ovarian capacity to produce eggs. However, its results are read differently than in the case of AMH – namely, elevated levels of FSH are understood as the confirmation of menopause.
Dr Santiago confirms that the percentage rates of fertility depend on age and ovarian reserve. The maximum percentage is observed in women at the age of 20-24 and it remains at a quite good level until 30 years old. However, from that moment on, the fertility rates decrease rapidly and they achieve a very low level from 40 years of age onwards.
As life passes, not only fertility rates but also egg quality becomes lower. But what does bad egg quality really mean? In the process of fertilisation, an egg and sperm come together to produce an embryo. Dr Elena explains that, with age, the probability of having chromosomal abnormal (aneuploid) embryo is much higher. From 35 years old onwards, the aneuploidy rate is increasing a lot. In parallel with it, the miscarriage rate is going up as well.
Age is the most important factor in female fertility. No wonder that the success rates depending on it change a lot even with the standard (meaning own eggs) IVF treatment. When women are under 35 years old, they have a nearly 60% chance of getting pregnant with own eggs IVF. Between 35 and 40 years old, these chances go down to 56% and – above the age of 40 – women won’t achieve more than 34% of success rates. However, Dr Elena stresses that each patient’s case should always be personalised and treated individually.
The prospects, on the other hand, change significantly when we take egg donation into account. While the standard IVF success rates lower with age, egg donation results do not change at all – independently of the fact how old the female patient is.
Dr Elena Santiago admits that in case of late motherhood, doctors always have to do something else – apart from only insemination or the standard IVF – to achieve satisfying results. This additional procedure is called PGS (pre-implantation genetic screening). However, if – for different reasons – it does not work either, the best solution is egg donation. As mentioned before, in the case of the latter the recipient’s age does not play any role – the success rates are still high for patients over 45 years old.
PGS is an extra procedure in IVF. When blastocysts (meaning day 5 or day 6 embryos) are in the lab, they are biopsied in order to select the chromosomally normal ones for the embryo transfer. PGS rises the success rates and the chances of a healthy baby by reducing the risk of miscarriages and increasing the chances of pregnancy per transfer. What is more, PGS will shorten the duration of treatments. Dr Santiago admits that with good-prognosis embryos, it is possible to reduce the number of cycles it takes to achieve pregnancy. From this perspective, PGS is of the highest importance as it significantly minimises the negative effect of maternal age in implantation rates.
However, depending on the situation, PGS may not always be an option. In such a case, the ultimate solution is to proceed with egg donation. Dr Santiago reminds us that in Spain, egg donation is anonymous. Donors undergo lots of psychological, medical and genetic tests to ensure the best match with the recipients. They include the blood type test, immunologic matching (KIR AA/HLAC1C1) and genetic matching (to avoid genetically inherited disorders and diseases). Normally, egg donors are less than 30 years old and are always chosen on the basis of the physical characteristics of the women doing the treatment.
When ready for donation, donors undergo ovarian stimulation and egg retrieval at the clinic. The recipients generally need to do the synchronisation with their donors – it means that their uterus and endometrium are being prepared for the embryo transfer. Once the woman is pregnant, the pregnancy is exactly the same as if it was achieved with her own eggs – she will become her baby’s real mother.
Summing up, Dr Elena Santiago reminds us that ovaries have an optimum time to operate – in other words, the sooner we make the use of their reserve, the better. She claims that women have to be highly aware of the influence their age has on fertility and reproductive outcomes. When going for late motherhood, it is always advisable to add PGS to IVF to increase one’s own pregnancy rates. However, when the ovarian reserve is very low, patients should think of egg donation as a direct solution.- Questions and Answers