Watch the webinar recording with Vladimiro Silva, PharmD, Embryologist, CEO, Founder & IVF Lab Director at Ferticentro, who is discussing IVF and pregnancy after the age of 40.
Dr Silva started his presentation by explaining that it is a worldwide tendency nowadays, and more and more women are getting pregnant at more advanced maternal age. In France, in 2016, 5 % of the babies were born to mothers older than 40. In one of the articles in The New York Times, they mentioned that more than 100,000 Americans give birth in their 40s each year. The Guardian in the UK talks about the issue of getting pregnant over 40 and explains that it is not always a question of choice, but a consequence of what happens in their lives.
Some data from France shows that at the beginning of the 80s, the number of babies born to mothers over 40 started to increase. Nowadays, we are almost at the same level as in the 60s, which is somehow surprising, but the explanation is quite understandable. In the 60s, 76% of the women were delivering after the age of 40, but they were having their 3rd or even more babies. Nowadays, most of them are having their first or their second child. Therefore, we’ve moved from a society where motherhood after the age of 40 was a consequence of having a large number of children to a model where people are having their first kids after the age of 40.
In one of the studies, the investigators showed that in countries such as Portugal, women are considered too old to have babies after the age of 38-39. While in some other countries like, for instance, the UK, France, and the Nordic countries, they only think that women are too old to have babies at the age of 45. Therefore, it’s also a very cultural thing. It is very directly connected with the level of education of every woman. In every European country, the more educated a woman is, the more likely she is to have a baby later in life.
Pregnancy after 40 – reasons
The countries where women work the most are the ones where fertility rates are higher. The explanation for this is very clear, women’s increased education is linked to later childbearing. It is attributed to difficulties in balancing student and mother roles, as well as the fact that better-educated women are more likely to pursue careers that entail a steeper career ladder and more investment in human capital. Women’s labour force participation is linked with the postponement, largely due to the incompatibility between caring for children and participation in the paid labour force. Young adults may also delay childbearing until their income increases, and they can afford children, but also to avoid the wage penalty of early motherhood. Another thing is that people are moving towards small family sizes, people are having multiple partnerships, women are waiting for their perfect man, and sometimes it takes longer to find one, there are also higher rates of divorce, all of these are factors that induce delaying childbirths.
There are other economical constraints like the housing market, and the fact that nowadays jobs are not as steady as they were in the past. This all contributes to delaying pregnancy.
It is well known that the peak in human fertility is at the age of 25, and then it starts to drop after the age of 34, and it reaches almost zero chances at around 46, which is more or less the age of menopause. The probability of having a miscarriage also increases with age, and this is why it is so difficult to have kids after 40. One of the studies published a few years ago where they evaluated the genetic content of more than 20,000 embryos showed that the percentage of chromosomally normal embryos (euploid embryos) is around 60% at the age of 34, then it starts to decline with age and at the age of 46, it’s around 10%. The probability of receiving at least one euploid embryo in an IVF cycle also decreases with age. After the age of 35, the drop is very clear is very steep. This study also showed the distinction between day 3 and day 5 embryos. According to this study, there are no differences, those are the same embryos, although the moment when the embryo was taken was different.
The probability of having an aneuploid (chromosomally abnormal) embryo increases after34. The probability of having a live birth is lower after 34, and the miscarriage rate also increases. Aneuploidies are changes in the number of chromosomes, and the probability of having a Trisomy according to maternal age increases after 35. In 1970, the mean mother’s age at the birth of her first child was 26, while in 2014, it was 30. Some studies suggest that the risk of Trisomy 21 at 10 weeks of pregnancy is 1 in every, 1064 at age 25. At the age of 45, it is 1 in 19.
There are many risks associated with age, and genetic risk was already explained, but there are other risks like obstetric risks, high blood pressure, preeclampsia, gestational diabetes, and stillbirths that can also occur. There are a lot of potential complications in pregnancy and their incidents according to age.
There was a study published in the British International Journal of Obstetrics and Gynaecology (BJOG) where they compared the pregnancy of the UK population of older women. They concluded that women giving birth at a more advanced age have higher of a range of pregnancy complications. Those risks were essentially associated with multiple pregnancies and the use of assisted conception. One of the most important things is to avoid multiple pregnancies because that always increases the risks significantly, but their relative incidence remains low.
Therefore, it is crucial to evaluate every patient individually, discuss risks with them, so that they can make informed decisions and avoid multiple pregnancies, and make sure the procedure is safe for both mother and future child.
IVF over 40 – first steps
The first thing that needs to be done is the pregnancy risk assessment. You need to ask yourself if you can with it if it is possible to have a safe pregnancy, and if the answer is yes, you can move on to the next step. This is an ovarian reserve assessment to see if it is still possible to proceed with your own eggs, or if you should go for an egg donation instead or maybe try Preimplantation genetic testing as an intermediate solution. It is also crucial to evaluate your uterus and if it is ready to take an embryo and the pregnancy to term.
The first parameter that helps with assessing ovarian reserve is FSH. A part of our brain called the pituitary gland produces 2 hormones, FSH and LH. Those hormones will act on the ovary, and they will boost the development of follicles available in the ovaries, every woman is born with more or less 400,000 ovarian follicles.
Under the action of FSH, from the moment the woman has her first menstruation, 1 of these follicles will grow, and every month, an egg will be released in the tube. FSH stimulates the ovaries to mature those follicles, and while they are developing, those follicles produce oestrogens, the pituitary detects the level of estrogen, and it stops producing FSH. Therefore, when the ovaries are not working anymore, the pituitary will increase the production of FSH. This is why older women have higher levels of FSH because their ovaries are not responding, and then the pituitary tries to compensate for it. The higher the FSH is, the lower the live birth is, this is also associated with age. It’s still preferable to be younger than to have a good FSH, for example, a patient aged 24 with an FSH of 10, still has a better pregnancy rate than a patient at 44 and an FSH level of 3. With normal FSH levels, pregnancy rates are better for all ages, while with elevated or borderline or perimenopausal FSH, pregnancy rates tend to decline for all ages.
The most important parameter is the AMH, which is produced by the antral follicles in the ovaries. Those are the follicles that are in the ovaries waiting for the FSH to recruit them. They produce a hormone called AMH, therefore, AMH levels are very closely associated with the number of available follicles that are available to participate in ovulation. The higher the AMH is, the more fertile the woman is. AMH starts to decline with age, and this parameter is very closely associated with the likelihood of pregnancy.
The number of antral follicles in the ovaries producing AMH can be observed on an ultrasound scan. Normally, all those 3 parameters are taken into account when assessing ovarian reserve. Criteria for normal prognosis include FSH below 15 and AMH at 0.5 ng/ mL, it’s very important to look into the units.
One of the possibilities while treating women over 40 is to do Pre-implantation genetic testing. The data from Igenomix, which is one of the biggest genetic testing labs in the world, showed that the implantation rates in cases where PGT-A (Pre-implantation genetic testing for aneuploidies) was done, there were no significant differences between age groups up to 35, 35 to 37, 38-40, 41-42 and above 42. If you look at the implantation rates where PGT-A wasn’t used, it is clear that the effect of age is clear. Thanks to PGT-A, it is possible to select only viable embryos. The same happens with delivery rates, and the opposite happens with miscarriage rates. What’s the benefit of doing the PGT-A? It is all about information, PGT-A will not transform a bad embryo into a good embryo, but it will give you and the doctors information, and that information is very important in a decision-making process, especially while deciding to go for egg donation or trying treatment with your own eggs.
One of the possibilities associated with PGT-A is egg banking. It is possible to do an ovarian stimulation and then freeze the eggs, nowadays, there is over 90% of survival rate for frozen eggs for women of all ages, although we need to remember the older the woman is, the less likely the eggs are going to survive. What can be done is repeated stimulations to accumulate a good number of eggs and then fertilize them and do a PGT-A assessment. Usually, the goal is to achieve 10 or sometimes 15 eggs or as much as possible, sometimes some patients are producing 1 or 2 eggs, but it is still possible to accumulate them and give the patient a shot at trying with her own eggs.
Egg donation is the last resource, no one starts this process because they want to become a mother with somebody else’s eggs, it’s never the first option, however, it is often the most reliable one. The data from the CDC, the National Authority in the United States, showed that for all age groups, the odds of having a pregnancy with donor eggs are more or less the same, they don’t change with age, it’s always between 60 and 70%. The chances of having a pregnancy using a patient’s own eggs are never as high as with donor eggs, and they drop very steeply after 35. Egg donation is a non-invasive approach, it’s also a very good solution for many patients, and sometimes it’s also the only solution for patients.
In Portugal, egg donation is non-anonymous, a donor needs to be matched with the recipient. The process has to be transparent, the child at the age of 18 will have the right to access the donor ID. It’s important to remember that the number of donations per donor should be limited, and the compensation type to the donor should be transparent and controlled by the local authorities. The whole process has to be very well counselled,
Nowadays there’s no such thing as an anonymous donor, there are studies on that with the current DNA basis, it is very easy to find the identity of supposedly anonymous egg donors, all human rights courts and authorities are issuing recommendations for not-anonymous egg donation, so we very strongly defend the cause of non-anonymous egg donation, and it’s also the best way to achieve a pregnancy when it is impossible using your own eggs.