What age is considered advanced maternal age? What are the risks connected with advanced maternal age? Can I undergo IVF with my own oocytes if I’m over 38? What are my chances? Is it recommended to try with donor eggs from the start?
IVF for patients of advanced maternal age, 38+ – summary of the presentation
What age is considered advanced maternal age? What are the risks connected with advanced maternal age? Can I undergo IVF with my own oocytes if I am over 38? What are my chances? Is it recommended trying with donor eggs from the start? In this webinar, Dr Juan Jose Sanchez Rosas and Dr Carolina Alonso Muriel from URE Centro Gutenberg (Malaga, Spain) discuss this important topic in great detail.
Dr Juan Jose Sanchez Rosas starts by reminding us that it is a common trend for women in Western societies to delay their motherhood. Today, in Spain, women usually have their first baby at the age of 33 years. The development of medicine and increased life expectancy makes them believe they can get pregnant whenever they can and without any problems. However, the rising number of fertility patients proves that age is a very important factor in conceiving. According to URE Centro Gutenberg, in 2018 over 38-year-old women constituted, 45% of all IVF with own eggs patients and 84% of all IVF with donor egg patients.
In 2018 over 38-year old women constituted, 45% of all IVF with own eggs patients and 84% of all IVF with donor egg patients
Quantity and quality of eggs vs ovarian ageing
Ovarian ageing comes with progressive (and unfortunately irreversible) deterioration in the quantity and quality of eggs. Additionally, it is accompanied by an increase in aneuploidy – an abnormal number of chromosomes. The latter results in reduced fecundability (probability to achieve pregnancy in one menstrual cycle) and an increased risk of miscarriages. When a woman tries to get pregnant for 6 consecutive months unsuccessfully, she becomes an IVF patient. Even if she gets pregnant as a result of an advanced IVF treatment, her pregnancy is at risk of pregnancy complications, such as e.g. congenital malformations, chromosomal abnormalities (Down syndrome), pre-eclampsia, gestational debates or preterm birth.
Dr Sanchez Rosas says that according to Spanish legislation on Assisted Reproduction, ART treatment should be used only when there is a reasonable possibility of success and there are no risks to either woman’s or her baby’s health. Taking this into account, one should separately evaluate both main treatments: IVF with own eggs and IVF with egg donation. In each case, the prognosis is completely different.
Egg donation and advanced maternal age
When it comes to egg donation, the pregnancy rates are high and do not depend on the woman’s age and her ovarian status. That is why this treatment is limited only by advanced age-related pregnancy complications. It is generally agreed that the upper age limit for egg donation is 50 years old. IVF with own eggs, on the other hand, is very much age-dependent and its chances of success drop dramatically as a woman ages. According to the Spanish National Health System, the upper limit for IVF treatment in terms of age is 42 years old. Dr Sanchez Rosas admits that the medical team of a fertility clinic has to conduct an individual study of every patient’s case to provide complete information on the prognosis. There are two main decisive factors, such an assessment is based on a woman’s age and her ovarian reserve. The female patient’s age is the crucial factor affecting IVF success
. Its negative impact on IVF performance is related entirely to ovarian ageing and aneuploidy in eggs. Another factor, ovarian reserve (OR), reflects the potential of female fertility and declines gradually with age (speeding up when a woman reaches the age of 40).
Ovarian reserve testing
Dr Sanchez Rosas says that there are two different tests to determine ovarian reserve: astral follicle count (AFC) performed using a transvaginal ultrasound and Anti-Müllerian Hormone (AMH) in the blood. Normal parameters of ovarian reserve are AFC=5 and AMH 1.2 ng/ml. The best option for doctors is to consider both predictive factors when deciding on IVF treatment type. They also have to keep in mind that a woman’s age is a crucial factor in excluding a patient from IVF treatment. Generally, it is common to recommend egg donation in the case of over 40-year-old patients (regardless of their ovarian reserves). Women that are younger than 44 years old will have their personalised recommendation prepared on the basis of OR conditions.
Generally, there are 3 main ways in which doctors can improve success rates in women who undergo IVF treatment at advanced maternal age – 38+.
These include ovarian stimulation with gonadotropins, improving egg quality before starting treatment and working with laboratory procedures. Ovarian stimulation is crucial for the optimisation of the IVF process. As most eggs obtained in one cycle are not valid for reproduction, a patient needs to undergo several cycles to get at least one embryo for the implantation. It is estimated that there are around 8-15 oocytes needed to increase the live birth rate in IVF.
Dr Sanchez Rosas says that depending on the ovarian response, patients can be classified into 4 groups:
- poor responders (if the number of eggs collected is 3 or less),
- suboptimal responders (4-9 eggs),
- normoresponders (10-15 eggs)
- and high responders (more than 15 eggs).
Most of the over 40-year-old women will be included in the first two groups. This naturally results in reduced effectiveness of the IVF process. In order to choose the best stimulation treatment, it is essential to predict ovarian response and include the patient in the correct group. In fact, the estimation of the results obtained in the previous IVF cycles is the best predictor of ovarian response. Biomarkers such as AFC and AMH, age and BMI (body mass index) are of great use as well.
When it comes to ovarian stimulation, achieving the optimal egg number is as important as the patient’s safety and comfort. However, the stimulation with gonadotropins may cause some problems, such as lowering endometrial receptivity, increasing the levels of estradiol and the risk of premature progesterone rise, OHSS (ovarian hyperstimulation syndrome)
and a bigger number of aneuploidy embryos. This all led to a new trend in IVF in the first decade of this century – mild stimulation that advocates the use of lower doses of gonadotropins, leading to achieving not more than 8 eggs.
Currently, the trend has changed again, and the most important progress is the vitrification of eggs and embryos. It led to a new strategy of frozen and deferred embryo transfer that is a great improvement for the advanced age group, making PGS (preimplantation genetic screening)
possible. Today, the trend among women of advanced maternal age is to get as many oocytes as possible. It significantly increases the cumulative live birth rate and reduces the number of stimulation cycles and time to achieve pregnancy. Dr Sanchez Rosas also discusses a new system to classify infertility patients – the POSEIDON (Patient-Oriented Strategies Encompassing Individualized Oocyte Number) classification. It helps to achieve greater homogeneity and individualisation of treatment. According to the POSEIDON criteria, the patients are classified as groups 1 and 3 if they are younger than 35 years old, and as groups 2 and 4 if they are older than 35 years of age. Apart from age, ovarian reserve factors (AMH and AFC) and the patient’s sensitivity to gonadotropins are also considered. It also involves a new group of patients – suboptimal responders.
When it comes to the patients with the worst prognosis, there are several strategies to achieve the best possible ovarian response. These include waiting for the right cycle (and higher AFC), adjuvant treatment (androgens and growth hormone) and special stimulation protocols. To increase the treatment efficiency, some alterations to conventional stimulation protocols have been proposed, such as mild stimulation with gonadotropins or the use of Letrozole and Clomifene. As follicular recruitment is possible at any phase of the menstrual cycle, stimulation can be started at any time (random stimulation) or it can take place during the follicular and luteal phases of the same cycle (double stimulation).
Improving egg quality
Many patients ask if it is possible to improve egg quality even before treatment
. Dr Sanchez Rosas admits that ovarian ageing can be influenced by lifestyle. For example, oxidative stress is well-known to cause severe damage to the ovarian reserve. In order to limit its negative impact, a patient should, among others, prevent obesity, quit drinking and smoking and increase one’s own antioxidant intake – meaning both healthy food high in antioxidants and some antioxidant supplements (especially coenzyme Q10). Of course, there are also new experimental treatments and therapies, such as e.g., autologous/heterologous mitochondrial transfers or autologous stem cell ovarian transplantation (ASCOT). However, they are not only controversial but also poorly effective at the moment.
In conclusion, Dr Carolina Alonso Muriel talks about different treatment techniques that URE Centro Gutenberg offers to patients of advanced maternal age
, such as extended embryo culture up to the blastocyst stage (improving in vitro embryo selection and reducing the number of multiple pregnancies) and Time Lapse imaging (that allows for uninterrupted embryo culture environment). However, the most important technique is surely preimplantation genetic testing (PGT-A) of embryos. As advanced maternal age involves an increased chromosomal aneuploidy of embryos
, PGT-A is crucial to assure higher pregnancy rates per transfer, lower miscarriage rates and a greater chance of having a healthy child.