Advanced maternal age (AMA) and fertility outcomes – patients’ stories

Emma Maria Adsuar, MD
Fertility gynaecologist at UR Vistahermosa, UR Vistahermosa

Category:
Advanced Maternal Age, Success Stories

From this video you will find out:

What is advanced maternal age, and why does it matter?
How does age affect fertility?
What risks are associated with advanced maternal age?
What can I do to prepare for pregnancy?
How long should I try to conceive naturally before seeking help?

Advanced maternal age (AMA) and fertility outcomes – patients’ stories

Pregnancy outcomes in women of advanced maternal age

In this webinar, Dr Emma Maria Adsuar, Gynaecologist at UR Vistahermosa, Alicante, Spain, has discussed advanced maternal age and has explained all the things that need to be done before embarking on the IVF journey to get to the final outcome – a healthy baby.

Advanced maternal age (AMA)

Dr Adsuar started by explaining that the age of maternity is increasing worldwide. Historically, it has been defined as more than 35 years old, but in recent years it has changed. Nowadays, advanced maternal age is defined as more than 35-38 years old. Extreme advanced maternal age means more than 48 years old. As of now, there is an egg donation technique available for a 48-year-old woman who can get pregnant. It’s really difficult to define a specific threshold as age affects the quality and quantity and is defined as a continuum, and we don’t exactly know when it starts.

Mean age at childbearing

in industrialized countries, it was 26.5-year-old in 1985 to 29.4 years old (2015)
in the 1970s, the first delivery was in the early 20s, nowadays, the first delivery is at around 27-29 in 2017
first delivery in women over 35 represents 9% of all the deliveries
age 45 to 49 rose from 0.39/1000 okay to 1.79 in 2010

Age & its effect on fertility

the continuous decline in the number and quality of oocytes
this dropping is faster from the age of 30
chances of pregnancy in every cycle when 30 y is 20%
when 40, less than 5%
above the age of 45, the possibility of pregnancy is almost 0
male fertility declines at around 60 y

Infertility

one year after regular intercourse with no protection or 6 months if you are more than 35 years old
15% of the couples in industrialized countries suffer from this condition
multiple factors: around 30% female factor, around 25-30% male factor, 30% of the cases are a combination of both, 10% remain unknown
The age of the woman is the most important factor

Advanced maternal age – possible complications

There is an increase in miscarriages, there is like 5% of probability of having a miscarriage when you are below 30, and there is a 22% of probability when you are more than 40-41 years old. If we are talking about 43-44, the risk increases. The most common causes are chromosomal and genetic disorders, it’s around 80% when you are more than 40 years old and it’s because of the low quality of the eggs. Other complications of advanced age include:

high blood pressure/ preeclampsia
- below 30 years old is 4%
- over 40, it’s 5-10%
- more than 50 years old, 35%
gestational diabetes
placental abnormalities
increases the probability of C-section
low birth weight and preterm delivery
the psychological impact increases the rates of depression and stress

What can be done to increase your chances?

lifestyle
- dietary quality
- the chronic administration of oral antioxidant
- melatonin
- caloric restriction
- increased of Omega-3 (fatty acids)
- folic acid
- Coenzyme Q10
- Inositol in PCOS

What can be done when you are approaching that age and you don’t want to be a mother or you cannot because you don’t have a stable partner or you don’t have a proper job. There is an option called oocyte cryopreservation. The best moment is to do it if you are below 30, most patients come to the clinic when they are between 30-34 as the fertility declines over the age of 35. Therefore, if we could freeze our eggs before 35 years old, we would gain a lot. It’s important to highlight that it’s not the same as having 10 eggs when you are 25 years old as when you are 43 years old. When you are 43 years old, 10 eggs is not a bad result, even though we don’t expect too many eggs at 43 years old. There are several techniques that we can offer to patients who are not able to conceive, the treatment has to be individualized, and it all depends on your particular case. For AMA patients, we can also offer artificial reproduction therapy, e.g., IVF/ IUI, egg donor/embryo donation.

Pregnancy outcomes in women of advanced maternal age - Questions and Answers

Why is the male factor increasing?

It’s because of the lifestyle, because of the exposure to metals, smoking, not enough exercise. Men tend to smoke more, drink more alcohol and are also more often exposed to metals and radiation. These are the main factors causing the male sperm not to be as good quality compared to 20-30 years ago.

Does calorie restriction have an impact on epigenetics?

It hasn’t been studied so far. The studies I was talking about mice. Mice and humans have something in common, so more than in epigenetics.

Do antioxidants affect AMH because you mentioned that the quantity of eggs can be increased in addition to the quality?

I meant the quality, not the quantity. Until recently, we thought AMH was stable during the cycle, intercycle meaning in the same month of the patient’s different days, so we thought it was a stable hormone. However, it has been proved that is not. AMH is linked to the quantity and quality of eggs, so the antioxidants can have an impact on the quality, not quantity. To calculate the ovarian reserve, we need AMH plus the ultrasound. Some years ago, they used to do only the measurement of the AMH, and they thought that it doesn’t give you a prognosis.

If you have a high BMI but are active and eat well, and it is still a negative?

I would recommend going to the nutritionist. Most of the time, we have the wrong idea of what it means to eat well. A person who is going to the gym every day and eats salad doesn’t mean that you’re eating healthy because as I said, you need a good proportion of protein, carbohydrates, vegetables, and fat is important. I would suggest going directly to the nutritionist, nutritionist expertise in fertility. The same thing is with sports, it hasn’t been recommended to do sports every day, we also need to rest to build muscle.

Can you repeat what you said about caffeine?

It has been linked to having a good impact on fertility. We don’t know the exact mechanism, and we don’t know the threshold. It has been said that more than 3 cups of coffee per day would do damage. Below 3 cups of coffee, that would be beneficial. When I’m talking about caffeine, I’m talking about the bean, and then you have to use the grinder, and then you have to take the coffee instantaneously. The problem with the coffee is that most of the time we use to take some capsules instead of using beans and a grinder, we do it because we’re always on the run. Those capsules contain metal, so it’s tricky to do things perfectly, but at least we need to be more conscious of what we are doing, and if we can make at least 1 or 2 changes will make a difference.

I’m 48, I have endometriosis history since 21 years old, have a normal BMI, no other health issues. I have embryos from donor eggs with genetic screening done. 1 transfer in 2018, implantation, then miscarriage at 8 weeks. What is my risk if I transfer 2 embryos in February? What are the main risk factors? Age, endometriosis since I have good quality embryos. What do I need to know and check before deciding to do another transfer? My period was regular until I got a COVID-19. I had 2 short cycles (17 days) then no period since September 1st, 2021, hormone tests are normal (not premenopausal)

It has been proved that people who have endometriosis, even though they do egg donation, have more probability of having a miscarriage or complications. Most of the time, it has to do with inflammatory factors, and there is a high probability that endometriosis is linked to adenomyosis, which is endometriosis within the muscle of the uterus. It’s true that in those women, even if you change the egg, even if you have the best embryo quality if you compare it to a person who doesn’t have endometriosis, who have a healthy uterus, you have more risk of complications. That doesn’t mean you are not going to succeed, it’s not the first time we see people with severe endometriosis, they have egg donation, and they succeed. I know that it’s hard, and after years of trying to find out you had a miscarriage, it’s hard to face the same issue again, but trying again is what I would recommend. I think that you’re talking about Pfizer because this vaccine is being recently linked to this kind of issue, we are still having a lot of studies, and it hasn’t been proven, but most of the patients are indeed complaining of this kind of problems. Despite this, you go ahead with your reproductive treatment.

Any way to limit risk factors such as high blood pressure when receiving donor egg transfer at advanced maternal age?

Exercise, lifestyle, this is the most important thing. When a patient has more risk of developing high blood pressure, we give them a preventive medication, and when you are pregnant and if you are of more advanced age, we consider it a high-risk pregnancy, and we will monitor it more closely. What you can do are exercise and have a healthy diet.

Do you recommend a depot before embryo transfer or having the contraceptive pill the month before the protocol?

There are a lot of protocols, and it hasn’t been proved that one is better than the other. Both of them are equal, but we do recommend this kind of natural cycle in women below 40 because those are the women that have more regular cycles, and we won’t expect any kind of irregularity. All three protocols have the same great success.

How big is a variation of AMH? Is it recommended to measure it a couple of times during a month?

I wouldn’t be so stuck on the AMH level. As I said, it has to be linked with the ultrasound, this is the most important, the ultrasound and AMH both. I had one patient whose AMH was almost 3 nanograms per millilitre in May, and in December she measured again, and it was 0.8 nanograms per millilitre. We were shocked because she was going to undergo treatment at the beginning of December, 2 weeks later, she had 1.8, so imagine this kind of variation. An isolated number means nothing unless it’s associated with another test. I wouldn’t like to give you the impression that being so stressed by measuring one thing doesn’t mean anything.

What are the biggest sources of metals, I noticed you mentioned metals a few times?

Capsules with coffee, fish, and rice contain a lot of arsenic. Mercury, arsenic and lead are the most frequent metals. You can do a blood test, and you can check the level of the metals. Not everyone, I don’t want to create drama and stress for anyone, but it is good for the patients who are trying to conceive, and they are not able to, but also patients, for example, who have suffered from a headache or amenorrhoea because of this kind of symptoms has been linked with that. You can do a blood test, and depending on the level, your physician can give you medication to get rid of those metals. In some countries like the UAE, where I live, the tap water isn’t drinkable, but sometimes we cook with that water, although we shouldn’t because it contains high levels of metals. To diminish the amount of Arsenicum that the rice contains, we should wash it with five portions of water. The rice grown in Spain doesn’t contain too much arsenic, I cannot say anything about other countries. I can say that whole grain rice contains more arsenic than white rice.

I’m 44, I’m doing another IVF cycle using the flare protocol, using Norethisterone. I only got 3 eggs last time, and none were fertilized. My AMH is 1.2 pmol. Is there anything I can do? Am I holding onto false hope at my age?

Your AMH is very low, and with your age, it gives you a few eggs of low quality. I’m not saying that it’s not going to happen, but the probability of being able to get pregnant with your eggs is low. At the age of 40, the probability is to retrieve 10 eggs, the probability of having a healthy baby is 25%. When we are talking about 44-year-old, that percentage drops a lot, and we are talking about 10 eggs. In your case, the only solution I could see if you want to keep on trying with your own eggs is to collect as much as possible and see what will happen. However, I would recommend going for an egg donation.

My hCG was 24 on 15 dpo, 17 days past Ovitrel 250 trigger – tested out, negative tests before a weak positive. Was it a residual trigger or pregnancy? Should I keep progesterone support and do another blood test? Or cancel all? What would you recommend?

It could be a residual trigger, or it could be pregnancy. 17 days is too soon, you did it too soon, so what I would do is I would repeat at least in 3-4 days and then see the level, so continue with the progesterone.

I’m 43 this month, I have an AMH of 10.3 pmol/mL, other than diet, what else can I do to help the chances of IVF? My partner has 1% mobility.

Your AMH is good for your age, so yes, I would try at least. I mean, I don’t know if you’ve ever tried to get pregnant and had any kind of cycles. The most important thing to understand is that we are always talking about percentages, this is not a certainty. i You should also do ICSI, apart from the mobility, I suppose that your partner will have less amount of sperm. He can also take CoQ10, antioxidants, but for the sperm to be able to see an improvement, he needs to take it for at least 3 months. There are a lot of techniques you know that we can do with sperm. Embryologists are the ones who are choosing the sperm so that issue will be solved. They also use MACS, they use different techniques to decide the best sperm. I would give it a try because your AMH is high, so most likely, you will have a high amount of eggs.

What is your take on the supplementation of DHEA in patients over 40?

I’m not familiar with that therapy of DHEA. I cannot recommend it then.

I had urticaria during my first transfer. I was on granulocyte protocol. Is it possible that I am allergic to granulocyte?

Most of the time it’s not the therapy itself, but its component. This is something you need to find out. It may not be the treatment. I have never heard of any urticaria because of the implantation, I’m not aware of that.

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Authors

Emma Maria Adsuar, MD

Dr Emma María Adsuar is a fertility specialist at UR Vistahermosa. Graduated in Medicine and Surgery from the University of Elche in Alicante. Trained in Obstetrics and Gynaecology. Dr Adsuar specializes in treating the diseases of the female reproductive organs and women's health during their pregnancy and just after the baby is born. The author of multiple scientific publications and attendee of international congresses in the field of reproductive medicine.

Event Moderator

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.

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