It is widely known that anti-Müllerian hormone (AMH) is an important ovarian reserve marker in fertility treatments. But what does it really stand for? What does it mean to have low or high AMH levels?
In this webinar, we have invited Dr. Valeria Sotelo Kahane from UR Vistahermosa Clinic, Spain to talk about IVF prognosis and pregnancy chances in case of low AMH levels. The doctor also talked factors that cause AMH to drop significantly.
Dr. Valeria Sotelo Kahane starts with precisely defining what anti-Müllerian hormone (AMH) stands for. It is a protein produced exclusively in the granulose cells of the ovarian follicles. When secreted by the ovary into the circulations, its levels can be determined in serum by a blood test. Its blood levels reflect the pool of ovarian follicles (follicular reserve) and therefore, AMH is a marker of the quantity of the eggs. It helps us measure the ovarian reserve – that is, the eggs that are stored in the ovary.
AMH has also other, less known characteristics. It is found in both men and women – but with different functions. Its main action consists of the sexual differentiation in the embryo state. In male embryos, it is expressed early and inhibits the Müllerian duct – the embryo structure that forms the uterus and the tube. In female embryos, it is expressed later on, when the uterus and tubes are already formed. In adult women, ovarian follicles are expressed. Anti-Mullerian Hormone is produced in a woman’s ovaries by the primary follicles (small clusters of cells that surround immature eggs).
Serum AMH levels seem to be the best ovarian reserve hormone marker since they correlate directly with the proportion of primordial follicles with a sensitivity of 80% and a specificity of 93%. The analysis of anti-Müllerian hormone (AMH) can be done any day of the menstrual cycle – unlike other hormones (e.g. FSH) which levels are practically constant throughout the cycle. Dr. Valeria Sotelo Kahane says that the measurement of AMH level is done through a simple blood test that doesn’t require fasting. It is good to remember that the AMH test tells us how many eggs remain in the ovary. It does not tell us anything about the quality of those eggs. The quality of woman’s eggs cannot be evaluated unless the eggs are collected and used for fertilisation attempts.
Resulting laboratory figures of the AMH test can be divided as follows: less than 1 ng/ml (low ovarian reserve and worse results for ovarian stimulation in fertility treatments), 1-3 ng/ml (levels considered normal) and above 3 ng/ml ( good reserve but special attention required in case of the ovarian stimulation). Basing on this data, we can classify patients according to their response to the ovarian stimulation during IVF treatment. The patients with AMH between 1 and 3 ng/ml are normal responders obtaining 10-15 eggs during the ovarian stimulation. The ones with AMH below 1 ng/ml are poor responders (with less than 3 eggs per stimulation) and those with AMH over 3 ng/ml are characterised by a high response to the treatment (even over 15 eggs).
However, it is worth considering that the AMH test results should not be understood as the only information determining a woman’s chance to conceive. The latter usually depends on many other factors, such as e.g. the quality of the partner’s sperm, the condition of the fallopian tubes, and the occurrence of ovulation. What is more, having a “normal” AMH value right now does not predict that it will stay the same in the future. All women will have a decline in fertility as they age – only the pace at which the decline occurs is difficult to predict.
According to dr. Valeria Sotelo Kahane, the AMH analysis an important fertility test to tell us about a woman’s ovarian reserve and should be suggested for all women who simply need advice about their future reproductive life. It is especially important for women who consider the so-called ‘late motherhood’ ( from 30/35 years of age) and those who experience infertility problems. The latter means being over 35 and trying for a pregnancy for over 6 months with no results. It is also advised for women who are thinking about cryopreservation of ovules or those having present risk factors of premature ovarian failure (family history of early menopause, smoking or health problems). Additionally, the AMH test is always obligatory prior to the ovarian stimulation in order to determine the indicated treatment.
Dr. Valeria Sotelo Kahane stresses that the explanation of the information provided by AMH blood test (together with the count of central follicles made in ultrasound and the maternal age) is essential in reproductive counselling. If it is determined that the ovarian reserve is good and the pregnancy is still not achieved, some tests may be necessary in order to try to find out the reason of infertility. If the ovarian reserve is compromised, IVF can be the best option to achieve a pregnancy. In the worst-case scenario (meaning the lowest AMH level), egg donation might be necessary.
Even before being born, women already possess the eggs that they will have throughout their whole life. Over the years, there is a decrease in the ovarian reserve – it refers to both the quality and the quantity of the eggs and it seriously affects the chances of a pregnancy. According to the Spanish Fertility Society (SEF), when women are born, they have about 2, 000, 000 eggs and when they are in the puberty, this number is reduced to 400, 000. Dr. Valeria Sotelo Kahane reminds us that this is exactly at the puberty stage when a woman starts ovulating. It is calculated that, in the reproductive life, a woman will ovulate between 400 and 500 times.
When, on the other hand, a woman in a menopause, her ovarian reserve is completely diminished. Therefore, we have to remember that a woman’s biological clock runs against her fertility. With every passing year, the chances of getting pregnant decrease – it is especially true for women over 35 years old. And although the age of a woman is the most common reason for the diminished ovarian reserve, there are other factors as well. These include mainly the presence of other diseases, such as endometriomas (ovarian cysts), teratomas or autoimmune disorders (rheumatoid arthritis, celiac disease, Crohn’s disease) as well as oncological or radiation therapies. The ovarian reserve may also be seriously affected by surgical interventions in the ovaries or lifestyle risk factors, such as obesity, tobacco smoking, increased alcohol consumption and stress.
Dr. Valeria Sotelo Kahane admits that the decreasing rhythm of every woman’s ovarian reserve is different. In some cases, ovarian reserves are over even before the menopause arrives. But whatever the reason for the decrease, we must realise that this situation is completely irreversible and there is no treatment to re-establish the amount of lost eggs.
According to dr. Valeria Sotelo Kahane, anti-Müllerian hormone (AMH) is one of the most significant prognostic determinants of the treatment outcome and pregnancy. It is considered a hormonal marker of ovarian ageing as its levels are directly proportional to the number of antral follicles and ovarian reserve. The advanced age of a woman is the most important factor for the diminished ovarian reserve and – as a result – a poor response to ovarian stimulation for IVF.
In terms of the time scale that she gave, 0.8 is a low level, taking into account the age so it’s considered a low ovarian reserve. Probably the results of ovarian stimulation will be low.
In the European measurement between 1-3 is considered normal. However, as you can see, less than 1 is already a low reserve. So, 1.1 will be in the lower limits of the normal configuration of ovarian reserve. So, it’s normal but tending to low.
1.1 pmol/l is a different measure. That covers counts to 0.15 ng. So, it would be on the lower side, because it’s less than1nanogram. That’s a low ovarian reserve.
The thing is that the quantity isn’t related to the quality. It’s not a matter of the number of eggs we have. The more we have does not mean that we have lower quality eggs. So, we won’t know the quality of the eggs until we use them. So, we can have a very good number of eggs and have an excellent quality or a very good number of eggs and have low quality. It depends, we will find out once we use the egg and the sperm and produce an embryo.
When we have these levels, we have to take into account the age also. So, it’s not the same that we have 8.7 pmol/l of Anti-Müllerian hormone and an Antral Follicle count of 12. Being 40 or over 40 years old, we consider this prognosis as more indicative of egg donation because of the quality of the eggs. If we look at these measurements with someone less than 39 years old, we consider doing IVF instead of egg donation.
So, according to one of the doctors’ tables, one of the measures with an Anti-Müllerian hormone level of 1-3.5 ng/ml would be considered not normal responders and we should expect between 10-15 eggs. We wouldn’t know the quality of the eggs because that depends on the age, but it should respond well.
There are no studies on improving the AMH levels. So far it hasn’t been proved. What we do is use growth hormone to try to increase the quality of the eggs. We don’t have experience of ovarian rejuvenation in any of our patients. As the doctor said before, we are born with a certain number of follicles, of eggs and once our ovarian reserve starts decreasing, this is completely irreversible. There is no treatment that will reestablish the amount of lost eggs.
At Harvard University, they are working with mother cells to try to increase the birth factors. This is a study and they are trying to defend this study, but it still hasn’t been proven.
There is a difference. The AMH levels can be tested at any time of the cycle so the patient doesn’t need to wait until the beginning of her cycle to do the test. However, FSH and LH are hormones that need to be studied during the first days of the cycle, between day 1-5 of the cycle approximately.
Having an Anti-Müllerian hormone measure of over 1 but no period indicates that there is a problem. We need to specify the patient’s case. We need to find out the age. If the patient is around 30, we need to see what is happening with this patient and complete all the studies. Anyway, it’s a low Anti-Müllerian hormone level and there are no periods so this shows that perimenopause is starting and this should result in a low ovarian reserve.
One of the most important factors is age. If the woman is advanced in age, this is the most important factor in a diminished ovarian reserve. Obviously, we must do all the rest of the studies but it’s clear that this age won’t help so she should be more directed towards egg donation than using her own eggs.
This happens to many patients. They have low AMH with normal FSH, LH and estriol levels. The AMH is not just about the number of eggs but it also gives a prognosis. This means a low ovarian reserve. Usually, when the Anti-Müllerian hormone level is less than 1, we should obtain a low number of eggs — around 3. Obviously, this will depend on the age of the patient, on the Antral Follicle Count scan and everything else. But the prognosis is not good.
But obviously, the doctor doesn’t want the patients to get stuck on the idea that low Anti-Müllerian hormone equals no pregnancy. You can have a low AMH but still have very good quality eggs and even if we collect a low number of eggs, these eggs are very good so we can obtain embryos. We can still obtain a pregnancy. In younger patients, this should work very well because of the quality of the eggs. This always depends on the specific case of each patient — age, Follicle Count and everything. We still have patients with these levels and pregnancies.
I had a patient with the same case. The patient didn’t have stones but I had to remove the gallbladder and this may have influenced the metabolism of the hormones. This could have been the reason for having 10 eggs first and then 5 eggs. Or it could have been a normal cycle with 10 eggs and the other cycle had 5 eggs, just because that cycle worked like that. But probably it was influenced by the gallbladder stones.
Firstly, this patient is asking if she should continue with IVF so she may have had some treatments before. If she has had more than 2-3 cycles with a low response then we would recommend looking for egg donations because the response won’t improve and egg donation will give better results and increase the chances of success. If she has never tried stimulation before, IVF, or maybe 1 cycle, we could recommend that she continue to try because obviously, every patient has the right to try her own eggs. We can never say ‘no’ because you never know. You must go ahead with the treatment and find out for yourself with proof whether or not it works. So, it depends. If she has had 2-3 cycles with low response, we would recommend egg donation. If she has never tried before, we would recommend trying IVF.
We should be open-minded. We should consider all the options. We can never say ‘no’ to something if this is not negative for the patient obviously. These alternative medicines or alternative options will not increase the quality of the eggs or the ovarian response but they will help. They are complementary. Acupuncture will help to reduce stress and anxiety and also increase blood irrigation. They will not improve the quality but will help the process in other ways.
You’re 36 so I perfectly understand that you still want to try with your own eggs. You’re very young. That Anti-Müllerian hormone is low so the prognosis is showing a low response. Stress is often a reason for losing periods and menstruation regularity. The bleeding is back but that does not mean that the AMH will be higher. Obviously, you will have a better chance with egg donation. However, you’re only 36 so we understand that you want to try with your own eggs.
The first and most important thing is that if you want to check the differences between Anti-Müllerian hormone levels or any other hormone levels then you have to use the same laboratory because different laboratories have different measurements and the levels will always turn out different. Now, you want to check in the same laboratory. A difference of 3 weeks in between tests will not show a difference in AMH levels. When you test FSH or estradiol you will find differences because it depends on the moment of the cycle. AMH does not depend on the moment of the cycle. 3 weeks is too short a time to consider any difference. AMH changes throughout the years but not over 3 weeks.
This case is very well specified. If there is no male factor here — 39 years old, 1.2 AMH, a good follicle count — then it may be an egg factor. Probably the quality of the eggs isn’t that good and that is why you haven’t achieved a pregnancy. Here at our hospital, we could consider a 3rd IVF trial. We’ve done 2 and we could maybe try a third and if not, then maybe try something else.
We also have to take into account psychological and financial factors. Obviously, if we had treated you here, we would have had more information about your cycles and why this didn’t work, if we had had a good number or embryos or not, what day they were transferred and so there are many other factors that we should consider. There could be other factors too — psychological or financial — so we could consider other options, to go directly for egg donation, but this is something very personal. This is something that should be explained and discussed in consultation with a doctor, taking into account all the factors. But with this information given right now, why not try a third one. But this will depend.
No, the use of contraceptive pills does not help, does not increase the quality or quantity of the eggs. We use contraceptive therapy to regulate the cycles or synchronise the cycles but not to help the quality or quantity of the eggs. That will not help.
Obviously, there is scientific evidence that Coenzyme Q10 helps. This is a bio-element that produces energy and helps the normal functioning of the ovaries. Through the years, we experience cell damage, so Coenzyme Q10 may help, but we can also consume Coenzyme Q10 through food. We use this more on men than women. Although it may help, it will never increase and it doesn’t help to increase the quality.
There has been a study in Canada of patients between 36-43 years old and they didn’t find any results. In any case, when we prescribe this medication here, we do so with doses of 100 mg.
Well, this depends on the specific case of the patient. Obviously, we need to know what kind of treatment she has undergone, if she has gone through a natural cycle, if she’s been stimulated, if she’s had IVF or egg donation, if they’ve focused on the endometrial thickness. So, there should be a study to see why she’s not improved the thickness. So, if when we know why or what treatment she’s had and why it’s not increased, then we can focus on increasing it.
This patient is 47 so 5 egg donations is a good number of cycles. When there is no male factor, she should consider a study of the uterus, maybe perform a hysteroscopy to see if there is a uterine factor, or any pathology, any implantation failure, auto-immune illnesses, NK cells test to show why the uterus is not implanting.
A few years ago, there was no vitrification. There was freezing of the eggs or embryos. So the eggs or the embryos went through major stress through the freezing so it was better to freeze embryos than to freeze eggs. But nowadays, there is a vitrification process where the gametes go through less stress and there is not much difference between vitrifying eggs than vitrifying embryos. All things considered, it might be better vitrifying embryos but there’s no big difference.
If the patient has been through many IVF cycles and she’s going in for egg donation for the first time, we don’t recommend the ER test, the endometrial receptivity test, but if in a case like the one like we had before with 5 egg donations, we do consider the endometrial receptivity test when we should consider when the endometrium should be more receptive during the cycle.
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