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Fertility hormones (FSH, LH, E2, AMH) – why, when, and how to test?

Esther Marbán, MD
Gynecologist & Fertility Specialist at Clinica Tambre, Clinica Tambre

Category:
Fertility Assessment

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From this video you will find out:
  • What hormones should be tested for fertility?
  • When should fertility hormones be tested?
  • What does an FSH test tell you?
  • What is a normal FSH/LH level to get pregnant?
  • What does Estradiol do?
  • What does your AMH level really mean?

When should female hormone testing be done, and how is it done?

In this webinar, Dr Esther Marbán, Gynaecologist & Fertility Specialist at Clinica Tambre, Madrid, Spain explained how to test fertility hormones such as FSH, LH, E2, AMH, when should they be tested and how it’s done.

Dr Esther Marbán talked about the FSH, LH, estradiol and AMH hormones and the importance of the hormonal assessment, which is essential for ovarian function and performing a proper diagnosis in each patient. They are also important for the ovarian reserve assessment and to predict the patient’s response to medication for selected treatment protocol and medication dose.

FSH

FSH is a follicle-stimulating hormone, it’s produced in the anterior hypothesis in response to pulsatile gonadotropin-releasing hormone (GnRH)) stimulation. The combined action of FSH and LH stimulates ovarian follicle growth. The test is done by a blood sample on days 2-4 of the period. The normal levels are the following:

  • below 10 mU/ml is considered normal
  • between 10 and 20 10 mU/ml, suggests a poor ovarian response to an ovarian stimulation
  • over 20 mU/ml suggests low ovarian reserve and poor reproductive outcomes

In general, high FSH levels may be found due to age, menopause, and primary ovarian insufficiency. Low FSH levels, in combination with low LH levels, may indicate a problem in the hypophysis. The hypothalamus produces the gonadotropin-releasing hormone, which is transported to the anterior hypothesis or pituitary glands, where both FSH and LH are produced. Both LH and FSH act to secrete estradiol and progesterone in the ovaries. The Hypothalamus and hypothesis notice an increase in both FSH and LH, and the production of FSH may decrease. The opposite happens with low levels of estrogen and progesterone. When low levels of oestrogens and progesterone are found, they could have the opposite effect, so in the end, we would find high FSH and LH levels. That’s what happens, for example, during menopause, no oestrogens are circulating in the blood, that’s the reason they have that negative effect, and in the end, we may see that FSH levels are quite high.

FSH is strategically used to evaluate the ovarian reserve, which means how many eggs are remaining in the ovaries. However, FSH is not the best ovarian reserve marker. It varies throughout the menstrual cycle and also from cycle to cycle, which is something that we need to remember. Apart from that, there are big differences in the normality levels, therefore, we need to add other hormonal tests to perform a proper diagnosis and to know the patient’s prognosis for stimulation in IVF. It cannot predict the success of an IVF treatment.

LH

LH is also produced in the anterior hypothesis in response to pulsatile gonadotropin-releasing hormone (GnRH) stimulation. The combined action of FSH and LH stimulates ovarian follicle growth, but the main important role of LH is that it triggers ovulation. The ovulation may happen, and 24 to 36 hours after the LH surge, it releases impulses, so a single blood or urine sample may not detect the LH rises. It’s commonly tested on days 2-4 of the period, in some cases of polycystic ovarian syndrome (PCOS), primary ovarian failure or menopause, they are related to high LH levels. The opposite happens in some cases of amenorrhoea, where we may find low LH levels.

Estradiol

Estradiol is a type of estrogen and is produced in the ovarian follicles as they grow. The normal level on days 2-4 of the period is between 25 and 70 pg/ml, and normally it improves the predictive information about FSH. Traditionally, high estradiol levels in the early follicular phase (days 2-4 of the period) are related to a worse ovarian response to stimulation, which means higher cancellation chances and a lower pregnancy rate. However, a systematic review concluded its lack of clinical usefulness in predicting low response. The role of basal estradiol determination in the prediction of ovarian reserve is currently debatable, but it may help in identifying patients with a low ovarian reserve and ‘falsely’ low basal FSH levels due to high estradiol levels.

AMH

AMH is the most important hormone that can help us to assess patients and their ovarian reserve. It’s a glycoprotein growth factor, produced by the granulosa cells of the antral and preantral follicles in the ovary. The antral and preantral follicles are the smaller follicles found in the ovaries, they are normally between 2 and 8 millimetres, and sometimes they can’t be seen on an ultrasound. We always perform another test which is a vaginal scan to test and count the number of follicles, an antral follicle count (AFC).

AMH is known to be a regulator of recruitment, preventing the depletion of all the primordial follicular pools at once. It does not vary during the menstrual cycle, which is something really significant to consider, as we may measure AMH at any point of the cycle without any particular changes. The normal levels can change depending on the women’s age, for example:

  • below 1 ng/ml suggests low ovarian
  • between 1-3, ng/ml is considered a normal ovarian reserve
  • above 3 ng/ml is considered high ovarian reserve

As the quantity of follicles in the ovary reduces, the AMH levels also drop, as the FSH increases, it could mean a low ovarian reserve. Antral Follicle Count (AFC) and AMH level both decreases as the woman gets older, which is a normal situation.

AMH is a predictor of ovarian stimulation in IVF, so it means that it can give us a good approximate number of eggs we may receive but is not related to egg quality. Therefore, age is still the best quality marker. AMH helps in predicting the risk of ovarian hyperstimulation syndrome in women with high AMH levels. This is something important to consider, in that situation, we should use low stimulation doses and try not to push the ovaries to produce many follicles and eggs in that patient. Low AMH levels are associated with a high cancellation rate due to low ovarian response. It is not a predictor of whether a woman will get pregnant or not, and can’t predict how quick your ovarian reserve will decline.

Conclusions

  • The hormonal testing is essential for correct ovarian function knowledge in reproduction.
  • LH and estradiol do not have any significant role in ovarian reserve assessment.
  • FSH on days 2-4 of the menstrual cycle is a significant ovarian reserve marker, especially in combination with AMH, which nowadays, is the most efficient and effective marker.

When should female hormone testing be done, and how is it done? - Questions and Answers

Does high FSH always mean menopause?

No, not always. When we are talking about a patient with menopause, the FSH level could be around 50 or even more approximately, so if that patient has that kind of FSH, we could think that maybe the menopause is there, but having 25 doesn’t mean that there is menopause. It does mean that your ovarian reserve is quite low, of course, it depends on the moment when that FSH is tested because if you test it, for example, at the end of the cycle, the meaning would be completely different. If we are talking about high FSH 50 or even more, we would think that that patient could be on menopause, but not all the FSH levels mean that the patient has menopause.

Can I increase my ovarian reserve naturally?

I am afraid you can’t. All women are born with around 2 million follicles and eggs in their ovaries, and as we get older, those follicles start to decrease, so at this point, there isn’t any way to increase the ovarian reserve. It’s known that if you have a healthy way of life and you’re trying to avoid some oxidants, in the end, it will affect the ovaries, but there is no way to increase the number of follicles or eggs. There is some data on some procedures that can be done on ovaries in young women who have a low ovarian reserve. At the moment, it’s nothing that we can suggest, there’s some examination and some research on that, but it’s not yet available at the clinics and in daily life. I’m afraid that we can’t increase the reserve at the moment.

 How can I boost my fertility hormones?

We don’t need them to boost them. We need a normal ovarian reserve, and apart from that, for the ovaries to work properly with the stimulation, which is not so easy to do. In the end, if we have a patient with a normal ovarian reserve or even with a low ovarian reserve, we’re trying to make the ovaries work better by giving the medication. That way, we try to make the follicles grow better, which may help to obtain a good number of eggs at the end of the stimulation. We know how it works, so we need the ovaries to work as good as possible during the stimulation, so it’s just a problem of finding a good way to stimulate the ovaries to try to have the best result in that patient and receive a good number of eggs, in the end.

Could ubiquinol improve egg quality?

Many different molecules could increase the egg quality. There is no scientific proof, and there are not so many papers stating what kind of medication or chemicals may help us improve the egg quality. In the end, no data shows good results with that. We know that many vitamins are supposed to increase that egg quality, but in the end, the results that we see are not different.

If we cannot improve egg quantity, can we improve the egg quality with supplements such as Melatonin, COQ10, etc.? It only takes one egg in the end.

Many patients take vitamins like Melatonin, for example, because they are quite powerful antioxidants. After all, it is known that sometimes when we are talking about a lower reserve, especially, in young women, on some occasions, it’s thought that maybe the problem is that there is quite an oxidant environment in the ovaries. That may affect the egg quantity and quality. Sometimes using that kind of antioxidants may um help us in the way of trying to improve the egg quality. But you need to understand that when we see the patients taking supplements daily, the results are not so different. They are not going to have any negative effect on the egg quality, but I think that it’s really difficult to change the egg quality, maybe in the future, we may find some kind of vitamin or whatever that may help us.

We’ve done some research on Melatonin some years ago, where we’ve tried to see if it could help young patients and improve the egg quality, but the results were not so different. Possibly, in the future, we will have more information on that. It’s clear that there are so many patients with poor egg quality that we should consider testing and doing more research on that, but there are no clear results yet available.

Could hormone level predict the egg quality for a woman who is 40? If yes, how? 

There is no way to predict the egg quality, so we know that the best predictor is age. Not all women in their 40s indeed have low egg quality, but we know that it is like the best marker, and it’s quite related to the egg quality. The hormones will just predict the egg quantity especially, with the AMH but not the egg quality. To test the egg quality to select the best is like pushing the ovaries to work for an IVF. Once we retrieve eggs, we work with them in the laboratory, we can see how the egg develops in an embryo and how the embryos are doing. Thanks to that information, we may find out more about the egg quality, but there is no test to know the egg quality exactly.

The only data that we should consider is age. As I mentioned before, not all women have the same egg quality. Of course, if you are older, the quality could be low, but not in all cases, it’s like that way because we have many patients that are quite young and yet the quality is not so good, so in the end, we know that age is important, but it’s not the only factor to consider.

Can stress cause low ovarian reserve?

I couldn’t say that stress may cause a lower reserve. What is known is that stress could affect some sort of hormones suppression. If the patient is going through a stressful moment, hormones like FSH and so on could work differently because the brain is related to one thing and the other. The stress itself wouldn’t cause lower ovarian reserve. In some stressful situations, it may cause amenorrhea which means that menstruation doesn’t come. Because of the alterations that the brain would have in a stressful situation, in the FSH, LH production, in the end, stress won’t cause a lower ovarian reserve itself, but of course, it could cause some alterations in some hormones.

Could Ibuprofen taken for pain during the period affect the egg quality?

If the patient needs to take some painkillers due to menstruation, it’s perfectly fine, and it won’t affect the egg quality at all. Apart from some other chemicals that we know could affect the egg quality, the normal medication we take for the pain is okay for the egg quality. You may take it without any issues with that.

 How is the ratio LH/FSH being used/ interesting to assess?

We normally use that ratio, especially in patients with the polycystic ovarian syndrome, which is the normal situation where FSH is slightly higher than the LH than the normal level. It’s known that in polycystic ovarian syndrome, there is an imbalance between both hormones and that it may change. I mean, the LH level could be quite high and the FSH not so high, so in the end, when we find a patient that has that alteration sometimes, we may think that maybe the patient is having the polycystic ovarian syndrome.

I had 2 IVF attempts 3 months ago but had only one egg retrieved, it did not make it to become an embryo. I just turned 44, my AMH is 0.18. If it’s too hard already with IVF help having it naturally will be impossible, right? I don’t need many eggs, just one.

There are 2 different issues to consider. The first one is age and the second one is AMH. We know that the AMH is perfectly normal according to your age because you’re 44 years, so it’s quite common to have really low AMH levels in that kind of patients. In some cases, what happens is that even if we give high doses of stimulation, the main problem is that there are no receptors where the medication could be joined. In the end, sometimes we use a natural cycle, so we just do a follow-up of the follicle that is growing normally, and then we try to retrieve that egg. It’s true that in that patient if you are just having one egg when we do the egg retrieval sometimes, that follicle may be empty, and apart from that, the embryo should develop to the blastocyst stage at least to see if it’s going a kind of fine and apart from that it’s really important to consider in women older than 40 years old the alterations that the embryos may have due to age.

I’m talking about the chromosomal alteration that the embryos could have due to that age. We know that it’s not very likely to have a healthy embryo transferred because you are 44 years old. It’s quite unlikely that you’ll get pregnant naturally. I would say that, especially if you tried several times, it’s quite difficult. Apart from age, we are talking about egg quality with a low ovarian reserve and the way the embryos are developing, but also the alterations that the embryos may have due to age. In this situation, it’s really difficult to deal with because there are so many factors that are affecting the stimulation negatively.

Is there a perfect level of hormones for women starting an IVF cycle/own eggs (age 35) -AMH level 0.6? Normal BMI. It’s the first IVF cycle.

When we start an IVF cycle, we normally test both estradiol, sometimes LH and progesterone values. When we are starting stimulation, we try to have the hormonal levels quite low, which means that the ovaries are like resting. When we find, for example, estrogen level a bit high, it could mean that maybe some small follicles are producing hormones and that hormones may affect the stimulation development, so that’s the reason why we always check the hormones before starting. In the past, we tested the FSH, but we decided not to do it anymore because the results wouldn’t change the protocol we were using.

So as you are young and your AMH level is not very high, it’s quite low, so I guess that maybe your doctors will start the simulation with quite a high dose of stimulation trying to retrieve as many eggs as possible. We normally consider the estradiol level below 70 picograms per meter to say that it’s perfectly normal to stop the stimulation.

What is the purpose of taking FSH and LH for daily simulation if the LH is for ovulation?

LH is also involved in follicular growth, so normally, when we are stimulating the ovaries, we start with FSH or a kind of FSH to stimulate follicular growth. Sometimes, we add some kind of LH, especially in older patients that should use LH action to try to make the follicles grow in a better way. We are trying to make the ovaries produce more follicles. We normally produce just one follicle in a natural cycle, and the idea is to try to make the ovaries produce more follicles. We are making FSH or LH go to the receptors in the external part of the follicles, and we’re making those follicles grow. When they grow properly we know that we are going to retrieve around 5 eggs which is not a natural situation that we may find in a natural cycle. We do that to retrieve a higher number of eggs.

 How do we know if the quality is good or not? If the embryo goes to blastocyst day-5 with a good rating, it means it is of good quality?

When the blastocyst is on day-5, we know that the first days of the embryo development are related to the egg quality. If the embryo is doing quite well between the day after the fertilization and day-3, normally, if the egg is of good quality, the embryo will develop properly. After the third day, we know that it’s a moment when the sperm starts to act, and if the embryos sometimes do not develop as the embryo should sometimes, it could be because of a male factor.

We normally consider that if the embryo is doing fine during the first days of development, it’s because the egg has a good quality, it’s not just as easy, but it’s like a slight idea of what we normally consider in the laboratory. In the end, of course, the egg should have some kind of characteristics, and that are normally seen in the laboratory just to know that the quality is at least normal, and after doing the fecundation of the eggs, we see how the embryo develops in the first days and normally as I was mentioning before if we have like a good quality embryo, it’s because the egg at the beginning had a good quality also.

Could a bad looking, PGS tested embryo be a good embryo?

There are two different things in that question. First is the quality of the embryo, and the second PGS testing. We may have a wonderful quality embryo, and once we test it with PGS, sometimes the outcome is like it’s not a healthy embryo, so the quality is not related to the result of PGS. There are so many embryos with really high good quality, and in the end, their result says it is not healthy, which means that they don’t have the correct chromosomes. The quality of the embryos is not related to the PGS result.

There is so much research trying to guess if the quality was related to the PGS results, but at the moment, there is no relation between egg quality and how the PGS result will be. If the embryo, for example, is not of the top quality but is a healthy embryo, the implantation rate of that embryo would be quite high. If the embryo is of perfect quality, but it’s not a healthy embryo, for sure, the embryo won’t implant, but in case it implants, it could end in a miscarriage. In the end, PGS tells us if the embryo is healthy, and in case it is, the implantation rate would increase, but egg quality is not related to the PGS results.

Could creating embryos in a cycle tell us about good egg quality, or it doesn’t matter? 

If we create an embryo in the laboratory, we can have quite a wide idea of how the eggs are. As I mentioned before, the quality of the embryos is not related to the PGS results. In case we perform that, and it’s known that the best way to find out how the ovaries are working is by trying to put ovaries under-stimulation to know exactly what we may expect from them. If we have the eggs in the laboratory we create the embryos, it’s quite likely that we are going to have a lot of information about the eggs and the embryos themselves.

We will be checking those embryos since they were eggs and until we decide to freeze or transfer them. The idea of the cycle is to create the embryos for transfer, not creating the embryos just for creating them as we want the patient to get pregnant. The information we will get is really important, but it will be information in the laboratory. It’s not so easy to have or at least to try to guess what we could have expected from the ovaries unless we do a stimulation, and we have to get eggs with the idea of making that patient get pregnant.

 If I take the COVID-19 vaccine, how long to wait until I schedule egg retrieval?

There is no data if the COVID-19 vaccine could affect the quality or quantity at all, but it’s true that if the patient wants to get pregnant, it’s recommended to wait between one and two months to get pregnant. In case she wants to get pregnant, I would recommend or suggest waiting and doing the vaccination and afterwards waiting between one and two months to get pregnant.

Could the E2 level during stimulation tell about the result? Does a higher level mean better result and better egg quality?

The estradiol level is related to the number of eggs retrieved. When we have a patient with a high estradiol level, it’s because the response was quite high, but it’s not always that way depending on the stimulation. Sometimes we may find not very high estradiol levels, and then we receive a high number of eggs. Estradiol is related to the number of eggs that we may retrieve, but it’s not the only data we should consider. I mentioned before, estradiol is not a good marker of ovarian reserve. During IVF, the only information that the estradiol may give us is the approximate number of eggs that we may retrieve. If the estradiol level is quite high, the ovarian response is also high, but it’s not related to the egg quality anyway.

Is it safe to simulate with FSH higher than 300 units?

I wouldn’t say that it’s not safe, of course, it is safe, but the issue that we should consider is whether it’s useful or not. When we have a patient with a really low ovarian reserve, we could give, I don’t know, 600 units if we want because the issue is that there are no receptors in the ovaries to make that medication work properly. In the end, we know that giving a stimulation of more than 300 units doesn’t make any sense because the effects won’t be so good. The ovaries are not having a good number of follicles and are not having any good number of receptors in where those medications could act. If we give that a high dose of stimulation, the idea is to try to make the ovaries work as much as possible but using more than 300 units nowadays, it’s not very common because we know that the results won’t change at all.

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Authors
Esther Marbán, MD

Esther Marbán, MD

Dr Esther Marbán has been part of Clínica Tambre’s medical team since 2010. She is a gynaecologist specialized in Human Reproduction with a brilliant academic career. In fact, she obtained a special honourable mention in her Master’s Degree in Human Reproduction that she completed during 2009-2010 (organised jointly by the Spanish Fertility Society and the Faculty of Medicine of the Complutense University of Madrid). Dr Marbán is known for her restless and proactive personality and her innate talent for empathizing with people which she proves every day by working with patients.
Event Moderator
Caroline Kulczycka

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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