# AMH, a marker of ovarian reserve but useful for predicting IVF response?



## tamsinw

Hi all

I'm in the unfortunate position - like many others - of being refused IVF based on my low AMH result (0.79 ng/mL; FSH <10 twice, 13 once). 

Because of this and because my job involves researching specific areas of medicine and writing about them, I've looked at some of the most recent research investigating the use of AMH as a marker.

In brief, it appears to be better than FSH as a marker of ovarian reserve (OR; number of eggs), providing an indication/estimate of OR (rather than 'absolute proof', as with most markers used in medicine).

However, the usefulness of AMH for predicting response to ovarian stimulation in IVF is unconfirmed , with some studies showing it may be useful and others concluding that it shouldn't be used as a sole reason for declining IVF treatment. I've added a few key recent findings with links to either the full medical papers (if available) or to the MedLine abstract (for those who don't know, MedLine is a database of all published research related to medicine, accessible to all). I've also included numbers of patients studied - as a general rule, larger numbers of patients provide more conclusive evidence.

Some studies are quite positive about the usefulness of AMH as a predictor of response, for example:

"AMH accurately predicts ovarian responsiveness to controlled ovarian stimulation with high sensitivity and specificity" (93 patients)
REFERENCE: http://www.ncbi.nlm.nih.gov/pubmed/18674663?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

"AMH cutoffs of >3.75 ng/mL and <1.0 ng/mL would have modest sensitivity and specificity in predicting the extremes of response" (165 patients), i.e. low levels may predict poor response in some patients (not all) and high levels might predict over-response in some patients. This study is by one of the consultants at St Mary's (Dr L Nardo) who have a low AMH cut off of 2.2 ng/mL. In this paper he concludes that AMH HAS THE POTENTIAL to be incorporated into treatment protocols... but St Mary's have already incorporated it.
REFERENCE: http://www.ncbi.nlm.nih.gov/pubmed/18930213?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

However, other research is less positive about using AMH to predict response in IVF, for example:

"Measurement of AMH supports clinical decisions but alone it is not a suitable predictor of IVF success" (316 patients)
REFERENCE: http://www.ncbi.nlm.nih.gov/pubmed/18387961?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

"The use of any ORT [ovarian reserve testing] for poor response prediction cannot be supported... entering the first cycle of IVF without any prior testing seems to be the preferable strategy" 
This is a slightly older publication (Oct/Nov 2006) but is an analysis of all high-quality clinical trials investigating ORT.
REFERENCE: http://humupd.oxfordjournals.org/cgi/reprint/12/6/685

Clinics will continue to refuse to treat patients based on markers such as AMH, FSH and other criteria, but at the end of the day these are only markers - they are not 'foolproof'. As is obvious from many posts on Fertility Friends, 'poor' results do not necessarily mean an individual would be pursuing IVF with no hope of success. Even if you are refused treatment based on low AMH or high FSH, it is worth considering finding a clinic that will allow you to try one IVF cycle - it seems that this is the only accurate way of knowing how a woman will respond. 

It makes sense that the NHS, with limited funds, needs to have certain criteria to refuse treatment - not necessarily fair and certainly upsetting for many women but perhaps it is unrealistic to expect them to try one IVF cycle in patients that may be poor responders?

I've tried my best to be balanced in this summary of a subject that is clearly emotive to me and many others, but I'd be very interested in what others think?

Good luck to everyone out there 

Tamsin


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## Guest

Hi there - this will be v useful I am sure to many - well done for posting it    ....I was refused NHS funding as my FSH was just over 10.

Allthough not yet properly pregnant (as far as I know!) I have always produced eggs and good embies (from 2-10 eggs) - I suspect my AMH to be v v low, although I have not had it tested as I know it would freak me out now and I know my doctors know enough about me from my tx history now...good luck to you.....are you planning on self funding?

Criteria do not need to be there for the first tx IMHO - every woman deserves a chance to try once 

xxx


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## Caz

Thank you for posting that Tamsin, and fpor providing links for everyone to do more research if they want to. Thatw as very well balanced considering your own situation. 

C~x


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## Jumanji

When they say it is a useful indication of ovarian reserve in a non-IVF context how do they know??  As far as I am aware there have been no studies of AMH in the general population ttc and no studies of AMH in relation to time period to menopause.  It is known to decline with age but presumably the rate can vary and some people may always have naturally hgiher levels than others.  There was that one study which found that AMH ranges were similar to age range at menopause but none of the ladies tested had actually reached menopause so we still don't know from that whether it was really a useful predictor.

I know this test is getting a lot of publicity but I do feel it is very far from being perfect.  My sister was told not to have it on the basis that it would be awful so what was the point?  Yet she did fine with IVF.  I have seen a lot of ladies on this site get very upset about their AMH results; yet it seems that not even the docs really know that much about this test yet and I think that is very unfair.






/links


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## tamsinw

I agree LittleJenny - its seems very premature for clinics to be incorporating AMH into criteria for refusing treatment when it is such a new and imperfect marker. 

I started having stupid thoughts like "OMG, am I going to have an early menopause? Am doomed to being childless cos I have so few eggs left?"   ... and then I gave myself a good talking to, reminding myself that there is HUGE inter-individual variation in humans and perhaps my AMH has never been very high? But I'll never know now...

I think there is no harm in clinics measuring AMH from a research perspective, i.e. carry on monitoring its relationship (if any) with IVF success, but its very frustrating that its been deemed a useful criterion for treatment refusal before its true value is known.

Lukey - so sorry to hear you got refused NHS treatment on borderline 'high' FSH and I'll keep my fingers crossed for you   We're already saving for a first Tx... and in the meantime we'll keep trying naturally  

xxx


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## Be Lucky

Dear ladies i am 43.had 3 failed ivf-amh  0.5 and fsh from 3 2 22.got bfp naturally.now 10weeks pregnant!never give up hope!berniex


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## Jumanji

I have posted this before but I think it is worth revisiting since I always get concerned when people are told their AMH is "low" by a clinic which then provides no support for that claim. Basically, I think there is still a LOT of confusion about AMH and what is "normal" and, to be honest, I don't think even the best in the medical profession have enough data yet to know what it all means.

The assay kit link (next but one link below) is the source of the "original" AMH ranges which everyone jumped on as representing the "norms". They are 2-6.8 on the ng/ml scale and 14.28 - 48.55 on the pmol/l. The conversion factor is 7.14. Most clinics rounded these numbers to 15-45 pmol/l being "normal". This is the scale which had people with AMH of say 1 (or 7.14) being told they had "low ovarian reserve". It was also the source of the statement that "optimal fertility" is about 28-48.55 pmol/l (3.92-6.8 ng/ml), while "satisfactory" fertility is 15.7-28 pmol/l (2.2-3.92) - see this scary link if you want to be really depressed http://www.tdlpathology.com/index.php?option=com_content&task=view&id=201&Itemid=73. This sample also gave a mean AMH of 4. But look at the sample they got this from. First, the size is small (335) and ALL the women are under 38 so chances are we know they probably mostly in their 20s! (I remember reading elsewhere that a lot were college students and thus 18-23 or so but I can't find the link now!). To be fair on the assay manufacturers, they clearly never intended their results to be taken as "norms". They do point out that AMH decreases with age and that suggest labs should find their own ranges. The trouble is many have not done that and simply trot out this reference range, with no idea where it comes from!!

http://www.mbl.co.jp/diagnostic/products/amh/AMH_nousho.pdf

Other research has found that in women of 37 the average AMH was 10 pmol/l (1.4ng/ml). This has 238 subjects but I don't know the numbers in age ranges. Anyway, it did find that AMH remained at about 20-25 pmol/l from age 18-29 (so satisfactory but not optimal according to the first link above!!) and then started to drop. Again, this is beginning to show lower AMH is still ok, especially for those over 30 and that even in those in their 20s, the average still looks lower than first thought. See the next link.

http://www.ingentaconnect.com/content/bsc/ajo/2005/00000045/00000001/art00006;jsessionid=o9h2pdwmbk56.alice?format=print

This next study was small (only 20) but the mean age was 26 and the mean AMH was 2.4 ng/ml (17.13 pmol/l) - this again suggests that even in young women typical AMH levels may not be as high as first suggested. The study also specifically notes that two women aged 33 and 35 had much lower AMH results (1.2 ng/ml and 0.39 ng/ml) than the rest. Note that this study was not in infertility populations - just individuals with normal hormones in all other respects, normal menstrual cycle, BMI etc. See the link below.

http://humrep.oxfordjournals.org/cgi/content/full/dem101v1

The next one was bascially showing that ladies with PCOS have higher AMH which declines more slowly than in control groups, but look at the control stats. Again, it's only a small number (41) but the study looked at the decline in AMH over time and consisted of 2 visits. The mean age at visit 1 was 29.9 and the mean AMH was then 2.1 ng/ml (written as ug/l here but it is the same and it's 15 pmol/l). At visit 2 the mean age was 32.9 and the mean AMH was 1.3ng/ml (9.28 pmol/l). So these "control" ladies would have, on average, had low ovarian reserve by their second visit according to the first stats. Even in their first visit, they are only just "satisfactory" on average!! See below link.

http://humrep.oxfordjournals.org/cgi/content/full/19/9/2036

Repromedix is a bis US lab and was the original supplier of the "mail order" AMH test to women in the US wanting to see how much time they had!! It was marketed as the "plan ahead" test or something similar. Personally I think it is very misleading to suggest a blood test can possibly tell anyone how much "time" they have left!! But, moving on from that, Repromedix will have got a lot of data from having supplied this. Take a look at what they consider normal!! It's right down - bascially from 0.7-3.5 on the ng/ml scale, which is 5-25 on the pmol/l scale is to them "normal" with 0.3-0.7ng/ml (2.14-5 pmol/l) being "borderline low" and 3.5-5 ng/ml (25-35.7 pmol/l) being "borderline high". This has shifted the goalposts considerably from 15-45 being "normal"!!! In this regard, I know that the Glasgow Centre from Reproductive Medicine regards 5-15pmol/l as "normal" and 15 and above as high. This fits in with the Repromedix scale. Clearly things are shifting here!!! I think this demonstrates how experience of AMH ranges (not just reading a supposed "norm" off a sheet with no understanding of its source) is all important.

http://www.repromedix.com/pdf/AMHbL17CF181.pdf

Other labs are of course making their own rules. This one from Germany regards 1-5 ng/ml as normal and 0.8-1 as redisidual. However it regards below 0.4 as "menopausal" which we know cannot possibly be correct since loads of women with lower AMH that that have got pregnant!!

http://www.labmed.de/en/uploads/labmed_letters/amh-engl.pdf

Personally, I think the main message is that it is all too up in the air for anyone to base too much on this one test!! The goalposts are clearly moving and plenty of clinics are surprised all the time. My last link is from a Swiss clinic warning that AMH use has its limits and advising of natural pregnancies in 2 women with completely undetectable AMH!!

http://www.ncbi.nlm.nih.gov/pubmed/17562340

Hope I haven't bored you too much but I feel quite strongly about this test. I have seen too many ladies upset and confused because they are told their result is "low" but the clinic can't really explain that properly because there is so little experience out there. I agree with Tamsin that this test may well be useful but docs should make it clear that it is very much in the research stages.


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## annacameron

Completely agree with LJ. 

The only things I can say with certainty about it are:

1. drs know little about it. 
2. drs are often not very scientific people. The scientific ones are in research and the last area they would enter would be the very easy one (medically) of fertility.
3. the scales are misunderstood. FF'ers please please note the 7.14 conversion factor. 
4. the potential relevance of it is to show women how they fit on a continuum of fertility and I think a test that does that has value. BUT....there is no definitive prooof that this one is clear enough to achieve it. And the whole point is that you can /cannot delay childbearing so the age relativity is essential. 
5. there are studies that show that IVF outcome varies with AMH levels. Well yes that makes sense. if your AMH is 0 then your IVF outcome is too so there will certainly be AN effect. 
6. it is not a direct correlation as massive AMH levels - PCOS - lead to worse outcomes so it's an upturned U shaped curve.
7. noone can tell me specifically what it actually measures. - the AMH produced by what exact cells/eggs/follicles and where?  
8. as a measures of fertility reserve it is expected to drop if anything voer time but many many women's  increases. now small increases are entirley possible within the bounds of the testbut not of the levels and frequency we read about.
9.  I hear frequently it correlates with AFC per cycle. now why is that? it is about reserve NOT the number of follicles recuited each month, which an AFc would show. 

yours confused, 
Anna xx


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## tamsinw

Wow LJ - I'm going to read up on all of those things in preparation for my appointment with the consultant in 3 months time (plenty of time!). Thanks so much for all the info, and to Anna too.

It seems that AMH it causing a lot of women confusion and anxiety without good cause...

x


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## Han72

Hi all

Many thanks to Tamsin, LJ and Anna for the detailed input and research!

Mods - is it all possible to make this thread sticky and flag it up with big red flashing letters somewhere? I have seen so many ladies absolutely heartbroken and thinking it's all over after hearing their AMH results. And when you look at the conflicting studies, it's no wonder we get in a tiswas about it if the professionals can't even agree whether it's a good indicator or not!

I think Tamsin has summed it up well here:



tamsinw said:


> It seems that AMH it causing a lot of women confusion and anxiety without good cause...


xxx


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## H1

Thanks for the information.

My AMH level came back at 0.9 this year.  I've been told by a local private clinic that I'd be wasting my money going for treatment as there is no chance of conceiving!  and that only option is to consider DE route. 

I'm looking at my options.

Jurys out on whether AMH level can alter at all?


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## Candee

My AMH was 5.4 in Jan and I was told not to go for IVF as I would be wasting my money.
It was awful to get these results. I was told them first over the phone, by a nurse, who
said "sorry, the result is very low, very disappointing", a month later I saw the
Consultant who told me _*not*_ to go for IVF. He seemed to have no uncertaintly whatsoever
about what my results meant. I am a complete novice with all of this and just trusted
that the Doctor knew his stuff and believed him that the test was completely conclusive.
I saw another Doctor in Czech Republic and he also said that with these results the chance 
of a pregnancy was very small, although he was prepared for me to give it a go. In the end
I decided to go for donor eggs. Reading these posts has left me in a right state  I thought
that AMH was an accepted indicator of fertility.
Candee


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## annacameron

H1, some good news - your E2 is irrelevant at 480 by the way. day 21 E2 means nothing. it is day 3 you want.   it is low!  xxx


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## Guest

All I will say is PLEASE PLEASE try one IVF cycle at least with your own eggs before doing DE or being told to give up just - so you can be sure at least.....I am convinced my AMH is below 1 (though never tested) and I know I get eggs!


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## scoobylooby

Hello girls!

Very interesting reading your posts. I have spoken to LJ a few weeks ago.

My AMH was 0.3 last November and my highest FSH 23. ( taken day 2, 2 months after ovarian surgery) I too was told not to waste my money on IVF and that no amount of drugs would make me produce eggs. I decided to give IVF a bash and One ovary responded. 4 eggs collected, x3 grade 1/2 embies made. Sadly no pregnancy...but hey...not exactly a no hoper!! I have now seen my consultant and he agreed, with those blood results, my response was pretty good! We are going to retest my AMH, FSH etc and  see what they are doing now (although lets face it..you can't get much worse than 0.3!!) 

The plan is to try another IVF in July all being well. Strange really, as i was planning donor egg IVF a few months ago. 

All i can say to any lady out there is...if you feel you want to give it a try, then do!  This is not an exact science by any means... i will be v intersted to see if there is any change in my AMH. 

It may be that i cannot get pregnant with my own eggs...but while there is hope i'm prepared to keep going...for now anyway! 

Best of luck to you all xxx


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## Jumanji

Scoobylooby - even though you weren't lucky this time your response shows you do have eggies and you got a trio of great embies!

Lukey - my sister never knew her AMH either but given her FSH it was almost certainly on the floor!  These results are not the absolute that some docs seem to think.


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