This time, Dr Elias Tsakos, FRCOG, Medical Director at EmbryoClinic, Thessaloniki, Greece, has been talking about AMH, what it means for fertility, and your chances of achieving a pregnancy are.
Dr Elias Tsakos is a UK-trained gynaecologist and fertility specialist; with more than 30 years of international medical experience; he is also a fellow of the Royal College of O & G in London; a member of BFS, ESHRE and ASRM; and a member of the Association of Greek Fertility Specialists.
The doctor begins the session by pointing out the importance of AMH. He says it is a marker of ovarian reserve. He and his team were lucky enough to identify this marker almost 15 years ago and because of this, they initiated some studies and added a bit of their experience and their scientific evidence to the world literature by publishing a couple of studies back in 2011.
One of their studies was on the levels of AMH, in the serum and the follicular fluid as predictors of very nice spawns and that was performed in IVF and ICSI cycles. That was quite groundbreaking at the time because, although they didn’t know about the effect of AMH on fertility, they weren’t quite sure how that would affect the ovarian response. They showed that it has a linear correlation with the ovarian reserve and the overall response to stimulation.
A similar article they also produced and published a bit later was also the relationship between AMH and antral follicle-stimulating hormone, which was the standard of an observed test at the time in the antral follicle count. Also, they checked on the correlation between those markers. To summarize, there is a very strong correlation between AMH and antral follicle count and these are the most important markers in their opinion to assess the ovarian reserve. He mentions they were very fortunate to present that, which gave them a lot of insight as to how to manage and educate patients, how to design the stimulation protocols, and how to answer some questions. They were also very lucky to be awarded for this work by the College of Gynecologists.
Moving on to a more practical part, Elias Tsakos says it is addressed for young couples wishing to have a child, for a slightly older couple wishing to have a child with their eggs; and for single mothers or single mothers-to-be.
AMH is a hormone which is produced in the female ovaries, men produce AMH as well. It’s produced by very small follicles, either the primary follicles or the preantral follicles of the ovaries. It’s a glycoprotein, and it is part of the ovarian reserve tests that they may perform. Over the last 15 years, it has acquired a lot of interest and a lot of research.
The doctor says they measure it in the blood. They take a blood test on the female. What is important about this is that it doesn’t vary monthly, so it has a huge advantage compared to FSH for example, or the LH or the estradiol. It can be taken anytime in the menstrual period, so it could be done on day two, day 10, day 20 or day 28 of the cycle without any significant variation.
Also, the units in which it’s measured are very important. Some huge variation in the results may be identified, if the units are, for example, nanograms per ml, normal values could be three to five nanograms per ml of AMH. That depends vastly on the age. And, of course, the picomole conversion is 7.14 times more. Most of the clinics in the UK, for example, use picomoles per ml, whereas the majority of clinics in Europe use nanograms per ml.
Moreover, AMH is stable throughout the cycle. This is very significant and very good in practical terms because, with all appointments and workloads, it’s not impossible to have it done any time day or night, evening, or weekend, regardless of the menstrual cycle.
According to the doctor, we cannot judge AMH without knowing the age of the patients. So, a figure of AMH of perhaps 2 nanograms per ml could be low for a 25-year-old but could be high or normal for a 40-year-old. The correlation between AMH and age should not be forgotten. Some interventions can be done to improve the AMH, and they hope that in the future there are going to be even more interventions. However, simple interventions may improve the AMH.
The answer is no. It does not correlate with oocyte quality. The AMH result correlates with oocyte quantity, with the number of potential oocytes. Dr Tsakos explains this remains a very fascinating topic because it has helped professionals to understand more the physiology of the female ovary, and also to understand the implications that different levels of AMH have on how they consult and manage patients.
It does because it relates linearly with the number of oocytes that professionals pick up after successful stimulation, and it is very well proven that the number of oocytes is related to IVF success. There’s a smaller contradiction here, although it doesn’t relate to oocyte quality, it does relate to IVF success.
If someone is 30 years old and the AMH result is low, for example, it is 1.5. does that mean that they’re infertile? Or does that mean that they need IVF? Dr Elias says the answer is no. AMH does not relate to natural conception chances.
Do AMH levels predict menopause? The answer is possibly yes. Although we cannot pinpoint exactly when it will exactly happen. So, for example, if a 42-year-old old with an AMH of 0.5 nanograms per ml, it is low, but we cannot predict if the menopause is going to happen at 45 or 47, but it will likely happen probably before the age of 50. It is a very important marker.
Dr Tsakos says AMH is a glycoprotein, and it is part of that list of ovarian reserve tests. These are the tests that aim at identifying how many follicles are potentially there that could produce oocyte material following ovarian stimulation. He highlights the biological ovarian reserve test number one is age. Elias says before professionals had those markers, the only denominator of ovarian reserve was age. Of course, this is an important denominator still now and is what doctors use in combination with the AMH results.
There are biochemical markers. AMH is part of that biochemical marker, as well as FSH. There are some dynamic and biophysical tests which are based on the ultrasound scan outcome this as the antral follicle count, and there’s the histological test. However, now, the doctor only highlights the importance of age, AMH and antral follicle count, which Elias thinks should be included in any assessment done for ovarian reserve.
Dr Tsakos continues the session by explaining the ovary contains tiny little follicles called primordial follicles, it contains small primary follicles, and a bit bigger follicles which are called preantral follicles, and it contains slightly larger follicles. All of these are lined up in the cortex in the outer layer of the ovary. AMH is produced by all of them, perhaps not all the other follicles, but all of these. and it’s produced by the little layer outside the follicle, which is a granulosa cell layer.
With this explanation, we can understand how important it is to have a biochemical marker to quantify the number of follicles that would potentially be stimulated if we choose to stimulate an ovary in the context of either an IUI or in the context of IVF.
Then, Dr Elias shows a conversion chart with rates of conversion. He mentions this is quite important because there are a lot of misconceptions. So, it’s important to look at the lab result and see exactly if it’s pickleball or nanogram that make the conversion and request the clinic to explain.
The doctor then explains egg count diminishes over time and that decline begins as early as birth. From the age of 20 or mid-20s onwards, it becomes even more pronounced. And from the age of 35, it declines even more. At the age of 40, the egg count is fairly low.
What’s important to remember at this point of the session, is that the AMH value, the normal value, the high value or the low value depends on the age. So, if somebody has an AMH of 3 nanograms, doctors cannot say if it’s normal or not. It is normal if they’re 30 years old; it is high if they’re 40 years old; and it’s probably low if they’re 19 years old. We must remember that AMH levels have to be correlated with age. At the age of 25, the standard medium is just under 6, and then it falls off further down.
What’s also important to remember is that the high range is also bad. There is a normal range, a high range and a low range. Of course, this must be calculated against age. He clarifies that, although the slide above says possibly polycystic, if it’s a high AMH, it could be an indication of an ovarian tumour. Also, with high AMH, if an ovarian tumour or PCO are excluded, it could be just a highly fertile person.
Regarding the causes of low AMH, age is the main one. Moreover, Dr Tsakos mentions there is a long list of causes that may affect the female ovary. Endometriosis is a big enemy of the ovaries and the ovarian count and AMH. Ovarian surgery is also a possible cause, for example, if somebody’s had an oophorectomy, lost one ovary or had a cystectomy which has damaged the ovary, or if during surgery there’s been too much damage on the ovary, that could affect AMH.
Genetic abnormalities, DNA-related issues, related to seriously low AMH. A pelvic infection could also affect the function of the ovary, and hence the ovarian reserve. Auto-immune conditions as well. Breast cancer is quite interesting according to the doctor because he mentions they started observing breast cancer patients when they came for cryopreservation, and then they discovered that, compared to the same age counterparts, they had in general lower AMH. And that became even more pronounced if they were older than 37 years old. Then, smoking is one of the mechanisms that affects fertility by diminishing the ovarian reserve. This becomes even more pronounced after the age of 35, causing irreversible damage to the ovarian reserve and it is reflected in AMH. Of course, chemotherapy and radiotherapy affect the ovarian reserve and AMH and hence it’s very important to preserve someone’s fertility before those toxic treatments. Dr Tsakos mentions there are some very good papers demonstrating that stress may reduce ovarian reserve and AMH levels and how stress management and cure may improve AMH levels. He also adds there are a lot of idiopathic cases that affect the AMH.
When it comes to a discussion about the treatment, there’s no drastic treatment now. There’s not something drastically professionals can do to influence low AMH. However, DHEA may be used, which is a mild hormone. Vitamin D levels are under a long discussion. For the time being, the advice is to keep vitamin D levels at an optimal range, perhaps over 30 and this may positively affect fertility. However, Dr Elias says there are some reports about a correlation between high vitamin D levels or vitamin D supplementation and a slight increase in AMH. Lifestyle, together with other lifestyle improvements in terms of body mass index, exercise, healthy diet and so on. Regarding acupuncture, there are some reports commenting that it improves stress levels and AMH levels.
Furthermore, more supplements on top of DHEA may improve AMH levels. Not as a drastic improvement, but more of an optimization, that may not be evident on the levels, but it may be evident on the response to stimulation. These days and in the last 10 years, there have been a lot of talks on the potential effect of platelet-rich plasma. This PRP treatment of the ovaries is still considered an experimental treatment. There’s no scientific evidence right now to suggest it and it should not be performed outside clinical trials. In his opinion, the doctor considers PRP perhaps not enough to improve AMH levels. Perhaps professionals need to enrich that with other substances, maybe some other stimulants of the ovarian cortex or the granulosa cells; and perhaps the stem cell technology might give doctors some more insight and some more solutions to this problem.
On the other hand, high AMH could also be a problem, related to polycystic ovaries, very high AMH levels may be related to ovarian cancer since granulosa-cell tumours produce high AMH results. But, if we exclude all of that, it could be just an indicator of high fertility.
Concerning the Antral Follicle Count (AFC), with the advent of ultrasound and the improvement of doctors’ technology, professionals take into account AMH, but they always check AFC. This is also a marker of ovarian reserve. According to the doctor, most of them agree with measuring follicles between two and nine millimetres. However, there are limitations to AFC. Some people prefer to perform it in the early days of the cycle, in the follicular phase, while others don’t pay so much attention. So, there is a little bit of variability here. However, if it is properly done, it correlates very clearly with AMH and it does have a predictive value for ovarian stimulation.
Dr Tsakos acknowledges there are pros and cons to using AFC or AMH. He thinks both should be used because, during the fertility assessment, professionals are bound to have the opportunity to scan patients and check AFC for themselves. They then confirm AMH results, and so they have robust evidence of the potential ovarian reserve and the potential response to stimulation to advise, manage, and explain their expectations.
A normal AFC depends on the age, so for a standard 35-year-old, this is a normal range. Five to nine follicles are counted on each ovary and with the new and high-tech technology, they can even colour them and classify them by size and so on.
Even if a patient had low AFC, with, for example, 3 or 2 primordial or small follicles, then this patient would still have one matured follicle. This is the reason why in the natural cycle, the reserve doesn’t matter so much in terms of natural conception rates, provided everything else is normal. What matters however is in a stimulated cycle. As shown on the slide, there is an ovary with a normal AFC with a normal AMH. If it is overstimulated, it produces all of the small follicles that would potentially become mature eggs. And that is what makes a difference in a stimulated cycle. On the contrary, if there were only two follicles and they were stimulated, they would still produce only two mature follicles. Perhaps this is the reason why, according to the doctor’s opinion, there’s no particular point in bombarding a low AFC patient or a low AMH patient with huge doses because if they only have 2 small follicles, those will grow whether you give them 150 units of FSH or 450 units.
To conclude, the doctor says we should remember that each one of us is made of one single mature egg. So we should concentrate on that egg and on the importance of the quality of that egg, which may not be related to AMH. However, it will be related to the female age.
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The straight answer would be no. However, it may vary depending on the age every six months, for example, in younger women, say younger than 35 years old, performing one AMH every year perhaps is enough. I would suggest as a screening tool to all of you to have an AMH test randomly, say at the age of 25. By doing this, we would pick up a potential low ovarian reserve, potentially polycystic ovaries, and some reasons to expedite fertility treatment or side preservation. And even if everything is normal, which is more often than not the case, we would have a comparison figure when the woman becomes 30 or 35. So, it doesn’t vary monthly, but if someone is older than 35, I would probably suggest and if they’re pursuing fertility treatment, to repeat performing a test perhaps every six months
Firstly, the standardization of AMH’s measurement took a long time to happen. So even now, as you saw in my presentation, there’s a variation in the technique of how AMH is measured and there’s also a variation in the units in which this is reported, so that could create a little bit of confusion. Equally, the question is which follicles do we measure? what machine do we have? how proficient in measuring the AFC and so forth. So, because of all of that, AMH is not 100% accurate and AFC is not 100% accurate.
So, you can also think of the combinations of those two being a little bit skewed. So, the overall assessment of which one of those has been right or wrong is the yield after their stimulation, provided that the ovarian stimulation was done correctly. So, even that is not always perfect. So, I’m sorry but yes indeed there is confusion. However, in the hands of specialists, I think the AFC is very clearly a very good tool if the specialist is using high-technology equipment and a good lab. AMH can be very accurate and if those provisions are met, those two correlate nicely.
If you’re 43 you may have normal AMH for your age, so let’s not be pessimistic. So, what is normal for a 43-year-old perhaps in nanograms perhaps 0.5 to 1, but it could be 1.2 which means that it’s very good, or it could be 1.9 or 2, which means that you may have polycystic ovaries because even at 43 you may have positive ovaries, and again I would double that with an AFC performed by an expert, to quantify where you’re standing in terms of ovarian reserve.
So, at 43 you could have a normal reserve for your age, you could have a low, or you could have a high. And then, of course, depending on the finding, we would advise accordingly. Now, if indeed you have a low AMH for your age, which means that you may have an AMH of less than 0.5, perhaps 0.3 nanograms per ml, then yes DHEA may help that, but please remember that the most important denominator is your age. So, I would not waste too much time waiting for the DHEA to kick in. I would just move on to having some sort of fertility treatment because at 43 we prefer the eggs of a 43-year-old than a 44-year-old. So, please try to balance that and, of course, do not forget all those lifestyle changes that you can make to assist your body and your soul.
There are a lot of discussions and, to be honest, we haven’t reached a consensus yet as to the exact value of DHEA. We don’t know the duration, the dose, all the side effects, and we don’t know what the exact outcome is. And equally, that applies to testosterone because DHEA is a mild androgen and testosterone is also being utilized to either improve the ovarian reserve or improve the response of the ovaries to stimulation. We don’t know very much about it, to be honest. In my opinion, we do not expect miracles from DHEA or added testosterone. Perhaps, it is advisable to be used for maybe three to six months. We would not expect huge side effects in that time and I think this is the practical advice I would give. Perhaps use it for two to three months before stimulation, but do not expect a miracle outcome from that.
I am not aware of reports or studies showing that DHEA can reduce the oocyte reserve or AMH. However, again it depends on the time, on the individual and the reaction. There’s no drug which is associated with no side effects, so I think we have to balance that. It’s a very difficult decision. There’s nothing that’s absolutely 100% safe. In my opinion, the most important factor for fertility is age, so no matter what you decide to do. Keep that in mind. Of course. do not panic, if you’re 35 it’s not a matter of months, it’s perhaps a matter of years. If you’re 30, it’s perhaps a matter of years, also if you’re 40, it may be a matter of months. I mean, try not to delay longer than maybe six months or eight months and so forth. So, it’s always a balance between what we wish to achieve, and which route we would like to follow.
It depends on the weight and of course depends on whether there are any contraindications or not, whether they’ve used it before, whether they’re aiming for a natural conception or assisted conception. For example, for somebody at 35 with normal weight, perhaps under 70 kilos, I would probably aim for a natural conception, I would give 25 milligrams twice a day for perhaps six months. If they have no side effects, I will consider extending that a bit longer. For someone embarking on fertility treatment, I would probably give a slightly higher dose of 25 milligrams three times a day if the weight is normal, and I would do that for about three months before stimulation.
We could have a two-day conference talking about endometriosis, which is something that we should not forget. I will give you a little bit of a long introduction. I have been fortunate enough to have been in this field for almost 30 years. In the early 90s, we paid a lot of attention, excluding endometriosis, to performing laparoscopies before IVF to complete the diagnosis of fertility. Now, as we moved on to IVF, we discovered that IVF can be very successful even without a laparoscopy, even without putting our finger to see whether it is endometriosis or not. We left a lot of areas uncovered. So, in my opinion, now we’ve moved on to the other side.
We’re doing very little investigations, and I think my webinar in a couple of days will focus on some surgical interventions that perhaps we may need to start reconsidering. So, the ultimate test for endometriosis is a laparoscopy. There’s no other way we can be 100% sure if someone is having endometriosis or not. Now, the effect of endometrial fertility, I think is well known, it does affect fertility by multiple mechanisms. One of them is diminishing ovarian reserve. The main issue with endometriosis is the silent epidemic. Unless we have a look inside, we cannot diagnose it. We may suspect it by the symptoms, for example, pain dysmenorrhea, painful intercourse, a low AMH or lower ovarian reserve on the scan which is not otherwise explained. But we may have no clues about it unless we do a laparoscopy. So, I think we should remember laparoscopy and hysteroscopy. We don’t diagnose individuals with hysteroscopy, but we should remember the endoscopic tools to assess and optimize the pelvic organs of the female before embarking on more complex treatments like IVF, especially for younger women. So, a woman younger than 35 with unexplained infertility deserves a laparoscopy to exclude endometriosis.
You are one of the very standard cases of someone at 37 with low AMH. I would suggest firstly investigations. Have a karyotype. I would like you to exclude genetic disorders. Also, make sure you have your breasts checked because as I mentioned it may be associated with breast cancer, very unlikely, but please do not forget that. Check for autoimmune disease, thyroid antibodies, and TSH, make sure you don’t smoke, that you have a healthy lifestyle and reduce your stress as much as you can.
Once you’ve done all of this, I would suggest you have just natural cycles. In my opinion, there’s no point in stimulating your ovaries if you’re only producing one egg because, as I showed on my slide, you probably have one follicle. Every month, find a friendly clinic where they can give you a little attention, perhaps give you a package. Be prepared that maybe in six months, you may just collect four eggs. Have them fertilized and grow them to blastocysts. And then, once you have a healthy blastocyst, have an implantation. If it’s a fresh or frozen cycle, it doesn’t matter. As long as the lining of the cycle that you produce the blastocyst is normal, and as long as the hormonal levels are normal, as long as you don’t have abnormal progesterone levels, for example, that would adversely affect the implantation. That would be my advice, and please remember that all of us in fertility and all the embryologists prefer 1 embryo at 37 or 1 egg at 37 rather than 3 eggs at 40. So, use the advantage of your age which is still manageable and keep going. I’m very hopeful that you will make it and when you’ve made it drop me a line and let me know.
This is one of the big mysteries that we face every day. Essentially, there are two protocols, simulation protocols. One is the standard long protocol. In general, if you use the long protocol, it’s more likely that you will have aligned follicles because it regulates the follicles, brings them to more or less the same size and then, when we start stimulating them, they seem to be more aligned, and if you’re a standard normal responder, if you say a 35-year-old with normal follicle count or a 30-year-old or 25-year-old or a 38-year-old with normal follicle count and normal responder patient, with the long protocol and the same dose of stimulation like FSH at 250 units or 300 units depending on your weight, you will probably produce more mature follicles with the long protocol through the alignment of the follicles because of the down-regulation.
However, if you’re not in this category, and you use the antagonist protocol, I think it’s very important to have a baseline scan where you need to ensure that you do not have any leading follicles, beyond 10 11 millimetres when you stimulate because if you do, the leading follicles suppress the smaller ones and this is the reason why you get discordant growth. However, if you’re a normal responder and if you’re producing 5 or 10 follicles and 10 mature oocytes, then I don’t think it makes a huge difference.
The answer is no. However, the protocol we use and how we manage the stimulation may do so. So, for example, the quality of eggs depends vastly on your age. This is the number one denominator of the quality of the eggs. How we manage stimulation also has a lot of tricks and tips. So, it is important to manage it properly. For example, if we overstimulate the ovary, perhaps that may decrease the quality of the egg and the quality of the endometrium sometimes. Again, the definition of hyperstimulation can be very complex and very confusing. When we add the antagonist, this is very curious and very variable.
Some people use the fixed protocol, some people do baseline scans, some people don’t, some people measure hormones every single time they do a scan, some people don’t, some people measure hormones twice a day during stimulation, and some people don’t measure at all. So, suboptimal ovarian stimulation may decrease the quality of the eggs, that’s my clear answer. The main reason why is either there’s a prolonged stimulation which over-matures the follicles or a very early trigger, which under-matures the follicles, and then we have immature follicles. The common stimulation challenge we’re faced with is when we’re afraid of hyperstimulation, especially on an antagonist protocol, and we reduce the stimulation of FSH. This totally burns out the follicles, and this may greatly reduce the quality of the oocyte we retrieve. So, let’s not underestimate the importance of stimulation, the importance of very tight protocols in our stimulation, and the importance of perhaps performing a few extra tests that may give us some more insight and some more understanding of how we should manage that very important period of the IVF treatment.
Use the long protocol, which is the most effective way. Then, the second option would be to use a very short contraceptive pill dosage before the antagonist protocol, perhaps for two weeks. The third option would be a natural cycle if you’re willing to use the antagonist protocol. Ensure that you have a baseline scan which is normal and the baseline hormonal test which is also normal before you start the stimulation.
Yes, most of the clinics would do. Remember that we prefer one egg at 30 rather than two or three eggs at 40. So low AMH means that you can conceive naturally if everything else is normal. If you have normal tubes, a normal uterus, a normal hormone profile and normal sperm. So, do not forget that if you don’t conceive naturally and if you move on to IVF, you will be given mild stimulation which may produce two or three mature oocytes, maybe four if we’re lucky and that will give you a very good chance of pregnancy. Make sure you have your diagnosis correct. Make sure you have looked for possible causes for low AMH, as I mentioned before. Make sure you’ve excluded genetics, infections, and autoimmune diseases. Make sure you’ve taken a little bit of add-ons, and I’m sure you will achieve it, and most units will celebrate with you.
This is an issue. Then, whether we move or not blocked tubes, is another big subject which I would like to discuss in a later webinar where I would like to share with you my experience with the new era of laparoscopic surgery, which involves robotic surgery, Da Vinci surgery. Let’s remind you all that IVF was invented 30 or 40 years ago because of our inability to treat tubes. We were unable to operate on tubes successfully and produce a successful pregnancy, and this is how IVF evolved. Up until the early 90s, most of us tried to fix tubes through laparoscopy. Laparoscopy became very popular. the technology improved; our skills improved.
However, tubal surgery although more successful than in the 70s or 80s, still with laparoscopy was not that successful. However, now with the advent of Da Vinci robotic surgery, through which we can do even more precise surgery, and we have a better view, better equipment, and a better approach, perhaps removing the tubes is not a way of road if the tubes are damaged. So, my advice is exploring the option of whether you would be suitable for perhaps Da Vinci tubal restoration or tubal surgery. Of course, if the tubes are severely damaged with endometriosis, then yes indeed they’re better off removed, but please look into the benefits of da Vinci’s robotic surgery for complex fertility tubal issues like yours.
The answer is no. As I showed on the slide, think of the ovary that contains one little leading follicle and three or four smaller follicles. So, every month in a natural cycle, the small follicles are wasted anyway. So, stimulation doesn’t waste the follicles. It may use the follicles that would be wasted otherwise in a natural cycle, so the clear answer is no. It would not cause a decline in your ovarian reserve.
The answer is yes. Let’s not discriminate against the people who either chose not to be vaccinated or they could not be vaccinated, or their turn has not arrived yet, or they have allergies and so forth. The answer is yes. We have instituted for just over a year now that anyone who’s attending the clinic for IVF is having a PCR COVID test, and the same applies to male partners. We all take the necessary measures and precautions and based on that we proceed with treatment as normal.
AMH is not written on stone. So, please do not take it for granted. So, for example, as I said, there’s variation between labs. It’s not the end of the world. And also, just by itself, is not the absolute figure that we should be focused on. Please correlate the AMH with your AFC, with your age and so forth. We have seen increases without doing anything. It means perhaps that the lab or another lab gave us a different outcome, or it may mean some lifestyle changes that a person did have an impact on. Stress management may improve AMH levels. So, let’s not focus on the figure. AMH is just a general indication of the ovarian reserve. It doesn’t answer the burning question, “Am I going to get pregnant naturally?” “Am I going to get pregnant through IVF?” It’s just giving us a rough estimate, not a clear estimate of how many mature oocytes are going to optimally produce if we optimize our stimulation techniques. That’s it. Nothing more than that. So, try to do all the lifestyle changes, take some vitamins, some supplements, perhaps a little bit of DHEA and hope for the best. But do not keep this AMH figure in front of your eyes all the time. It is an indicator. It’s not by itself the answer to whether you’re fertile or not, or whether you’re going to achieve a pregnancy or not.
I wouldn’t take DHEA; you don’t need it. Your AMH is normal to high. So, I would have a pelvic scan to measure AFC, and I would question a little bit the possibility of maybe having polycystic ovaries. But again, polycystic ovaries are not the end of the world. It’s very common, especially in the south of Europe or in the Indian subcontinent. It doesn’t mean anything my mother had endometriosis and polycystic ovaries, and it didn’t mean anything. She had a little bit of scanty periods and a little bit of pain with the cycle. Please do not label yourselves. So, if you’re suffering from infertility of some degree, you’re bound to have a little bit of an issue with some of those.
Just listen to your fertility specialist, I’m sure they can advise you and make sure you correlate your AFC with your AMH. Double-check it with a scan that it’s right. So, with an AMH of 3.38, I would probably expect you to have maybe eight follicles from its side, so double-check that with a scan.
First of all, congratulations. You did the right thing and congratulations for producing 16 mature eggs. Of course, I would strongly agree with your Australian doctors, and you did the right thing. You don’t have to worry about it at all. This stimulation has not reduced your ovarian reserve at all. It hasn’t reduced your chance of conceiving naturally. So, carry on with your life with the security that you have frozen eggs in case you need them. I would still perform a couple of tests to see if there’s any genetic link and that would give you some insight into your health, not just your reproductive health. So, I would check maybe the karyotype, a full thyroid screen, as a start, and retain a healthy lifestyle.
I’m afraid no medication could help you get rid of the cyst and 6 centimeters is a pretty big cyst, so I would follow the gynaecologist’s advice initially. I would expect them to perform a couple of blood tests, some tumour markers, perhaps some hormonal tests and some specialist ultrasound scans, and following this they would probably advise on some sort of surgical intervention. If it’s a simple cyst containing clear fluid with everything else normal, maybe a vaginal aspiration could be an option, of course with some pros and cons, and with the high possibility of the cyst growing back in, and, of course, the standard gold option would be a laparoscopy.
I would start by considering, to be honest, that based on your low AMH, one-year infertility and your age, I would still perform full investigations for low AMH but for the rest of fertility issues as well, and yes I would probably start considering IVF with optimism because of the age is more important than AMH.
It’s still under investigation. But yes I have heard positive things and I have heard some doubts, so I think we still need to wait and see.
I’m sorry, but I cannot answer this because I would need more details on your history, your age, the stimulation protocol they used and so forth. All I can say is that we do see a lot of variation between cycles, and even with the same dosage and the same protocol, we do see a great variation from cycle to cycle. This by itself is a sign of perhaps reduced oocyte quality, but given that your age is reasonable, I would just keep trying. You may be lucky. You may get more good quality eggs. It’s not the end of the road if you only have two.
Then, the question is how long do we try for? Since the topic is low AMH, all I have to say is that low AMH combined with advanced female age is producing very poor results, either through natural conception or through IVF. And my advice for couples is that they should be aware of the option of egg donation. Although, there are some pros and cons. There’s a lot of counselling that’s involved and so forth. It should be discussed, in my opinion, as an option, especially for women with multiple failures of IVF or women of advanced reproductive age, over the age of 40 with low AMH, over the history of failed attempts. Egg donation has evolved amazingly in the last 10 years and is providing us with another valid, very safe and successful option for our patients with low AMH.
To be honest, at 45, I think you’ve done the right thing. I don’t think you can do much more than that. PGT-A testing is necessary because I’m sure, as you have found, most of the embryos at your age would be damaged, DNA damaged. That would be my advice. As I said before, I don’t know what options you have been cancelled about, but maybe at 45 with three failed IVFs egg donation would also be one of the options to be discussed.
The answer is maybe in Greece, hopefully this year. There are a lot of talks now between the fertility specialists’ associations and the government to increase the upper age limit to 52, to 53, but because of COVID, we haven’t had an answer yet.
Tricky question. I don’t know is the answer. But that was an observation that stemmed from our attempt to perform fertility preservation for breast cancer patients. So, we found that the cancer status was associated with low AMH. But I’m not aware of the mechanisms for which this is happening. However, this is making it even more crucial the discussion and the counselling in regard to fertility preservation for breast cancer patients and, if someone has unexpectedly low AMH levels, it may be worth screening for breast cancer.
Now, you’re learning the tricks of the trade. In my practice, I do not check for testosterone. I don’t think it’s necessary. Although, as part of the work up, the pre-ivf testing, I would, and I do, but not in the IVF cycle. In the IVF cycle, I always do a baseline scan on day 2 or day 3 of the cycle, and certainly before the onset of stimulation, during that assessment, I would check for progesterone, estrogen, and estradiol to be exact. If this is combined with a normal scan result with no cysts and a nice thin lining of the uterus, then I would start stimulation.
Again, in my practice, we do very intensive monitoring, so every single time we perform a monitoring scan for follicular growth assessment, we perform progesterone, and estradiol. If I were to cut corners and if I were to pick and choose, if I were to save some trouble from doing too much hormonal assessment, I would definitely keep the progesterone, estradiol and on the baseline and also keep the progesterone measurement just before the trigger because we need to ensure that progesterone is kept at bay and therefore that the endometrium is not adversely affected by high levels of progesterone.
Tricky question. My suggestion and advice would be to grow the embryos to the blastocyst stage. This is becoming more or less the norm for the majority of our patients, but with the lower sperm count and with someone at 40, I would like to see blastocysts before I implant them. Then, of course, your chances would depend on whether you would perform PGT-A on those blastocysts or not, and on how many blastocysts you would use, if you produce any because, sadly, you have two adverse factors for producing healthy blastocysts.
One is the low sperm count and the other is your age. Having said all that, if everything else is satisfactory, if your skin is normal, if your hormones are fine if you have a normal weight with no history of smoking or any bad habits and so forth, I can’t see the reason why you can’t produce perhaps 5, 6 or 7 healthy eggs, and I can’t see why you can’t produce maybe one, two or three healthy blastocysts. Again, all of this would depend on whether you have a transfer of euploid blastocysts or not. So, worth trying, but aiming at creating blastocysts, plus or minus the genetic screening.
