Watch the webinar with Dr. Alejandra Aguilar Crespo, a Gynaecologist and Consultant Specialist at Equipo Juana Crespo, Valencia, Spain, where she discussed how patients can achieve a successful outcome with IVF and low ovarian reserve.
What your possibilities are, we don’t know. If I don’t perform a scan, I cannot be sure about your chances because as I said before every patient is different and every patient has own possibilities. I can only tell you that at 39 years old the probability of having normal embryos is around 40%. It means that at least 60% of the embryos, which are issued from an IVF treatment would be abnormal, it means that they won’t have the correct number of chromosomes. In women who are older than 37 years old, the quantity matters. If I know that among all those embryos I will have only 40% normal embryos, it’s important to have at least more than 2 embryos. With a low AMH, which is 0.44, it is sometimes difficult to get at least 2 or 3 embryos in a single IVF.
If we see that we won’t have at least 2 good quality embryos, it is best to repeat another cycle, it means to perform an embryo accumulation to get at least 2 good quality embryos. If we have 2 good quality embryos and of course we can’t forget about the uterus, we need to see that your uterus is okay and the embryos are okay, of course, your chances of having a baby are okay. It also depends on the ovarian reserve, it depends on how the uterus is and this kind of things, but I will never ever reject any patient or any IVF treatment with a low AMH.
I’ve used that before, I’ve used that several times but there are some controversial papers regarding the growth hormone, some say that it can improve the oocytes yield and others that they don’t. Even though they have more oocytes, it doesn’t correlate with good pregnancy rates. So we’ve stopped using it because I prefer to use the DHEA because from my own experience there is more evidence regarding DHEA and we have good results with that. It won’t harm the growth hormone, this is used only during the ovarian stimulation, but it has not been demonstrated. I mean we lack evidence of that.
It depends, it means if we have a good quality blastocyst, I will put it in the patient, depending though on the patient. Depending on the age of the patient and depending on if the uterus is well prepared. Then, of course, I would prefer to put the blastocyst, which means that the embryo is more developed, also if we have 2 good quality embryos on day-3, it will probably be the same.
The answer to your second question again depends on the age of the woman. If you have a low AMH, but you are young, it means that probably your oocytes could be in of good quality, so why not. It’s better if you ovulate from the tube that you have patterned, but we can think about an IUI. If you don’t have a history of infertility and has not done a lot of previous treatments, I can go ahead with IUI. The problem is that if we see that there is a low AMH and there is a young woman – I prefer to do a cycle to preserve her embryos. Sometimes we do that because we want to preserve her fertility, we do a cycle, and then we get some embryos because if we see that she has a low ovarian reserve, and she’s young probably she will have an early menopause and if she gets pregnant with an IUI and then she comes back for the second child probably we won’t get any oocytes, so, therefore, she will be two years older and the oocytes will not be of good quality. Sometimes it’s better if we perform an IVF treatment and then if she wants to go ahead with IUI, she can. But first I want to have those embryos frozen.
Regarding your third question, well without specific findings, we don’t like to give drugs if there is no indication. Prednisolone we give to patients that have some immunity disease or they have several implantation failures. If they have any immunity status that can lead to implantation failures, such as the KIR or the HLA discordance. We can give it, but if there is a first IVF cycle, if there is no indication of getting prednisolone or granulocyte, we don’t think that this can improve the outcome, so probably we won’t give it. Only if it’s indicated.
They don’t hut the egg quality and quantity, the only thing that hurt egg quality and quantity is the age. The hormones that we use, they, don’t hurt because when we do the stimulation, we try to save those follicles that are ready to die because, in each menstrual cycle, there is only one. We have recruitment of eggs, among those eggs that are recreated only one would be in charge of ovulating, so the rest of them die. With an IVF treatment, we give hormones, we give gonadotropins to try to rescue those follicles, so there are no future implications, and with more stimulation that it doesn’t hurt the quantity and quality. It’s very important to stimulate properly, it should be prepared, we cannot forget that because the high dosage can hurt the egg quality. The egg quality also depends on when we give high doses of hormones or where we stimulate. For example in a PCOS patient when we don’t give the correct dose of the trigger or sometimes we get low-quality eggs, but this is not because we have given stimulation drugs, it is because we have not used them correctly.
On one hand, you do have a borderline ovarian reserve but having 10 eggs retrieved at 44, that’s a good result. Then it’s different because it can be a lot of causes, the first one if you have a balanced translocation we have to perform the PGS to just try to get a normal embryo and to improve the property of pregnancy, and then knowing how to stimulate this kind of patients is very important, so from my point of view, I don’t know the cycle, the doses of hormones, the levels of estrogen but for me, I think you had high doses of hormones. This maybe has not helped you. It’s very important to do proper stimulation. Sometimes even if we perform correct stimulation, we only have 2 and then 1 blastocyst. If those blastocysts are of good quality, probably that would be a good stimulation, depending also on how many eggs were mature, how many got fertilized because we have to know the whole pathway.
If you had 2 miscarriages, you should do a karyotype. If the miscarriage were because of chromosomal abnormality, you have to perform a karyotype just to confirm that you don’t have any balanced translocation. Then you can also perform the recurrent miscarriage test, it can be by a blood test so we can see if the fallopian tubes are okay, if there are no hydrosalpinx and of course we need to see your uterus because your miscarriages were caused by balanced translocation, so we have the causes of the miscarriage, but also we have to check the uterus. In your case, performing a good stimulation, not with high doses, probably 150 and 75 will be okay. Just to perform a correct protocol and to give you also other drugs to try very slowly to get good follicles and therefore good oocytes and to try to get more blastocysts. The more blastocysts you have, the more probability of a normal embryo you have. If you have a balanced translocation, you have to know that at least 25% of the embryos won’t be good, so it is important to do that.
At 40 years old having 4 abnormal embryos is what we can expect. At 40, the probability of having an abnormal embryo is at least 60-65%, it doesn’t mean that we will never have a normal embryo. The more cycles you get, the probability of having a normal embryo is higher, but I think doing another stimulation cycle sometimes it’s exhausting, sometimes it can be psychologically very difficult, so it all depends if you are open to doing another cycle.
Some papers say the long protocol used with the agonist in low ovarian reserve patients is better, but in our case, we prefer to do a personalized treatment to try to stimulate the person when the ovary is ready to get the injections. So in your case, we would try to do a cycle with different protocol to try to improve, a short protocol, but it’s difficult because sometimes it takes even a day to understand why those treatments have failed and how to manage this kind of changes and sometimes we need to think and discuss it within our team.
After all, that is what we do. Sometimes, it is very difficult to stimulate a patient properly. If you have 2 stimulations with no viable embryos, we have to change everything, we have to do a pre-treatment to try to improve the quality and also a stimulation protocol with different drugs. Also, we need to manage the stimulation to see how are your estrogen levels, if they are good etc. Having an AMH of 1.2 and having 4 embryos and those embryos reach day-5, that’s not a bad stimulation.
The problem is the chromosomal abnormality, and this is related with the age, so, unfortunately, we cannot go back to be 30 years old, so it’s difficult. We have several patients that have had abnormal embryos in the previous cycles, and then with us, they have normal embryos.
Yes, as I’ve mentioned in the presentation, there are some protocols where they explain that mild stimulation can help these patients. They think that if they only stimulate a very low quantity of follicles, so those that are growing are of the best quality, so probably they will have the best quality embryos. It depends on the patient for example if we see that we have done a mild stimulation and we have a good embryo probably we’ll say, let’s repeat the cycle because we have a good embryo. Sometimes if it is the first IVF stimulation and we see that the patient has low ovaries, but at least we can expect to have more than 2 embryos, I will go ahead with a short protocol, not with a mild one. If we see that even if we give the patient low doses, I can’t expect to have only 1 or even 2 embryos. I will try the mild stimulation, but it depends because sometimes that doesn’t have good results.
I’m not sure, I will try to find out. I’m pretty sure that the microbiota, the dysbiosis can affect the ovarian stimulation, it can affect the pregnancy rate. It has been demonstrated that when we do a stimulation cycle the vaginal and the endometrial microbiota changes. This is due because of the higher levels of the estrogen and the changes with the progesterone. In our patients, when we are performing an ovarian stimulation, we get them probiotics, and this is because we want to avoid the dysbiosis. We give them probiotics, once we are doing the stimulation, and then we change the probiotics with the vaginal probiotics for the embryo transfer. So I think it could be correlated, but I’m not sure if there is a direct cause of a low ovarian reserve. I don’t think so, this is more related to the quality and also with the fresh embryo transfer, but not with the low ovarian reserve. I will find out though to make sure.
An AMH of 3.5 depending on if it’s in picomoles or if it’s in nanograms. If it is in nanograms, it means that your ovarian reserve is really good. If this in picomoles, it is a low ovarian reserve. But it also depends on your FSH levels because if your FSH levels are not very high and we perform a stimulation, we think about your personalized stimulation protocol, I think that we will have a chance of getting oocytes. We have had a lot of pregnancies with an AMH at 0.02, but it does depend, sometimes we have to wait at least 4 or even 6 months to get at least a good cycle. Sometimes if the FSH is very high, we need time to decrease the FSH level and therefore to get the ovaries ready for the stimulations, and this takes time, but once the ovary is ready of course, we can start with appropriate stimulation, and retrieve some oocytes.
It’s difficult, an AMH of 5, I think it would be 5 picomoles, as I’ve said, it depends on your FSH levels, also depends on your antral follicle count because sometimes if they are very accurate the antral follicle and antimullerian hormone, there are some differences and when we see that there is a very low anti-Müllerian hormone, and we see the antral follicle count, the prognosis is better.
To answer the second question if you have sperm collected at least, the chances of getting embryos are high. At your age probably it’s better to have at least between 2 to 4 embryos because of the probability of embryos with chromosomal abnormalities. An AMH of 5, if this is 5 nanograms, it means it is very good because probably we’ll have a lot of embryos. If it is 5 picomoles at your age and with the sperm retrieval, you have to be aware that probably we will have to repeat 1 or 2 cycles to get between 2 two to 3 embryos.
In that case, I wouldn’t probably use high doses high. A long time ago we thought that when we give more stimulation drugs, you will respond better, and that’s not true. It has been demonstrated that in this kind of patient if we give low doses between 2 to 5 and 150, it’s better for them. We’ll avoid high doses of estrogen, and these high doses of estrogen can affect the implantation rate if we are going ahead with a fresh embryo transfer. The higher doses of estrogen can affect the uterus, so if you had an AMH of 0.52 and you got 6 eggs collected, that’s good.
When we see that at 35 years-old, 6 eggs were collected and we only got one day-7 blastocyst, it means that the quality is not very good, so in your case, I would try a different protocol with a short one or even a long one but with low doses. In a stimulation we have to take into account that in a stimulation, lots of things have to be taken into consideration, the drugs, the pre-treatment, the triggering the trigger, the dose, which we’ll be using. If we’re using LH or FSH, we have to take into account also the trigger if we are using Ovitrelle or Decapeptyl because every step matters, so we have to consider everything because if one of this step fails, the whole cycle fails.
When we’re going ahead, we need to think about the easy way or the difficult pathway. In your case, egg donation will give you a higher chance of pregnancy. It’s very high, at least 80% of probability to succeed. If you want to get pregnant soon, my advice will be let’s go for egg donation, but if you want to fight and still try with your own eggs, it would be difficult because you have to take into the account that you have only had 3 eggs on the first cycle, and then 1, it means that your ovarian reserve is very, very low, but not only that, at 41 years old we need at least 4 embryos to get a single one that is healthy, so it’s extremely difficult. If you want to go ahead, we can try to improve everything, we can try, here in our clinic the average age of the patients is 39-40, and we always want to try with their own eggs, but sometimes it’s not possible because of the quality and the quantity.
If you are open to an egg donation, it will be my advice, but if not, we can try, we have tools for low responding patients, and we can try to improve the oocytes yield, but if we improve the oocyte yield, but then the chromosomal abnormality rate is still there, it is difficult.
The IVF protocol depends on the BMI, on what we are expecting to get, on the ovarian reserve and on patients characteristics, so if I see that your AMH is very low, and you are 41, and this is your first IVF cycle, I probably would try with a short protocol, not very high doses and also I would perform some blood tests before the stimulation just to be sure that your ovaries are ready to receive the hormones, and this is a personalized treatment. It means that we will only start the stimulation protocols once your hormone levels are okay, so probably I would do that. I want to stress that here our clinic when we do the first consultation, we don’t give the treatment protocol straight away because this is a very important issue, so we need to think about that, once we have performed the scan, once we know the patient, once we know all their background, all characteristics, we think about the treatment protocol because it’s very important, and not everyone knows how to stimulate the ovary correctly.
We have to go inside the ovaries, we need to focus on that, so it’s very difficult. I cannot give you what protocol is the best for you because I don’t know you nor your background. So I’ve mentioned that I would probably use a short protocol, but sometimes if I do a scan and then I see something different, I might change my mind, so we need to be very careful with this.
Unfortunately, not. The AMH measures the antral follicles and these decrease with age. If you smoke, you have to stop because it has been demonstrated that smoke can decrease the ovarian reserve, then if you see that your ovarian reserve is very low and you don’t want to get pregnant, my advice would be to perform fertility preservation. If not, and you are looking for a pregnancy, you can go for IVF treatment. You can also take antioxidants, this is not to improve the quantity, but at least if you have a low quantity, that way you can try to increase the quality. There are no tools to improve the quantity, we’ve seen that there are some experimental treatments with ovarian rejuvenation. With this surgery, some dormant antral follicles are activated and with that, it can increase the AMH. That is in the context of an investigation. We have to perform a lot of trials regarding that.
I’m pretty fond of CoQ10 it can increase the quality, it doesn’t increase the quantity but can increase the quality of the oocytes. The diet and low carb intake, I’m pretty fond of that, especially low gluten, low lactose intakes because the gluten and lactose can provoke a bowel inflammation and can provoke inflammation of the ovaries, it can also lead to a low quality. To all our patients, I recommend, at least during the stimulation or preparation for the cycle, to take a gluten-free diet and low lactose. Sometimes, for example, women with endometriosis, when they feel that they have stomachaches etc. , and sometimes when they reduce the gluten and the lactose, they feel better, so this means that it’s working. The lipoic acid, I don’t really know, if it’s not harmful, you can use that, and vitamins like vitamin E, D are indicated for the stimulation cycle.
Two most common measurement of the ovarian reserve nowadays is the antral follicle count (AFC) and the AMH. There were a lot of previous ones that were used like clomiphene test, which is the basal estradiol. There were a lot of tests, but nowadays the most common are the ones I’ve mentioned, they give an accurate measurement of the antral follicle count and the AMH.
With an AMH of 0.20, it correlates with 4-5 follicles, so I have to be honest at 42, it’s difficult with such a low ovarian reserve, but of course, we can try, every patient is different, and we have a lot of patients that are 42-43 with a low ovarian reserve and with a good stimulation they have had 2 or 3 good quality embryos, and they achieved pregnancy, but it’s not always the case. I don’t know if you have any chance to get pregnant, I cannot tell you that you can’t get pregnant.
If you want to get pregnant quickly and soon, you can go ahead with egg donation, that’s for sure, but with your own eggs there is an option, there is not a zero per cent of chances, but we have to think of a good stimulation and to perform one, or more than one cycle because we have to take into account that if you have 4 to 5 eggs, those eggs need to fertilize if the sperm is okay at least 80% of the eggs will be fertilized, so for example, if you have 4, we will have 3 eggs fertilized in the best-case scenario, and then those eggs need to develop in embryos, so sometimes it’s very difficult because 50% of the embryos will develop until day-3 or day-5, so it’s difficult. We do have a lot of patients of your age with your AMH, and they get pregnant, so we just have to try. If you don’t try, we won’t succeed.
She was probably with medications that are in high immune super source and also high doses of antibiotics I suppose, so yes those can affect it. We have to take into account that if the body is okay if your mind is okay, the oocytes are going to be of good quality, but if there’s something wrong, we have a basal pathology, such as endometriosis, cancer, for example, it can cause the loss of quality, but I need to see the development of the embryos. I need to see how the cycle was going, so I cannot tell you that there is a 100% chance that IVF before the kidney transplant caused the poor quality of the eggs. I’m not sure, but of course, some drugs can affect the quality.
I think it’s very good estrogen level if you had at least more than 6 follicles, I think it’s pretty good. Sometimes when the estrogen is very high at the beginning, and you have a low quantity of follicles, it means that they are growing very fast and it is associated with impaired quality. It depends on your age because if you are over 37 years old, my advice would be to use a combination of FSH, which is Fostimon and LH activity, such as Menopur or Meriofert because the LH activity can increase their follicular recruitment. But I don’t think that this estrogen level can affect the embryo quality, it depends on the number of follicles, it depends on how much bigger they were, so I cannot tell you 100%.
Here we are facing a low ovarian reserve and also a low ovarian response, and then there is a problem with the chromosomal abnormality of the embryos. If you want to keep trying, I mean, of course, it’s up to you. If you feel that you can try again that you want to try and fight to try with your own eggs, you can try, but with 4 embryos that had an aneuploidy it’s very difficult, I have to be honest that to improve that, it will be very difficult, but you can try and change several things. In your case, you have to at least be open-minded regarding the egg donation because I don’t know if you will get a better chance or better embryos.
In our clinic, we perform this surgery as well to improve the implantation rate, to remove the uterine fibrosis and to improve the vascularization of the uterus, so that we can improve the implantation rate. Sometimes 20% of our patients having unexplained infertility and having previous cycles, they get pregnant spontaneously, and this is because they had a uterine problem. I cannot tell how big your chances are after the surgery exactly, but the chances increase, it’s better to do the hysteroscopy to improve the implementation than not doing it, so go ahead with that.
Yes, and they have to do it. The ovaries are more or less between 2 and 3 centimetres, and the small black area, the small black bubbles that you see inside the ovaries are the antral follicles, they measure between 2 and 9 millimetres, so they are easy to see on the ultrasonic scan. However, sometimes it’s difficult to count the antral follicle count because it depends on the cycle. If you have already ovulated, it means that one of those follicles have been already selected, has reached maturation and you have ovulated, and the rest are dying, so sometimes you cannot see. To check the antral follicle count it’s better to perform it with the period between day 1 and day 5 of the menstrual cycle. If the gynaecologist has some experience, it’s pretty easy to count the follicles.
Yes, we can do it. If you have to do that because of a genetic condition, and you have to perform the PGT-SR or PGT-M, you can do it in a single biopsy, you can perform those 3 tests. So just one single biopsy and then one same goes for the PGT-A and then with the same we go for the PGT-M.
Regarding the mild stimulation, it is a modified natural cycle, it means just to follow the oocytes, the follicle is growing by your own hormones and sometimes just push it a little bit with some kind of stimulation drugs, just a little bit. There are some other protocols with low doses of hormones. There are also different drugs, which are the Clomiphene Citrate or Letrozole that are not commonly used in a patient with a good prognosis, like young women with a good ovarian reserve and we can try this with such patients.
A mild stimulation means that sometimes we use different drugs, different conventional drugs, and also they are with low doses of hormones like 150 or even lower. Regarding the second question, it also depends because the Decapeptyl is very good to avoid hyperstimulation syndrome. Sometimes in patients that have higher levels of estrogen at the day of the trigger injection or they have a polycystic syndrome sometimes we have to use the Decapeptyl to avoid this hyperstimulation. From my point of view in low ovarian reserve patients, I prefer HCG because it can give a better maturation, nowadays, we are performing the dual trigger, which is a combination of HCG and Decapeptyl together because they do the same action but in different ways. So sometimes just to control everything, to control all the pathways, we do a dual trigger, and with that the maturation rate of the oocytes increases. In low prognosis patients, sometimes we perform a dual trigger, which is HCG plus Decapeptyl.
From our point of view, it’s better if the ovarian cyst is a benign one, I mean it is like a simple cyst or an endometrioma, and we probably would know by doing a scan that it is a benign cyst, we’d prefer not to touch it – if it’s less than 6 centimetres and it doesn’t affect the egg collection because sometimes we have to remove the ovarian cyst if it is affecting the egg collection techniques because we cannot retrieve the eggs. If we see that the cyst is very big and other follicles cannot grow because the other cyst is growing and is taking healthy tissue. In your case, if you have done previous cycles and you got blastocyst, my advice would be not to touch this cyst because if we touch it, there is a risk of getting a healthy tissue and we can decrease the ovarian reserve. At your age, if we decrease, your ovarian reserve, even more, it probably would be catastrophic.
If you had 5 embryos and 1 blastocyst, it’s a good response. It’s what we normally can expect, and there were 2 failed attempts with 2 good quality blastocyst, it can be different, but in that case, it is probably related to a chromosome abnormality. At 42 years old, at least 75% of the embryos will be abnormal.
Every patient is different, but I’m talking about the vast majority of people. We also have to take into consideration your uterus, your fallopian tubes, your endometrial lining, your endometrium was 11-12, I think it’s a little bit thick, I mean it is a good one, but from our point of view, we prefer for it to be a little bit thinner. When it comes to a natural IVF, if it would be better, it depends because if we see that the stimulation was done properly and in the end, you got 2 good quality embryos – it was not a bad stimulation. In that case, probably you will benefit from the PGT-A to be sure that it is because of the embryo. If we see that the embryo was normal, we have to go and to think about all the causes of implantation failure.
You have a donor egg who is 23 years old, it means that she will probably have excellent embryos, and then if the sperm is excellent, you will have even more good quality embryos. Then if the surrogate is health, Her uterus is okay, we are facing the best quality of everything, better quality embryos, a better quality of the uterus, so the chances of being pregnant are excellent, in that case.
The percentage depends on if we put just a single one embryo, it also depends on the endometrium, but normally with that first attempt it will be between 70-75%, then the 2nd attempt if the first fails will be 85%, and the 3rd attempt would be around 90%. I cannot tell you exactly, of course, but this is our experience.
She can, of course, but a long time ago this mutation was very controversial because nowadays we don’t treat this mutation. If we have this mutation, we give her high doses of acid folic, and that’s all. If she’s a healthy woman if she has previous pregnancies and she has a good uterus, and she’s healthy probably I wouldn’t test her.
When we are trying to conceive spontaneously we don’t even look at this type of mutation, so probably in the first attempt, I wouldn’t check it. In case, the attempt fails, or we see that there is something wrong, then we will check it but not in the first attempt.
In fact, we are carrying our own study regarding the ovarian rejuvenation, and we have promising results, but we’ve also seen a that in woman over the age of 40 years old this surgery doesn’t improve the outcome. It can improve 1 oocyte or slightly increase the quality of the embryos, but that doesn’t increase the quantity. In younger women who have failed IVF treatment or if they had poor quality embryos, we offer it, and we try it but in a context of an investigation, it means that if the woman needs any surgery because she has hydrosalpinx or she has a fibroid we offer it, we don’t indicate this type of treatment to only perform the ovarian rejuvenation because it is a surgery, it can have its risks like the risk of bleeding, so we have to be very careful with that, but if there is an indication of any surgery, we can perform it but in the context of an investigation. Our results are promising, and we do such procedure more and more, but we’re trying to perform it in younger patients below the age of 30 years old.
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