Low ovarian reserve – patient success stories

It is not very common to have 12 follicles and only 1 mature egg with AMH over 8. In this case, the problem is mostly with maturation because 12 follicles is a good number. The problem with maturation may be due to different reasons. One of the reasons is a low dose of stimulation, so follicles were not big enough at the moment of triggering. There is no information in this question, but there probably was only 1 follicle 18 millimetres, and others were like 14-15. The second reason could be not good triggering. Some patients don’t react well to agonist triggering, it is around 5% of patients. Sometimes patients don’t react well to hCG triggering, it is mostly less than 3% of patients, but it may occur. It also may be the issue between the triggering and egg retrieval. Normally, it should be 35-36 hours, but it may be a bit more individual maturation, and it may take more than this standard 35 hours. There is also a possibility of some defects inside the oocytes, and it is not related to medication, it is like an internal issue.

For the next stimulation, it is necessary to change triggering, possibly waiting a bit more between triggering and egg retrieval will be beneficial. Stimulation should be probably used with growth hormone. Sometimes in such cases, I’m using growth hormone, and we receive a little more eggs and more mature eggs, however, it may be some issue inside of follicle and oocyte, some biochemical problem, and in this case, medication will not be able to resolve this problem.

IUI is not better nor worse, it is a different method. IUI is the method where we are using sperm after special preparation, and we put it inside the uterus the moment we expect to have ovulation. The probability to have a pregnancy with IUI even at 30-35 years old mostly do not exceed 10%. Theoretically, it may work, but the problem with IUI is difficult to analyse because we don’t see the egg, we don’t see the embryo, we don’t understand if this embryo reached the blastocyst stage or not. That’s why it is difficult to say why pregnancy does not occur after failed IUI.

One IVF attempt mostly gives the same probability of pregnancy as one year of another kind of treatment. When we are talking about a 42-year-old, it’s probably better to move to IVF because there is no time to waste.

Regarding protocols, it’s necessary to see the antral follicular count at the beginning of the cycle, and if we have 3-4, we can try the stimulation with Clomid or Letrozole with FSH. Sometimes it helps to stimulate more follicles than with standard FSH. Sometimes we can use a high dosage of FSH, but if we can see only 1 or 2 follicles, it’s probably better to follow them with a natural cycle or probably give some oestrogens and check it after ovulation in this cycle or the next cycle. Sometimes we can see more antral follicles, and at this moment, we can start stimulation immediately.

We can use Letrozole, which is the medication that also decreases oestrogens and increases FSH. Normally we are using such medication for stimulation as well.

Every follicle has fluid inside. We call follicular cysts in case we don’t receive eggs. Normally all developing follicles have oocytes, so for me, triggering day 7 is a bit early, but it is necessary to see all protocols, all sizes of follicles and probably estradiol level day of triggering.

8.4 pmol/mL is a decreased ovarian reserve, but 12 follicles is a good number, so as I have mentioned, sometimes we can have an AMH level that does not correspond to the plasmatic level due to some laboratory condition. In your case, it is probably necessary to change the medication. You can use, for example, Pergoveris, and this is the medication where you not only have FSH but also LH. Urinary Gonadotrophin is also useful because they contain HMG, which has the same activity as LH. The stimulation should last a bit more than 7 days, however, I would need to see the whole protocol in detail.

It was around 10 or maybe 12 years ago, and it was very popular to prescribe DHEA, there were some publications in The United States about 1 gynaecologist who following a woman who started the stimulation for fertility preservation and receiving DHEA and a couple of months later he received a lot of follicles, a lot of eggs and it was very popular. Nowadays’s scientific works do not show there is a big influence of DHEA on follicle number, and now it is mostly transdermal testosterone proposed for that, and it seems that it is working better than this molecule.

This situation is more or less typical with patients over 40-42 years old. There may be several problems in this situation. First, with a low blastocyst formation rate, 7 MII, all fertilized by ICSI and only 1 morphologically good blastocyst means that the embryo is not developing. This may be due to some genetic issue inside the oocyte, so abnormal nucleus, but also it may be due to abnormal cytoplasm of oocytes. We know that over 38, the number of mitochondria inside an oocyte decreased dramatically, at least double when we compare it with a 30-year-old. In this case, the oocytes don’t have enough energy to develop till blastocyst.

A second issue may be a lack of ions of calcium inside the oocyte, it happens a lot more often in advancing age and with decreased ovarian reserve. All intracellular processes are related to the increasing of ions of calcium. In your case, I think will be more promising to change embryological strategy rather than stimulation. With stimulation, we can improve your response a bit with growth hormone, with a higher dosage of recombinant LH, we could probably do a double trigger hCG plus agonists, but in this case, you described the main problem it is the low blastulation rate.

Continuing with your own eggs would depend on you and your doctors. You can try to modify the strategy, for example, try Piezoelectric activation, calcium ion or spindle transfer. In this case, it is about seeing the blastocyst formation rate. It might be also good to see if your blastocyst is genetically normal and then take further decisions or start talking about egg donation.

When your FSH level is more or less normal, priming will not be very helpful, but in this case, you can try to start the stimulation just after ovulation to 3 days after. When the second wave of follicle growing starts, and probably in your case, it may be helpful.

These luteal phase stimulation protocols have the same results as follicular phase protocols in a number of eggs, quality of eggs and lengths of stimulation, the general number of FSH total dose. It has started when doctors proposed to do fertility preservation for cancer patients. Cancer patients have a very short time for stimulation, 2-3 weeks, and it is necessary to start immediately because there is no time to wait. For this category of patients, different kinds of protocols were used. E.g., luteal phase protocol, mid follicular phase protocol. Finally, it has been shown that most of the time, all give the same result.

Now luteal phase protocol is more or less a standard protocol for women with a decreased ovarian reserve, and we are doing what we call DuoStim. First stimulation from the first day of the cycle, then ovulation, egg retrieval and in 2-3, we start second stimulation. We are using twice the number of eggs, so the answer is yes, it is mostly the same.

Normally, for 5 days and then stop because these molecules decrease the level of own estradiol, and as we know, the level of FSH is regulated with estradiol, so the less estradiol we have, the higher FSH we will receive. We will use FSH, which will increase and add in FSH with injections, and we’ll receive a higher amount in circulation and more effect of stimulation.

At 41 years old, the probability that the egg will have normal genetics is quite good, but if you will try to do the same at 43-44 years old, this probability will decrease dramatically. If you can freeze extra 2-3 embryos, it will be a good idea. With AMH 2.3 pmol, you will probably have only 1 follicle during the cycle. During 3-4 cycles, you will be able to receive 2-3 three eggs and extra 2 embryos. If you have this possibility, I think it will be good to do that.

The idea of using estradiol is first to decrease the FSH level a bit. In the second phase, it regulates these waves of follicle growth. Sometimes a little amount of oestrogens can give anti-apoptotic effects, which means that follicles, even when menopause is established, they continue to grow, but they stop at some point in their development. When we add a little amount of oestrogens, androgens or some medicine that improves ovarian blood circulation, it may decrease these apoptotic reactions, and in a couple of months, we can sometimes see an increased number of antral follicles.

Even when a patient comes to see me and is in established menopause, after 2-3 of replacement hormonal therapy, which consists of 2 milligrams of oestrogens and 10 milligrams of progesterone, we can receive 1-2 follicles and 1-2 eggs. This effect does not last for years, it is probably 1-2 years after the beginning of menopause, after this serious decrease of the ovarian reserve, but sometimes it may be helpful.

With this AMH, it should be around 5-7 eggs, but sometimes the level of FSH does not relate to the ovarian reserve. Sometimes we can have a better situation than we expect to have with FSH level, and sometimes worse. It’s always necessary to check the antral follicular count (AFC), but it should be something like 5-6 eggs. 

If it is FSH 54, it is quite high, which means that the estradiol level is low and probably the cycle is very irregular, and some cycles are without follicles, 2-3 months without menstruation. In this case, we can try PRP, but I would prefer to prescribe replacement hormonal therapy first. I would recommend coenzyme q10, something like molecules that improve blood circulation, and we can also do PRP. However, it will not be very successful because of your low level of ovarian reserve.

According to hormonal level, of course, it is possible to receive eggs. The main question is the quality of your eggs, as we have mentioned, it depends on age rather than on AMH level etc. If you have done 5-6 stimulation and never had a normal embryo, good quality blastocyst, in this case, it would probably be better to move on to egg donation. If it is your first simulation, you can try it with your eggs. There is no possibility to predict the quality of eggs and embryos with hormonal level or whatever analysis, we can only see the quality after egg retrieval. Until 43, rarely 44 years old, we can receive a live birth with our own eggs, after it, it’s almost impossible.

Sometimes it is 2 mg, sometimes it depends more on how many antral follicles we can see and the patient’s weight. If you are not overweight, we can give a lower dose of oestrogens, if the weight is higher, the dose needs to be higher, it may be from 2 to 6 mg.

Yes, sometimes it may be helpful, and we have quite a lot of cases where we have mostly day-3 development arrest, and after Piezoelectric activation, we have a good number and good quality of blastocysts. Sometimes it may be helpful but not in all cases, it depends on which kind of problem we are dealing with. It’s impossible to say whether, in your specific case, it will work or not. If we take 100 cases like this, probably one-half of those cases will have a better result with Piezoelectric activation and Calcium(2+).

Estrogen priming is done to make follicles more homogeneous. The problem with starting a stimulation in patients with a poor ovarian reserve that comes on their 2nd or 3rd day of the cycle is that there are follicles, but follicles have different sizes. When we start normal stimulation, in 5 days one of them is already formed, and the other 3 or 4 start to grow. This is the main question when to do the egg collection? When we are waiting, these big follicles will be post-matured or ovulated. The estrogen priming may be helpful to make this cohort of follicles more homogeneous.

Clomid and Letrozole is another story. To make follicles grow in poor or normal responders, we should increase the basic FSH level by 10%, 20% or 30%, 30% is better, but as a minimum 10% on the basic level. Each medicine contains 75 units of FSH increase basic FSH level less than 0.8 to 1, so not very high. If basic FSH level, for example, 12 or 10, 11, 30% is 3-4, so we should give 5-6 samples of FSH so a very big dosage, and sometimes it doesn’t work. Clomid and Letrozole help us increase our own FSH, we decrease for a short time own estradiol, and your body produces much more FSH at this moment, and we add extra FSH from the outside, and we receive this increase of 30-40% easily and not with 6-8 samples per day, this is the main idea.