Overcoming low ovarian reserve – real-life cases

María Calomarde, MD
Fertility Specialists at IVF-Spain Madrid (Former Clinic), IVF-Spain Madrid

Category:
Low Ovarian Reserve, Success Stories

From this video you will find out:

What are the indicators of good ovarian reserve?
What is the correlation between the mother’s age and aneuploidy?
How does maternal age affect the incidence of Down syndrome?
Which IVF protocol is best for low ovarian reserve?
How many eggs are retrieved with low AMH on average?

Overcoming low ovarian reserve – real-life cases

Fertility with reduction of ovarian reserve: what IVF options are there?

In this webinar, Dr María Calomarde, Fertility Specialist at IVF-Spain located in Madrid, has talked about low ovarian reserve and provided some of her patients’ stories who were struggling with a low ovarian reserve and were able to achieve pregnancy.

Mother’s age & ovarian reserve

Dr Calomarde started by presenting a graphic where it is shown how live birth percentages decrease from 39-years-old onwards. The most important indicator of a good ovarian reserve is the mother’s age, and with the help of an ultrasound, we can study the antral follicle count. AMH test done by a blood test decreases with age, and we can see that a 25-year-old has a normal range of AMH at 5.4 ng/ml, and in women more than 40 years old, we can see that it’s lower than 1. The antral follicle count also becomes lower in women over 40. However, we can’t study the quality of the oocytes with these indicators.

Aneuploidy rate

The next graph represented the relationship between maternal age and the aneuploidy rate. In other words, the quality of the embryo depends on the quality of your oocytes and the sperm. It can be observed that until the age of 35, the rate of aneuploid embryos is established at 50%. After this, the percentage starts to decrease, and after 40s, it decreases more drastically. Women younger than 35 normally have a good ovarian response, the capacity of the ovary to provide egg cells, hence at this age, there is a high probability of finding a healthy embryo without any issues. However, over 35 years old, the ovarian reserve starts decreasing along with the quality. It is more common to have problems with getting pregnant, and there is a higher miscarriage risk. Finally, we can see that at the age of 43 and onwards, it is almost impossible to get pregnant naturally with a woman’s own eggs.

What do we mean by genetic issue? An aneuploid embryo has an abnormal number of chromosomes in a cell (46 is the usual number). For instance, if there is an alteration in the chromosome, i.e., 21, the diagnosis will be Down Syndrome. If it is in chromosome 18, then it will be Edward Syndrome, and when it occurs on chromosome 13, it will be Patau Syndrome. These 3 cases are known as Trisomies alterations. Other alterations also exist, and in most cases, those will end in a miscarriage or a negative pregnancy test.

Low ovarian reserve – real-life cases

a 35-year-old with low ovarian reserve; male partner was diagnosed with teratozoospermia, no previous IVF cycles

In the first presented case, the woman had a low AMH level of 0.8 ng/ml, and 5 follicles were found, in total. The partner was 36-years-old and was diagnosed with teratozoospermia, they never got pregnant, and they tried to conceive for 2 years, there were no previous IVF cycles. Since she had a very low ovarian reserve we suggested an IVF cycle, we started a short protocol with 5 days of Omifin and 150 of Pergoveris for 10 days, and the result was 3 follicles in development, and finally, during the egg retrieval we found no eggs, so there was no embryo transfer.

In the second cycle, we tried again with a short protocol, we prescribed Gonal-F 225 and Menopur 75 UI. This time, we got 3 follicles in development, during egg retrieval we got 1 mature and 1 not mature egg. We got 1 embryo that didn’t reach the blastocyst stage, therefore, no embryos were transferred. Then we tried with a third cycle because the patient was young and wanted to do everything as soon as possible, so we tried with another cycle. A similar protocol was used with lower doses, 1 follicle was in development, and then we got 1 mature oocyte and no fertilization, so again nothing to transfer.

By that moment, as we had no embryos, no blastocysts, we discussed what to do, whether to change to egg donation or whether the couple wanted to continue trying. That always depends on the psychological situation of the couple and the economic situation. The couple decided to try again.

We suggested proceeding with a mild-stimulation protocol, which means very low doses of medications. We started with Omifin 50 mg daily and Menopur 225 UI on the 4th day of stimulation. The result was the same, 3 follicles in development, we got 3 mature eggs, 2 fertilized, and finally, we got 1 blastocyst of medium quality. We performed a fresh transfer and the pregnancy occurred, and the patient delivered a healthy baby girl.

a 39-year-old with a low ovarian reserve and 1 ectopic pregnancy; male partner had previously 2 children, no previous IVF cycles

In the second case, the woman’s AMH was also low, it was 0.7 ng/ml, and there were 6 antral follicles in total. The partner was 41 and had 2 children from a previous relationship with normal sperm count. The female partner had an ectopic pregnancy with left salpingectomy before, then they tried to conceive for 1.5 years. They had no previous IVF cycles. The couple wanted to try IVF with their own eggs.

We suggested doing PGT-A because of the age. We started a short protocol with Pergoveris 225 UI, 6 follicles in development were found, we got 5 mature oocytes, 4 fertilized, and we obtained 2 embryos. We performed a biopsy of both of the embryos and then froze them. After 3 weeks, we got the results, 1 of them was euploid, normal, and the other was abnormal. As we had only 1 embryo, we tried to know more about the window of implantation, and we performed an ERMap test to check the receptivity, and it was P+6, which means 6 days of progesterone. After that, we did the frozen embryo transfer, and we had a positive pregnancy test and a healthy baby boy.

- Questions and Answers

What is your opinion/experience about human growth hormone for oocyte quantity or quality?

I have heard about that hormone to be used in fertility treatments, but we have never tried it because there are no conclusions in the studies. We never use that hormone to improve oocyte quality or quantity. At the moment, we don’t have treatments that can improve the egg quality or quantity. The quality is going to depend on the age also on other diseases, for example, PCOS or endometriosis is going to decrease the quantity and quality.

Do you use estrogen priming to prepare follicular growth synchronization?

We normally use that, but it’s just to prepare synchronization of the follicles and in terms of organization here in our clinic (IVF Spain). However, we don’t use this to improve ovarian reserve or egg quality.

Can you have too low AMH to get help with your own eggs?

One thing is the AMH, and another thing is the quality of the eggs. I have a patient who was 36-37 years old and with an AMH of 0.09, so very low, we got in total 2 follicles. She never tried with her own eggs, and I advised her to continue trying, and so she did, she had 1 follicle and a half, and she got pregnant the second month with that AMH. Therefore, AMH is not the only information we need, it’s not the same if this AMH level occurs in a patient at 35 or 37 or 42.

For how long do you freeze embryos (sperm donation)?

We have no limits, I think you are talking about IVF with donor sperm, in that case, you can come here, but we can’t give you a solution for your fertility preservation. We can cryopreserve your oocytes or we can do an IVF with donor sperm. We can freeze the embryos, we can go ahead with the transfer of your embryos right away or in 2 months, it is up to you. The embryos can be frozen for years.

Does higher BMI affect the quality of eggs?

Yes, what we can see in all the studies about BMI is that it affects the quality of the eggs. Overall, if you have, for example, Polycystic Ovary Syndrome (PCOS), we have seen that if you lose a bit of your weight, at least 5%, the quality of the eggs is going to improve. If you are obese, for example, we can see that the egg quality is lower and also normally, here in our clinic, we try to do the treatment for the patients who have a BMI of no more than 35. If it is more, we always advise losing weight till 35 because the risks in pregnancy with that BMI are high.

Is it common for someone to have relatively high AMH for age and respond poorly to stimulation? I am 40, and my AMH is 21.5 pmol/L. I got 9 eggs on my first cycle and 6 eggs on my second one, the same dosage (300 IU) of medication on both cycles.

9 eggs is a good number for your age, that those of 300 is high, but it is correct. I don’t know your body mass index (BMI) because it’s going to depend on that, but the doses for me are correct. I would advise accumulating embryos, to do embryo banking. I don’t know if you have a partner or not, but that’s what I would advise, and you could do PGT-A because possibly the quality is not so good.

I’m 40 with reduced ovarian reserve (AMH is 0.51, normal FSH, normal Estradiol). I had undergone two long protocol stimulation cycles in the Swiss fertility centre. During the first cycle, ovulation occurred before harvesting, and of initially 11 follicles only 3 oocytes remained. 2 could be fertilized, and 1 developed to the blastocyst stage. We did PGT-A, unfortunately, the blastocyst had too many mosaics. The next cycle was the same protocol but with additional Ibuprofen. At that time, ovaries weren’t synchronized, so at harvesting 5 oocytes were retrieved from only one ovary, 3 fertilized, 2 blastocysts were sent to PGT-A. We got 1 goody quality euploid blastocyst. Unfortunately, implantation failed. Would you recommend trying another IVF cycle with the same protocol, switching to another protocol, or considering donor egg IVF? Are there other factors to be considered, such as uterus lining or immunological factors? Would you recommend some testing for that? I already had a hysteroscopy before starting the cycles.

You have quite a common case, but you have a lot of information, so I think the best thing is to get an appointment with us. What I can see is that you have tried 2 times with PGT-A, both times with long simulation cycles, possibly in your case, you can do another protocol, it’s called short protocol with agonist, we could try that. We have seen that one it’s not good for you, but we can’t know if it’s going to be similar or we’re going to improve. We don’t know if your response is because of the protocol or the quality of the eggs. My advice is just to accumulate more embryos, at least 5-6 embryos with several cycles, and then to do PGT-A to find out if they are normal or not. We have more or less 50-60% of chances to succeed with a normal embryo. Egg donation would be easier and quicker, the success rate of the egg donation is higher compared to IVF with own eggs. We can check the window of implantation, hysteroscopy, and a biopsy also can help, so we can do a lot of things.

I’m 49, and I have only 1 year to try to get pregnant. My AMH is 0.2, I don’t have menstruations. Is it still possible somehow to try stimulating my own eggs, or should I go straight for an egg donor?

You have to go to egg donation. From 44 years old, it’s difficult. The AMH, in that case, is not important because we know that the quality of the eggs is going to be low, so in your case, it’s better to go for egg donation.

What do you recommend for patients to improve their egg quality?

The egg quality can be improved, for example, with vitamins. It’s going to depend on each case, but for example, we can try to add Metformin, if there is an overweight, we can lose weight, and that will improve it as well. A healthy lifestyle is also important, you have to exercise, a diet is not necessary but healthy food is crucial. If you have a low egg quality because of the age, there aren’t many things we can do. Another thing is, for example, endometriosis. It is difficult to improve the quality because it’s a common and difficult disease to treat.

How long does it take to see eggs forming after PRP?

Normally, we see better results after one-two-three months, we’re going to see the differences in more time but more or less 1-3 months.

During my first IVF, 12 eggs resulted in 4 perfect blastocysts. In my second IVF, 11 months later, the same protocol was used, 10 eggs resulted in 3 morulas arrested on day-6. I gained quite a lot of weight before my second IVF. If I lose weight, I can improve my egg quality? I’m 35 with unknown AMH.

Yes, I think so. Perhaps, you have a normal AMH because you have a normal number of eggs, so your AMH is possibly not going to give us more information. If you have gained weight between the first and second treatment, if you lose that weight, you might see the difference. Not all stimulations are going to be the same, it can change, the stress, for example, can have an influence, but of course, I think that that situation of your overweight has an influence.

Is mild IVF stimulation suitable for someone with low ovarian reserve?

Yes, of course. Normally, I always try with standard doses first because we have to try to get as many oocytes as possible. Normally, when we try with normal doses, and we don’t have a good response and a lot of eggs, in that case, I always advise trying a mild stimulation for a 35-year-old but also with 37-38-year-olds, I think it’s a good protocol.

I’m 43, I have a low AMH, I haven’t tried IVF yet. Do you recommend IVF for me or not?

It’s going to depend on if you have tried with your own eggs with an IVF or not. It’s also going to depend on if you are prepared, psychologically, to do several cycles, probably at least 3 to complete the embryos, to analyse all the embryos. In that case, it’s going to take another 5-6 months at least. If you want to fight and use your own eggs, because you’ll need to try without guarantees, we can’t guarantee that it’s going to work. If you have never tried with your own eggs, I always advise trying at least once to see how you respond. That way, you can also find out how many embryos you might have within a simulation and the quality of your eggs.

Where does someone go to find embryos in the preservation, and what is the cost? In the U.S.? Spain, which may cost less, I can travel to.

I think you mean embryo adoption. It’s different between clinics, so the best thing is to ask two different clinics if you want to compare the prices. Here in Spain, embryo adoption is legal, it’s anonymous, we can give you the characteristics of the donors because it’s like an adoption of a baby but with an embryo. They are frozen and are waiting for someone who adopts them, and we can give you the same race as you.

What are the advantages of Comprehensive Chromosome Screening (PGT-A/ CCS) for Advanced Maternal Age patients (+38)?

Non-Invasive Prenatal Testing (NIPT) following IVF or IVF+PGT-A, beneficial or not?

How important is male factor and how to overcome that?

PGT-A Success Stories Explained: Outcome vs total cost of IVF treatment

IVF & fertility treatment for women over 40 – what are your chances?

What to do after failed cycles and miscarriages?

Authors

María Calomarde, MD

Dr María Calomarde graduated with a degree in Medicine and Surgery and specialized in Obstetrics and Gynaecology, Dr Colmarde is a leading expert in Assisted Reproduction and one of the fertility specialists at IVF-Spain Madrid (Former Clinic). She is also the author of numerous scientific publications and has been a speaker at various courses and congresses in her speciality.

Event Moderator

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.

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