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Single embryo transfer & advanced maternal age: how to succeed?

Esther Marbán, MD
Gynecologist & Fertility Specialist at Clinica Tambre, Clinica Tambre

Advanced Maternal Age, Success Stories

From this video you will find out:
  • What is the definition of advanced maternal age?
  • What are the effects of advanced maternal age on pregnancy?
  • How does age influence a woman’s ovarian reserve?
  • What is the correlation between oocyte euploidy and maternal age?
  • Is single embryo transfer always recommended in patients of advanced maternal age?

Should patients of advanced maternal age only transfer a single embryo?

During this live session, Dr Esther Marbán, Gynaecologist & Fertility Specialist at Clinica Tambre, Madrid, Spain talked about advanced maternal age, explained why single embryo transfer is recommended. Dr Marbán walked through her past patient success story from the diagnosis till the pregnancy.

Should patients of advanced maternal age only transfer a single embryo? - Questions and Answers

I am 38, and my first IVF cycle produced 12 follicles. Only one egg was retrieved, and this did not make it past day-2. I was told I had cysts that are formed. In my next round, I have been recommended mild IVF. I have a fibroid that is 10 centimetres outside my uterus. Would you recommend single or double embryo transfer?

Normally, I recommend a single embryo transfer, so it is true that in the past, we knew that if we transferred 2 embryos, maybe 1 embryo could help the other embryo to implant. Nowadays, it’s known that if the embryos are good quality ones, in the end, we are increasing a twin pregnancy. Especially if you have a fibroid in the uterus, it’s outside, so it’s not supposed to affect implantation, but in the end, if you have that fibroid, I would also recommend just doing a single embryo transfer.  

In general, we always recommend doing a single embryo transfer if the embryos are of good quality.

I’m 40, and I have 2 frozen embryos when I was 40. Do you recommend other IVF procedures before I proceed with the transfer, given that at 40 most embryos can be genetically abnormal? The embryos have not been tested. Also, do you recommend implanting 1 at a time or both of them at once? The frozen embryos are day-3, I was told it is best to freeze day-3 embryos if I only have a few. They told me that they were grade 1 embryos. What chance do these embryos have to reach the blastocyst stage?

We know that approximately 50% of the embryos that starts developing on day-1 reach the blastocyst stage. However, this is in general, so it’s impossible to know how the embryos may develop from day-3 to day-5. We already know that in most cases, when a male factor occurs, it could affect embryos from day-3. If there is any problem with the sperm, it’s quite typical that the embryos stop their development from day-3.  That’s the reason we normally recommend culturing them for all our patients. It’s about getting an idea of how the embryos are developing. That way we can transfer the embryo that could have good chances of implantation, if possible.

Regarding transferring 1 or 2 embryos, as I’ve mentioned before, it’s true that the implantation rate in patients over 40 are not high, but I would recommend doing a single embryo transfer anyway because if there is any chance of having a twin pregnancy at that age, it’s not good news. If possible, I would suggest doing a single embryo transfer. I would say that is recommended almost for all patients, but especially for patients of advanced maternal age.

We have 2 tested (normal) frozen embryos after 3 egg retrievals. My lining is thin due to D&E in February. Any recommendations to help improve the lining? We are considering PRP this month, I’m 39, I was diagnosed with unexplained infertility.

Some procedures may affect the endometrial lining, it’s difficult to make it grow, but it’s possible to use different protocols. We can add aspirin, pentoxifylline to try to make the endometrium thicker.

We have different protocols, including estradiol, and it’s also possible to perform a mild stimulation in the ovaries so that all the hormones that those ovaries will produce could also impact the lining and help that lining be thicker.

My biggest problem regarding embryo transfer has been thin endometrium and its quality. It does not grow to have a trilaminar structure, even though I have used 8 mg of Progynova per day. Do you have any suggestions on what could help to achieve a trilaminar structure of endometrium? 

It’s important to consider performing additional tests in patients with thin endometrium. It would be good to do a hysteroscopy to make sure there are no other issues with the uterus. Sometimes, we find that the cavity is not big enough, or there are other alterations in the uterus, etc. It’s significant to double-check that.
If that is fine, as I’ve mentioned before, we can do stimulation with low doses of gonadotropins to try to make it thicker.

Apart from Progynova, it’s also possible to use the protein vaginally, and sometimes we need to add aspirin in lower doses, also Pentoxyphiline or vitamin E. We try to add different medications that may affect endometrial lining. However, it is true, sometimes it’s difficult to make the endometrium grow, but we do have different ways of improving that.

If a woman ends up getting pregnant naturally before going in for IVF, is there anything she can take to maintain that pregnancy, such as progesterone? Any recommendations when progesterone levels are low?

Normally, when a woman gets pregnant spontaneously, the progesterone level should be normal otherwise, that pregnancy wouldn’t develop. occur. In patients with previous miscarriages, we sometimes use progesterone to support the luteal phase a bit. Also, progesterone could affect uterine contractions.

In general, when a patient gets pregnant, we just need to do the scans but nothing special because we know if a miscarriage is happening, we can’t do anything to avoid it. It’s possible to use progesterone in a very specific group of patients, but not in general.

What are the rates of single versus double embryo transfers in patients over 40? Is single embryo transfer always recommended?

It depends on the quality of the embryos, on the personal history of that patient, the number of previous attempts, etc. It’s also important to know if the embryos are blastocyst or day-2, day-3 embryos.

Many factors could affect the implantation and the implantation rate. In general, if we have a good quality embryo, especially if that embryo has been previously tested with PGT-A, I would recommend doing a single embryo transfer. If we are talking about an embryo on day-3, maybe of not very good quality, and if it’s the third attempt, I would possibly be more flexible, and we would transfer 2 embryos. However, there is a very small group of patients where it would be recommended.

In our clinic (Clinica Tambre), we always try to have embryos on the blastocyst stage, and it’s quite typical to transfer just 1 embryo despite the embryo not being tested.

How often does a single embryo split?

It’s not a common situation, but of course, it’s another reason why we recommend just transferring 1 embryo. I don’t remember any patients in the last year that had a situation like this, but of course, it may happen.

What is the suggested vitamin E dosage per day if I would use it to boost the growth of the uterine lining?

We normally recommend between 400 and 800 mg every day, so the most typical dose is 400 mg of vitamin E every day.

I’m doing acupuncture to help with a thin lining, how can we prove this is helping if I’m taking vitamins at the same time?

The main problem with acupuncture is that we don’t know the effect it may have. There are no major clinical studies done to prove that.

The main reason is that when a patient undergoes acupuncture, it’s quite typical to have many other treatments at the same time, and it’s not easy to know the specific effect that the acupuncture may have in the future and for the treatment.

At our clinic, our patients can try acupuncture if they want to, and it helps them to be more relaxed. I’m not sure that it could affect the eventual endometrial thickness. I would also recommend changing the protocol the doctors are using or adding aspirin or vitamin E to help the endometrial growth, but I’m not so sure that acupuncture could play a role in that specific situation.

Is PRP (plasma rich platelet) a good therapy for ovarian rejuvenation for women with low AMH and high FSH?

We are now using the PRP in patients with problems with endometrium, we are doing a study to try to see if PRP may help patients with having a better endometrium, and we are waiting for the results.

All therapies on ovarian rejuvenation are not used in our daily practice, they are used in a very specific small group of patients, and it is still done for clinical studies. There is no clinical evidence that PRP could help in that kind of patient, but of course, we need to wait for the eventual results of studies. Possibly, in the future, we will have some information that it can help, especially in young patients with low AMH value.

Can you use vitamin E and aspirin both at the same time?

That’s perfectly fine, and actually, it’s the way we always do because we try to push that endometrium to be thicker and do the transfer as soon as possible.

If my last 2 IVF attempts did not work out at the age of 43, to have a chance to conceive naturally is likely 0, right? The doctors are recommending going for an egg donor, but for now, I am not ready for it.

It’s quite likely that the embryos you had were aneuploid, and that’s their main reason. If egg donation is not an option for you, which is something understandable, and you would like to repeat embryo transfer, you could do PGT-A on the embryos.

If your ovarian reserve is low, we sometimes recommend doing a dual stimulation. It means doing the first stimulation, retrieving the eggs and 5 days later, at the same time as the embryos are being tested, start a new stimulation to get more eggs and more embryos.

It’s recommended for patients when we expect a low response because of their low reserve. The chances of having healthy embryos at that age are indeed around 10% maximum, so we should be realistic in that way, and it’s possible to try again, but we need to realize the chances are not very high.

Any other vitamins you’d suggest taking to help with lining? I’m taking vitamin D, vitamin E, prenatal vitamins and fish oil?

We know that vitamins may help our general health, but the one that has shown to have some effect on the endometrium is vitamin E. Apart from other treatments such as aspirin, sometimes we also use Viagra to try to have like a better blood flow in the uterus, and when we face a patient that has a problem with the endometrium, we try to use as many protocols as possible to try to make that endometrium grow.
The prenatal vitamins, fish oil, also vitamin D, do not affect the endometrium. They may help with helping your body to be in the best condition, but they don’t impact the endometrium.

Esther Marbán, MD

Esther Marbán, MD

Dr Esther Marbán has been part of Clínica Tambre’s medical team since 2010. She is a gynaecologist specialized in Human Reproduction with a brilliant academic career. In fact, she obtained a special honourable mention in her Master’s Degree in Human Reproduction that she completed during 2009-2010 (organised jointly by the Spanish Fertility Society and the Faculty of Medicine of the Complutense University of Madrid). Dr Marbán is known for her restless and proactive personality and her innate talent for empathizing with people which she proves every day by working with patients.
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Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing 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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