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Oocyte quality – factors to think about after failed IVF #IVFwebinars

It may surprise, but oocytes are the rarest cells of the human body. The most rapidly ageing as well. They are the key issue for fertility. Both with spontaneous and assisted reproduction. From that perspective, all the factors affecting oocytes are the biggest concerns along the IVF process. As their quality is crucial for infertility treatment, it’s very important to know that it’s not only a matter of a medical laboratory. Also, we as patients and our lifestyle play a huge role here.

So with this in mind, we have a webinar with Dr Natalia Szlarb from IVF Spain, who will explain what aspects related to oocyte quality doctors focused on most and patients should be aware of. This webinar is just for you if you have experienced infertility issues or IVF failure. Maybe you wonder what problems can be caused by low-quality eggs and what impact this fact has on the whole IVF process? Is woman’s age important at all or there’s no such indication?
You will find answers to all of these and many more questions in the recording of the webinar presented by Dr Natalia Szlarb, Medical Director at IVF Spain. If you’d like to ask your question feel free to contact us or join our next live event – every Tuesday at 8 PM [London time].

Oocyte quality – Questions & Answers

Question:

Will Brexit have an impact on UK citizens seeking treatment in Europe? What changes, if any, might Brexit bring?

Answer:

Thank you for the question. After coming back to Europe after 20 years I have seen massive positive change in Europe, with countries opening up their borders. My hope is that despite Brexit, borders will stay open for medicine and that patients from UK will be able to come to IVF Spain just like any other EU citizen. As an American citizen, I was still able to stay in the EU for up to three months – so even though you will be outside of the UK, you can stay in Spain long enough for us to plan not just one, but three cycles. We do however expect the British Pound to go down following Brexit, so finances might become an issue. Personally, I believe in medicine without borders – everyone should have the same level of access to specialist treatment, no matter where you come from or what language you speak.

Question:

Can gluten intolerance affect egg quality or cause implementation failure?

Answer:

There are no evidence-based papers published that link gluten intolerance and poor egg quality. Implementation failure is most commonly a result of three factors: the egg quality, your endometrium receptivity and endo-immunology.

Question:

Do you provide Skype consultations? How much does it cost?

Answer:

Of course, we provide Skype consultations. I can’t imagine patients coming all the way from the United States, Canada or Australia for a first consultation. Drop an email to patients@ivf-spain.com to schedule a full one-hour consultation on Skype. Make sure you provide all your medical documentation so that the doctor we assign to your case has the time to familiarize themselves with your case before the consultation. This service costs about 150 EUR.

Question:

Why do you only recommend egg donor treatments instead of PGS for patients over 42?

Answer:

From my professional experience of working in Berlin, pregnancy rates between the ages of 35 to 42 are too low to recommend going forward without additional genetics work. On the other hand, doctors in the United States are reluctant not to perform cycles without any genetics work, because if a miscarriage as a result of a genetically abnormal embryo can result in a lawsuit. If you’re over 42 years old and want to go through with an IVF treatment using your own eggs I’ll be more than happy to support you – however, be aware that while it is possible to carry such a pregnancy to term, statistically it’s very unlikely, which is why for patients over 40 we recommend egg donation.

Question:

Do biopsies have a negative effect on embryos? Wouldn’t it be better to implant embryos without DGP and then analyze the DNA in the maternal blood when a pregnancy occurs?

Answer:

This approach is problematic, because if a genetic disorder – for instance, trisomy 13, 18 or 21 – is detected during maternal blood testing, you would have to recommend an abortion to the patient. The current approach, which involves freezing embryos for testing actually improves success rates because it allows us to know for certain which of the embryos is most likely to result in a successful pregnancy.

Question:

I am 42 years old. My first ICSI cycle resulted in two grade 1 embryos transferred, which led to an ectopic pregnancy. The second cycle resulted in three embryos but failed to progress on the second day. I would like to try another cycle using my own eggs. Is there anything I can do to improve the number of eggs with low AMH?

Answer:

Low AMH tells me there’s an issue with your ovarian reserve. The dose of hormones you receive during your next cycle has to be adjusted to match your AMH. Some low AMH patients experience more success with a smaller dose of hormones. However, if your embryos cannot achieve the blastocyst stage, this means your egg quality has deteriorated to the point where the only viable option would be egg donation.

Question:

You say that you recommend genetic tests in women that are over 35, but is there an age where DGP or PGS becomes obligatory?

Answer:

Sometimes we do genetic testing for patients as young as 27 – for example, if they have had three or four failed cycles in their home countries, as a specialist I need to know why those cycles failed. While genetic testing is never truly obligatory, we strongly recommend them in cases such as this, because it’s pointless to attempt a process that has already failed several times – something has to change, and DGP and PGS allow us to give you a different way forward.

Question:

Referring to your slide about embryobanking and PGS – do patients need to meet all three indicators, or is one enough to participate in embryobanking and PGS?

Answer:

You don’t need to meet all three indicators to have embryobanking recommended to you by your doctor. If your AMH is low, for example, and you’re not able to generate enough eggs, that’s when I would recommend it to you. There are many scenarios in which it becomes a viable option – make sure to talk to your doctor.

Question:

Is the success rate of egg donation independent of the age of the patient?

Answer:

Yes, it is. Egg donation success rates are the same if you are, for instance, 35 years old and you experience ovarian failure or if you’re 50 years old and have gone through your menopause. As long as your uterus is working and doesn’t have any anatomical abnormalities like fibroids, polyps, clotting issues etc. your pregnancy rate would be around 70% with blastocyst, independent of your age.

Question:

Besides AMH, what other tests should we do to see if using our own eggs is possible? I’m 45 years old.

Answer:

We should do a cycle. If you have low AMH, but can generate blastocysts and you develop genetically normal embryos, you can become pregnant by your own eggs. AMH only tells us how many eggs we’re going to generate. However, I would need to see those eggs in a lab to measure their quality and ascertain whether or not they’re going to get to the blastocyst stage. By performing a cycle, we can see if it’s possible for you to become pregnant with your own eggs.

Question:

Does AMH involve the egg quality in women under 30 years of age?

Answer:

No. AMH only tells me how many eggs we can generate. It does not tell me how strong the eggs are.

Question:

Why are the blastocyst percentages higher when patients have 7-10 embryos rather than 4-6? Does the number of embryos affect their quality?

Answer:

Statistically, the more embryos I have, the higher the probability of finding a genetically normal one. The number doesn’t affect the quality, it affects the statistical probability of finding a good embryo for someone who’s over 40 years old.

Question:

I am almost 43 years old. I have been diagnosed with PCOS. My AMH level is 16; I had two failed IVF cycles with my own eggs, eight of them were fertilized with five reaching the blastocyst stage, but only one was good enough. Two embryos were eventually transferred, but it didn’t result in a pregnancy. The second treatment resulted in two eggs being retrieved, but they were of poor quality, so no transfer. I started a course of 1500mg of metformin six months ago and last month I went down to 1000 mg. Considering another IVF cycle – should I use my own eggs again, or should I go for egg donation?

Answer:

This breaks my heart. This type of treatment is what we used to do at IVF Spain over 20 years ago. These days, we use our own in-house protocol for treating patients with PCOS. With an AMH as high as yours, you could be an egg donor. However, we have to be mindful of egg quality. With a mild treatment and an antagonist (to avoid overstimulation), we could expect over 20 eggs. These eggs, however, are not guaranteed to fertilize well. Usually, for five embryos the success rate would be about 50%. However, with PCOS that number drops down to 30%. Don’t worry, however. If you can generate 30 eggs, I expect about six or seven blastocysts. At your age, 10 percent of blastocysts should be genetically normal. That means out of eight blastocysts, one – maybe two – will be good to go. What you need to do is prepare yourself for a totally different approach. In cases like yours, we focus on the embryo – generate the embryo, freeze, genetics work and biopsy. Then, in the next cycle, we attempt a transfer. However, if we see that despite you being able to generate a lot of eggs but they can’t reach the blastocyst stage due to your age, that’s when I would recommend egg donation. In this day and age, however, I would fight for your own genetics until the very end.

Question:

I’m in my early 40s – is it worth taking co-enzyme Q10 to improve egg quality? 

Answer:

Q10 is FDA approved and there are some papers showing that it has a positive effect on eggs quality, so I would say yes.

Question:

I’m 39 years old, had three failed IVF cycles with my own eggs. I’m thinking about trying egg donation. Do you think I should try with my own eggs instead? I feel tired of disappointment, but I’m not sure if this is the correct decision. None of my cycles involved PGS testing, so I’m not sure about the genetic of my embryo – I did have blastocysts, though.

Answer:

The fact that you had blastocysts is already a very good sign. I would like you to come to IVF Spain so we could see your ovarian reserve and your antral follicle count. Please send us your protocols and pictures of embryos that you had when you did cycles at your clinic at home. If you’re able to develop blastocysts, we’d need to measure their quality – if it was at least a B, we will be more than happy to do one more IVF cycle with genetic testing. If their quality is C or lower, the best option would be to go with egg donation.

Question:

Do you recommend PGS with egg donation cycles?

Answer:

I do. I’ve performed more than a few egg donation cycles and I’ve seen miscarriages from genetically abnormal embryos of egg donors. It’s not something done routinely, but we do recommend it and I personally believe in the future it will become a standard procedure.

Question:

We have two recently failed embryo transfers with PGS normal eggs, aged 40 at the time. What would you recommend as we found our own normal eggs?

Answer:

We have to be aware that after so many cycles the endometrium in the womb is not receptive to the embryo. We would recommend a uterus lining biopsy to see if you need five or more days for the implantation window. We have offices all over the UK that perform this type of biopsy for us. If you’d like us to design a cycle for you, drop an email to patients@ivf-spain.com and I’ll be more than happy to put one together so you know when the biopsy needs to be taken.

Question:

Is it possible to fly after embryo transfer?

Answer:

We have patients that fly from Spain to Australia after a transfer. What you should avoid, however, is hard work, baths, swimming – no underwater activities, basically, just showers. Also avoid standing for long periods of time, cycling and sexual intercourse. These are the things you should avoid. Flying, however, is safe – a lot of our patients fly home the same day as the transfer.

Question:

Do you offer egg donation programs with PGS? How much do they cost?

Answer:

Exclusive egg donation costs 10,000 EUR. PGS comes at an additional 3,000 EUR. We were the first clinic in Europe to introduce an egg donation PGS program.

Question:

I’ve just had my fourth failed cycle of ICSI IVF. I have never been pregnant. Is there anything you could suggest to explain why it consistently fails? I have had two full stims / clomid banking and a naturally supported cycle.

Answer:

I would have to know how old you are, what kind of cycles you’ve had before, which hormones were you given and if you have reached blastocyst or not. The key is to know if you’ve had euploid blastocysts – if yes, then the pregnancy rate should be around 70%. If not, you have to start thinking about egg donation. Send us an email to patients@ivf-spain.com and schedule an appointment so we can see your AMH and your ovarian reserve. This will tell us if the numbers are on your side, that is, if it’s possible to work with your own eggs.

Question:

I was made to understand that a uterus that is bulky due to adenomyosis should be treated, that is, it should be shrunk before the egg donation treatment.

Answer:

What we do in cases like yours is put the patient into an artificial menopause for about two months so that you do not produce any hormones on your own. After this period of down-regulation we perform a test cycle along with an oral estrogen treatment and afterwards we scan your uterus to see what your lining looks like and what dose of hormones you need to grow a proper lining. Then I know enough about how to proceed during the transfer cycle so that the bulky uterus should not be a problem.

Question:

I’m taking 1000 mg of Metformin, 1000 mg of fish oil, 400 IU of folic acid, 300 mg of Ubiquinol, 800 mg of calcium, and Ovasitol. I have PCOS, I’m going to be 43 with poor egg quality and my AMH is 16. What can I do to improve egg quality?

Answer:

You’re already doing a lot to improve your egg quality. If you are able to produce genetically normal embryos at the age of 43, please send us an email to patients@ivf-spain.com, set up a first appointment and a first cycle with genetics. This should tell us if you cocktail of medication allows you to develop an euploid blastocyst. If yes, your chance of pregnancy is 70% per transfer. If we see that your egg quality is not sufficient, then we would strongly recommend a donation treatment.

Question:

I have severe endometriosis which has had a huge negative impact on my egg quality, only discovered when my IVF cycles failed. How do you ensure your donors do not have a similar issue?

Answer:

When you come to IVF Spain, you sign an agreement which gives you not just eggs, but complete embryos. If for some reason the donor eggs aren’t of a sufficiently high quality, we simply stimulate a new donor to make sure we have new blastocyst stage embryos ready to be transferred at no extra cost to the patient.

Question:

Can AMH rise?

Answer:

I have seen it a couple of times in patients treated with (???) due to underlying autoimmune issues. It’s a medication commonly used in chemotherapy, but small dosages are also used to treat autoimmune disorders. AMH going up after such treatments happens, but very, very rarely. Unfortunately, for most people AMH will only go down with age.

Question:

I live in Norway. Do you work with any doctors in Norway? I know a lot of people here who seek fertility treatment. 

Answer:

Thank you for your support. Every year before Christmas, key people in the company sit down and discuss where to travel next year, where we can find patients that need us. If you say that there are many patients interested in IVF treatments in Norway, we would be more than happy to come to your country in 2020 to organize a meeting with potential patients. 

Question:

Can donors have PCOS?

Answer:

No. The donors cannot have PCOS. They can, however, be high responders.

Question:

Does sperm quality affect embryo quality? If so, what can be done to improve it?

Answer:

I like this question a lot because we tend to talk a lot about the female factor while not giving enough attention to the male factor! At IVF Spain our main focus is on producing strong and healthy embryos – I want to have a blastocyst, I want the embryo to be 100% genetically normal. If your sperm quality isn’t sufficient, here’s what I would do: first, a karyotype analysis. Secondly, vitamin treatment, and, believe it or not, high ejaculation frequency. Many centers in Europe recommend an abstinence period of one week before giving the sperm sample, but this tends to actually lower sperm quality – often, the samples given after such a period have very high fragmentation rates and high op(?) doses. At IVF Spain, we recommend an abstinence period of just 48 hours. Aside from karyotype analysis, we also do screenings for carrier genes for cystic fibrosis, because we know that goes with some sperm abnormalities, as well as testing for the ACF gene, and hormonal studies. When every single test fails, we recommend sperm donation.

Question:

Which clinic in the UK performs endometrium receptivity biopsies and is it sent back to Spain for testing?

Answer:

There is an office on Harley street where Dr. Karoshi does biopsies for us – she serves the central London area. IVF Matters performs biopsies for other parts of the UK. We design a cycle of 15 days of oral estrogen, two days of progesterone and the biopsy has to be done on day 21. Following the biopsy, IVF Spain arranges the sample transport with either IVF Matters or Dr. Karoshi to a GLS lab, which performs the test and tells us if you’re receptive or not. Send us an e-mail at patients@ivf-spain.com if you want us to design a cycle for you.

Question:

Is there any treatment for endometriosis when doing IVF cycles?

Answer:

Endometriosis is a headache if we’re doing egg retrieval and we encounter chocolate cysts. Endometriosis is something that takes eggs out of the good ovary and occupies the space, lowering your AMH. The treatment for it – out of IVF – consists of long cycles, which means you take birth control pills and you have one or two bleedings annually. This means you do not have your period. Endometriosis is basically your endometrium that originates in your body through retrograde menstruation and is developing inside your tubes and ovaries. This becomes a problem while retrieving eggs. For embryo transfer, however, the “bulky uterus” should be treated with a down-regulation of four to three months before a transfer. Every patient receiving a transfer at IVF Spain receives prednisone, because endometriosis is seen as an immunological factor.

Question:

What drugs do you use during stimulation? In the UK I was given a high dose of Menopur, 450 IU.

Answer:

Due to laws regarding pharmaceutical companies I cannot tell you which medications we use at IVF Spain. I can only tell you that it’s a mixture of FSH and LH and there are two medications that contain it. One is American – it’s expensive, but very good; the other is Italian. I think I already said more than I should have!

Question:

Is there some sort of age limit for men to produce good quality sperm as it is for women with good quality eggs?

Answer:

The answer is no. Men can have children for a long time – the oldest father we had at IVF Spain was 85 years old. As long as the egg quality is sufficient, the age of the father isn’t the problem – low testosterone issues with erection are. So even if your sperm is good, sometimes due to your age and problems with your blood vessels you may have erection problems. If there are no contraindications, we recommend oral medication to solve those issues. 

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Donor Conception Network UK

About the Author

Natalia Szlarb

Natalia Szlarb

Dr Natalia Szlarb is a Medical Director at IVF Spain, clinic in Alicante, Spain. She graduated from a medical university in Poland in 2002 and then has worked in gynaecology and obstetrics wards at several German hospitals. During her medical studies she also took part in international internships in Egypt, Brazil and Poland. In 2011 Dr Szlarb obtained her PhD diploma in Immunology in the United States of America. Since 2013 she has been involved with IVF Spain. She has extensive experience in IVF with donor eggs and is known by patients as a friendly and warm doctor.Dr. Szlarb speaks fluent English, Polish, German and Russian. In the EggDonationFriends’ webinar she was talking about the process every fertility patients needs to go through when undergoing IVF treatment using donor oocytes outside their home country, specifically in Spain. Dr Natalia Szlarb, as a medical specialist, explained how to prepare for such treatment and travel, what medical records or prescriptions are needed, how many appointments are usually required for different types of treatment and what the treatment milestones are.

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