Oocyte quality – factors to think about after failed IVF

Natalia Szlarb, MD
Gynaecologist & Fertility Specialist, UR Vistahermosa

Advanced Maternal Age, Donor Eggs, Failed IVF Cycles, Success Rates

From this video you will find out:
  • Can anything be done to improve oocyte quality?
  • Are there pharmaceuticals or treatments that can improve egg quality?

Failed IVF and Oocyte Quality

Today we are going to discuss egg quality as a factor in failed IVF treatments. Our featured speaker, Dr Natalia Szlarb, will share her experience and knowledge gained from more than a decade of working all over the world.

The life of a modern European woman is quite different from that of our mothers – today, we focus on our careers and our lives; we work, we take birth control, we fight for our independence – which often results in us deciding to have children later, such as in our late thirties. Compare to the previous generation – our mothers tended to have their first child in their mid-twenties or early thirties.

However, one thing that hasn’t changed is our biological clock – it’s the same for us as it was for our mothers and grandmothers. It doesn’t care for our careers and birth control – it wants us to have our first child before we are thirty or thirty-five years old. According to current research, women in Europe tend to have fewer children and only start planning their family after their egg quality drops significantly – usually after the age of 35. Due to this, conception becomes difficult – in some cases, even impossible, leading to a diagnosis of infertility, which leads to women seeking help from fertility specialists.

Many countries have laws which favour IUI treatments over IVF.  Unfortunately, insurance companies still insist on performing several IUI treatments before moving on to IVF, wasting precious time and money. Even after moving on to IVF, insurance-covered cycles usually only use day three embryos, which again leads to lower pregnancy rates.

Is IVF outcome age-independent?

Due to all these factors, Dr Szlarb recommends we should plan our cycles ahead of time; because egg quality goes down with age, women under 35 should consider freezing their eggs so that they can become their own donors in the future. If that isn’t a viable option, we need to keep in mind that women are designed to have children until they are 36 years old – after that point, fertility drops dramatically. It’s almost impossible to become pregnant with your own eggs after the average age of 46. On the other hand, pregnancy rates when using egg donation are age-independent.

Women are born with a certain amount of eggs in their ovaries and as they age environmental factors take their toll and their quality steadily declines over age. What this basically boils down to is that the older we get, the higher the chance for us to generate a genetically abnormal egg, which in turn leads to lower pregnancy rates.

Can we do anything about oocyte quality?

A question then must be posed: should we do something about egg quality? Does medicine offer a solution? The answer is yes – fertility rates can be improved with genetic testing and embryo selection. By simply identifying genetically correct embryos we can bring fertility rates of someone who is older than 35 years very close to someone who is around 30.

Thanks to advances in modern medicine, fertility specialists are able to check every single chromosome in an embryo – a decade ago, we only checked for the most commonly affected chromosomes to rule out trisomy 18 or 21. Now we can be completely sure that the embryo is 100% unaffected by any genetic abnormalities, which, again results in much higher pregnancy rates.

Because the amount of genetically normal embryos we can produce drops significantly with age – for instance, women aged 35 to 37 are able to produce genetically normal embryos 44% of the time, while women aged 42 and above-average around 11% – we always recommend genetic screenings if the patient is older than 35. This alone makes pregnancy rates shoot up.

However, this does not address the root concern, which is egg quality. This is simply a methodological adjustment which allows us to pick out the embryos with the highest chance of success. For this method to work, however, the patient needs to be able to produce enough eggs of sufficiently high quality that we have enough eggs that can reach the blastocyst stage. Unfortunately, this is not the case for all women.

Unfortunately, some women just don’t have the ovarian reserve or AMH required to produce enough good-quality embryos to guarantee a chance of success. In these cases, it is possible for patients who still want to press on with their own eggs, but we only do it for one cycle – thereafter, we strongly suggest egg donation.

Egg donation is the final step of fertility treatment for many patients. It allows us to bypass many issues stemming from age or other factors, such as low AMH or poor egg quality. We are aware that this may be a difficult choice, which is why patients that decide to proceed with egg donation are provided with psychological counselling at every step of the way.

While there are certain pharmaceuticals and treatments that may slightly improve egg quality, these only tend to work if there’s an underlying medical issue. Ultimately, the patient is fighting against time; there are unfortunately no treatments that will definitely increase your egg quality; after a certain point, egg donation becomes your best shot at pregnancy.

To summarize, if you’re a young woman and you want to get pregnant after the age of 35, freeze your eggs – as you grow older, their quality may deteriorate to the point where generating enough high-quality embryos may be difficult. If you’re over the age of 35, consider IVF cycles with genetic testing, as well as diagnostics to ensure your ovarian reserve is sufficient to generate enough high-quality embryos. If you are over the age of 40, strongly consider the possibility of egg donation if other methods don’t result in a pregnancy.

- Questions and Answers

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

Thank you for the question. After coming back to Europe after 20 years, I have seen a 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 the UK will be able to come 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 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.

Can gluten intolerance affect egg quality or cause implementation failure?

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.

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

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.

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

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.

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?

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.

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

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.

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?

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.

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

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.

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

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.

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

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

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

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.

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?

This breaks my heart. This type of treatment is what we used to do 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 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 your 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.

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

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

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.

The fact that you had blastocysts is already a very good sign. I would like to 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.

Do you recommend PGS with egg donation cycles?

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.

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?

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.

Is it possible to fly after embryo transfer?

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.

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

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.

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.

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.

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.

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.

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?

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.

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?

When you come to the clinic, you sign an agreement which gives you not just eggs, but complete embryos. If for some reason the donor eggs aren’t of 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.

Can AMH rise?

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.

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

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. 

Can donors have PCOS?

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

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

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! Our main focus is on producing strong and healthy embryos – I want to have a blastocyst, and 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 centres 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. 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.

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

There is an office on Harley Street where Dr Karoshi does biopsy – 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, and two days of progesterone and the biopsy has to be done on day 21. Following the biopsy, the sample is transported with either IVF Matters or Dr Karoshi to the lab, which performs the test and tells us if you’re receptive or not.

Is there any treatment for endometriosis when doing IVF cycles?

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 bleeding 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 receives prednisone because endometriosis is seen as an immunological factor.

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

Due to laws regarding pharmaceutical companies, I cannot tell you which medications we use. 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!

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

The answer is no. Men can have children for a long time – the oldest father we had 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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Natalia Szlarb, MD

Natalia Szlarb, MD

Dr Natalia Szlarb a Gynaecologist & Fertility Specialist at UR Vistahermosa, Alicante. She graduated from a medical university in Poland in 2002 and then worked in gynaecology and obstetrics wards at several German hospitals. She also participated in international internships in Egypt, Brazil and Poland during her medical studies. In 2011 Dr Szlarb obtained her PhD in Immunology in the United States of America. 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.
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