The new parameter you should definitely check after multiple IVF failures

Harroula Mathiopoulou Bilali, BSc, MMedSc
Founder & CEO, Ferticeutics Co., Reproductive Biologist – Corporate Health & Wellness Coach, Ferticeutics Co.

Failed IVF Cycles

Multiple IVF failures and all the parameters that you should check before another attempt
From this video you will find out:
  • Why IVF fails?
  • What are the two main areas we forget to consider?
  • What is the new parameter we should start to consider after many failures?
  • What is the human microbiome?
  • What is dysbiosis?
  • What are the 4 ways to improve your microbiome?

What to check before your next IVF cycle if you've had multiple failures?

In this webinar, Harroula Mathiopoulou Bilali, B.Sc., MMedSc, a molecular biologist specialized in reproductive health, and founder & CEO of Ferticeutics Co., a medical/pharma company that provides advanced health and fertility products, services and therapeutics has been discussing microbiome as a new parameter that should be checked if you have had multiple IVF failures.

What to check before your next IVF cycle if you've had multiple failures? - Questions and Answers

Can a lack of water or dehydration affect implantation? Is water from the tap ok?

Yes, of course, and what happens with dehydration and the lack of water in the body? Apparently, for survival issues, the reproductive system is not the one that keeps us in conditions of survival. That is the one that our organism does not care about, so that comes from a long, long time ago. The water is taken from our reproductive system, and when we are dehydrated, and we don’t cover the 8 to 10 glasses of water per day needed for homeostasis of our body, you have a less optimal environment. Dehydration also affects hormonal balance in the body because water is very important for hormonal homeostasis. If you do not have enough water in your system, you have hormonal imbalances as well. You don’t need hormonal imbalances when you’re thinking about endometrial function and implantation. So, the answer is yes, and not directly but there are at least 3 different proves that lack of water can alter endometrial function. I prefer tap water compared to plastic bottled water. If you can have a good filter that takes some of the bad bacteria in the water off, but I would not worry so much about that, to be honest.

I’m doing an embryo transfer in a few days. Is it too late to detox?

I wouldn’t put so much stress in the body right now. Detox is not always something easy for the body because it’s a new situation. My advice is that from now on, it’s not about detoxing, it’s about starting a healthy diet. There’s only one good fertility diet, and that diet is the Mediterranean diet that has lots of fruits and vegetables. Some years ago there was a great study done that showed that women that ate more fruits were getting pregnant quicker, it’s probably because of the antioxidants, it worked even better than eating vegetables, another good nutrition. They have a very good impact on fertility, so I wouldn’t do detox now, but I would start having a healthy diet to support everything.

We have unexplained infertility – we’ve had 4 failed IVF cycles with my own eggs and 1 failed donor egg cycle. I have IBS (Irritable bowel syndrome) and wondered if that could have an impact? If so, what do you recommend? We are due to another donor cycle in March, so I have a few months to make changes.

IBS is one of the microbiome diseases, I would suggest to get in touch and be in close contact not only with your reproductive specialists but also with your doctor that is looking after your IBS problems. I believe that you should make some changes and increase the health of your gut and include all these four stages that I recommended probiotics, stress management, good nutrition, and exercise. I definitely believe that you should start those changes and control your IBS in the best way that you can increase the homeostasis in your microbiome.

I recently had a chemical pregnancy, it was my first cycle. I’m 44 years, had a donor egg that was PGD tested. I have IBD (Inflammatory bowel disease), but I wasn’t on an immune protocol but had intralipids after my transfer. What else would you recommend for my second cycle e.g. immune testing, hysteroscopy?

This is not a question with an easy answer. Every time that you go so deep, you need to have the whole medical history of the couple. IBD has high levels of inflammation, and this, in general, is not good for the body and especially for fertility. High levels of inflammation have a big impact on fertility. What I do with my patients before any IVF cycle, I have a hematologist that we work closely together. I strongly believe that everything should be consulted with an expert in their field. I mean, I don’t want to do things that a hematologist or a reproductive immunologist does. In our team, we have a doctor who assesses problems like IBD or Celiac disease, or other immune problems before any IVF cycle, and we have a very specific protocol for that patient. In regards to immune testing, I would probably recommend performing them but not any immune testing, it doesn’t mean that because you have this, you should have a practitioner that can define and personalize what kind of immune testing you may need. Hysteroscopy and IBD, I don’t know if there is any connection. Generally, as a rule of thumb, and especially if you’re doing donor eggs and if they’re PGD tested by doing hysteroscopy, you will also assess where the embryo is going to be transferred. That would also be advisable, but probably your doctor would be more appropriate to answer this. In our practice, and my husband who’s a medical doctor, he’s an obstetrician-gynecologist specialized in reproductive medicine, we recommend hysteroscopy.

How can we improve our microbiome?

There are four stages, this is the basic thing that we should all do. I’m about to receive accreditation as a microbiome expert. I had to go back to the university because microbiome infertility is the next revelation in the field of fertility. When I started studying the microbiome, the first thing that I did was to get worried about where am I having all this sugar from, so I could never believe how bad sugar is for the microbiome. The first thing to do if you want to start tomorrow just cut sugar. I don’t want you to cut sugar completely, even when I’m doing fertility coaching with my patients, I don’t like radical measures that say don’t do this, don’t do that, don’t eat sugar anymore. I prefer to work with tools. If you like to have some organic dark chocolate that is full of tryptophan and magnesium and it’s good for the endometrium and your mental health – you can have it.

Let’s say every afternoon right along with some almonds or walnuts. You can also have some honey with your tea. I want to put you in the mindset that everything that makes you happier and brings your stress down, you should do it, so you can improve your microbiome by taking little steps every day. One day you reduce the sugar a bit, you go out for walking even 10 minutes of walking every day has proven signs that can improve the microbiome. Then you try to improve your sleeping patterns, then try to put more prebiotic fiber in your nutrition protocol, then start having a yogurt every single day, little steps every day, and you’re there, you can do it, I’m sure you can, all of you can.

Is it recommended to cut out sugar completely?

As I’ve mentioned, you don’t need to cut it down completely. You should cut down Coke, you should cut down unwanted sweets, you can replace bad sweets with good sweets. When you want something sweet, the brain can only understand that you gave it something sweet, it cannot understand if you’re giving it chocolate or a very unhealthy sweet, the only thing that is recognized as something that sweet. So, gradually you can have something sweet, but it can be really healthy like yogurt with live bacteria inside, with live culture bacteria inside, and you can add some very good honey that has anti-inflammatory capacities, and there you have it. You can have some chocolate when you feel you want some comfort food, but this chocolate needs to be of good quality with more than 78% cocoa beans inside and as little sugar as possible. So no, I don’t believe you should cut it completely unless there is a medical reason for you to do it.

How long would it take to improve the endometrial microbiome?

It’s not only how long it will take to improve the endometrial microbiome, it also has to do with what you can also improve. Let’s say that your endometrial microbiome is not so disturbed, but at the same time, you need to improve the quality of your eggs. What we need to understand is that egg quality, bad egg quality, good egg quality, it’s not an independent factor. Sometimes, I have patients who didn’t succeed, and they say that they had multiple failures because they had very bad egg quality, but at the same time, you’ll see that the sperm was not good as well, and then you see that the nutrition is bad, the patient is not sleeping properly, the working conditions are very, very stressful, etc. Why don’t we take that person as a whole and address every single problem instead of just saying okay, how do you improve egg quality? Even if you’re using donor eggs, if the general health of the recipient is not good, you may fail again, even if egg donor cycles may go up from 75 to 85% success rates, so everything has to do with good preparation. Invest in the 3 months before going for the transfer.

Do you recommend colonic hydrotherapy just before a transfer?

I don’t have enough data to support that, and I’m looking forward to new data coming probably in the next 1 or 2 years. I cannot recommend something that I do not have enough scientific data to support. Generally speaking, as a rule of thumb just before a transfer, the best thing I do recommend is normal body function, nothing really extra. You’re doing a transfer, you are already stressed, what you need to do is eat properly, sleep properly and cuddle, find a supporting environment, do not add things that don’t have scientific evidence that can support that they can improve success rates before transfer because then you do not know what is working, what has gone wrong and what you can do better next time. Reproductive science many times is much simpler than we think. I insist on focusing on the basic ones.

I have an anxiety disorder, but my GP doesn’t want to prescribe anything. I walk, meditate, practice yoga, and I do lots of other things to try and manage anxiety, but it doesn’t help. Do you think I should get a second opinion from another GP?

Sometimes, I have patients that do yoga because they believe that yoga and meditation help them with stress management because another friend may have done yoga or meditation for stress management, but it’s not working for them. I ask them why aren’t you changing, what you’re doing to relieve your stress, you cannot live your life with all that stress every day, and especially now with COVID-19, we need to address every single problem especially, if it has to do with an anxiety disorder. I do believe that every single patient that accepts the fact that they have an anxiety disorder, already have done the first step towards a better situation, so they really need to be supported by their doctor. If you’re not happy with what you’re getting, just ask for a second or third opinion. I don’t believe in too many opinions, but in that case, if you believe that you have not found the solution to your problem, just simply try to find the solution to your problem.

How can we check the microbiome?

In our practice, but there are more complex ways to check the microbiome. We’re taking two things I’m doing a vaginal culture test, we take a specimen from the vagina all around and also the cervix deep inside, and we check for dysbiosis. It’s a very comprehensive test, I collaborate with the pathophysiologist and a gastroenterologist who is also assessing my patients if they have all these symptoms that I mentioned before like the bloating and the diarrheas and constipation and the fatigue, etc. I rely on his expertise to see if we need extra testing to see if the gastrointestinal tract is healthy or not. I have those two doctors that I collaborate with to check both the reproductive microbiome and the gut intestinal microbiome, and when I get my answers and when everything is clear, and it is either dysbiosis, or there is an inflammation of the gut, then we apply all the evidence-based protocols to improve the microbiome with probiotics and differentiation in the nutrition. These four steps that I’ve already mentioned above.

I had an egg retrieval today, and I only got 5 MII and 1 MI eggs (short protocol). I’m 41. 2.5 years ago, I did an egg retrieval and got 34 eggs (long protocol), so really disappointed today. I have 23 frozen eggs. If this fails, shall I go for the long protocol next time? Do I need to change clinics?

First, it’s not about disappointment because every single menstrual cycle has its own characteristics and its own hormonal profile. One thing that we do know is that it doesn’t matter how many eggs you may have because we do know that if you have 15 to 18 good eggs, one of those would be a successful pregnancy. These are the statistics that we have up to now, every 15-18 or every 25 egg can be the one that will support a pregnancy successfully. I wouldn’t be disappointed, it all has to do with the whole situation. I don’t know why you have so many eggs not used, and it’s not that the long protocol will as successful as this previous one next time. The reality is that if you can’t be sure that if you use the long protocol, you will get eggs. I prefer as well as my husband the long protocol over the short protocol, it goes more smoothly with the ovarian cycle, but you cannot be sure that if you are over the age of 40-41 that the long protocol will be successful. If you came to me, I do believe that I would also go for the short protocol. If this fails, it has to do with what your doctor knows, your medical history, and how your hormones are in the last cycles. If you’re ovulating properly, and if your FSH is right, I would do it, but it would be riskier compared to the short protocol. I do not believe that changing clinics after 1 failed IVF is a good thing because it adds extra frustration as well. I believe that you need to build trust with the doctor that is looking after you.

Should we completely stop eating cheese to improve our microbiome?

There are some cheese out there like Roquefort and that can help your microbiome, and there’s this greek cheese called Katiki, and I am sure that if you google it, you’ll find cheese that has live cultures inside. If there are no other contraindications, I don’t think that you should completely stop eating cheese. But keep in mind that cheese has a very high-fat content, and sometimes you do not want to have other hormones coming from animal fat that can probably disturb the estradiol balance in a woman’s body. If you just eat everything in moderation, it will not do any harm.

You’ve mentioned that one of the parameters to be hormones When going through menopause, should the microbiome also be checked? Could it be a negative issue for bad morphology endometrium in the event of implantation of embryos? What can someone do in that case?

Microbiome and menopause have a very big connection. Menopause and perimenopause cause a drop in estradiol levels and all these imbalances in the hormones. The microbiome is directly affected by it. This is one of the first things you should look after when you are going through this phase in your life, but I want you to understand that it’s not only if you have this and probably a little bit expensive test to check your microbiome, don’t worry so much about testing. As I told you, there are also more medical ways to test the microbiome through endometrial biopsies and specialized cultures and PCR and Next Generation Sequencing (NGS) for the genome of the microbes. Biotechnology and new sciences are growing so fast that we have at least 6-10 different ways to check dysbiosis and the microbiome either in the endometrium, vagina, stomach, and guts. I want you to understand that besides testing, start implementing parameters that will improve the microbiome anyhow. Start doing things to improve it anyway, especially if you are in perimenopause or going through menopause already. Menopausal hormonal abnormalities affect the microbiome. There is a new science that has to do with menopause and the microbiome in the oral cavity. This is how much menopause and the alterations in the hormonal balances affect the microbiome. If you’re going through this phase, start implementing procedures that will improve your microbiome even if you do not check it.

How long before a FET is it important to eat healthily?

We should always eat healthily with a little bit of unhealthy. You have to understand that you’re not eating healthy because you’re having an embryo transfer, it doesn’t matter if it’s frozen or it’s a fresh cycle. You should eat healthy because you deserve to eat healthily, you deserve the best and be in your best position possible. Fertility diet although, we say the word diet, it’s not a diet, it’s nutrition, so you cannot have a break from good nutrition, you can have a break from a diet. If you are on a very strict diet, then yes, but if you’re eating properly, and if you’re having great nutrition, you just do not need to break it because you’re already doing it. While you are having good nutritional habits, it is okay, if you want to have something sweet or even a glass of wine from time to time. I hate alcohol consumption during IVF procedures because it destroys the microbiome, provokes hormonal imbalances, it has high toxicity. Generally speaking, pregnancy and alcohol is a no, trying to conceive and alcohol again is a no, even though you will have one glass of wine, that would not be the reason for not having a successful frozen embryo transfer. If you’re having an embryo transfer, and you eat pizza every day and drinking fizzy drinks – don’t do that, just eat properly, basic things like fruits, vegetables and drink water.

Harroula Mathiopoulou Bilali, BSc, MMedSc

Harroula Mathiopoulou Bilali, BSc, MMedSc

Harroula Mathiopoulou Bilali, BSc, MMedSc is a Molecular biologist specialized in Reproductive Health. Certified Health and Wellness Coach. Founder & CEO of Ferticeutics Co, a medical/ pharma company that provides advanced health and fertility products, services and therapeutics. Founding partner of Bilalis Women’s Health Clinic, which combines cutting-edge medical science with integrative care in Assisted Reproduction and Obstetrics. Co-Founder of IVFSUCCESS.GR More than 15 years now, active as a health educator and fertility consultant. Proclaimed medical communicator. Continuously being educated on various health topics, with a special interest in human reproduction, pregnancy, family health, health IT and health management. As a reproductive health specialist, my purpose is to inspire individuals to take charge of their health and fertility management. Married to Highly Acclaimed Obstetrician - Gynaecologist Dr Dimitrios A. Bilalis MBBCh MMedSc CCST FRCOG and proud mom of two girls.
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Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is an International Patient Coordinator who has been supporting IVF patients for over 2 years. Always eager to help and provide comprehensive information based on her thorough knowledge and experience whether you are just starting or are in the middle of your IVF journey. She’s a customer care specialist with +10 years of experience, worked also in the tourism industry, and dealt with international customers on a daily basis, including working abroad. When she’s not taking care of her customers and patients, you’ll find her traveling, biking, learning new things, or spending time outdoors.


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