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IVF with Donor Eggs and PGS diagnostics – success rates, costs vs. outcome & time frame

IVF with donor eggs with PGS – what is the correlation between the cost of the treatment, the outcome, the success rates, and time frame. Our expert, Dr. Natalia Szlarb is talking about PGS diagnostics with IVF with donor eggs and possible outcomes of various treatment options. If you are interested in the topic, watch the video above which is the recording of this live event and check the Q&A session for doctor’s answers to participants’ questions.

In 2018 Dr. Szlarb was a guest speaker during our webinar on “Process of IVF with donor oocytes abroad”. You can watch this webinar here.

IVF with Donor Eggs and PGS diagnostics – Questions & Answers

Question:

I’ve had 6 embryos transferred so far over 3 cycles of IVF in England, but none have implanted. I have 5 frozen embryos left on my third cycle. Would you recommend that I try PGS for these 5 that I have left? I’m 38 with AMH of 27. My partner is 42 with good sperm. I have blocked tubes, which is the only issue that I know of so far. It’s frustrating that an embryo is yet to implant… I haven’t had any tests for my body. I’ve had a scratch 3 times.

Answer:

The tubes that are blocked are not an issue at all because you can imagine that we generate embryos in the lab and then we place them inside you at a certain moment of a cycle. What I do is I go around the tube so I wouldn’t worry about this at all. The thing is, what we have observed at IVF Spain is that the more cycles the patient undergoes, the more demanding is your endometrium. There are three reasons why the IVF cycle might fail. The first is that we transfer genetically abnormal embryos. At the age of 38, your euploidy rate is about 20–30%. Out of 10 embryos, 3–4 should be genetically normal. I know that PGS is not done routinely in your country and that the embryos are transferred consecutively one after another in the hope that one of them will be euploid and the cumulative pregnancy rate per cycle will be 30–40%, so there is no way back. The embryos are frozen; then they need to be thawed and biopsied—it’s not good. PGS is best platformed on fresh blastocysts. However, if you were not to get pregnant with your own eggs, at the second attempt I and every doctor in IVF Spain would be happy to help you to perform an IVF with PGS due to your age. Then we would have to focus on implanting your embryos on time. Before placing the embryo back inside you, I would recommend performing a uterine biopsy to see exactly how many days of progesterone you need to open an implantation window. Among all my particular patients, 70% of them have needed five days progesterone for 5-day blastocysts but in my career, I’ve seen girls who required even 7–8 days of progesterone to open an implantation window. When it comes to immunology, by performing the uterus lining biopsy we verify the number of your NK cells so basically we will be able to establish if you need any immunological protocol or not after the biopsy.

Question:

I’m 54 and using young (mid-20s) donors from good agencies so I’m expecting the embers to be good. My fertility clinic wants me to PGS test all of the embryos but at $800 it will be very expensive. How many embryos would you recommend to have tested to guarantee at least one healthy embryo? My main concern is my uterus has only reached 5 mm and so I am concerned the embryo won’t stick. This is off-topic but I’m not sure my doctor is being completely transparent about my chances.

Answer:

$800 for PGS testing is a very good price because in Europe patients usually pay €2,000–3,000 for 6 blastocysts tested so you have to ask your doctor how many embryos will be tested for $800. If the answer is 6 blastocysts then it sounds to me like a good deal, so go for it. The good news for you is that when you do PGS, the embryo is frozen so basically we do not
have any pressure that you have to be synchronized with the donor and that the fresh embryo has to be transferred to you after donor egg retrieval. In a PGS cycle, I can grow your lining in something called a long cycle. Usually, when we grow the lining we do it in a substitute cycle, which means that the patients take oestrogen orally for 14-15 days and then we add five and a half days of progesterone depending on your implantation window. When I have an issue with a thin lining, I can extend the oestrogen phase—not for 14 days but for –30. In IFV Spain, we have sometimes patients who grow their lining for 2 months and they grow it until I like it, until the long side had been performed until you reach a certain thickness. So don’t get disappointed. You can imagine, I was raised in the Detroit area and used to work in Western University Michigan and the medicine that may be used in the stage until FDA has to follow certain rules. In Europe, if we have linings which are too thin, we also use Viagra (Sildenafil) vaginally, Viagra vaginally is good for you. Then the patient is given a high dose of oestrogen, Viagra and long cycles so this would be my first approach to you. If we grow the lining over a couple of months through long protocols and we cannot reach a certain thickness, this means that you are oestrogen-resistant and then to grow the lining probably you wouldn’t go for natural cycles to make it happen, so your doctor will have to decide. PGS is definitely a great approach in egg donation. The growth lining is something that you have to work on.

Question:

How do you know if you have immune problems which cause miscarriage?

Answer:

The immune issues with miscarriages probably account for 10–15% of miscarriages. How do I know? It’s very simple: I verify your uterus lining biopsy through the measurement of natural killer cells. There are machines called flow cytometers and then you process the tissues with the machine, which tells me how many NK cells you have. Actually, the machine tells me more: your th1:th2 ratio, your cytokine balance. This is how I know. I don’t like immunology performed in blood because we have to have full respect for rheumatology, for immunology in internal medicine and then blood is definitely sensitive to rheumatology and the lining is more sensitive for proactive immunology and then if you have a lot of NK cells we perform intralipid protocol at a PH1:PH2 ratio issues Humira with patients with cytokine issues, then with PH1:PH2 issues there are amazing papers published about tacrolimus and granocyte protocols, but first of all you have to see if you generate euploid, genetically normal embryos and if the number of chromosomes in your embryos is okay. If this is fine and you transfer one and you cannot achieve the pregnancy, then look at the implantation window and then at immunology—in the womb, in the lining

Question:

I have had two cycles using an egg donor. The first did not work. With the second I got pregnant but I lost it at 6 weeks. I have one embryo left which we will be testing in February but I would really like to come and meet your team to see how you can help me and my husband. We were trying for seven years and the NHS here kept telling me there was nothing wrong we even though I had explained that both my mother and my maternal grandmother went through the menopause in their early 30s. Thank you for taking the time to reply.

Answer:

When I started having my own problems, the German NHS didn’t want to help me much either. I’m very proud of you that you want to look abroad. I had two cases like yours where I was transferring euploid embryos from great donors and I knew that if I were to implant these embryos in myself—and I have 2 kids—I would have been pregnant right away. There are some patients who are super immunologically demanding and we developed an immunological study at IVF Spain: when we know that you had two donor recurrent implantation failures— with egg donation—then we verify your immunology and match a donor to you according to your age. So go for the embryo transfer that you have left. I wish you all the best with this embryo. If this doesn’t work out, please contact patients@ivf.com. We have assistant nurses speaking fluent English answering your questions within 24 hours and who can schedule an appointment within 3-4 weeks. We have done everything we could to reduce the waiting time. If you cannot come to IVF Spain for the first appointment, we can organize a Skype consultation. I wish you very good luck with this and if it doesn’t work out, I’ll be more than happy to help you.

Question (cont.):

I have also had some extra testing done and it showed my NK cells were the right quantity but too active.

Answer:

The activity and number of NK cells is one thing the other thing is what these NK cells accept. We match HLA to NK cells so this is a blood test and we need to know which HLA your NK cells are going to accept and then we match a donor to your NK cells—not to their number but to their receptors on their surface.

Question:

We recently invested quite a bit of money in an egg donation program having done two cycles of IVF with own eggs. Whilst partner has slightly poor sperm mobility, they managed to get two eggs per cycle and with ICSI we were able to fertilize 2 grade A embryos in one transfer and one in the other. Unfortunately, they did not implant. Although I had 6 donor eggs with ICSI, non fertilized!

Answer:

When I see an egg donation cycle with 6 donor eggs, it’s a little bit slow. When we talk about accumulated pregnancy rates in egg donation cycles, the accumulated pregnancy rate per cycle, I have to have at least 3 blastocysts, not one. With three blastocysts I can get 12–16 eggs, so if you are aware that the fertilization potential of your husband’s sperm is low, then you need an egg donation cycle with more eggs. In IVF Spain the programme that we develop—exclusive or exclusive plus egg donation—gives you a guarantee of 3 or 5 blastocysts from a donor. If we see that there is a low fertilization potential and we are only able to generate 2 blastocysts from this donor but you have signed documents for 5, we have to stimulate a new donor for you without any extra cost to fulfil this guarantee. If we see that we have stimulated 2 donors and the embryos are poor—and we know that from C quality embryos it’s super difficult to achieve pregnancy—then we have to sit down together and we go through the documents. We’ll show you the cycle protocols and then if we see that we still owe you 1–2 embryos, we seriously consider sperm donation. This would be my approach.

Question:

What is the difference between PGD and PGS? If using donor eggs (21 year-old) + donor sperm (30-47 year-old), which tests would you suggest?

Answer:

This is quite straightforward: PGD stands for diagnosis and S stands for screening. In genetics, there are 2 types of genetic abnormalities. The first is the number of chromosomes, if there are numerical mutations where the embryos that we transfer have a bad number of chromosomes. In a 21-year-old, we want to match for down syndrome, trisomy 18 edwards, trisomy 13 patau—these are the more common genetic, numerical mutations that are due to your age and pre-implantation genetic screening if the biopsy is testing for the number of chromosomes. There are people who come to us and they say, ‘Listen, we are both carriers of this process. We have a child at home who is sick.’ So, we do PGD when we have both parents who are carriers of a recessive disease or one parent stick in a dominant disease to make sure that the embryo does not carry the same point mutation because that there are certain diseases where the issue is in the punctual mutation in your genes and the child can develop certain diseases. So, routinely if the parents are healthy we perform screening of blastocysts to see the number of the chromosomes only. Donor eggs from a 21-year-old should have 80% euploidy but, as I said, you trust what you can check. In the American study that I was showing you, there are centres that have just a 40% euploidy rate and there are some centres where it is 80%. So, when you see that you cannot achieve pregnancy with one or two donors in one centre then go to a centre that specialises in egg donation. There are a couple of centres in the United States there are well-known in Europe they do it well and in Europe, IVF Spain is one of the centres that performs 700 egg donation cycles per year for fresh, new patients. The more that you do and the more that you see, the better you get so if you are not happy with your centre, go to somebody who specializes in donation only.

Question (cont.):

I’m 47 and using donor egg and donor sperm.

Answer:

47 is an amazing age for having a child from egg donation. In egg donation cycles, your age doesn’t matter. The Spanish recommendation is 50 years 11 months old. You can imagine that we had a few super complicated cases. One of mine involved an African lady from Rwanda who had five children who died in the war and she was 54 when she came to IVF Spain. In order to treat her, all the partners in the clinic had to agree that we were going to treat her. On top of this, she had to present medical records from internal medicine doctors to show that she doesn’t have diabetes, lung function test, echocardiography, a lot of paperwork. She presented it and she was when she had a child from egg donation with us, so 47 years old doesn’t matter to me at all. In egg donation, the pregnancy rate is age-independent.

Question:

I was distraught… Should the clinic do research on the donor egg? I took all the meds but ended up with no transfer. I am 46.

Answer:

If you look at the beginning of my presentation, or you can review it tomorrow, you will see the pregnancy rate on the first couple of slides. You can see the pregnancy rates with own eggs (the red curve) at 35 and then pregnancy rate drops dramatically at age of 40. There is no chance for pregnancy with your own eggs in an egg donation cycle. You see this blue curve—it’s stable between 35–50, so your age in egg donation is ok. Egg donation can cause miracles. It’s like Botox erasing your age. So, regarding research on egg donation, in order to do research, in order to do PGS on egg donation, you have to fail a couple of times with fresh egg donation cycles to allow yourself to do PGS on egg donation. As I said, go to somebody who is specialized in egg donation. The reason why I started doing PGS in IVF Spain on egg donation cycles was an amazing couple—two lawyers from Berlin—and I transferred good-looking, high-quality embryos with good morphology and time-lapse. Imagine that the lady had D&C because of a miscarriage and I will never ever forget her genetic report and the miscarriage material. One embryo was a euploid girl and the other had trisomy 13 patau syndrome. This was the moment where our world turned upside down. Of course, I expected a lawsuit but they both came to us and this lady, this lawyer from Berlin told me that she wanted to go for another transfer, have a second egg donation cycle, and that she would like us to perform genetic testing on the embryo. It was the first PGS procedure on egg donation that we had ever done in IFV Spain—five years ago. We did it and she had a child from PGS egg donation right away and then basically we reserved each year for a second egg donation. Now, after so many years, I tell you we have higher success rates with PGS in egg donation embryos than with fresh ones. I’m telling you this from a perspective of 5 years, 700–800 egg donation cycles every year. As a doctor, you have to mature to prepare yourself for this kind of embryo selection.

Question:

I miscarried a donor egg that was day 5 and PGS tested at 6 weeks. What tests would you suggest to check there is nothing medically wrong with me before I transfer my next embryo?

Answer:

I would agree. I would prepare the lining according to the American school. If the biopsy is not available, perform the uterus lining scratch to increase the receptivity of the lining in the following cycle and if you have a good PGS-tested embryo transfer, then maybe prednisone after the transfer or maybe blood thinners and let’s see what happens. Good luck!

Question:

If you do the exclusive donor with 5 blastocysts, how many would you expect to be normal? Can you also explain the benefit of an ER map?

Answer:

If the cycle has been done properly, I expect 3–4 blastocysts out of 5 to be normal. The benefit of an ER map is that there are patients whom we call GAPP zero. GAP means gravida-zero, pregnancy-zero, abortus-zero, para-zero—never pregnant, never had a miscarriage, never delivered. It’s GAPP in English. I have to ask myself a question: if I have a patient coming and she has never had a positive pregnancy test, is it because of her age that she started too late or maybe there is something in her womb that stops the embryos implanting? And this is the moment when we recommend a uterus lining biopsy upfront here at IVF Spain. I have had patients who failed 1–2 transfers with euploid blastocysts that were genetically normal. I have to I have to ask myself a question when I have a genetically normal embryo with a 70% percent pregnancy rate, why hasn’t this embryo implanted in this patient? This is the moment where I have to review your case. In IVF Spain, Tuesday is a busy day. I’ll have one meeting and then a second meeting where we discuss all the negative results so when we talk and we see that we failed with 1–2 transfers with good quality blastocysts, this is the moment where we recommend the lining biopsy to see if you need 5 days of progesterone to open an implantation window or 6 or 7. Believe it or not, we have had 700 biopsy failures and I have a few patients whom I’ll never forget in my life. Twice a year, you have somebody who needs 80 days of progesterone to open an implantation window, do the transfer, find the blastocysts and this is the moment when the patient gets pregnant.

Question:

Do you manage patients through the first 12 weeks—hormone monitoring—to maintain the pregnancy?

Answer:

We manage until 12 weeks. Of course, if there are issues, later on, we do not run away from complicated cases. There are cases with certain complications that we manage with obstetricians till the end.

Question:

Do you perform an NK cells test from the same endometrial lining sample taken for the ER map, or do you perform a separate biopsy on a different day than the ER map biopsy? How important is the NK cells test and is it very different from the test performed with a blood sample?

Answer:

We usually perform the uterus lining biopsy on day 21 of a substitute cycle and a piece of the lining goes for an ER map test, which is a genetic test of the lining that tells me about the timing of your lining, and then the other part of the endometrium goes to the flow cytometer and then we see the immunology there. The immunology of blood and the lining is completely different. Why? Because we have a lot of cells in our body but we have to be able to identify them. How to identify them? The cells have C receptors and then the uterine NK cells express different CDs than the NK cells in the blood so the NK cell population in the blood is a lot less sensitive—because it’s not uterine—to your immune issues than your uterine one.

Question:

Aged 46 and fertilized with my own egg so why not with donor eggs? My husband doesn’t want me to use a sperm donor.

Answer:

If your own eggs get fertilized with your husband’s sperm but the donor eggs don’t, try a different donor. Then if you know you fertilize fresh eggs once, twice with your partner’s sperm and this doesn’t work then you can think about donor sperm but before you go for fertilization with donor sperm I would prefer to try this sperm with a different donor and definitely with fresh eggs.

Question:

If we do the PGS, how many transfers are cancelled because of the aneuploids found in the embryos tested? On average, as far as I understand, while increasing pregnancy rates with PGS, we’re decreasing the number of transfers or at least the number of embryos to transfer.

Answer:

That’s a very good pragmatic question. Can you imagine flying to Spain for a good-looking embryo transfer which is aneuploid but you are unaware of this? Of course you will have fewer transfers but I don’t want you to have a high accumulated pregnancy rate per cycle. When I do PGS—and I do it well—my goal is to reach accumulated pregnancy rate in one PGS tested embryo transfer to make your time to pregnancy as short as possible for this embryo selection. You don’t need more transfers; you just need one transfer to have a baby.

Question:

What other tests do you perform when the donation cycles fail? How do you match the donor immunologically? What tests do you perform on the recipient and which on the male partner and what are these tests for? You mentioned them in your presentation. Could you give more details on these immunological tests?

Answer:

I was raised in the tough city of Detroit. The only positive thing that I remember about Detroit was the Detroit Institute of Arts and a couple of hours drive and we were in Chicago. In Chicago was Mrs. Ilby—a very well-known immunologist—and she was publishing which NK cell tests are necessary in order to implant certain HLA embryos. Drop an email to IVF patient and Elise or one of the assistants will be more than happy to send you this article that we use for the immunological matching of patients and donors. Our knowledge about HLA matching is from Chicago from Mrs. Ilby and it is published that in certain immunological considerations, only HLA C1 embryos are implanted. So, I’m more than happy to support you in all this.

Question:

What do you advise if my uterus does not reach 8 mm after taking your advice, extra long cycle, viagra etc.? Do you think I should risk having a transfer at 6 mm?

Answer:

You should risk a transfer at 6 mm. I have had pregnancies with 6 mm. You will not know until you try it. If the embryo is good genetically, normal and strong, you have a chance of having it implanted. The ideal thickness of the lining that we wish is usually between 6.5–12 mm with utrogestan. Without utrogestan and only with oestrogen, it should be about 7.5–13 mm because after utrogestan the lining shrinks about 1 mm, so if this is 6 mm with utrogestan, it means that it would be 7 mm without and that’s not bad at all. Give it a try!

Question:

Does being on the contraceptive pill have an effect? I was put on the pill at 15 and stopped when I was 32.

Answer:

Very good sexual education! Well done! Everybody in Europe should be educated like this. If you know at the age of 32 that you have infertility issues and a low ovarian reserve, it’s definitely not because of the birth control pill. There are probably genetic factors. It has been shown that in a family there are women that per cycle recruit more follicles than other women and they use the ovarian reserve quicker. There have been papers published showing that premature ovarian failure runs in the family, that mother, sister and cousin had it. So don’t blame yourself. Well done with the sexual education and that you were put on birth control pills so that you could study and pursue your career and we have to take it from there.

Question:

I am 45, due to transfer 1 or 2 embryos with donor eggs next week in Portugal. We have 3 good embryos, day 3. What are the success rates for transferring 2, or would you suggest 1 embryo? I have never been pregnant but only started trying at age 42.

Answer:

In reproductive medicine, definitely be on the safe side. That means a single embryo transfer. You want to avoid twins. Although twins can be a nice pregnancy, it can also be an emotional rollercoaster. You can imagine that in gynaecology we are nice quiet people but when you are pregnant with twins, I have to see you more often—every 2 or 3 weeks. I have to see the length of your cervix. If it’s too short then I will forbid you to work and if you are at home and the cervix is too short, I’ll send you to the hospital. I’m afraid of putting the … [1:03:09] and trust me—with twin pregnancies it’s either my way or the highway. We gynaecologists know exactly what we want, so definitely go for a single embryo transfer. The success rate with three embryos is a lot lower than with blastocysts and way lower than with blastocysts genetically tested. These kinds of cycles are quite convenient economically, but I wish you all the best. I hope you get pregnant with the 3 embryos. If not, we will be more than happy to grow a blastocyst for you.

Question:

Do you perform the HLA-B test as well and are these important for the RIF women?

Answer:

Embryos are smart—they do not show mama immunogenic HLAs. HLA-A and B are very immunogenic and when you do a kidney transplantation in the United States, we match about 9,800 HLA-A and B. When the embryo doesn’t show it, I don’t check. We only check HLA-C in reproductive immunology and it makes our lives a lot easier.

Question:

When doing a fresh cycle with a donor egg and partner’s sperm, how long before egg collection would we need to be there and for how long after fertilization etc.?

Answer:

First things first, we have to meet either physically in Spain or online via Skype to discuss the patient history and plan the cycle. So, basically on the day of the first appointment or Skype, you have a medication plan that we write for you. With each medication plan, you need a mock cycle—this is a test cycle where when you have a period you take oestrogen orally in your country and then, period, through the medication plan through birth control pills I synchronise you with your donor. It’s really straightforward. You take birth control pills at home, the donor takes control pills in Spain. You stop it at the same time and then you take substitute cycle oestrogen pills only. Parallel to you, the donor does injections—IPF cycle. All this happens at home. You just let us know. You write us an email and say, ‘Hi Elise, Hi Isabella! I have a period!’ and then everyone knows how to synchronize you with the donor. Then you just fly to Spain for a transfer. How? When we do a fresh egg donation cycle, you have to stay in Spain for about 7 days and then from Monday till the next week on Tuesday we do a collection of the donor, fertilization with your husband’s fresh sperm and basically I need your husband in the timeframe during which we agreed to work—from Monday to Wednesday. Then we wait for embryos to develop until day 5 and at IVF Spain, fresh blastocyst is transferred from Friday until Monday the next week. So these are fresh cycles. We want you to have 1 embryo transfer and the rest of the embryos are frozen in case you are not pregnant and you want to go back. We have to do the lining biopsy. You have embryos frozen to have an accumulated pregnancy rate of 90% after three consecutive transfers. For the modern lady who wishes to have a PGS cycle, I have very good news. On the day of the first appointment, if the sperm quality of your husband is good, the sperm is frozen and then when we have a donor prepared for you and we have fresh eggs from the donor, they are fertilized with your husband’s sperm—either fresh or frozen, according to our decision. Then the embryos are grown to the blastocyst stage biopsied frozen. We wait two weeks for the result of PGS testing. You apply for a transfer just for 1 day in a PGS cycle. If it’s a frozen embryo transfer, the embryo is thawed in the morning. The lab technicians work very hard. They are at work 7 a.m. and they start thawing. At 9 a.m., professional gynaecologists arrive and I want to see all the thawing so from 9 a.m. we start transferring and on the same day in the evening you can fly home.

Question:

I would be interested in having more details on egg donation with you. Can I contact you via email? If so, could you leave your address?

Answer:

I’ll be more than happy to do this. You can google me. My name is Natalia Szlarb. I’m the medical director at IVF Spain. Alicante. Send an email to IFV Spain patients. All the girls that respond to emails have 24 hours to do so. I’m more than happy to help, so if you do it today or tomorrow, probably we can have a chat next week. If you want to come physically, at least we’ll schedule you for an appointment at the next available time, usually within a week.

 

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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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