First IVF Magazine
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Intralipid infusions – indications and prospects

Uliana Dorofeyeva, MD
Director of International Cooperations at IVMED, Medical Director at OVOGENE Egg Donor Bank, IVMED

Category:
Failed IVF Cycles, Miscarriages and RPL

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From this video you will find out:
  • What are the most common immunological factors?
  • What is the mechanism of the immune system?
  • What are the common autoimmune diseases?
  • Why do autoimmune diseases occur?
  • What is the role of natural killer cells in implantation and pregnancy?
  • What causes high uterine NK cells?
  • What kind of immunological testing and treatment can be performed?
  • What are intralipids for IVF and when they can be indicated?
  • What is IVIG, what are the risks and side effects?

What is the role of intralipid immunotherapy and when can it be used?

In this webinar, Dr Uliana Dorofeyeva, Director of International Cooperations at IVMED, Ukraine, and a Medical Director at OVOGENE Egg Donor Bank, discussed intralipids, how they work, when are they recommended and in which particular cases should they be considered.

What is the role of intralipid immunotherapy and when can it be used? - Questions and Answers

How long do intralipids take to work?

In comparison to the medications given by pills, which are still existing intravenous, either intralipids or immunoglobulins are acting immediately. That means as soon as this medication is getting into the blood. The NK cells and the immune system, in general, work differently, so it takes out from the central organ all the NK cells so just mechanism of action and all these NK cells they are going into the periphery to fight with the structure with the molecules which came together with these medications.

We are getting the central organs, which include the uterus, being free from the high levels of the intestines. It is how the mechanism works. It’s valid for 21 to 28 days, it’s very individual, and we need to consider each patient individually, and the treatment should be individualized in terms of prescribing the dosage the frequency of the immunoglobulins. It’s easier to predict in patients who’ve been treated with any kind of immunological treatment before that treatment cycle, however, it’s as easy for those who’ve been unsuccessful. It’s hard to say, but some patients are losing their pregnancies just because we haven’t repeated the IVIG in this particular period.

It happens because, for example, these medications are not used in some countries, and if patients visited Ukraine for the treatment and they’ve got their injections, it would be okay. However, they fly back home, and there is no possibility to repeat it after the positive pregnancy is achieved, even if the heartbeat is confirmed, we need to repeat it, but if there is no opportunity, the result could be different. They will come for the next pregnancy, or we will think about how to get the medications in their country or where to go, so it’s still very temporary action for the immune system by receiving the immunological treatment, and it needs to be checked, and we need to remember that.

At what pregnancy week is it recommended to stop intralipids, and usually, how often do they need to be administered?

They need to be administered every 3 to 4 weeks. This is what we know from the mechanism of action. For most of the patients, I would say for 80% of patients, we stop prescribing IVIG and intralipids after the first injection, and as soon as the clinical pregnancy is confirmed, so 6 weeks of the pregnancy on first ultrasounds scan if they see the heartbeat and if there is no haematoma. However, sometimes it starts very rapidly, and this is very common for immunological issues, today everything was fine, we checked the pregnancy on the ultrasound and in 2-3 days, there was intense heavy bleeding, and that’s it.

That’s why for most of the patients, we recommend keeping injections until the first trimester of the pregnancy is completed. The first trimester of the pregnancy is when the placenta is developing properly. The placenta is responsible for this crosstalk between the mother’s body and the fetus, and it supports a lot of the fetus’s development once it is completely developed. The first trimester is when we can think about it, and mostly we stop the IVIG treatment. Since the embryo transfer until the end of the first trimester, we have 3, sometimes, 4 injections of the intralipids every 3 to 4 weeks.

Is there any exam to evaluate the effect of intralipids? Do you consider normal any special range of NK cells? Blood NK cells or uterine natural killer (uNK)?

As I said during my presentation, we still rely on both tests. All patients are tested, however, we also consider the previous anomalies of the patient, and we are discussing the treatment plan with the patient, we go ahead with immunological treatment, immunological testing and treatment or some other way of treatment and then the strategy for the treatment cycle.

We know and agree that uterine NK cells are more certain and more predictive in terms of the treatment, and we base the treatment mostly on those tests. However, our previous experience until we started to analyse uterine NK cells, also the peripheral blood, but mostly the anamnesis works well and helps us decide and be successful with the treatments.

We do not perform any confirmation that immunological treatment worked, the best confirmation for this is the clinical pregnancy and the development of the pregnancy.

Would you connect hematoma in early pregnancy, a consequence of immunological factors?

I cannot say that haematoma is always the prediction of immunological infertility. However, if we are talking about proper early pregnancy development, we should avoid having haematomas. If they are present, especially for the patients for whom we initiated immunological treatment, if we see any risks for the first-trimester development, we would consider repeating IVIG treatment or any immunological treatment just to prevent the risk of losing that pregnancy.

How much is each intra-lipid infusion in Ukraine?

It depends on the dosage and the volume of the infusion, which is recommended. However, the average dosage of 10% of IVIG would be 200, again it depends on the patient, but from 200 to 500 millilitres and the costs we would need to double-check with the coordinators. I think it’s about 800 EUR, but it’s better to write to us and to get this confirmed by email.

What causes an imbalance of natural killer cells?

We need to talk about each case individually for the causes. The NK cells can be evaluated in an autoimmune disorder, which may be found in humans, and as we said, we are talking about more than 80, these are just known diseases. I’m sure that with development, we will get more factors. It’s a very hard question to explain.

What kind of dose of Prednisolone would you prescribe for high cytokines?

We use between 4 and 40 milligrams per day of Prednisolone. However, the individual dose is the individual prescription, also about high cytokines, we need to talk specifically about the case.

Do you recommend medical mushrooms for immune issues? E.g., Mesima and Coriolus?

No, unfortunately, I have no experience in that. Even the medications we are talking about right now have no evidence, and if we are talking about up-to-date and the coherent database, etc. They are not level A as a recommendation, but considering the risks and the benefits, we decide to recommend those. However, I don’t know these medications, and I have no practice using them.

Do you use Enoxaparin in these cases?

Yes, for any kind of heparins like Clexane or even low dosage Aspirin, we previously check the factors of the coagulation and thrombotic factors, and after that, we decide about the prescription of that medication in the cycle.

I was told that at 8 weeks the embryo (not PGS tested) was measuring 5 days behind in terms of size. Would you consider that a consequence of immunological factor or more likely a problem with the embryo itself?

The question would be, what was the problem. If there was a miscarry or the embryo stopped its development, have you done the histological evaluation to consider also the genetics of the embryo, it’s really hard to say. However, it is more likely that the embryo itself was a factor than the immunological factors. The immunological factors mostly play their role in the implantation itself. This is either a very early term of the pregnancy or the absence of the implantation in general.

Is biochemical pregnancy linked to the immunological issue?

Mostly yes. However, the embryo factor should be checked. If this is an issue with the euploid embryo, this is an issue of the implantation. If this is an issue with the implantation, we should be looking for the immunological factors.

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Authors
Uliana Dorofeyeva, MD

Uliana Dorofeyeva, MD

Dr Uliana Dorofeyeva is a Director of International Cooperation at IVMED, Ukraine, and a Medical Director at OVOGENE Egg Donor Bank. She is a multi-talented, engaging and results-oriented fertility specialist with significant experience in ART. She is trained in all aspects of andrology and reproductive endocrinology with exceptional knowledge in the areas of laboratory quality control, vitrification of oocytes, cryopreservation of gametes, embryos and unique ovarian tissue, micromanipulation of gametes including Intracytoplasmic Sperm Injection and Assisted Hatching. Worth mentioning that Dr Uliana is a member of ASRM and ESHRE (American and European Society of Reproductive Medicine).
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
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