Hyperinsulinemia, hyperprolactinemia, hypothyroidism and immune thyroid disease causing recurrent IVF failure

Antonio Rodrigues, MBBCh, FCOG, MBA
Director of Medfem Fertility Clinic, Medfem Fertility Clinic

Failed IVF Cycles, Miscarriages and RPL

Immune disorders that are causing recurrent IVF failure.
From this video you will find out:
  • What factors play a role in successful IVF (live birth)?
  • How does hyperinsulinism, hyperprolactinemia, immune thyroid disease lead to IVF failure?
  • What is male hyperinsulinism? And how does it affect the outcome of IVF?
  • What eating plan is best?
  • How do we treat hyperprolactinemia?

Immune diseases and recurrent IVF failure - what's the connection?

Watch the recording of the live webinar with Dr Antonio Rodrigues, Director of Medfem Fertility Clinic, who is explaining IVF failure and hyperinsulinemia, hyperprolactinemia, hypothyroidism and other immune diseases.

Immune diseases and recurrent IVF failure - what's the connection? - Questions and Answers

How much does Hypothyroid and Hashimoto’s affect IVF, which is done with a donated embryo?

IVF from a donated embryo, we’re now getting an embryo that is potentially very normal. If we don’t treat the thyroid in such a way that you’ve got the levels of thyroid hormone right, and if we don’t treat the immune side of it we will have reduced implantation rates. Your hypothyroidism needs to have thyroid hormone replacement. It needs to have levels of hormones that are controlled perfectly, and then as far as the antibody goes as I’ve said we use that protocol that I described which contains different cortisone and immunoglobulins. From our experience, that deals with this problem perfectly.

I have had many PGS tested chromosomally normal blastocysts transferred that have all failed. They can’t find anything wrong with me. What tests should I be asking for?

I think that’s an important question. I’m making assumptions that the uterus and things like fibroids pushing in the uterus, a septum in the uterus have been ruled out. It’s also important that the fallopian tubes have been checked, that they are not blocked because if there’s a blocked fallopian tube, and it causes what we call a hydrosalpinx or water on the tube, that will prevent a normal embryo from implanting. There’s a lot of other immunological factors that need to be looked at. Like as anti-cardiolipins and antinuclear factors, the thyroid is important, and I don’t know if they’ve done your thyroid antibody, but if they haven’t, that’s important. I

’m presuming again the fact that been through so much, that the lining looks good and what we found in our particular experience with tested normal embryos that it’s critical if you can to put them back in the natural cycle, so you get a much better pregnancy rate if you use the natural cycle in terms of timing the natural cycle, releasing the egg and timing the transfer for 5 days afterwards. There are also some new tests available these days where you can go and biopsy the uterus and see if the uterus is synchronized, with the time that you’re putting the embryos back. I don’t know how much you’ve done, but those little tips will help.

I recently had a failed IVF with an egg donor. The embryo quality being 2BB. Would it be my underactive thyroid that caused me not to become pregnant with this embryo?

The answer to that could be yes, so if your thyroid is well controlled hopefully they have checked your antibody levels, and if there are antibodies again, we found that the protocol we use is really very effective. If it’s not a tested embryo even though it was a donor egg, you’ve still got around 60% pregnancy rate with one embryo transfer, and it might go up to 75% if you’re having 2 embryos, but it’s not a 100%. As I said, in the beginning, most of the time the failure will be related to the embryo, but I must say that because you have a thyroid problem make sure you’ve had your antibodies checked, and one needs to manage that antibody environment to prevent rejection of the embryo.

I have hypothyroidism & I’m taking thyroxine. During egg retrieval,l 3 oocytes responded to stimulation, but it was cysts. Could this be due to underactive thyroid? What can I do for a successful IVF next time?

As long as that thyroid is controlled, then it wouldn’t have been directly related to the thyroid, but it needs to be properly controlled, so the levels need to be normal, and then the other thing is that needs to be checked is what we discussed fasting insulin levels, which can play a big role, and then prolactin can definitely play a big role. The thyroid and prolactin are linked. So your prolactin levels need to be normal. What I often do if someone’s got a thyroid problem, I tend to let them come in a natural cycle and have a look at that physiology in that natural cycle and see if their lining is perfect when they’re not having an IVF program. If it’s not right to try and find a way of improving the natural look of that uterus, the natural physiology. If you can get the natural physiology to go well, then one should be able to retrieve better eggs the next time, and sometimes it’s also just changing the stimulation in order to achieve a better result.

What is the effect of hyperthyroidism on fertility?

In terms of hypothyroidism often has a similar effect. So, if you have a hypothyroid, overactive thyroid, those patients are going to be jittery, they’re going to lose weight, they are irritable. From a thyroid point of view, it can affect the lining of the uterus. It is best to make sure that the overactive thyroid is controlled. Once it’s in the normal range it doesn’t have an effect on that. Just remember that often those patients also have an antibody, so if you’re either fall pregnant naturally, or you would have had an IVF, it’s important to treat the antibody in terms of that protocol that I mentioned.

Could ADHD/anxiety medication impact on prolactin levels?

Yes, absolutely, any of those central nervous system drugs can affect prolactin levels, so it should be checked and controlled. You cannot generally have too low prolactin, but it can fluctuate, usually, it shows up on a program because the lining is not good during the program. Obviously, patients can have headaches, and they have other symptoms, but it should be checked in anyone that’s going to have an IVF program should have the insulin, prolactin and thyroid checked.

Are there specific tests for thyroid patients when it comes to IVF and implantation?

When it comes to the levels of thyroid, you want your TSH, T3 and T4 and antithyroid antibodies, so those things in terms of control you want your TSH to be below 2.5 and you want your T4 levels which is the level of hormone that is active in the body to be in the mid to high-range. As soon as pregnancy takes place, the demand for thyroid hormone goes up, and you don’t need more tests than that. It’s a really simple and straightforward test.

I have been told, I have cysts and fibroids, but I am not told this is preventing a successful embryo transfer. I have had four failures. What should I ask to be tested for? I have hypothyroid and type 2 diabetes. I’m controlling my diabetes, but my last test result reading was 51, should I go on Metformin now before my next transfer?

You’ve been diagnosed as diabetic, and generally, people with type 2 diabetes always have raised insulin levels. If one’s trying to manage one just by diet in terms of fertility, it’s better to be on Metformin and to try and bring that insulin level below 9. It plays an important role, I gather from a cyst you have probably you’ve got polycystic ovaries, so you will get better quality eggs if you control insulin levels, and as far as the thyroid goes back to the story we need to control, it properly because it can also cause problems with the quality of eggs and number of eggs, and a number of blastocysts that are formed. From our point of view if fibroids are close to the lining of the uterus so if they are closer than about 3-5 millimetres, they’re not pushing on the cavity of the uterus they will definitely affect implantation. We do see in a lot of people worldwide, that they don’t pay attention to that. From our point of view, if a fibroid is close to the uterus, it’s going to cause a problem with implantation. These days if one focuses on getting rid of those fibroids, you definitely will have a better success rate especially if you’ve been having failures, and 4 failures is a lot. I think you need to also just make sure that there are no antibodies whether that’s thyroid or antinuclear factors or endocardial lipids. There’s a lot of immune factors that they should be paying attention to as well. They should be managed from the transfer up to the 6-8 up to 10 weeks of pregnancy.

You mentioned fasting insulin earlier, is that HbA1C?

HbA1C is a measure of glucose in the haemoglobin, in our bodies. That is for a diagnosis of diabetes insulin is a separate factor it’s measured separately it’s not routinely measured, we measure it routinely. Most people that come for treatment are not diabetic. We see diabetics, but they’re not diabetic, their insulin is raised, they are called insulin resistant, they are called pre-diabetics sometimes, and at the end of the day it’s a different measure. It’s a specific thing that needs to be asked for and it actually quite dramatic how many people have raised insulin and how rewarding it is to treat it, and in some people, that’s the only reason they’re not falling pregnant because their insulin is playing a role in the female in creating an abnormal egg and creating an abnormal environment you put them on it the insulin goes to normal, and you get pregnant. It plays a big role in the male, so they are different tests.

Does acupuncture help with fibroids or a healthy embryo?

If we look at fibroids they will definitely not be affected by acupuncture. They definitely can’t get smaller, it is a benign tumour, it is there, it’s got a blood supply, it won’t disappear with acupuncture. As far as healthy embryos go, acupuncture has some value in some people where it has an anti-stress mechanism, it has been shown in some studies to be helpful in terms of implantation of the embryo. Having said that I personally do not believe it will make an abnormal egg into an abnormal egg, but I think acupuncture for people that like going for it and enjoy it and are not stressed, it has definite benefits for that group of people.

I have raised insulin, but I can’t take Metformin at the moment due to fibromyalgia. What medication can I take?

That happens to some of the patients. That natural product that I mentioned is inositol, and different types of inositol are available. In research projects, it has been shown, it is effective during IVF to be of benefit, but you know so you can take that but what is critical then is also to be then on a strict eating plan in relation to carbohydrates. There is also another drug that we are using in a very specific people called Galvus, it’s a relatively new anti-diabetic drug, and it might be tolerated more in fibromyalgia, and that could be used if you’re really struggling to manage the insulin levels, but otherwise, inositol which is a natural product that’s very strict dietary habits will get that right.

What is the lowest acceptable TSH level?

That is a good question because you’ll find people over worry about TSH levels. What we need is a TSH level below 2.5 and anything below it, and then the T4 level, which is the measure of the hormone that’s actually doing the work needs to be normal. There is no such thing as a too low TSH level, so long as the T4 is now not becoming overactive so you don’t want to overtreat someone so the T4 needs to be in the normal range and then one can ignore the TSH level so long as it’s below 2.5.

How much is my endometriosis affecting my blastocyst transfer?

Endometriosis has always been a contentious thing. From our point of view, it’s played a major role. It can play a major role in egg quality, so if we look at someone who we know has endometriosis and they go through an IVF process, 80% of the time the IVF will not be affected by it. 15-20% of the time the endometriosis hasn’t been treated. Usually, that treatment would be a laparoscopy. In that 15 to 20% it can affect egg quality, it can affect embryo quality, therefore, and it can affect implantation, so if you’re having recurrent failed blastocyst transfers in our opinion it’s important to manage endometriosis and not ignore it.

Any natural elements one can take to raise healthy embryos?

If you are deficient of vitamin D, you should be on vitamin D, coenzyme q10 plays a role in women with very low egg reserve, DHEA can play a role in helping eggs. We do put all our patients on a combination of inositol which is the thing that helps insulin, coenzyme q10, certain vitamins and certain amino acids. We use these products almost routinely in our female patients and in our male patients in South Africa. We use a product called StaminoGro which has high protein amino acids in it, and those amino acids have been designed in such a way to boost growth hormone, and that’s given to our males at night to boost sperm together with all the other essential antioxidants and those are all important things, so balanced eating plan and taking extra minerals and vitamins and amino acids do play a role. They’ve all been shown to be worthwhile.

Does hypertension (managed with Labetalol) impact a successful pregnancy in any way?

The Labetalol is a beta-blocker so that won’t prevent pregnancy, so no problem with that.

I am 48. Would you suspect endometriosis if there are no symptoms of it and it doesn’t show on a scan but I had 6 failed implantations? All donor transfers. I had a natural pregnancy that ended in a missed miscarriage at age 45.

The interesting thing about endometriosis is it doesn’t directly affect implantation, so it has more effects on egg quality and what kind of quality of egg you get and obviously natural pregnancies if there’s endometriosis it has a dramatic effect on the mucus and mucus is affected at the time of ovulation, it acts as a barrier to entry for the sperm. In terms of this particular patient, the endometriosis wouldn’t have played a direct role. Having said that endometriosis is an autoimmune disease you’re having cells growing in the abdomen, so there is definitely an association between endometriosis and other conditions including thyroid including the other antibodies such as endocardial lipid antinuclear factor and obviously as I mentioned earlier prolactin levels can also be raised.

It’s a question of just making sure that that uterine environment is perfectly fine, the problem with the polyurethane usually they are not ovulating or not properly so you cannot use a natural transfer and so these extra little things need to be taken care of to make sure that environment’s right and as I mentioned earlier your fallopian tubes open or any of them blocked which can actually then lead to fluid killing off the egg are there any fibroids or septums in the uterus, so those things have all need to be answered but endometriosis on its own, will not affect this outcome.

I was told that fibroids assist with the pregnancy when I was 28. But he removed it, and I lost the baby.

That’s a bit contradictory but at the end of the day if the fibroid was removed and the uterus was normal, and the operation was done fine then the loss of the baby would not be directly linked to the fibroid unless there were more fibroids. Having said that there is a condition that looks like fibroids called adenomyosis and I’m not saying you have that, but adenomyosis is like having endometriosis in the uterus, and it causes a very thickened muscle in the uterus. Those particular patients definitely have a higher incidence of losing babies between 12 and 28 weeks. It’s actually affected the muscle, you can’t cut that tissue away, so again hard to judge this particular situation but if the uterus was normal after the operation then generally you would not have lost the baby related to the fibroid itself or the removal of the fibroid.

Antonio Rodrigues, MBBCh, FCOG, MBA

Antonio Rodrigues, MBBCh, FCOG, MBA

Antonio Rodrigues, MBBCh, FCOG, MBA, is a Reproductive Medicine Specialist and the Founder and Director of Medfem Fertility Clinic in the Republic of South Africa. Dr. Antonio Rodrigues is a founding member and director of Medfem Fertility Clinic. Over the past 14 years, Tony has taken a special interest in the diagnosis and management of Time Urgency Stress in infertile women with special reference to endometriosis, and in this time has assessed over 4000 patients. In addition to his fertility background, Tony is an expert in lifestyle and its effect on the fertility of females and males. Tony is also an expert and leader in minimally invasive surgery. Medfem Fertility Clinic is one of the first institutions in South Africa to have developed a fully comprehensive operating theatre with all the necessary equipment to perform minimally invasive surgery. The specialists at Medfem Fertility Clinic have all undergone extensive training abroad and teach endoscopic surgery on an ongoing basis to visiting gynecologists.
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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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