Endometriosis and infertility

Harry Karpouzis, MD
Fertility Specialist; Founder & Scientific Director, IVF Pelargos Fertility Group


Endometriosis and infertility #OnlinePatientMeeting
From this video you will find out:
  • How can endometriosis affect fertility?
  • Does endometriosis affect the quality of the eggs?
  • When do we need to operate on an endometrioma before IVF?
  • Do we always need GNRH agonist injections before IVF?
  • Is laparoscopic surgery always required before IVF in patients with endometriosis?

Endometriosis and its impact on your fertility

Watch the Online Patient Meeting with dr. Harry Karpouzis who is answering the most common questions about endometriosis and infertility.

- Questions and Answers

How can endometriosis affect fertility?

The most common way is that we know that endometriosis can cause adhesions, scar tissue, that can alter the relations of organs inside the pelvic anatomy and what can affect the tubes. Many times when endometriosis is advanced, there is a blockage on the tubes, or hydrosalpinx and is this obviously affect fertility. It’s not the only way, we know that endometriosis may affect the amount of the eggs. There is plenty of research, even though it is not conclusive evidence that it can affect the quality of the eggs, of the embryos, it can also cause problems with fertilization, moving of the sperm by local inflammation, all these ways contribute in infertility. Patients that have endometriosis very often also have some immunological issues. The immunological theory behind the endometriosis can play a role as well, in this way it can also cause problems with implantation. It can affect fertility in many different ways, some of them are still not very well understood.

Does endometriosis affect the quality of the eggs? 

The answer is not clear. First of all, the quality of the eggs has nothing to do with the quantity. The quantity of the eggs is something that we measure with AMH, FSH. Endometriosis and previous surgery can affect the quantity, but we have quite a lot of research that shows that the quality of the eggs can be affected, as well f.e. we have studies where we compare treatments from eggs that came from women with endometriosis to women that didn’t have endometriosis, it has been found, that there was a decrease in success rates in women with endometriosis, the reason is the egg that is coming from the women with endometriosis, it has been proven that it is the reason that the embryo is not good quality and is not implanting, it is not conclusive, but there is some evidence that the quality of the eggs can be affected. The blood flow to the ovary is affected by endometriosis, and this may compromise the quality of the eggs. F.e. we have hormonal changes in the local environment of the ovary, and again this can compromise the quality of the eggs, and in the end, we are 100% sure that endometriosis is inflammation. This makes a lot of substances to go inside the pelvis and this toxic environment is suspected to affect the quality of the eggs as well.

When do we need to operate on an endometrioma before IVF?

This is a very tricky question, and this is a very difficult question. It’s not realistic to give a certain answer. So I don’t like to put labels f.e. when endometrioma is more than 5 cm we do operate when it is less, we don’t, it’s not like that. Every case is individualized, we need to exactly see what is happening in every case before we decide if we operate endometrioma or not. This is very important because surgeries can play a negative role many times, and if the surgery is not done properly, and something goes wrong, the surgery can compromise the AMH, reduce the quantity of the eggs, so we need to make a very careful decision on whether to operate it or not. In general, we need to operate endometrioma when we cannot access the ovaries, f.e. when we have a very big endometrioma, usually more than 5 cm and the ovary is displaced, and we know that we cannot access the ovary because of that, then the surgery would be important. On the other hand, if the AMH is reduced already, then surgery needs to be balanced because we know that after the surgery, the AMH goes further down, especially if the technique is not perfect, so the decision for the surgery also depends on the AMH, and it is important to check the AMH before the surgery so that we can compare the result before and after the surgery. We definitely know that big endometriomas can affect the quality of the eggs more. If we have an ovary that has been operated on before, we try to avoid the second surgery, nowadays, the data show that on very rare occasions we would reoperate on the endometrioma and ovary because this can reduce the eggs a lot and it might be very difficult to stimulate the ovary for the IVF treatment.

Do we always need GnRH agonist injections before IVF?

Well, the answer is no. GnRH agonist injections are Zoladex, Gonapeptyl injections, lots of people that have endometriosis have heard about them. In the previous years, we preferred to down-regulate the ovaries. Nowadays, what we usually do before in IVF protocols, especially if we have reduced AMH and poor ovarian reserve, is we go ahead with the protocol straight away without suppressing the ovaries because with those injections we can down-regulate the ovary and then make it more difficult to get the eggs, we stimulate the ovaries, we get eggs, we fertilize them, we create embryos, we freeze them by vitrification and the success is almost the same as in fresh transfers nowadays, and then if there is a lot of endometriosis, we prefer to give the GnRH agonist injection before the embryo transfer, so that we can suppress the disease and increase the chance of implantation. The timing of GnRH agonist injections is very important. Usually, we prefer not to give it before the IVF. At least here in our unit, unless there is an ovary that has been operated on before, we don’t want to operate again and we try to minimize the size of endometrioma so that we can access the follicles.

Is laparoscopic surgery always required before IVF in patients with endometriosis?

The answer is no. If the infertility is associated with pain as well, then maybe surgery is needed because it treats the pain. If the infertility is not associated with pain, the main reason that someone wants to have the surgery is infertility, then we need to balance all the factors. First of all, we need to see if we have other factors that lead straight to IVF, or not and to decide depending on what exactly we have. If we have made the decision already on IVF, and we have mild endometriosis only, then surgery is not necessary. If we have a grade 3 or grade 4 of endometriosis and we haven’t operated before, and we have a good AMH, the surgery may be needed, but if the AMH is compromised and the access to the ovaries is good, then maybe it would be better to go straight to IVF and consider surgery before frozen embryo transfer.

What do you think about agonist gonadotropin-releasing hormone(GnRH) 3 months before IVF?

As I’ve mentioned it depends on your AMH if you have a poor ovarian reserve or not, in such cases, I usually prefer to avoid it before the IVF as far as the ovaries are accessible. We use GnRH agonist, especially if you have severe endometriosis before the frozen transfer. I prefer to freeze, give GnRH 1,2 or 3 months depending on the stage of endometriosis, and then do the transfer.

I am 35 years old and have endometriosis. My doctor says that although my illness is advanced, he doesn’t think that it is the reason why I didn’t get pregnant. I have had a laparoscopy and several hysteroscopies and he considers that my uterus is not very bad, except that they found endometritis a year ago. It was treated, but I could not get pregnant. I had ICSI procedure as well. I have been diagnosed with implantation failure. Blastocysts are healthy, but when I get pregnant. I have a biochemical pregnancy, but mostly the result of the transfer is negative. I have achieved a natural biochemical pregnancy with a tube and chromosomal translocation in my husband’s karyotype (that’s why we have done PGD). Do you know many patients with endometriosis and implantation failure? Previous transfers, the doctor took a hydrosalpinx from me. I produce a lot of eggs. In one cycle they got 32. I would also like to know if I have endometriosis, is it better to consider to do a natural cycle transfer? I have read that endometriosis patients need a few hormones.

There are a lot of things here that would require a proper consultation. It wouldn’t be right to comment on your case just from this information. By any means, let me try to tell you a few things. We know that there is a translocation in your husband’s karyotype, this is an important factor, and in such case, PGT-SR is required, and many times we need to have a lot of blastocysts, only to find one that is chromosomally normal and will get implanted. This can also be a reason for the failure of implantation. The fact that you produce that many eggs at the age of 35, shows that perhaps you had also PCOS in the past because it is a very big amount of eggs, which is not bad in your case, because we need many eggs to get chromosomally normal embryos. Since the hydrosalpinx had been removed, and you’ve done hysteroscopies and laparoscopy as well, I am not sure if implantation failures only depend on the endometriosis or not, but it is possible. Because of your history, and unexplained failure of implantation, I would advise to down-regulate you with GnRH injections before a frozen transfer so that we can suppress any disease, perhaps that would increase the chances of implantation. In many cases, it is associated with immunological issues, it is not clear if you’ve done any natural killers etc., but I would cover you with some immunosuppression as well. After embryo transfer like intralipids or steroids. Endometriosis is associated with some problems with endometrium, with the lining of the womb, implantation. We do see local inflammation from endometriosis on may occasions, sometimes we do suggest some antibiotics as well before embryo transfer, especially if there is an element of endometritis as you’ve mentioned. If the previously failed transfer was unexplained, I would also suggest an ERA test, to make sure that the implantation window is right or not. I cannot confirm that endometriosis is definitely the reason for failed implantation but since you know you have endometriosis GnRH as I’ve said, might help.

Does diet play a role in endometriosis?

Yes, in any infertility cases, a healthy diet and a healthy lifestyle do play a role. When it comes to endometriosis we know that antioxidants, a lot of vegetables, fruits can help with endometriosis, we actually cooperate with a dietician who is quite innovative in diets that can help. You need to know that this is not randomized and conclusive evidence behind it, but there are reports which are quite well explained from the mechanism of endometriosis. I am not saying that it will get you pregnant, but they can help either in combination with fertility treatments or spontaneous conception.

If endometriosis has affected the egg quality, but your uterus is clear and there is no endometriosis in your tubes. Could you still get pregnant naturally?

It depends on many factors as well, let’s take for granted that we don’t have any other factors like sperm decrease or anything else. I suspect that you’ve done an IVF, and the quality of the eggs and embryos was not good. This may be associated with endometriosis, but it can also be associated with your age as well. But if you have been trying for 6 months or 1 year, you can try a bit more but if you have been trying for 2 years and have done IVF, and there are no good quality eggs, then maybe the best option for you would be IVF. The quality of the eggs is something that you don’t know if you don’t do IVF. The quantity of the eggs can be assessed by the AMH, FSH, but not the quality.

How we can reduce inflammation, is there anything we can take?

If we are talking about someone that has endometriosis and it is painful, the anti-inflammatory drugs can help with that. If we’re talking about endometriosis and infertility, the point is not exactly to reduce the inflammation, it is to take the general picture and to see what is the best treatment whether it should be IVF or surgery because surgical removal of endometriosis reduces the inflammation as well, we help to build a healthier environment that can help with the quality of the eggs but can help with implantation as well. It is not the only solution, every case is different, the most important thing in treating endometriosis and infertility is to make the right decision whether we need to operate or not if we need to give GnRH or not, it all depends on each case.

If I had stage 2 endometriosis removed 2 years ago, is it likely to have grown back by now?

It is likely, especially if you were not on any pills or you were not on any suppression of hormones, it is quite likely it is back now.

Is there a higher chance of getting cancer in later age if I’ve had endometriosis all my life. It keeps growing back even after 2 laparoscopies and 2 hysteroscopies?

To be honest with you, it is a benign disease. When we have endometriosis, and we have endometriomas, we have cases that have to go from benign to malignant. When the endometrioma is growing quite fast or when f.e. special blood test like CA125 are going high, those are the things that sometimes can give us a suspicion of checking a bit more. It is not the case though, that if you have endometriosis, you will have cancer. Even people that had endometriosis just once, it happened that they got cancer. This is very uncommon, it’s very rare, and it’s not the case. When we see something like an ovarian cyst or endometrioma is getting bigger, then we need to investigate further.

Is there some sort of test we can do to ensure I don’t have endometriosis before my IVF with donor eggs?

Yes, apart from ultrasound if it shows that you have a cyst-like endometrioma, it will give you a clear suspicion of endometriosis, it’s a clinical picture. We don’t suspect endometriosis if we don’t have any symptoms at all, and the symptoms are like menstruation pain, or during sexual intercourse. If there is a high suspicion of endometriosis, then the golden standard of diagnosis is laparoscopy. We put the camera inside and that way we can identify if there is endometriosis or not. This is the only test that gives 100% confirmation. If it is really needed or not, it depends on how high is the suspicion and what has happened before, if you had failed implantations etc. because if there are no symptoms, you don’t really need a laparoscopy before the egg donation treatment.

Can endometriosis be related to fibroids behind the uterine wall?

No, endometriosis is not usually related to fibroids. Endometriosis can sometimes be related to adenomyosis which is a fibroid-like disease in the womb. Patients who have endometriosis have a higher degree of adenomyosis. Adenomyosis is suspected in an ultrasound, but it’s clinical actually, we cannot remove adenomyosis like a fibroid in a surgery.

I have a high NK Cells in the uterus, it is because of endometriosis and adenomyosis?

No, I wouldn’t say that. But as I’ve said before patients that have endometriosis, they have a higher degree of other immunological issues as well or increased natural killer cells, but women with increased natural killer cells it does not mean that 100% it would be related with endometriosis. So it may be associated because we have found out that there is a correlation, but there is not 100% that endometriosis has caused that.

I’ve read that endometriosis can travel to other parts of the body f.e. lungs, heart etc. What are the symptoms?

It depends on where it goes, so f.e. if it is in the lungs, then we have Hemoptysis, which means that when we cough, we may have blood. If it is in the bladder we may have increased urine frequency, there might be blood in the urine, on very rare occasions if it is in the heart, we may have some arrhythmia, it depends on where exactly it is, but it is very rare.

Which is the best protocol in IVF endometriotic patients?

There is no perfect protocol for everyone, there might be a perfect protocol for each case. There are many different factors we need to consider before choosing the best protocol. It depends on age, it depends on factors like PCOS or not. As a general rule though, the endometriosis is associated with poor ovarian reserve, and we prefer in our clinic, not to suppress a lot the ovaries before we stimulate them, and we always prefer to freeze, especially in high degree endometriosis and do a frozen embryo transfer. The protocol depends on many factors, AMH, age and so on, so it is not possible to answer this question.

What do you give your patients with adenomyosis? Decapeptyl depot, Visannette or other medicines? How long?

I usually do that. I prefer to give this medication before the frozen embryo transfer then before we do the embryo transfer, especially if we have a big size womb of more than 8 cm f.e., I do prefer to give about 2 to 3 months of Decapeptyl, which suppresses a bit the adenomyosis. Visannette is an option as well, but in our clinic, we don’t use it that much in that case.

Can endometriosis be inherited?

It is one of the theories behind the endometriosis that there is some genetic background. We don’t know exactly what way, it is not confirmed 100% that there is a hereditary background. It is not the only theory behind the endometriosis though. It doesn’t mean that if your relatives or your mother doesn’t have it, you will not get it.

Is there any evidence for aspiration of the endometrioma before IVF cycle?

We don’t usually prefer to do that. If we aspirate the endometrioma will definitely come back. When we aspirate endometrioma, it may cause bleeding. It’s not a preferred way of doing that, even at the time of egg collection. If we do see endometrioma, we try to avoid it to aspirate the follicles first as if we do it the other way around it may affect the amount and the quality of the eggs.

During OPU (oocyte pick-up) if my needle enters in the endometrioma what will happen?

It does happen sometimes because it is very difficult to get all the follicles without passing through endometrioma. The right technique is to change the needles, get a new one and carry on with the egg collection and at the end of egg collection, to make sure that there is no bleeding or anything else.

I am 47 and had 2 IVF with my own eggs and 2 egg donation. I didn’t succeed in implantation, but with egg donation, I did get pregnant, then miscarried. Am I eligible to get pregnant again?

Definitely, you are eligible, you did get pregnant, so this is a good thing, you need to investigate all the possibilities reasons why you had that miscarriage, sometimes it can be just bad luck, sometimes the endometriosis may play a role but, it can also be related to other things so I would suggest f.e. hysteroscopy to make sure there is nothing in the womb that can affect that. I don’t know if after the embryo transfer you got steroids or intralipids for immunological reasons. Or if you had thrombophilia checked, or a DNA fragmentation for your husband has been checked as well because the sperm, of course, does play a role in all this. If you ruled out all the other factors, you are 47, so I would not quit.
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Harry Karpouzis, MD

Harry Karpouzis, MD

Dr. Harry Karpouzis is an Obstetrics and Gynecology Consultant, specialized in Reproductive medicine/infertility and minimally invasive surgery, with over 7 years of full-time experience in the field of assisted reproduction. Dr. Karpouzis was fully trained and specialised in the UK. He has worked at some of the busiest hospitals in London (Guy’s & St. Thomas NHS Trust, King’s College Hospital, Newham University Hospital, University College Hospital, Homerton University Hospital. He has been a member of the Royal College of Obstetricians and Gynecologists since 2011 and is a scientific director and founder of IVF Pelargos Fertility Group.
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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.