In this webinar, Dr. Harry Karpouzis, MD, Founder & Scientific Director at IVF Pelargos Fertility Group, Athens, Greece has been explaining how endometriosis can affect implantation rates and what can be done to improve your IVF chances.
In the first place, Dr Karpouzis addresses the significance of endometriosis in the field of infertility as it affects not only 7-10% of women of reproductive age but also the quality of life for these individuals is compromised. On top of that, it is mentioned that 25%-50% of women are infertile. In comparison, another 30%-50 of individuals are said to be subfertile.
According to the doctor, endometriotic lesions are described as having a variable appearance. On the one hand, typical early red lesions, adhesions, and powder burns are likely to be found, whereas lesions of deeply infiltrating endometriosis are known to be of a yellowish serous type and considered atypical. On the other hand, regarding the ovaries, endometriomas and sub-ovarian adhesions are highly likely to develop. All in all, many theories can explain endometriosis to some extent such as the transplantation theory and coelomic metaplasia.
The most significant theory is the one of retrograde menstruation. According to this theory, at the time of menstruation, the period can go through the tubes inside the tummy and remain implanted over there. In addition to this theory, this fluid can stimulate the immune system to cause natural killer cells that can produce a toxic environment for the endometrium in the long term.
Speaking of the grading, the doctor stated that the stages are determined by a point system during surgery. Stages are classified by the amount of size, location, depth, and adhesions.
As indicated by the doctor, it is common knowledge that endometriosis can cause infertility due to mechanical causes that can either affect the tubes or the ovaries. As previously mentioned, the inflammation markers of the endometrium can affect sperm mobility and ultimately implantation. In addition, the immune system response is also said to be altered as a reaction in the form of anti-endometrial antibodies might be likely to take place.
Hormonal factors are also known to be involved as indicated by the doctor since a deficiency in the second cyclic phase is to be encountered as well as increased prolactin that affects fertilization.
Firstly, ovulation is affected by structural alterations in both the ovaries and the tubes. Therefore, a reduction of ovarian reserve is highly possible in these cases. Endometriosis is widely known to cause endometriomas that can mechanically damage the ovarian tissue affecting the blood flow. Altogether, a toxic environment is the result of it.
As it was explained in the webinar, AMH levers are expected to be lower in patients with severe disease. In the same way, women with unoperated endometriomas were found to have a lower AFC level as well in comparison to contralateral healthy ovaries.
The implantation of the embryo depends on the quality of the egg and the endometrial receptivity, as an alteration of the interaction between the embryo and the endometrium is related.
As stated previously, the golden standard for diagnosis and treatment is laparoscopy, which was proved to be enough to make a diagnosis. Moreover, it was proved that the surgical treatment of endometriosis improves the spontaneous conception rates in mild cases. Concerning severe cases, when surgical treatment is necessary, an experienced surgeon will be highly regarded for the performance as it is described to be a difficult surgery that commonly entails a slow technique and avoidance of blood loss. Moreover, the surgery itself in the ovaries is known to reduce the ovarian reserve and AMH levels.
Nonetheless, regarding spontaneous conception and IVF, there is an increase in pregnancy rates. According to the NICE and ESHRE guidelines, a laparoscopy can increase spontaneous conception and possibly IVF conception as well based on some research as stated by the doctor.
Alternatively, concerning pregnancy rates, the existence of an elevated expression of protein bcl-6 is known to be associated with low pregnancy rates and inflammation of the endometrium, which is usually caused by endometriosis. Therefore, the biopsy of this protein is a way to identify endometriosis as well.
The removal of a big endometrioma is not necessary in all cases as it causes a lowering of ovarian reserve, so removal should be executed when pain is present.
Clinicians can prescribe GnRH agonists for a period for a period of 3 to 6 months before treatment with assisted reproductive technologies to improve clinical pregnancy rates in infertile women with endometriosis.
It is confirmed that repeated surgery for endometriosis in women with poor ovarian reserve can further compromise AMH and AFC.
Repeat surgery in ovaries must be avoided in women seeking fertility
Even though the previous data suggested that higher amounts of eggs and more availability of embryos to freeze could be achieved with a long protocol it was later proved that long protocols are less convenient due to increment of injections in the individual. Therefore, one viable option is the pre-treatment.
Finally, as stated by Dr Karpouzis, conclusions are associated with the causes of implantation failures in endometriosis, which are caused mainly due to eggs/embryos. Immunological factors and toxic natural substances can also affect the implantation. Furthermore, surgery to treat endometriosis and endometriosis itself can reduce the ovarian reserve. In order to properly treat patients with endometriosis, a complete evaluation is necessary, as every case is different.
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IVF bypasses a lot of endometriosis issues, for example, if the tubes are blocked, then the only solution is IVF. If the AMH is very low, then all other treatments have much lower chances of success. If there is a lot of toxic environment inside the tummy with the correct protocol and fertilization outside the body, we can increase the chances of creating a good embryo. Definitely, IVF, as I said in the presentation, is the best treatment, but as we know, IVF does not guarantee anything in any patient, I mean even in women who are 30-years-old. IVF has got a ceiling of success rates, and we don’t know why it doesn’t work in some cases. Endometriosis is a very weird disease, there are a lot of things that we don’t know about it. In general, the success rates in endometriosis patients are lower without really knowing why it is lower even with IVF. IVF is the best treatment and bypasses a lot of issues, so no, they are not wrong.
You need to go ahead with IVF because I don’t know how long you’ve been trying, especially if you’ve been trying for more than one year or more than that, the answer is IVF. I wouldn’t operate you either with that low AMH. I would start with a protocol with the right dose and the right protocol and stimulate your ovaries because you do have disease inside your tummy, and you do have active disease. According to our protocols, if we get embryos and we have some good embryos, we would probably freeze them, down-regulate the disease with GnRH injections, and then transfer on a frozen cycle. Every clinic has got its own policies and its own protocols, so that can differ.
I was trying to explain the ways that endometriosis affects the ovaries. One of the ways is that endometriosis is deposits of blood inside the tummy. Blood has got iron inside, hemoglobin has got iron, so we have a lot of iron inside the tummy because of the disease, and this iron can be toxic to the ovaries. This is a theory to show how it can affect the ovaries, so it’s not anemia related, it doesn’t have anything to do with that. About the miscarriages and the inability to get pregnant, it depends on many things, it can depend on the disease itself, the quality of your eggs, your age, and other factors. There are a lot of investigations of miscarriages that most probably you have already done, and usually, IVF is the best solution, but it depends on your medical care.
GnRH analogs medications are injections that are given to down-regulate the ovaries, or they can be given daily for 14 days in a smaller dose to do the same job. Actually, GnRH is a medical treatment of endometriosis but not only endometriosis, it suppresses the ovaries and the disease at the same time, which is dependant as we know on hormones, it controls the hormones so that we can deactivate the disease and transfer embryos or stimulate the ovaries.
There’s a long protocol that we give injections for many days, which are different, it’s GnRH agonist. In a short protocol, we give injections for less time, and we use a different sort of medication to prevent ovulation, which is the antagonist. Every protocol depends on its independent situation, on the age, the AMH. In our clinic, we usually prefer to use the antagonist protocol, which is more convenient for the patient as well. We think that we get more eggs, and we prefer freezing and transfer on the frozen cycle after we down-regulate the ovaries, and we down-regulate the ovaries with the injections that I just mentioned before or the pill, the combined pill. In a frozen embryo transfer, you can do it in 3 ways. The first way would be in a natural cycle.
The second way would be on an estrogen replacement, which means that you get estrogen to increase the thickness of your endometrium, and then you start the progesterone. There is a third way, which is to suppress the ovaries. We suppress the ovaries by the GnRH analog injections, which are given either on day-21 or day-1 of the cycle. After that, you start the estrogen replacement. In endometriosis usually, we prefer to do that especially, if we know or we suspect that there is active disease inside.
Keeping a healthy lifestyle, taking some multivitamins, some antioxidants, avoiding smoking and drinking alcohol, such things can help you with endometriosis actually, that can help in the IVF or the medical treatment to get better results.
When you don’t have surgery in the ovaries, and you have surgery in other parts of the tummy, usually this surgery does not affect the AMH. The disease itself even, without surgery can affect the AMH, and as I said in my presentation, we have seen that women with endometriosis even with endometriomas or without endometriomas, which means even with cysts or even without cysts have been shown to have lower AMH. There is data that shows that it’s not only that the AMH is lower, but it’s also declining more steeply. Your low AMH can depend on the disease itself or can be completely irrelevant. It’s not because of a surgery, that doesn’t have to do anything with the ovaries. If you are in pain, it is a priority if you need to make the quality of your life better, then surgery is needed. If it is a matter of fertility, then it needs to be a very well balanced decision. Given the fact that you have some eggs stored and frozen, this is a good investment.
If we are talking about fertility, there is no golden standard of what we need to do or what protocol we need to use. That’s what I have explained in the presentation. There are many different things that we can do and what we need to do in each case depends on it. It’s a personalized decision, it depends on many things like ovarian reserve, the grade of the disease, the age of the woman, of the tubes if they are patent or not, many things.
The upper age limit to have IVF in Greece is 50 years old. We cannot do egg donation or IVF after 50. If we are talking about IVF with own eggs legally, it can happen up to 50, but for patients over 45 years old, the chances are very low.
First of all, when you have a frozen embryo transfer, there is no ovulation. The whole point is not to have ovulation, so if you are having a cycle with estrogen usually, you take the estrogen between 12 or 18 days depending on if the lining of your womb will increase in size nicely or not. Then, you need to start the progesterone, and depending on embryos, you have day-3 or day-5, and then you have the embryo transfer. If you have frozen embryos, the whole point in transferring an embryo is to stimulate your ovaries, to prepare your ovaries with estrogen so that you can increase the lining of your womb. You don’t want ovulation at the time of the frozen embryo, so the pills that you take stop the ovulation.
It was a 47-year-old woman, but it doesn’t happen often. We have 1 patient like this every year. Honestly, the chances with own eggs at the age of 47 are very, very low, and at the age of 45 and more, the chances of success are very low. Depending on the case and AMH levels, someone can try as long as the person is aware of the real chances. I always try to be honest with my patients and give them real chances, and then the decision depends on them.
There are other ways of doing it, you can do it in a natural cycle or with Letrozole, which is a special medication that keeps estrogen low. There are other options, if you cannot take any estrogen and there is a specific reason for that, then yes, you can do it in other ways.
Some data is non-conclusive that relates endometriosis with miscarriages. Fibroids also can cause miscarriage depending on their position, but not all fibroids. If we have a fibroid that is outside the cavity, then usually that won’t cause miscarriage. Can repeated IVF cycles increase and worsen endometriosis? The answer is yes, it can happen. If there is an active disease at the time of the stimulation, sometimes we see that the disease may flare up, but of course, if you get pregnant, then the disease is getting much better. It’s the same with cysts in the breasts sometimes, an increase of estrogen can increase them but imagine that in pregnancy, the estrogens go up more, so this can happen in pregnancy too.
It needs to be more than 8 ideally, more than 9, sometimes more than 7, less than 7, is not good.
Usually, in a natural cycle when you do the embryo transfer, when you have a follicle, which is the right size, you do have an endometrium which is more than 7, you just need to keep an eye on the follicles. You need to know when you give the trigger injection when you have the embryo transfer. The correct timing of the whole procedure in the natural cycle is very important because sometimes the right timing can be missed. If there is a problem with the endometrium and it is not getting thick enough, then usually you cancel the cycle, and the next time you try with estrogen pills. You can also try another medication, which is called Letrozole if you cannot take estrogen, so there are options.
If someone has PCOS and needs IVF, there are special protocols that we can use to stimulate such patients. We minimize the risk of hyperstimulation, and we get as many eggs as possible, so it’s a different thing. There are a lot of people that are having PCOS and some of them, if they don’t succeed in pregnancy with other ways, reach the stage of IVF, and then we have special products for them. Usually, patients with PCOS have got a lot of eggs as well, so usually, we do get lots of eggs.
First of all, it is very good that you have 4 blastocysts, which means that you have reacted very well. We have a chance of success of about 45%, sometimes even more. At 40, one of them at least can be healthy, and you don’t need anymore, you need one to get a baby.
