In this webinar, Dr. Luca Gianaroli, Scientific Director of S.I.S.Me.R. located in Bologna, Italy, has been talking about reasons for failed IVF attempts and how to turn them into a successful outcome.
No, you shouldn’t be too worried because you shouldn’t forget that a part of the program in which you have a pregnancy guarantee. One embryo transfer appears to be considered from the physiological point of view, like you being a fertile, normal young woman having intercourse with a fertile man. If pregnancy does not occur, you are not surprised too much, so here you are comparing the same thing, and before being worried, you should have at least another or two other attempts.
I also agree with your clinic, it’s possible that it’s an implantation issue, and for this reason, before you go for another embryo transfer, you should do an endometrial receptivity array (ERA) test first.
What has been suggested and recommended to you is the right way to go.
Yes, I think that if hysteroscopy has not been done, it should be done just after the period, while a 3D ultrasound scan should be done in the luteal phase, so just before the menstrual period appears. It’s important to understand if your uterus is ready for implantation. I would not be worried about the endometrial receptivity. I would be happy to see your cavity as it has been already damaged by those five natural miscarriages.
There is not enough data showing that the TSH low level is crucial for implantation, but the range 0.5 to 2 is now an accepted range, and anything that can be done modulating or tuning the treatment the thyroid therapy or anything that could help to maintain these values is the most important thing. I think that skipping the medication as it has been suggested is correct. Actually, your TSH level looks like it’s being too compressive. That’s maybe stopping the treatment for a few days will make your TSH level increase and reaching the normal range. I am in favor of this decision.
If no pregnancy has occurred before and if your uterus never had a reproductive accident, miscarriages, or termination of pregnancy, or so on, then no. Otherwise, hysteroscopy is recommended, and don’t forget that at the age of 42, your chance of delivery is around 12-15%. If you want to have a decent percentage of a full-term pregnancy, you should enter the concept that you need 5-6 embryo transfers if you want to use your gametes. The fact that you had a pregnancy 12 months ago is encouraging because it shows that your body is ready to get pregnant. As you had an ectopic pregnancy, this could also show inflammation of the tube and a small malformation of the uterus, so it would be good to double-check your uterus and your uterine cavity before you start another cycle. It has to be done with double test 3D ultrasound and hysteroscopy.
I cannot answer the second part of the question as the price is very much depending if you’re using a national health service or if you’re going to a private clinic. I can tell you that in Italy both tests would cost not more than 600 EUR in a private clinic and they are for free in a public hospital. Hysteroscopy should be done just after the period, while a 3D scan should be done just before the period.
The only reason why growth hormone could be recommended is if you are a poor responder. Apparently, in some subgroup of poor responder patients, growth hormone seems to be of some benefit in growing more follicles, hat means more oocytes to be collected.
To say that there are only two options is too drastic, but if you want to look in a pragmatic way at the chance you have to deliver your baby and using your own gametes, your chances are extremely limited. It’s a combination of your age, AMH, and most probably how your body has been designed in terms of conception. Perhaps, you started to have periods quite early, or maybe somebody in your family had early menopause, your aunt, your mother, etc. It looks like your age is different from your biological age or the biological age of your ovaries.
Most probably if for you and your partner a baby is not defined as a complete overlapping of genetic material, but if for you, a baby is an individual that you are carrying on, that you are delivering, that you will educate, and you will accompany during his life, maybe the oocytes donation is a good program for you or is the best program.
Don’t check anything else but recheck your uterus because sometimes polyps can come back, and there is a tendency for patients that have a polyp to repeat the production of this pathology. That is not only a mechanical pathology, but polyp is a sort of the tip of the iceberg of inflammation. Actually, when you have a polyp, the total endometrium can be inflamed and thus imply a reduced chance of pregnancy.
The elective way to understand if you have inflammation is to do a hysteroscopy. There are now tests that are in progress that can avoid even the office procedure just producing or aspirating a little bit of fluid that is inside the cavity of the uterus.
Yes, you should, and you should also increase a little bit the amount of estradiol valerate because it would be nice if your lining were above 7.
I would say when you are desperate because the chance of getting good results in terms of being positive results from immunological tests is quite rare. You have to be sure that all the other aspects that we have looked at are negative, so keep this as the last point of your diagnostic procedures.
I would only suggest keeping the level of TSH in the normal range, as we have discussed before.
No, definitely not because it’s not going to make your oocytes better. It will only delay it and make it a long time to achieve pregnancy. Again, check your uterus and try to get as many eggs as possible. If you can produce many embryos, maybe you should accumulate after one or two or three oocyte recovery and do PGT-A to check the euploidy in one shot to reduce the costs. Since two accidents have occurred to your uterus in this case, hysteroscopy is compulsory.
When you have very large follicles that are not with the others, they look like follicles, but they are empty follicles, or it’s a small cyst with a very limited quality of egg if the egg is collected. You can collect, or you can aspirate follicles even if you have already ovulated, but to have good quality eggs, ovulation should have occurred very recently because otherwise also the remaining follicles, containing the remaining oocytes impair the quality of the gametes so, in other words, you will collect not very good quality oocytes.
It would be possible for the clinic to tell that this happened, but not with 100% accuracy. If you do a blood sample and you measure your progesterone, this could also be helpful to tell you the real story.
You can do it, but I’m not sure that it will help. If you tend to have a thin endometrium, I think that you should go for a full artificial cycle, starting with Estradiol valerate since the first day of the cycle and carry on with 4-6 milligrams per day.
If you are a so-called easy patient, you don’t need much monitoring, but if you had already failed cycles or if you are a poor responder or if your cycles are not regular, you need a different and a few monitoring. You should think about a personalized treatment every time if more than one failure has happened to you. The general concept of all the clinics is quite simple, you can divide all the clinics around the world into 2 categories, and this doesn’t mean that one is better than another or that one is worse than another, the two categories are as follows: the first category is to make everything easy, reduce the stress, reduce the cost, reduce the visit to the clinic. The other group of clinics is in which everybody is obsessive to monitor more, to get more information from you, to personalize more your treatment. I think that the best clinic is the one that can combine the 2 previous categories.
If you are an easy patient, if the indications are clear, if the diagnosis is properly done, if no failure has occurred before, maybe for you, a so-called easy IVF is sufficient. On the contrary, if you are in advanced maternal age, you had recurrent miscarriages, you have failed many cycles, and you feel like it’s your last chance, you are looking for something that can give you an answer, so the same clinic should perform a personalized treatment for you.
You are not a poor responder. There is a definition for poor responders that is accepted all around the world, and it’s called Bologna criteria for poor responders. It has been published 9 years ago, and now it has more than 1500 citations all around the world. The criteria are very simple, 3 or fewer oocytes, the age over 40, failed oocyte recovery. If one of these criteria has already occurred, you can enter the category of the poor responder.
There are two major factors for this. One is a morphological situation of the uterus. If you have leiomyomas, fibromas, fibroids, or your uterine wall is not normal, vascularization is impaired, this could play a role in the thickness of the endometrium. On the other hand, you can have a perfectly normal uterus with perfectly normal endometrium, perfectly normal myometrium, no pathology in the uterus, but then the level of hormones is not the correct one, so the endometrium does not respond, or it responds pathologically because it doesn’t just receive the right amount of information from the endocrine system. There can be both or a combination of two.
There could be a male problem, so it would be very important for you to perform a FISH test, which is a chromosomal analysis on a certain number, generally a few thousand sperm. When you do chromosomal analysis from your blood, you know everything about the chromosomal composition of all the cells of your body, skin, eye, heart, Sidney, any organ but not of your eggs, and that’s the same for your partner.
The reason for this is that when you or your partner wear 8 cell embryos inside the tubes of your mother, you already had 1 cell that has been designed to prepare gametes. Sperm for your partner, and oocytes from you. The only way to know if your oocytes, or in this case, the sperm of your partner is chromosomally normal, is to check directly that. The FISH test should be performed using the highest technology with the highest number of chromosomes to be analyzed.
If in the first round you had decent embryos or good quality embryos, you should go for another attempt. If you have quite a large number of embryos, PGT for aneuploidy could be an option to shorten the time to pregnancy.
Not all the machinery is designed for 3D, and even if they are designed, the clinician can perform a simple 2D. I think that in the era of IT and computer, it’s very easy to understand that what the 3D does is to construct because of a specific software the 3 dimensions of the womb and the uterus, so is a sophisticated way like magnetic resonance and this can help the clinician to check for small pathologies or small abnormalities. If you combine the direct visualization of the cavity of the uterus via hysteroscopy with 3D, you will have a full vision of this extremely important organ. Since it’s not invasive or just a bit invasive and is not painful, and it also requires only 20-30 minutes of exams, I think that in that sense, it should be done.
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