Before the embryo transfer, it is necessary to take progesterone and we continue taking it for 10 days then, we are doing pregnancy tests and normally if it is positive we continue taking it depending on the protocol of preparation but usually it’s taken until ultrasound examination. There are different kinds on the market: vaginal suppositories, tablets and also we can use injections. There are forms which act for one week, there are forms that we can inject every day. So, different kinds of progesterone. Most RCT studies do not show the real benefit of one over another preparation so, if we have good dosage most of them act well. We have doctors preferring vaginal suppositories because they give a good endometrial transformation and also sometimes we are using injections of natural progesterone.
Here’s a question that specialists all over the world have been discussing for decades and still the answers are not quite clear. We need to specify which phase of the IVF, the In Vitro Fertilization, process we’re talking about before the oocyte pickup and before the fertilization of the eggs, the progesterone level needs to be low and there are actually studies that suggest that if the progesterone level is say higher than one nanogram per milliliter or 1.5 nanogram per milliliter, that a transfer should not be performed in this cycle. The eggs will be collected, they will be fertilized, the embryos cultivated but cryopreserved and saved for a later transfer when the conditions are indeed perfect. So, the increased level of progesterone should not be premature but mainly we’re aiming this question at the phase after the oocyte pickup or the ovulation which is actually represented by this step, by the collection of the eggs and the eggs are fertilized at the same day, then usually cultivate it for five days and then the transfer is performed so, the progesterone that needs to work with the endometrium, it needs to have an influence on it, usually for five days but even this may be individual from patient to patient. Now, finally, what is possibly the the perfect or a good or sufficient for just their level for the transfer and for the implantation of the embryo, it’s not an easy question because the progesterone levels they probably oscillate, the progesterone is produced in phases during the day so, the level might actually be changing during the day. Also there are some different forms of progesterone, not all of them can be analyzed and detected easily. However, there have been some very interesting studies from Spain published earlier this year, Bosch, Labarta are the main authors and they have shown actually some very interesting data where the cutoff of the progesterone on the day of embryo transfer was 8.8 nanograms per milliliter in one study, 9.2 in another study so, from that we can possibly extrapolate that anything over 10 nanograms per milliliter should be perfectly all right for the transfer and the implantation of the embryo.
I do give the progesterone, always I believe in progesterone. It is good but to be honest to mention that there are a lot of women that during the preparation and despite taking high doses of medications, they have very low progesterone. I think it is the case that it does not go together like “give the progesterone to help the embryo”. The body has to be ready to deal with it. I couldn’t explain this case where women are taking five tablets a day of progesterone because the progesterone level was low. I believe that the progesterone level is a good indicator of the immunological status of women. When the immunological conditions get better, then you see that the progesterone level with the same dose gets better.
Progesterone levels for IVF they’re measured at different points in the cycle and some clinics don’t even measure progesterone levels and I think there’s two arguments for it. First of all, progesterone shouldn’t be any progesterone until after egg collection or until you start taking progesterone because it should be suppressed and then you can measure progesterone at various different times either like the day after egg collection or the day of embryo transfer. The problem with progesterone levels, certainly measuring them in a natural cycle, it’s not helpful because progesterone levels can actually vary up to, I think, between eight and ten times in a day because progesterone doesn’t just stay at a constant level and with progesterone supplementation, it should be a bit more of a constant level and some clinics will check progesterone levels. Some very recent research that’s just been published in the last month or two which suggests that a blood level of more than 10 nanograms per ml is more likely to go on to lead to a successful pregnancy than one less than that but having said that it’s very difficult to check those levels and then decide to not do an embryo transfer and certainly even having a low level, doesn’t necessarily mean that it’s guaranteed it’s not going to work. So I’d be really cautious about taking progesterone levels and certainly anything above 10 it doesn’t matter if it’s 20, 30, 40 – the chances are going to be the same. I think the main thing is don’t get too hung up on what the actual numbers are, instead take the medication as you’re supposed to and try and remember to take it on time, to use it in the best way. Often people use vaginal pessaries for progesterone – they’re awful, they’re very messy and that doesn’t mean you’re not absorbing the progesterone so, you don’t necessarily need to worry too much about that but checking levels is not necessarily helpful, it can also add another element of kind of anxiety around a cycle as well because at the end of the day, other than taking the medication, there’s not a lot you can do about it.
The main problem with progesterone levels in IVF is that they can be really different, and of course, it is related to the number of eggs and the number of follicles you’ve produced. Nowadays, the levels of progesterone are being tested. We are trying to find out the correct levels in cases where the conditions are very similar, for example, in cases of cryotransfers, in egg donation, and if the patients are in hormone replacement therapy. In such cases, the conditions are quite strict, and you can repeat the same conditions in future cycles. In these cases, there are even some differences between some groups, we accept that progesterone levels, I would say over 9.2 -10.2, are the cut-off point. In cases, where the levels are lower than this, we recommend adding some subcutaneous progesterone to vaginal pessaries.
In IVF, I wouldn’t say that there is no reference at this point, and it depends a lot on the number of eggs, as I’ve mentioned. Levels of progesterone that are over 15-16 are quite common. However, there is no advantage, for example, to take intramuscular progesterone that is going to increase your levels to 50-54. Keep in mind that the units can be confusing sometimes, as progesterone can be measured in nmol/L or ng/Ml, so we need to be aware of that. In our case, we use ng/ml, so if your levels are over 15-16 ng/Ml, you can be absolutely relaxed because the levels are never going to be a problem.
