Right, very good question. A frozen embryo transfer is very different from a fresh cycle. In a fresh IVF, there’s a lot of hormones being injected to stimulate the ovaries to produce the eggs. In a frozen embryo transfer, we’re not interested in making surgery, in making those eggs because the embryos have already been frozen, so in a frozen embryo transfer all we’re interested in doing is getting the lining of the uterus in a very receptive state. What happens is on the second day of the period, the patient starts taking tablets of estrogen. Again, it could be anything from four to eight milligrams daily -it’s just two tablets in the morning, two tablets in the evening. We give eight milligrams here, the patient would take those tablets for about 12 days, come for a scan to see if the lining has built up to a nice thickness. We would expect the lining to be around seven to eight millimeters after 12 days of estrogen tablet that has been taken by the patient and if the lining is good, we will then start them on progesterone pessaries or injections for about six days and on the sixth day of the progesterone, the embryo will be defrosted and transferred back into the uterus.
A frozen embryo transfer can happen on a natural cycle sometimes, or in most cases, it happens in a medicated cycle. In medicated IVF cycle, you usually start with a menstrual period, which can be provoked by the contraceptive pill or can come spontaneously. In cases like that, you start taking estrogen tablets either through the skin or pills, and this estrogen supplementation needs to be carried out for many days. What we usually suggest is a minimum of 12 days and preferably not more than 18 days. But of course, the protocol can be different in every clinic, and then you have an ultrasound, and we make sure that the endometrium is okay and that no violation can affect the chances of implantation.
After that, we usually start with supplementation of progesterone, and embryo transfer is usually done after 3 or 5 days of progesterone so that we can implant the embryo in the endometrium at the time of the implantation window. This is usually the process of the medicated frozen cycle in many cases, especially in women with endometriosis, but sometimes in other women as well, we prefer to down-regulate the ovaries first either with one of the intramuscular GnRH agonist injection or with daily supplementation of GnRH agonists, so that we can make sure that we put down the chances of premature ovulation to zero.
In cases of endometriosis, this helps in suppressing the disease as well in cases, like that we usually prefer to administer this injection on day 21 of the previous cycle, and 10 to 12 days later after the period, we can start the same process with estrogen and then progesterone supplementation. This is usually the process of a frozen embryo transfer and the days of progesterone depend on the days that the embryos were frozen. So 3 days if we have a day-3 embryo, 5 days if we have a 5-day embryo.
We can say that in general, there are two different types of treatments or ways of preparing a cryotransfer. The most usual one is to work with hormones, oral hormones. The hormonal replacement therapy involves taking oral pills from day one of your cycle, having a scan done on day 8-10 of the cycle, and if the thickness of the endometrium and the pattern are okay, then deciding when you want to start progesterone to carry out the embryo transfer. That’s probably the easiest way of preparing the embryo transfer because that allows the patients to decide when it’s better for them. In this sense, when there are logistic issues, it’s really helpful.
The drawback is that if the patient gets pregnant, she must continue with the treatment until the placenta takes over the ovaries. It’s something that happens around week 11. The patients continue taking oral pills of oestrogens and the vaginal pessaries because these treatments prevent them from ovulating. They are not going to produce any hormones at all. We must support the pregnancy until the hormones that come from the placenta start working. The other protocol is the so-called natural cycle, in which we monitor how the follicle grows during the cycle. Once this follicle reaches 17-18 millimetres, we trigger the ovulation, and we usually trigger the ovulation first because it’s easier than doing LH tests that should be done every 4 hours to try to detect the LH peak. It also helps us to decide when the transfer is going to be done. If you take that injection for triggering the ovulation, you are going to ovulate 36 to 40 hours later, and we know that 5 days after that day, the transfer can be scheduled. In this kind of treatment, the patients usually need some progesterone, not at the same dose that if they are doing a hormone replacement therapy, and the good thing is that if they get pregnant, they must continue the progesterone, but they don’t need to take it until the placenta takes over the ovaries. So it’s usually after week 8, or something like that, when we see an embryo with a heartbeat, they can stop the progesterone and continue as if it was a normal pregnancy.
In terms of results, it’s the same. The big studies confirm that pregnancy rates are very similar. There are indeed some studies that suggest that the miscarriage rate could be slightly lower if you work with a natural cycle, but we do not recommend any special treatment. It’s true that if the patient has had two cycles of hormone replacement therapy, and she has not got pregnant, we may change it and try with the natural cycle, or vice versa if they have been on natural cycles, and we don’t get success, we may change it. Some things may be out of our control that may make slight differences between hormones and the natural cycle. In the beginning, we just leave it up to the patients to decide. It depends on their schedule and what they prefer. If they want to take hormones or want to go with the natural cycle.
