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What is the difference between a natural vs. medicated frozen embryo transfer? Will I be given an option of which one to do?
—Tough Decisions
Let’s specify a couple of things before diving in.
First, by “natural” cycles here we mean cycles where ovulation happens, either on its own (natural cycle) or with the help of medications (modified natural cycle). Similarly, by “medicated” cycle here we mean fully medicated and ovulation is not occurring. Let’s also assume that you have regular menstrual cycles and have not gone through menopause (though we will circle back to this point with your question about choice).
The way that I tend to start these conversations with patients is by providing context. Currently, these are the two main methods, or protocols, of preparing the body for pregnancy before a frozen embryo transfer, and for many people, there is no data to suggest that one has a higher chance of leading to a pregnancy or live birth over the other. In one review in 2020, the authors suggested that this may be because many of the studies on this subject do not disclose how they select which patients to include in their study, leading to the possibility of bias. This is definitely an area where more data is needed to help guide decisions.
For now, it can be helpful to understand that the main ways these protocols differ is in terms of logistics.
With medicated cycles (also called “programmed cycles”), we are giving your body everything it needs to prepare for a pregnancy. The specifics are going to vary slightly depending on your fertility center, but, in general, it will involve taking estrogen (typically pills) to grow the lining of the uterus to a point where it is thick enough to support a pregnancy and then adding progesterone injections.
The timing of the transfer is based on the start of these injections. These injections are different from those used during the first part of IVF in three important ways: the medication is progesterone in oil, and the oil means that a thicker needle is needed to inject the medication. Similarly, these are intramuscular injections (as opposed to the ones in your belly during IVF), and the injections continue for a longer time because progesterone in oil provides the hormonal support for your pregnancy while the placenta is still developing. Again, the specifics are going to depend on your fertility center, but these injections can go as long as 10 weeks of pregnancy. These cycles tend to be very well programmed, meaning they can be very predictable and can be nice for those who value the ability to know their predicted schedule as far in advance as possible.
The other downside, as I have written about before, is that there is growing data to suggest this protocol may lead to a higher chance of developing high-blood-pressure disorders (like preeclampsia or gestational hypertension) during pregnancy.
In contrast, with a natural cycle, the idea is to carefully monitor your body as it prepares for a pregnancy, either on its own or with the help of medications to help you grow a follicle, and then to do an embryo transfer at the appropriate time. Most protocols also include supplementing your hormones with progesterone through early pregnancy, but these are vaginal inserts rather than injections.
In this sense, this protocol is very similar to an IUI cycle, except you would be having an embryo transfer instead of the IUI. The upside is that you are avoiding injections and also the possible increased risk of high-blood-pressure disorders in pregnancy. The downside is that these protocols often mean more “monitoring” visits, which may increase costs, less ability to predict exactly when your transfer is going to take place, and a slightly higher risk of having your cycle cancelled because we don’t have as much control as we do during a programmed cycle.
To circle back to your question of choice, I made a few assumptions at the beginning that are worth double-checking with your doctor. Aside from having irregular cycles, other things in your medical or fertility treatment history may make one of these protocols a better choice for you over the other, such as a history of endometriosis and how you have responded to IUI cycles in the past. It’s also important to note that because of the relative unpredictability of the timing of embryo transfer in a natural cycle, some centers may not be able to offer natural cycles.
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