In IVF we create embryos by fertilizing eggs with sperm. Once you have an embryo, you can do one of three things with it:
- put it in the uterus right away - this is called a FRESH embryo transfer
- freeze it and sometime later (typically 1-2 months) do a FROZEN embryo transfer
- biopsy it to test for chromosome complement or genetic disease, then freeze it (CCS or PGT-A). Once the test results are back, a FROZEN embryo transfer is performed
The pros and cons of each of these options would be reviewed with you by your doctor. Most of the time you enter an IVF treatment cycle knowing which of the three you are going to do. Many times people will do more than one. More and more we are recommending frozen embryo transfers (#2 or #3) instead of fresh embryo transfers. Why? If the estrogen level during the IVF treatment (checked in your blood) is high, for example greater than 15,000 pmol/L, there can be a negative effect on the endometrial lining so pregnancy rates can decline. In this situation we will often recommend freezing the embryos and putting them in at a later time when the hormones are lower. Sometimes the endometrial lining doesn't look good on ultrasound during the IVF treatment and we will suggest you freeze the embryos, fix the endometrial lining and then do a frozen embryo transfer. There are a few other reasons we identify during the IVF cycle that might make us change plans from a fresh embryo transfer to a later frozen embryo transfer.
Bottom line, we are doing a lot more frozen embryo transfers. In 2017 about 75% of our transfers were frozen and 25% were fresh.
In a frozen embryo transfer we have to time the transfer of the embryo(s) so the uterus has been exposed to the right duration and dose of estrogen and progesterone beforehand. This can be done through medications (medicated frozen embryo transfer or FET) or in a natural cycle (natural cycle FET). About 90% of our embryo transfers are medicated. We typically only do natural cycle FETs if the woman cannot take estrogen or progesterone, the woman requests (perhaps she had a pregnancy from a previous natural cycle FET or simple preference), or medicated FETs don't work.
We prefer medicated FETs as they allow us to time the transfer precisely, they involve fewer blood tests and ultrasounds for patients, and historically most studies showed a higher pregnancy rate than with naturall cycle FETs. A review article published this month in Fertility & Sterility suggests that natural cycle FETs do have a lower pregnancy rate than medicated FETs but MODIFIED natural cycle FETs are similar. Modified natural cycle FETs involve monitoring for ovulation and triggering the woman to ovulate with a shot of HCG. Then the transfer is booked 6 days later. Progesterone may or may not be used but there is a trend to higher pregnancy rates with progesterone use.
So, there are two main options for frozen embryo transfer treatment: medicated with estrogen and progesterone (MEDICATED FET) OR no estrogen, trigger ovulation and use progesterone (MODIFIED FET). Knowing this why are 90% of our embryo transfer still medicated? There are a few problems with the modified protocol:
- some women do not ovulate so you they won't grow a follicle you can trigger to ovulate
- some women will ovulate before the trigger shot can be given
This means that a fair number of modified natural cycle FET cycles are cancelled - more often than medicated. Cancelled FETs cycles are extremely upsetting for patients. Their chance to conceive gets put off even further. Ultimately we are open to modified natural cycle FETs, but we really do need to consider time, past successes or failures, the challenge of multiple tests of ovulation and other patient characteristics before opting for modified FETs.
Another advantage to medicated FETs is that we can replicate them with good consistency and that allows us to analyze uterine receptivity with ERA (another blog topic!).
If you wish to dig deeper into the literature on FETs a good place to start is the review cited above.