What is the ‘ideal’ duration of progesterone supplementation before the transfer of cryopreserved–thawed embryos in estrogen/progesterone replacement protocols?

Different studies dealing with the start of progesterone supplementation in assisted reproduction treatment cycles have shown that the problem apparently is the correct timing. We therefore would like to discuss the data on: (i) the start of progesterone replacement in oocyte donation programmes; (ii) the start of progesterone replacement in frozen-thawed hormone-supplemented cycles; (ii) the problem of too early a rise of progesterone in fresh IVF cycles as a model of too early an administration of progesterone; and (iv) the benefit of high progesterone levels on the day of embryo transfer in fresh IVF cycles. From the data reviewed in this paper it seems to be appropriate to start progesterone administration before transfer in oocyte donation programmes as well as transfer of cryopreserved/thawed cells as soon as the endometrium is developed sufficiently (> or =8 mm, trilaminar pattern), and to perform the embryo transfer not before day 3-4 of progesterone treatment, i.e. embryo development on day 2-3. Studies dealing with the influence of too early a rise of progesterone in fresh IVF cycles have shown different results. In fact high progesterone levels seem to reflect a high response but not a lower probability of conception. Furthermore, high progesterone levels on the day of embryo transfer in fresh IVF cycles could lower myometrial contractility and therefore increase implantation rates. Since the experience from oocyte donation programes shows the benefit of a longer preparation time using progesterone, and high progesterone levels seem to have a benefit during embryo transfer, this would suggest extending progesterone administration before transfer. However, we have to find the optimal individual transfer protocol after mock cycles, for example with pinopode detection or other methods applicable in routine IVF programmes. We need more studies to be sure whether reproductive outcome after transfer of cryopreserved-thawed cells in estrogen/progesterone supplement cycles is influenced by the duration of progesterone pretreatment. If this is so, we must look for practicable methods to modify the protocols according to the individual patient, the embryonic developmental stage during transfer and other variables.