Practically from incept, ART has been associated with controlled ovarian stimulation (COS) in order to foster multiple oocyte harvests. We all recognize that COS improves ART outcome by the sheer fact that more oocytes are inseminated and thus, more embryos are available to chose from at the time of embryo transfer (ET). Yet, it is also well established that the functionality of the endometrium – its receptivity to embryo implantation – is impaired by the very mechanisms at the core of the COS process itself. The harm caused by COS on endometrial quality is taken as the primary explanation
for the fact that embryo implantation still remains the bottleneck for the whole ART system (Fig. 1).
Recently vitrification – an ultra-fast cryopreservation technique first reported decades ago – has gotten adapted to the practical needs of ART. With this new approach, vitrification was reported to have remarkable efficacy for the cryopreservation of zygotes and blastocyst-stage embryos. Numerous investigators have indeed published near-fresh implantation and live birth rates following embryo vitrification at the zygote and/or blastocyst stage. Vitrification therefore offers fascinating new possibilities for avoiding the negative consequences of COS on the endometrium through deferment of ETs that will be performed in a perfectly primed endometrium. The clinical challenge therefore is to determine the clinical conditions in which it is clinically savvy to vitrify embryos and differ ET to a later stage, in an optimized E2-and-progesterone cycle.
Differing ET attractive at it may appear suffers from increasing the duration of the overall treatment and further boosting the costs of ART. Fig. 2 details the relative timeframes of differed ETs as compared to the classical fresh ET in the very ART cycle. We see that in our clinical setup, differed ET adds one extra clinical examination timed a week after the oocyte retrieval. This is aimed at assessing recovery from COS and oocyte retrieval and serves for reviewing the practical steps of the differed ET protocol. The patient is given an appointment for assessing endometrial thickness and verifying that serum progesterone is <1.5ng/mL. ET is then scheduled on the 4-5th day of progesterone exposure, depending on the embryo stage at the time of FET. Looking at the time frame of differed ET, we see that the whole treatment is lengthened by approximately 5 weeks. Hence, systematic cryopreservation as attractive as it sounds may not be always justified. Indeed, there remain clinical circumstances when reverting to fresh ETs is likely to remain the most appropriate option. The relative advantages of fresh vs. differed ET are illustrated in Table 1.
In conclusion, the cryo-preservation of embryos through vitrification at the 2PN or blastocyst stage is possible with nearly no losses in embryo survival and implantation potential. This unleashed all sorts of new possible schemes for transferring embryos in perfectly controlled endometrium in an effort to optimize implantation rates. Considering the practical impediments encountered – increased treatment duration and cost – we reckon that differed ETs are particularly indicated when the response to COS is excessive or there are reasons to suspect that either the embryo or endometrium are suboptimal. Conversely in case of ideal embryos and endometrium, as often encountered in 1st ART attempters, fresh ETs will be preferred because of the time and cost advantage.
