Fresh vs. Frozen Embryo Transfer – Which is More Successful?
What is the best embryo transfer option for me?
Choosing between fresh vs. frozen embryo transfers
The last decade has witnessed a dramatic improvement in frozen embryo implantation and pregnancy rates. This has resulted in a growing number of IVF practitioners recommending to their patients that they consider frozen (FET) over fresh transfers, preferentially.
The dramatic switch was largely brought about by three developments:
- The first was the introduction, almost a decade ago, of ultra-rapid embryo cryopreservation (vitrification), which freezes the embryo rapidly (about 60,000 times faster than was the case using the older “conventional” slow freezing approach). The slow, “conventional” freezing approach resulted in the formation of intracellular ice that damaged the embryos, resulting in a low survival rate. Those that did survive had significantly diminished implantation potential. Simply stated, pregnancy rates were dismal. In contrast, the ultrarapid freezing process (vitrification) avoided intracellular ice formation with the result being that >90% of pre-vitrified embryos survived, essentially unaffected by the freeze-thaw process AND with an implantation and pregnancy generating potential at least as good as (and possibly even better than) fresh embryos.
- The second was the move to preferentially vitrify and cryopreserve blastocysts rather than early (day 2-3) cleaved embryos. This development stemmed from the recognition that embryos that fail to develop to the expanded blastocyst stage (day 5-6) will in the vast majority of cases, be chromosomally compromised (aneuploid) and thus unable to propagate viable and healthy offspring. Moreover, implantation and pregnancy rates could be markedly improved by selectively transferring expanded blastocysts. Thus fewer embryos needed be transferred at a time, thereby reducing the incidence of high order multiple pregnancy (triplets or greater) with its incumbent risks to both mother and babies.
- The third was the relatively recent introduction of full embryo karyotyping or preimplantation genetic screening (PGS) using methods such as comparative genomic hybridization (CGH) and most recently, next generation gene sequencing (NGS) (the development of which we at SIRM proudly played a pivotal role). Full PGS allows for identification of those “competent” embryos that contain a full numerical component of 46 chromosomes (i.e. euploid). The advantage of combining full PGS with embryo freezing allows for the “stockpiling” (banking) of embryos over several cycles before performing single or double blastocyst transfers. This combination vastly improves the efficiency of embryo transfer while at the same time reducing the risk of miscarriage and chromosomal birth defects. Such embryo banking can slow or erase the otherwise inevitable adverse effect of the advancing biological clock (in older women and those who have diminishing ovarian reserve – DOR). In fact it offers the only potential alternative to egg donation.
Earlier on, I indicated that results obtained with FET are “at least” as good as those obtained when transferring fresh embryos and “possibly” even better. But it would be ludicrous to suggest that the vitrification process would actually improve embryo “competency.” So how then might one explain reports that suggest a higher implantation/pregnancy rate with FET? Frankly, while I do believe FET results to be at least as good as when fresh embryos are transferred, I am as yet not convinced that FET’s yield better results. However, if that were to be the case, the only possible mechanism by which this would occur would be that use of estrogen/progesterone hormonal therapy in preparation for FET, somehow establishes a more receptive endometrium than can be achieved through controlled ovarian hyperstimulation, where gonadotropin drugs (e.g. Follistim, Gonal F, Puregon, Menopur) and/or gonadotropin inducing agents (e.g. clomiphene and Letrozole) might create a more non-physiological hormone environment.
Regardless however, we are definitely entering an era where “staggered” embryo transfers (i.e. embryos being transferred in a different cycle than where ovarian stimulation and egg harvest was conducted), are fast becoming commonplace and for the following reasons, I believe this to be a move in the right direction:
- By reducing the imperative to transfer available embryos fresh in order to give them the best chance of propagating a pregnancy, it will reduce the incentive to transfer “multiple embryos” at a time, and so herald a significant reduction in high order multiple pregnancies.
- For the many women who are particularly sensitive to fertility drugs and “overstimulate” with fertility drugs, it will (by avoiding pregnancy in that cycle), remove the risk of fulminant severe ovarian hyperstimulation syndrome (OHSS) caused by ever increasing production of hCG.
- It provides an opportunity to control and optimize the endometrial environment for implantation.
- It provides an opportunity for older women and those with DOR who are running out of time on the “biological clock” to bank euploid embryos for subsequent dispensation to the uterus, and in many cases, provide a tangible alternative to donor egg-IVF.
With pre-implantation Genetic Technology rapidly advancing, there is little doubt that we will in time be able to diagnose and perhaps (through genetic engineering) even reverse many chromosomal/genetic abnormalities affecting the embryo. Frozen Embryo Transfers, by providing the time/opportunity to implement such strategies, could ultimately provide the most important advantage of all, namely to optimize the quality of life after birth.