A Case for Transferring Blastocysts on Day 5-6 Post-Fertilization Rather Than on Day 2-3 as Cleaved Embryos.

Embryo transfer (ET) is undoubtedly the single most important step in IVF. It takes confidence, dexterity, skill and timing to optimally perform ET. Of all the procedures conducted in IVF, embryo transfer is the most difficult to perfect. Sadly, far too many women fail to conceive simply because of poor timing and technique of ET.

While the debate over whether it is better to transfer cleaved embryos (day 2-3 post-fertilization) rather than blastocysts (day 5-6) continues to rage, an ever-growing percentage of IVF practitioners are reaching the realization that it is more beneficial to transfer blastocysts than cleaved embryos and here is why:

Cleaved embryos (day 2-3, post-fertilization) that fail to develop in culture to blastocysts by day 5-6 post-fertilization are almost invariably “incompetent” such that had they been transferred earlier they would not have propagated a pregnancy anyway. While in about 70% of such cases, this arrest in embryo development is due to numerical chromosomal aberrations (aneuploid) it can also be due to genetic or metabolic abnormalities, most of which are presently undiagnosable in advance. 

There would have been no benefit in transferring such cleaved embryos because they would not have developed into blastocysts in the uterus anyway. Simply stated, there appears to be absolutely no validity to the assertion that an embryo would develop better and have a greater chance of propagating a baby in inside the uterus earlier than it would by being allowed to first develop into a blastocyst in an incubator.

A recent publication suggested that embryos that require 7 days (rather than 5-6) to reach the blastocyst stage of development are capable of developing into healthy concepti. In my experience this is not accurate. We have transferred many such day 7 blastocysts, and none have propagated viable pregnancies. Accordingly, I am not a proponent of transferring such late blastocysts.

Transferring expanded blastocysts allows for the transfer of fewer embryos and minimizes the risk of multiple pregnancies with its incumbent risks. The reason is that each embryo that develops into an expanded blastocyst by day 5-6 post fertilization has a much greater chance of implanting and propagating a viable baby than does the transfer of a cleaved (day 2-3) embryo. a cleaved embryo. While this differential in baby rate per embryo is affected by the age of the egg provider, it occurs in every female age category.  So, by waiting to day 5-6, many the selective transfer of fewer embryos will produce the optimal success.

The advent of preimplantation genetic screening (PGS) has heralded the era where we can further improve the assessment of embryo competency, by identifying euploid embryos that have a normal numerical chromosomal configuration (karyotype), thereby further improving the baby rate per transferred embryo. The fact that optimal PGS analysis relies on chromosomal analysis of cells biopsied from blastocysts, further highlights the advantage in growing embryos to the blastocyst stage.

Don’t get me wrong! I am not saying that there is absolutely no place for transferring cleaved embryos. I say this because taking an embryo to blastocysts does absolutely nothing to improve its implantation potential. It is simply a selection process because of the culling effect achieved by growing it for 2-3 days longer (see above). Simply stated, an embryo that is destined to propagate a baby will just as readily do so whether it is transferred cleaved or as an expanded blastocyst. It is just that we can’t identify “competent” embryos without challenging them by allowing them 5-6 days to try and reach the blastocyst stage of development.

We know that >80% of euploid day 3 embryos subsequently develop into expanded blastocysts (regardless of the age of the egg provider). By comparison, untested embryos (where it is not known whether the embryo is aneuploid or euploid) have at best, a 30- 40% of developing into blastocysts.

The only scenario where the transfer of cleaved embryos might be preferential, is where the patient only has 1-2 cleaved embryos in total by day 3, post-fertilization. In such cases it is often pointless delaying 5-6 days before ET. Earlier transfer will save the woman having to wait 2 additional days before undergoing ET. 

The following are strong arguments in favor of blastocysts transfers:

  1. Diagnostic Advantages:
    1. Since aside from the woman’s age, the protocol used for of ovarian stimulation also impacts egg development and “competency” it follows that knowledge of how many fertilized, mature (MII) eggs develop into blastocysts will play a role in selecting a future approach to ovarian stimulation
    2. The growing popularity of Single Blastocyst Transfers (SBT) to virtually eliminate the danger of multiple pregnancies, requires as much information regarding embryo “competency” as possible. The proven ability of an embryo to reach the blastocysts stage, helps considerably in this regard.

Of course, for the treating physician it is far less stressful not have to have to confront a patient with their having no surviving embryos to transfer. Undoubtedly, this is one of the main reasons why IVF practitioners often, erroneously prefer to transfer cleaved embryos rather than blastocysts. But as far as I am concerned, this is not in the in best interest of the patients. It is in my opinion, far better to advise the patient to opt for a blastocyst transfer.

Ask a question or post a comment

Your email address will not be published. Required fields are marked *