This is the 12th in a series of answers to common questions about failed IVF.

(Note: I’ll be hosting a live video chat on Aug. 2 on the topic of Failed IVF where I’ll discuss the issues addressed in this series of posts and take your questions. For more information on this live IVF chat, click here.)

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Undoubtedly, embryo transfer is the single most important step in IVF. It takes confidence, dexterity, and skill to perform a good transfer. Of all the procedures in ART, embryo transfer is the most difficult to teach. Many women fail to conceive simply because the practicing physician could not perform this procedure optimally.

The issue of whether it is better to transfer early cleaved embryos rather than blastocysts continues to rage. Here I wish to focus on the reasons why I strongly favor transferring day 5-6 blastocysts rather than earlier (day 2-3), cleaved embryos. In the past, the presumption has always been that it is better to transfer healthy embryos into the uterus sooner rather than later, once the best ones for transfer have been identified.

It is against this background that attention has been focused on the transfer of more-developed embryos (blastocyst stage). Since the late 1990s, this process, known as blastocyst transfer (BT), has become increasingly prevalent among ART programs. The transfer of good-quality blastocysts is associated with a high rate of pregnancy, but it carries with it the risk of high-order multiple pregnancies unless fewer blastocysts are transferred, because they are considered more likely to implant.

What we now do know for certain is that cleaved embryos (day 2-4, post-fertilization) that fail to develop into blastocysts are with few exceptions aneuploid or “incompetent embryos.”. So if these cleaved embryos had been transferred, they almost certainly would not have developed into blastocysts, and would not have propagated a pregnancy anyway. Thus, there would have been no benefit to transferring them earlier. In my experience, there is no validity to the often quoted assertion that an embryo would develop better and have a greater chance of propagating a baby by being inside the uterus earlier, than it would by being allowed to first develop into a blastocyst in an incubator.

Don’t get me wrong! I am not saying that there is no place for doing earlier pre-blastocyst transfers. Indeed, were it possible to determine with confidence, through microscopic grading, which embryos would develop into blastocysts and which would not, then it would not matter whether those embryos were transferred sooner or later. What we do know is that cleaved, day-3 embryos that are found through CGH testing / karyotyping to have a full quota of 46 chromosomes (i.e. are euploid) will, in about 90% of cases, 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 but a fraction of the chance (at best 40%) of developing into blastocysts. While chromosomal integrity of the embryo is not the sole determinant of “competency” (epigenetic and metabolomic factors also play a role), it is by far the most important variable.

So…given the fact that embryos determined to be of a “high grade” microscopically are by no means always euploid, and because the likelihood diminishes with advancing age of the egg provider, I see nothing wrong with transferring 2-3 day-3, untested embryos in women under 39 years and 3-4 embryos in older women . Conversely, I would NOT recommend transferring more than 2 (untested) blastocysts to women under 40 or more than 3 to older women.

The following are strong arguments in favor of blastocyst transfer:

1. By waiting to day 5-6, many unworthy, aneuploid and “incompetent” embryos can be culled out, thereby allowing for the transfer of fewer embryos and minimizing the risk of high order multiple pregnancies.
2. Diagnostic Advantages:
   a. Failure of the expected number of cleaved embryos to advance to this stage of development suggests either inherent embryo “incompetence” (which is usually a function of the age of the egg provider…the effect of the “biological clock“) and/or may be due to the wrong protocol of ovarian stimulation being applied.
   b. It facilitates the performance of Comparative Genomic Hybridization (CGH) to identify and then selectively transfer only most “competent” (euploid) blastocysts. In such cases, the transfer of a single blastocyst (SBT) should yield a 60-70% baby rate per embryo transferred to the uterus, provided there is no underlying uterine implantation dysfunction.

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 (blastocysts) to transfer. Undoubtedly, this is one of the main reasons why IVF practitioners often prefer to transfer cleaved embryos rather than blastocysts. But as far as I am concerned, this is usually not in the patients’ best interest. It is far better in my opinion to advise the patient to do a blastocyst transfer and face the possibility of not having any embryos to transfer, than to transfer embryos that have no chance of making a pregnancy and simply delay the inevitable disappointment.