This is the 8th in a series of 10 answers to common questions/concerns about IVF treatment.


Question 8: Should I opt for Day-3 or Day-5 embryo transfer?

(Note: This is a repost of an article I posted in December that comprehensively addresses this question)

The issue of whether it is better to transfer early cleaved embryos rather than blastocysts continues to rage. I have previously written in this blog on this important topic. Here, I once again wish to refocus on the reasons why I personally strongly favor transferring blastocysts.

What we do know for sure (and reported on in 2008) is that cleaved embryos (day 2-4, post-fertilization) that fail to develop into blastocysts are with few exceptions “incompetent” (unable to propagate a viable pregnancy in a “receptive ” uterine environment). So had they been transferred in the “cleaved” state, they almost certainly would not have developed to blastocysts and thus could not propagate a pregnancy anyway.

Simply stated, there is no difference in pregnancy potential by doing an earlier transfer of pre-blastocyst (cleaved) embryos versus forgoing an embryo transfer because none of the embryos developed into blastocysts. There is no validity to the often-stated opinion 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 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, if it were possible to determine with confidence, by microscopic grading alone, which embryos would develop into blastocysts by day 5-6 post fertilization (and this is currently not possible), then in terms of outcome, it would not matter whether such embryos were transferred sooner or later. What we now do know for certain (and have reported on) is that if a day-3 embryo is found to have its full quota of 46 chromosomes (i.e. it is “euploid”) as assessed by day-3 metaphase CGH, then, regardless of the age of the egg provider, more than 90% of such embryos will develop into a blastocysts by day 5-6 post fertilization.

By comparison, in the absence of CGH testing, about 40% of embryos derived from the fertilization of eggs extracted from a woman under 35 years, (and +/-10% in women in their mid 40′s) will subsequently develop into blastocysts. Certainly, chromosomal integrity of the embryo is not the sole determinant of “competency” (epigenetic and metabolomic factors also play a role) but, it is by far the most important variable.

So…given the following facts:

• The odds are relatively poor that embryos determined to be of a “High Grade”, microscopically, will turn out to be euploid (chromosomally normal)
• The likelihood of aneuploid (chromosomally abnormal) eggs increases as the age of the egg provider increases.

It is my opinion that there is nothing wrong with transferring up to three (3) such early (day-3), untested embryos to women under 39 years and/or no more than four (4) to women over 40 years, especially if they would agree to pregnancy reduction to twins in the unlikely event of a high order multiple pregnancy (triplets or greater) where the risk to mother and offspring would be greatest.

The strong arguments in favor of blastocysts transfers are:

1) By waiting to day 5-6 many unworthy, aneuploid and “incompetent” embryos can be culled out, thereby providing “relative” confidence that you will not end up with a high order gestation. This allows for the transfer of fewer embryos, minimizing the risk of high order multiple pregnancies.

2) Waiting until day 5-6 post-fertilization affords important diagnostic benefits:

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. (For expansion on this important concept, I urge you read the article “An Individualized Approach to Ovarian Stimulation for IVF“)

b) It facilitates the performance of CGH to identify and then selectively transfer only the 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, after everything IVF patients go through, it is much easier and far less stressful on the treating physician not have to have to confront patient(s) with the heartbreaking news that they have no surviving embryos to transfer. Undoubtedly, this is one of the main reasons why IVF practitioners still prefer to transfer cleaved embryos rather than blastocysts. But as far as I am concerned, this is not justification to do what ultimately might not be in the in the patents’ best interest. Rather, it is about doing what serves patients best and what they choose after being fully informed regarding associated risks and benefits.