Embryo transfer (ET) is undoubtedly a rate limiting factor when it comes to IVF outcome. In fact, in my opinion, it is the single most important procedural step in IVF. Optimal performance of ET takes practice, confidence, dexterity, timing, gentility and skill. Out of all of the hands-on procedures involved in the IVF process, embryo transfer is by far the most difficult to teach. In fact, any women may fail to conceive simply because the practicing physician did not (or could not) perform this procedure optimally.
The issue of whether it is better to transfer early (day 2-3 post fertilization) cleaved embryos rather than (day 5-6) blastocysts continues to be a controversy among practitioners in the field. Here I wish to focus on the reasons why I favor transferring blastocysts.
Not too long ago, it was believed that the sooner an embryo was transferred into the “natural environment” of the uterus, the greater would be the chance of it implanting and propagating a viable pregnancy. Thus most IVF physicians advocated day 2 or day 3 embryo transfers preferentially. About 20 years ago, we began to realize that there was no validity to the belief 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. About a decade later, it was realized that cleaved embryos that fail to develop into blastocysts are with few exceptions numerically chromosomally “incompetent” (aneuploid) such that had they been transferred earlier, they almost certainly would not have developed into blastocysts and would not have propagated a pregnancy anyway. Now most of us practicing in this field believe it to be preferential to selectively transfer blastocysts rather than earlier cleaved embryos. Don’t get me wrong! I am not saying that there is never a place for doing earlier pre-blastocyst transfers. Patients that only have one or two cleaved embryos available might as well transfer them early.
The recent popularization of full preimplantation genetic sampling (PGS) using methods such as comparative genomic hybridization (CGH), next generation gene sequencing (NGS) and SNP array, now allow us to identify those blastocysts that are the most “competent”. Selective transfer of such embryos improves the implantation rate per embryo by a factor of 2-3.
It is important to bear in mind that morphologically good looking day 3 embryos/blastocysts that are determined microscopically to be of a “high grade” , are by no means always numerically chromosomally “competent” euploid , and the likelihood of such embryos being “competent” diminishes progressively with advancing age of the woman. Only through the performance of full PGS can his age-related discrepancy be reduced.
While it would be acceptable to me to transfer 2 PGS-untested blastocysts to women under 39 years, and to transfer 3 to older women, I would not recommend transferring more than 2 PGS-normal embryos at any age.
The following are arguments in favor of performing blastocysts transfers:
- 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.
- Diagnostic Advantages:
- Failure of the expected number of cleaved embryos to advance to the blastocyst stage of development in culture, raises the suspicion of underlying inherent embryo “incompetence”, which is usually (but not exclusively) egg-related rather than due to a sperm factor. While age of the woman is the most important factor involved, it can also be due to the wrong protocol of ovarian stimulation being used).
- It facilitates the performance of PGS to identify and then selectively transfer only most “competent” (euploid) blastocysts. In such cases, provided there is no underlying uterine implantation dysfunction implantation and pregnancy rate is enhanced significantly.
Of course, for the treating physician it is far less stressful not have to have to confront a patient with her having no surviving embryos to transfer. The avoidance of this has in my opinion, in the past, been one of the main reasons why IVF practitioners have elected to transfer cleaved embryos rather than blastocysts. But such a policy is usually not in the in the patients’ best interest. In my opinion, it is far better to advise the patient to do a blastocyst transfer since that is almost always in their best interest.