Should I Have a Blastocyst Transfer?

Blastocyst transfer is commonly but erroneously believed to result in higher live birth rates than transfer of embryos at an earlier stage. In fact the main advantage of blastocyst transfer lies not in providing superior live birth rates but in achieving acceptable pregnancy rates with transfer of just a single embryo. Single embryo transfer, of course, eliminates all high order multiple births and fraternal twins (The Dilemma of Twins). Transfer of two blastocysts, however, leads to a twin rate in excess of 50%.

A perfect 8-cell embryo 3 days after retrieval
A perfect 8-cell embryo 3 days after retrieval

Traditionally embryos have been transferred into the uterus 2-3 days after egg retrieval whereas blastocyst transfer usually takes place 5-6 days after retrieval. The theoretical rationale for growing embryos to the blastocyst stage is that, with longer time in culture, it is easier to select the single best embryo out of a large number of fertilized eggs than it is at an earlier stage. For successful implantation to occur an embryo must become a blastocyst. In natural conception an embryo reaches  the uterine cavity 4-5 days after ovulation when it is at the blastocyst stage. In the laboratory embryos take a day longer to become a blastocyst hence the transfer on day 5 or 6. Thus embryo selection and physiology both appear to favor blastocyst transfer.

Blastocyst with an inner cell mass which gives rise to the fetus
Blastocyst with an inner cell mass which gives rise to the fetus

As usual though, the reality of human IVF is a bit more complex. Embryo selection is important in women who have a large number of normally fertilized eggs, for instance more than 12, and in whom it is advisable to limit the number of embryos transferred to 1. This situation pertains primarily to young (<35 years old) women undergoing IVF with their own eggs and older patients using donor eggs. Many women above the age of 35 years have a smaller number of fertilized eggs and may wish to compensate for the lower viability of their embryos by transferring more than one at a time (What Is Age Factor? How Do We Test for Ovarian Reserve?).

In a program such as ours, where most patients are above the age of 35 years and reduced ovarian reserve is common, there are relatively few ideal candidates for blastocyst transfer. Couples with severe male factor often have low fertilization and embryo development rates so they seldom benefit from extended culture to the blastocyst stage.

Without careful selection of patients for transfer on day 5 or 6, a significant number of couples (5-10%) may end up with no blastocysts suitable for transfer.  Yet some of these patients conceive with a day 2-3 transfer. Despite major advances, laboratory conditions remain less than ideal and some embryos may develop only in a more physiological milieu of the reproductive tract.

Finally, extended culture to the blastocyst stage reduces the number of embryos available for freezing. In our experience and the experience of others, transfer of frozen-thawed embryos adds significantly to the overall live birth rate per retrieval (Our Results). In some fresh cycles uterine receptivity towards embryo implantation is compromised and better receptivity can be achieved in controlled frozen embryo transfer cycles (What is Involved in Embryo Freezing?). Therefore, maximizing the number of embryos available for freezing is a key element of our overall treatment strategy.

In summary, single blastocyst transfer has an important role in the practice of assisted reproduction, particularly in the care of patients who should avoid twins. However, most of our patients elect to have embryo transfer at an earlier stage. This practice is in agreement with the national trends: in 2006 67.8% of all transfers of fresh non-donor eggs occurred on days 2-3 and 28.6% took place on days 5-6. Fortunately, the final decision of when it is best to perform the transfer in a given cycle can be usually made on short notice once it is known how many embryos are developing normally.