Blastocyst Culture and Transfer

A human blastocyst on day five of development (in vitro)

The first human pregnancy after in vitro fertilization (IVF), reported in 1976 by Robert Edwards and Patrick Steptoe, was achieved after replacement of a single blastocyst in the uterus. Although that pregnancy was ectopic (occurring outside the uterus) and was not delivered, it demonstrated the feasibility of extended embryo culture and replacement at the blastocyst stage.

In the years that followed, blastocyst transfer was virtually abandoned because it was very difficult to obtain blastocysts in culture using the available technology. It was also argued that reducing the time spent in culture to a minimum may be beneficial to the embryo and improve pregnancy results. However, in 1985, IRMS Scientific Director Dr. Jacques Cohen and his colleagues at Bourn Hall Clinic in England reported the first successful pregnancies after replacement of frozen-thawed blastocysts; this generated renewed interest in blastocyst culture and replacement. The recent re-emergence of this technology is a result of major advances in culture techniques and media preparations that more consistently support the development of early human embryos for five to six days.

At the blastocyst stage, an embryo contains approximately 100 cells. It has developed to the point at which, following hatching from the zona pellucida, its implantation is imminent. The cells on the outer layer of the blastocyst eventually form the placenta, the sac that protects and nurtures the developing fetus during pregnancy, while the fluid-filled inner core of the blastocyst contains cells that will form the fetus. Blastocysts are easily recognizable, allowing for relatively easy selection by the embryologist. By contrast, embryo selection during earlier cleavage stages is more difficult and requires more experience.

IRMS and many other IVF programs reserve blastocyst replacement for patients who are under the age of 40, produce 10 or more eggs and are at risk for high order multiple pregnancy. The eggs must be fertilized normally and exhibit good development during the first three days in culture. It is becoming increasingly evident that many patients and embryos do not benefit from this treatment modality. For instance, patients with poor embryo morphology are encouraged to have replacement of day 3 embryos with assisted hatching and fragment removal, since these embryos do not tolerate extended periods in culture. Those over 40 years of age may be more likely to achieve an ongoing pregnancy after preimplantation genetic diagnosis and replacement of embryos that appear free of genetic abnormalities that can affect implantation and miscarriage rates.

Studies at IRMS and elsewhere indicate that pregnancy rates for blastocyst transfer are similar to those resulting from day 3 embryos. However, implantation rates may be higher. Also, since replacement is limited to two blastocysts, high order multiple pregnancies with three or more fetuses are largely avoidable – as they are when day 3 replacements are limited to two embryos in patients with very good pregnancy prognosis.

Articles with additional information on Blastocyst Culture can be found in our research articles page.

 

Disadvantages of Blastocyst Replacement

While nearly 80% of fertilized eggs survive through the third day in culture, even under ideal circumstances, only about 30%-40% become well-structured blastocysts by the fifth day. Although embryos are carefully examined on day 3 and selected for extended culture, there are no guarantees that they will continue to develop. As a result, a couple with viable embryos on day three could end up with no blastocysts for replacement. Moreover, there may be fewer embryos available for cryopreservation and the freeze/thaw process is less successful for blastocysts than those frozen at earlier stages of development.

There is also concern regarding the sex ratio among children born after blastocyst replacement. At least one large study suggests that more males than females are born. Another possible risk of this treatment is the apparent increase in the incidence of monozygotic (identical) twinning, and the associated obstetric complications of such pregnancies.

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