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What is Blastocyst ?

Preimplantation development culminates in the formation of the blastocyst. Until the 16-cell stage, the blastomeres of the morula are quite distinct and can easily be identified. The process of compaction, which involves the formation of a variety of junction between the individual blastomeres starts ~4  days after fertilization.

On day 5 after fertilization, the blastocyst starts to form. Generally, total cell numbers in normal human blastocysts should exceed 60 cells. The human blastocyst has approximately 60 cells on day 5, up to 160 cells on day 6 and over 200 cells after hatching on day 7.

The blastocyst consists of two cell types. The inner cell mass gives rise to the embryo, the trophoblast gives rise to the placenta.

History of day 3 and day 5 transfer

Until the late 1990s, preembryos were routinely culture until only day 2 or 3 before being transferred to the uterus. The primary impedance to culturing for longer periods involved the lack of an appropriate culture medium to sustain the viability of compaction and blastocyst development.

Researchers then found that better than acceptable clinical pregnancy rates could be achieved with extended culture using specialized media and replacement of only two conceptuses that had grown to the blastocyst stage. The identification of key regulators and recognition of changing physiological requirement over the course of 5 days of preembryo growth led these researchers to refine the basic culture media used during critical days, and to develop what are now commonly referred to as “sequential media”.

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Advantages of blastocyst culture and transfer

1. Synchronizing embryonic stage with the female tract. This is important as the levels of nutrients within the fallopian tube and uterus do differ. Furthermore, the uterine environment during a stimulated cycle cannot be considered normal. Certainly it is known from animal studies that the hyperstimulated female tract is a less than optimal environment for the developing embryo, resulting in impaired embryo and fetal development. Therefore it would seem prudent to shorten the length of time an embryo is exposed to such an environment before implantation.

2. When embryos are selected for transfer at the 2 to 8 cell stage, it is not possible to identify which embryos will be viable in the long-term with the highest developmental potential. Only by culturing embryos up to the blastocyst provides more opportunity to choose the most competent ones for transfer.

3. Not all fertilized oocytes are normal , and therefore a percentage always exists that is not destined to establish a pregnancy or go to term. Most such abnormalities are chromosomal, It has been determined that around 25%  of oocytes are aneuploid, and that this problem is exacerbated with maternal age. The culmination of this is that many abnormal embryos arrest during development in vitro. So by culturing embryos to the blastocyst stage, one has already selected against those embryos with little if any developmental potential.

4. Uterine contractions have been negatively correlated with embryo transfer outcome, possibly by the expulsion of embryos from the uterine cavity. Uterine junctional zone contractions have been quantitated and found to be strongest on the day of oocyte retrieval. All patients exhibited such contractions on day 2 and 3 after retrieval, but contractility decreased and was barely evident on day 4. It is therefore feasible that the transfer of blastocysts on day 5 is by default associated with reduced uterine contractions, and therefore there is less chance of embryonic expulsion and loss.

5. A longer time in culture that provides the opportunity to perform pre-implantation genetic diagnosis (PGD) when such is indicated.

6. Clinical pregnancy and implantation rates after the replacement of only one or two day 5 conceptuses has been demonstrated to be quite high, without the associated risk of high-order multiple births.

7. Spare blastocyst embryos may be cryopreserved until they are needed in the future.

References

1. Michelle Plachot, The blastocyst. Hum Reprod (2000);15(Suppl 4): pp. 49-50
2. David K Gardner, Michelle Lane,16: Embryo culture, Textbook of Assisted Reproductive Techniques(2001); p212
3. Lucinda L. Veeck, Nikica Zaninovic, 6: Preembryo selection and blastocyst quality: how to choose the optimal conceptus for transfer, An Atlas of Human Blastocyst(2003); p139-140
4. Lucinda L. Veeck, Nikica Zaninovic, 4: Cell allocation and differentiation, An Atlas of Human Blastocyst(2003); p85