The quality of an embryo is an important factor in determining the success of IVF, possibility of a healthy pregnancy, and eventually a live birth. Once the male and female gametes are combined to make an embryo, they are typically allowed to grow for 5 days before transfer. These Day-5 embryos are called blastocysts and are considered the best for transfer, while the remaining embryos that do not reach blastocyst status by then are discarded. However, that practice needs to be questioned as research suggests that even Day 7 embryos may result in healthy pregnancies.
Considering the standard embryo grading in IVF, it is common practice to study the blastocysts on the fifth day of embryo culture and select the ones considered “good” for transfer.
Such Day 5 embryos are either transferred to the uterus, tested with PGT, or frozen for future use but the remaining are discarded. However, that practice may be questionable.
Not all embryos grow equally
It has been seen that not all embryos develop at the same rate and some might form the perfect blastocyst at day 6 or 7.
Most clinics will watch the embryos grow up to Day 5, select the blastocysts for cryopreservation, biopsy, or transfer and discard the ones not looking good by then.
Generally, the embryos developing to proper blastocysts by Day 5 or Day 6 are considered good for transfer, freezing, or biopsy but the ones developing at a slower rate and not growing into blastocysts by Day 6 are often discarded. However, that might not be the right practice, always. Even the embryos that grow into blastocysts by Day 7 can result in a perfectly healthy pregnancy and live birth.
Unfortunately, since many of the embryos are discarded before achieving their Day 7 potential, there is not sufficient data to analyze the clinical outcomes of embryos that develop into Day 7 blastocysts and compare it with Day 5 or Day 6 blastocysts.
Evidence in favor of Day 7 Blastocysts
A study paper titled Euploidy rate of Day 7 blastocysts derived from in-vitro fertilization, presented at the presented at 16th International Conference on Preimplantation Genetics 2017, Valencia, Spain, Dr. Colin Lee Soon Soo et al. demonstrated that 7 out of 15 embryos that were day 7 blastocysts (taken from 12 patients) were found viable after preimplantation genetic screening.
46.7 percent of the embryos were euploid, which means that nearly half of day 7 embryos had the potential to reach a healthy pregnancy.
In a different study, researchers biopsied a total of 1,925 blastocysts for pre-implantation genetic screening over a 12-to-16-month interval. NextGen sequencing (NGS) was employed to study the chromosomal integrity of day 5 (145), day 6 (92), and day 7 (16) blastocysts.
The implantation, pregnancy loss or ongoing pregnancy rates between Day 5 and Day 6 blastocysts were found to be similar.
Euploidy was higher in Day 5 blastocysts at 53.5% compared to 40.4% in Day 6 and 35.9% in Day 7 blastocysts.
Irrespective of the day of development, the embryos that were vitrified and warmed were found to have a high implantation potential of 56.3% to 79.3%.
Miscarriage rates however were higher with Day 7 blastocysts, and live birth was lower at 43.8 % as compared to almost 70% in day 5 blastocysts.
In another study paper titled Live births following Day 7 Blastocyst Transfer after Preimplantation Genetic Testing for Aneuploidy (PGT-A), which was presented at the 18th International Conference on Preimplantation Genetic Diagnosis 2019, Geneva, Switzerland, our fertility experts from Malaysia demonstrated that how day 7 blastocysts can result in healthy babies.
On analysis 58 Day 7 blastocysts with NGS, the doctors found that 27 were euploid. All the blastocysts survived freeze-thaw procedure and 10 patients had frozen embryo transfer. The clinical pregnancy rate was 70% (7/10) with an implantation rate of 63.6% (7/11) as one patient had a double embryo transfer.
While 3 pregnancies succeeded, 4 ended in miscarriages.
The findings of these studies clearly indicate that Day 6 and Day 7 blastocysts can be chromosomally normal and have the potential to result in a healthy pregnancy. Even though the rate of miscarriage is possibly higher in late-stage blastocysts, nearly half of them are capable of producing healthy pregnancies and babies.
Conclusions
With better media and ART lab capabilities, it is possible for good clinics to prolong embryo culture to the blastocyst stage.
An IVF cycle involves so much expense and hormonal injections for a patient, it becomes the moral obligation of embryologists to consider each and every embryo as a possibility for success.
With strong ability to culture embryos for longer, the embryologists should be able to watch embryos upto 7 days after fertilization and select the best quality blastocysts for transfer.
This will give the patients more chances at having a pregnancy with viable embryos that may otherwise would be discarded for not achieving blastocyst potential after 5 days of growth.
Should you consider transfer of Day 6 or Day 7 blastocysts in IVF? Some of the research mentioned above was performed by Infertility Aide member doctors. Consult with an expert and learn about the best way to proceed in your fertility treatments.
Resources:
Yap, Wei Yuan et al. Euploidy rate of day 7 blastocysts derived from in vitro fertilization (IVF) Reproductive BioMedicine Online, Volume 36, e30 DOI: https://doi.org/10.1016/j.rbmo.2017.10.072
Whitney, J. B., Balloch, K., Anderson, R. E., Nugent, N., & Schiewe, M. C. (2019). Day 7 blastocyst euploidy supports routine implementation for cycles using preimplantation genetic testing. JBRA assisted reproduction, 23(1), 45–50. doi:10.5935/1518-0557.20180089.
C.W. Chan, Y.X. Lim, M.W. Lim, C.S.S. Lee, C.S. Tan, 30. Live births following day 7 blastocyst transfer after preimplantation genetic testing for aneuploidy (PGT-A), Reproductive BioMedicine Online, Volume 39, Supplement 1, 2019, DOI: https://doi.org/10.1016/j.rbmo.2019.04.083