Table of contents
How does the quality (morphology) of the embryo affect the implantation and birth rates?
It is often assumed that if the embryo according to PGT-A has the correct set of chromosomes (i.e. euploid), then its quality (Grade) is no longer important for the success of implantation and pregnancy. Many studies prove that the quality of the embryo (its morphology) is important and embryos for transfer into the uterine cavity should be prioritized depending on their morphology.
Zhao et al. (2018) studied the birth rates in women under 35 years of age after the transfer of a euploid embryo depending on the morphological indicators of the embryos.
- High (AA) and good (AB or BA) quality embryo morphology gave a fertility rate of 50.0% and 49.7%, respectively
- Medium quality (BB or AC, CA) = 42.3% fertility
- Low quality (CB and BC) = 25.0% fertility.
How do developmental dynamics affect the success of euploid embryo implantation and fertility rate?
An important prognostic factor for the success of the fertility rate is the rate of embryo development to the blastocyst stage (the stage of embryo development at which it has from 156-200 cells and must enter the uterine cavity for further attachment – implantation).
Giulia et al. (2022) compared fertility rates after transferring euploid embryos to the uterine cavity at the blastocyst stage on days 5 and 7 of development. It has been found that the birth rate is higher after the transfer of a euploid embryo at day 5, which indicates its energy potential (state of mitochondrial activity) for successful cell division and proper development. This means that for successful implantation, it is best when the embryo reaches the blastocyst stage at day 5-6.
Does female reproductive age affect implantation and birth rates after euploid embryo transfer?
Reig et al (2020) analyzed implantation and birth rates after single euploid embryo transfer depending on the female reproductive age. The study found that the fertility rate decreases from 63% in women younger than 35 years to 53% percent in women older than 42 years. This is well demonstrated by the following diagram:
If no euploid (chromosomally healthy) embryo is obtained during preimplantation genetic testing, is it likely to be obtained during the next IVF cycle?
For those patients who did not receive any euploid embryos after the first stimulation, there is no need to worry too much. Herlihy et al. (2022) showed in their analysis that the absence of a euploid embryo after the first IVF cycle does not affect the possibility of obtaining a euploid embryo in the next fertilization cycle and corresponds to the probability indicators according to the female reproductive age.
What is complex aneuploidy, complex mosaicism, chaotic embryo?
Sometimes as a result of the PGT-A study, you can see the result: “complex aneuploidy” or “complex mosaicism”. Complex aneuploidy means that the embryo contains 3 or more chromosomal abnormalities. Accordingly, complex mosaicism means 3 or more mosaic chromosome abnormalities.
A chaotic embryo is when 6 or more chromosomal abnormalities are detected in the embryo after PGT-A; chaotic mosaicism is 6 or more mosaic abnormalities. Such embryos will not be recommended for transfer.
On what day of embryo development should a biopsy be performed for PGT-A?
Previously, when the technique of freezing (vitrification) and thawing embryos was not perfectly developed, PGT-A was performed to determine only 4 pairs of chromosomes (the so-called syndromic) – 13, 18, 21 and sex X or Y. To be able to obtain the results of genetic research and transfer the embryo on day 5. With the development of technologies for effective ultra-fast freezing and carrying out PGT-A on all pairs of chromosomes, a biopsy of embryos on day 3 is not performed and is recognized as ineffective. The first reason is that at the stage of development on day 3, the embryo contains only 8 cells, and the impact of taking 1-2 cells for it is quite significant. At the blastocyst stage, the embryo contains 156-200 cells, and a biopsy of 5-8 cells for genetic testing does not affect its further development and ability to implant. Secondly, not all embryos in nature pass the transition stage from the third to the fifth day of development, and they can stop the development of the embryo, usually due to chromosomal abnormalities incompatible with their further development. Thirdly, some mosaic cells (embryo cells containing the wrong set of chromosomes) can self-correct, and if such a cell gets into the biopsy for PGT-A, it can give aneuploidy and false rejection of such an embryo for transfer. Despite the fact that at the blastocyst stage, this probability is sharply reduced.
How to understand the result of low-level or high-level mosaicism?
A mosaic embryo is when the embryo cells taken during a biopsy of the trophectoderm (the cells of the future placenta) contain euploid cells (with the correct set of chromosomes) and aneuploid cells (with a broken set of chromosomes).
To make a decision about the possibility of transferring a mosaic embryo (embryotransfer), it is important to consider the level of mosaicism. Not all genetic laboratories indicate this level in percentages, although it is important for interpreting the result.
If “low level mosaicism of the embryo” is indicated, this means that 20-40% of the embryo cells taken during a biopsy contain chromosomal abnormalities (aneuploidy).
If “high level mosaicism” is indicated, this means that 40-80% of the cells contain aneuploid (with a chromosomal abnormality) cells. Although some genetic laboratories and clinics may change these percentages independently, this question can be asked to the genetic laboratory in case of receiving such a result. Since recommendations on the possibility of transferring such an embryo, the frequency of pregnancy and the fertility rate may differ significantly depending on the determination of the percentage of mosaicism of the embryo.
- J Assist Reprod Genet. 2020 Mar 16;37(3):595–602.
The impact of age beyond ploidy: outcome data from 8175 euploid single embryo transfers
Andres Reig, Jason Franasiak, Richard T Scott Jr, Emre Seli
- Chin Med J (Engl). 2018 Jun 5;131(11):1261–1267.
Overall Blastocyst Quality, Trophectoderm Grade, and Inner Cell Mass Grade Predict Pregnancy Outcome in Euploid Blastocyst Transfer Cycles
Yan-Yu Zhao, Yang Yu, Xiao-Wei Zhang,
- Hum Reprod 2022 May 30;37(6):1134-1147. How slow is too slow? A comprehensive portrait of Day 7 blastocysts and their clinical value standardized through artificial intelligence
Danilo Cimadomo, Daria Soscia, Valentina Casciani, Federica Innocenti , Samuele Trio, Viviana Chiappetta, Laura Albricci, Roberta Maggiulli, Itay Erlich, Assaf Ben-Meir, Iris Har-Vardi, Alberto Vaiarelli, Filippo Maria Ubaldi
4.Fertil Steril. 2022 Sep;118(3):484-491.
The chances of obtaining a euploid embryo and subsequent live birth remain consistent with national age-based rates after an in vitro fertilization cycle that produced only aneuploid embryos Nola S Herlihy, Amber M Klimczak, Jessica K W Cheung, Emre Seli
