Embryo Selection: How to determine if an embryo is of good quality

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Embryo selection helps to identify those embryos with the best chances of implantation leading to a successful pregnancy. This process allows for a reduction in the time needed to achieve a pregnancy safely.

We spoke with Dr. Álvaro Martínez Moro about the criteria for embryo selection and address frequently asked questions regarding embryo quality.

Álvaro

What is Embryo Selection and how is it performed?

Embryo selection is a crucial process in fertility treatments involving the evaluation of embryos to determine which have the best chances for successful implantation and development into a healthy pregnancy.

This procedure is conducted in the laboratory by carefully observing various parameters, providing information to select the embryo most likely to succeed.

Criteria for Embryo Selection: How to Select Embryos

Embryo selection can be performed using different techniques that evaluate the embryos with the best prognosis for post-transfer:

  • Morphology: Morphological assessment is the most standardized technique in embryology laboratories due to its proven success. This selection method evaluates embryos based on morphological criteria such as embryo size, number of cells, cell symmetry, and other parameters that help to classify the embryos and select the one with the best likelihood of success.
  • Kinetics: This technique assesses embryos based on their division timings. This method uses algorithms based on data analysis to predict and select the best embryo for transfer.
  • Genetics: Genetic analysis is one of the most established techniques in assisted reproduction. It involves a biopsy of the trophoectoderm to check for any chromosomal or genetic abnormalities.
  • Artificial Intelligence: AI employs advanced algorithms based on image analysis and pre-established databases.

Embryonic Morphology

Embryos are evaluated daily by observing a variety of morphological characteristics that are crucial for their final classification. Depending on the day of development, we differentiate between these stages:

Embryo on Day 1 After Fertilisation – Zygote

Embrión en Día 1 - Cigoto

The day following ICSI or in vitro fertilisation is critical to assess the success of the procedure by observing the formation of the zygote, which occurs between 16 and 20 hours post-fertilisation. Although morphological characteristics at this stage do not predict the future evolution of the embryo, they are crucial for gathering relevant information about the oocyte and sperm.

Embryo on Day 2 and Day 3

Embrión en Día 2-3

After fertilisation, the embryo must begin to divide, surpassing the phase of the first embryonic division.

The assessment of the embryo is carried out around 44 and 68 hours post-fertilisation during the second and third day of development, respectively, aiming to identify those embryos of good morphological quality. This embryonic classification is based on factors such as the number of cells, their symmetry, multinucleation, the presence of vacuoles, cellular fragmentation, and the size of the zona pellucida, all of which are crucial in the success of assisted reproduction treatments.

Embryo on Day 4 – Morula

Embrión en Día 4 - Mórula

The fourth day of embryonic development, though providing less information about the embryo’s status, is vital as it marks the transition from a stage of cells to a more complex compaction that will become the blastocyst.

Around 92 hours post-fertilization, the cells begin to cluster and adhere in a process where the cell membranes merge. This compaction culminates when the cells are no longer individually distinguishable and form a uniform mass known as the morula.

Embryo on Days 5 and 6 – Blastocyst

Embrión Día 5 6 - Blastocisto

An embryo that reaches the blastocyst stage generally has a good prognosis for implantation.

The development to blastocyst can be influenced by various factors such as male factors (e.g., testicular biopsy, Oligoasthenoteratozoospermia, or altered sperm fragmentation index) or the age of the oocyte Female Fertility Age.

At this stage, due to the large number of cells in this structure, the same parameters used for the classification of embryos on days D+2 and D+3 cannot be analysed. Therefore, the parameters used to establish a selection order in the blastocyst stage are: size (valued according to the diameter, zona pellucida, and indirectly the blastocele), inner cell mass, and trophectoderm.

Embryonic Morphological Classification: Types of Embryos

Embryonic morphological quality should be understood as the ability of an embryo to result in a pregnancy, and we only assume it is of good quality if there is gestation and a live birth occurs.

There are different types of embryonic classifications, with those of the Association for the Study of Reproductive Biology (ASEBIR) and Gardner’s being the most widespread. The criteria they use to classify embryos are similar, the main variation being the name given to the category assigned to each embryo. In ASEBIR’s case, the four categories are named with letters ranging from A to D, with embryos categorized as A being of the best morphological quality. In Gardner’s classification, there is a variation, especially at the blastocyst stage. They use a number to assess size (from 1, considered an early blastocyst, to 6, which is a blastocyst that has completely emerged from the zona pellucida), the inner cell mass (categorized from A to C), and the trophectoderm (also categorized from A to C).

These morphological embryonic categorizations are based on and supported by scientific studies. In this sense, morphological classifications of embryos facilitate the selection of the embryo with the best prognosis, regardless of the classification used.

Causes of Poor Morphological Embryonic Quality

There are mainly two causes that can affect the morphological quality of embryos: the woman’s age and the male factor.

Traditionally, the age of the woman Female Fertility Age has been considered the main factor affecting the quality of the oocytes. This is because there is an increase in the percentage of chromosomally abnormal embryos as the woman ages.

In the case of male fertility, it can also be affected by age, especially in some semen analysis parameters. The male age has also been associated with epigenetic changes linked to disorders such as schizophrenia or autism. Additionally, altered sperm DNA fragmentation contributes to the development of embryos with poor morphological quality.

Frequently Asked Questions about Embryo Selection

How many embryos are implanted in an assisted reproduction treatment?

Dr. Álvaro Martínez responds:

In Spain, legislation allows the transfer of up to three embryos for women under 35 years old in their first IVF cycle, although the general trend is to transfer one or two to reduce the risk of multiple pregnancies and associated complications. At Vida Fertility, the recommendation is to perform a single embryo transfer. The policy of recommending a single embryo transfer is driven by the good cultivation conditions and success rates of our laboratory embryos, as well as concerns about the risks associated with multiple pregnancies that may affect our patients.

How to determine if the embryos are of good quality?

Dr. Álvaro Martínez responds:

Embryonic morphological quality is assessed differently depending on the stage of development. On days +2 and +3, embryos are evaluated by observing various parameters such as cell number and symmetry, the percentage of cellular fragmentation, or the presence of multiple nuclei. Embryos are generally graded from A to D, with A and B considered good quality as they demonstrate a higher likelihood of implantation. In the case of embryos on days +5, +6, or +7, known as the blastocyst stage, the classification is different since counting is not possible due to the high number of cells. This morphological classification of blastocysts uses size (ranging from 1 to 6, with 4 and 5 being the highest rated), inner cell mass (categorized from A to C), and the trophectoderm (also categorized from A to C).

Mosaic Embryo: What It Means and How to Detect It

Dr. Álvaro Martínez responds:

A mosaic embryo contains both normal cells and cells with chromosomal abnormalities. When we talk about mosaicism, imagine the embryo like a Roman mosaic, with small pieces – cells – of different colors – our genetics. These mosaic embryos appear after a biopsy and genetic analysis PGT-A (Preimplantation Genetic Testing for Aneuploidies), conducted before embryo transfer. The decision to transfer a mosaic embryo is based on clinical evaluation and appropriate genetic counselling. Therefore, this embryo will not be the first to be selected if we have euploid embryos in the treatment outcome.

Is it possible to achieve pregnancy using embryos of low morphological quality?

Dr. Álvaro Martínez responds:

All embryos that maintain developmental potential have the potential for implantation. Morphological assessment of embryos allows classification based on their morphological category, with those graded higher selected first due to their better pregnancy prognosis, and later those of lower quality. The relegation of low-quality morphological embryos to a secondary option aims to achieve pregnancy as quickly as possible by selecting embryos with the best morphological category first due to their better prognosis. However, it should be noted that any embryo that continues to develop has the potential for implantation, more or less depending on each case’s characteristics.

What is the morphological quality of frozen embryos?

Dr. Álvaro Martínez responds:

Freezing and thawing do not affect the morphological category of the embryos. Regarding the freezing-thawing process, the embryo may be affected in terms of survival but not its morphological quality. Moreover, vitrification has significantly improved the survival rates and success of frozen embryos.

What is the morphological quality of embryos from egg donation?

Dr. Álvaro Martínez responds:

In egg donation treatments, the resulting embryos usually exhibit better morphological quality. This is because we avoid egg quality issues (due to pathologies or age) affecting embryonic morphology. This is because the eggs come from young, healthy donors who have undergone rigorous selection processes. Therefore, it is expected that this situation will be reflected in the high success rates of treatments using donated eggs.

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