Embryo quality as a predictive value

It’s about improving the probabilities.

In the current world of assisted reproduction, the predictive values of embryo quality are increasing, given the need to reduce the number of embryos to be transferred, such as the legislation in different countries that condition fewer and fewer oocytes to work in the laboratory. Likewise, many countries have single embryo transfer (SET) regulations, this translates into optimizing and assessing in a tangible way the quality of the embryo or embryos to be transferred.

Numerous literature exists about predictive values both in time and in morphology, and lastly; in genetic information of the embryo.

However, prior to all this systematic assessment, there are innumerable factors that can modify or deteriorate the quality of embryonic development. Below we highlight some of them that we believe are important for people to be aware of:

  • Women’s age.

  • Metabolic syndrome.

  • Endometriosis.

  • Low response to medication.

  • Premature ovarian failure.

  • Immune Disease (Rheumatoid Arthritis / Lupus).

  • Smoking.

  • Moderate – Severe Male Factor.

  • Nonsecretory Azoospermia (Testicular Biopsy).

  • Total Asthenozoospermia (Immotile Spermatozoa).

  • Total Necrozoospermia (Dead Sperm).

  • Retrograde ejaculation.

  • Hormonal Status (Anti-Müllerian Hormone Measurement).

To mention a few, in addition, the previous history of the couple can also favor having a lower embryonic quality, such as:

  • Previous Failed Cycles of In-Vitro Fertilization.

  • History of non-transfer due to blockage of embryonic development.

  • Implantation Failure.

  • Repeat abortion.

  • Long Evolution Infertility (> 7 years).

  • Stimulation Protocol (Ovarian Hyperstimulation).

This with the intention that patients are aware of the multiple variables that can condition us to a poor quality of embryonic development.

From the view of the fertilized zygote (embryo) we will mention the most important points where embryonic quality can be seen and give a predictive value as such.

Cellular division.

It is important to highlight that a zygote should preferably have 2 polar bodies and two pronuclei visible the day after the in vitro fertilization procedure, in addition to the morphology of the pericytoplasmic space, the cytoplasm and the zona pellucida, important is the orientation of the pronuclei with the polar bodies, how the nucleoli of each pronucleus.

This only occurs on day 1 of fertilization and the times in which zygote formation occurs have been studied, reporting that this should occur preferably before 20 hours after the in-vitro process.

On the second day of cell division, 2 cells or 4 cells, preferably, are visualized, thus visualizing each of its cells (blastomeres), its shape, symmetry, their organization, their cytoplasm, the pronucelles and their nucleoli. In this step, the most important thing is to generate an exponential division from 2 to 4, although the presentation variables can be from 1-3, from 2-3, from 1-4, from 2-5, from 2-5 between others. And depending on the division on day 2, we have a predictive value.

It is important to highlight that not only these parameters are visualized, but also that the blastomeres do not have vacuoles in the cytoplasm, such as fragmentation (cytoplasmic debris) of the blastomeres when making cell division.

On day 3 of development they are practically the same parameters considering an adequate embryonic clevage (cell division) as long as there are preferably 5,6,7,8,9 or 10 cells and in the same way as on day 2, the division preferably be exponential. Although here the division of 3-6, 4-8, 5-10 is no longer so important, since the time of division and the moment in which the assessment is made by the Biologist must also be considered within these aspects. Even so, the experience of the observer (Biologist), as well as the doctor in charge of the case, and the laboratory conditions are what will make a transcendental difference for decision making.

There are many international centers, such as Mexico, which continues to use the transfer on day 3 of development to carry out the embryo transfer process.

However, worldwide in the large international forums, the discussion and urgent implementation of the transfer on day 5 of development (Blastocyst) is increasing, since it has many advantages compared to day 3, which we will mention some such as:

  • Less number of embryos to freeze vitrification).

  • Greater selection of quality, but also of chromosomal well-being of the embryo.

  • Decreases the number of embryos to transfer.

  • Lower multiple pregnancy rates.

  • Improves the implantation rate.

The Morula stage in embryonic development turns out to be one of the most delicate and difficult to perform. This occurs after day 3 of development when the blastomeres begin to undergo compaction (fusion) originating a common mass that gives the appearance of a blackberry, hence its name Morula. We can divide it into two steps: initial compact morula (MCI) and compact morula (MC).

In the same way, arriving at day 5 of cell development of the zygote, it is named Blastocyst. At this stage, there are 4 different types of blastocyst depending on morphology and time. In order not to go too deep, they are named Initial Blastocyst (BI), Compact Blastocyst (BC). , Expanded Blastocyst (BE) and Hadching Blastocyst (BH). Which their 3 valuation structures are the following:

  • Trophectoderm cells.

  • Blastocele.

  • Internal Cell Mass.

It is necessary that these 3 characteristics have been assessed according to Gardner’s criteria, which divides them into:

Starting with this type of assessment, we can have different reproductive prognoses depending on the quality of the blastocyst and the number to be transferred.

Initially at CREAFAM we transferred only two blastocysts for reasons of systematization of our assisted reproduction programs, substantially improving the pregnancy rate, but reducing multiple pregnancies.

There is currently an embryo video surveillance system, which provides us with information about division times, morphology, embryo mobility and well-being of the culture medium.

In other words, Time-Lapse (Primovision) is a daily monitoring system that provides quantitative and qualitative information on division times, as in morphology. This has given us better implantation rates, mainly, such as fewer biochemical pregnancies. In our center, Time-Lapse has considerably exceeded the Gardner criteria, being much more predictive in the gestational prognosis. For this reason, the advantages of primovision are much more considerable than the daily observational assessment by the biologist, an issue that has been always explained to patients in the reproduction consultation by the specialist.

The key points to highlight is that primo vision should be preferably recommended in the following clinical cases:

A video is shown with an example of the primovision system.

The genetic study of the embryo initially called PGD (Preimplantation Genetic Diagnosis) gives us information about specific chromosomes of the embryo and favors implantation rates, as well as reducing the chances of early pregnancy loss (Abortion).

However, the initial recommendations were:

  • Age of the woman equal to or greater than 40 years.

  • Severe Male Factor.

  • Implantation Failure.

  • Repeat abortion.

  • Genetic Factor (for example, history of a child born with Down syndrome).

A new competitor is currently emerging within the predictive value and genetic well-being of the embryo, such as PGS (Preimplantation Genetic Screening), which can perform a complete mapping of the 22 pairs of chromosomes and the 2 sexual ones, increasing the rates of pregnancy and implantation of substantially, without taking into consideration; that the cost increases around 50% of the total value. Today world trends mark and lead us to the fact that in the future the vast majority of our patients have access, but also have a better reproductive prognosis by implementing this type of technology such as PGS.

It is necessary to say that every patient who goes to an assisted reproduction center must be well informed about the processes to be carried out, firstly, and secondly, have a concise knowledge of the possible treatments and procedures that they are going to carry out.

“En Creafam contamos con las tecnologías de vanguardia y especialistas con experiencia para brindarte todas las opciones posibles de tratamiento, pero sobre todo, el panorama más factible para lograr un embarazo.”

Biol. Luis Machorro
Biol. Luis Machorro
IVF and Andrology Laboratory

Vitrification of eggs and embryos at the Mexican Institute of Infertility.

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