Monthly Archives: November 2020

Endometrial Receptivity test: All you need to know

The Endometrial Receptivity test (BioER) consists of the genetic analysis of an endometrial lining tissue sample in order to determine when is best for transferring an embryo into the uterus for the in vitro fertilization procedure.

In this article we will describe the phases of the test, its advantages and who it is meant for.

 

Phases of the Endometrial Receptivity Test

For the Endometrial Receptivity test to be performed, it is required to obtain an endometrial biopsy seven days after the endogenous LH peak (LH+7) of a natural cycle or 5,5 days after the first progesterone dose (P+5,5) in a hormone replacement cycle.

The procedure is simple. During the first cycle, the oocytes are collected and fertilized in order to obtain the embryo culture. In the second cycle, the endometrial biopsy is obtained.

It is an ambulatory procedure, therefore it does not require an overnight hospital stay. The sample is taken by a gynaecologist and sent in a cryotube issued by Bioarray.

This sample is then analysed in order to check the endometrial receptivity and estimate the optimum day for embryo transfer. Following this analysis, there are three possible outcomes:

  • Pre-receptive: Indicates that the endometrium is not ready to receive the embryo, therefore the transfer on that date is not possible.
  • Receptive: Indicates that the moment in which the biopsy was obtained was optimum for embryo transfer.
  • Post-receptive: Indicates that the endometrium reached its optimum implantation phase but has already passed it.

 

Advantages to the Endometrial Receptivity Analysis

The Endometrial Receptivity test is especially useful for increasing the probability of successful in vitro fertilization procedures.

The shift of the endometrial receptivity time window can be a cause of infertility in women who have had two or more failed embryo transfers after in vitro fertilization.

Thanks to this analysis, the necessary adjustments can be made in order to personalize the fertilization procedure and arrange the embryo transfer to when the endometrium is ready and most receptive to the embryo for its successful implantation.

For example, if a post-receptive result is obtained, the optimum embryo transfer day would be one before usual. In a hormone replacement cycle that would be 4 days after the first progesterone dose instead of 5.

Bioarray uses the BioER test in which the expression of 72 genes related to endometrial receptivity are analysed, as well as the immune response associated to implantation. Therefore, it is more sensitive than the classic method of dating the endometrial status based on histological criteria, which are highly subjective.

Also, the BioER analysis is the result of over 10 years of experience in developing studies on genetic expression (transcriptomics), which can be directly applied to health services.

 

Who is the endometrial receptivity test meant for?

The endometrial receptivity analysis is meant for patients who have initiated assisted reproduction treatments, especially for those who have experienced several failed IVF attempts due to issues related to implantation.

Therefore, it is especially recommended for patients who have had two or more unsuccessful in vitro fertilization cycles, regardless of using good quality embryos with good morphologies and chromosomally normal (PGT-A).

Scientific evidence also backs up the effectiveness of the BioER, as recent studies show that it has helped improve pregnancy rates, up to 51-63% in patients who had previously shown reoccurring failures in implantation.

If you have any doubts about Bioarray’s Endometrial Receptivity test, feel free to ask us with no commitment.

Séquençage de l’exome pour le diagnostic clinique

Le séquençage de l’exome est un test très utile en tant qu’outil de diagnostic clinique , car il permet l’identification de variations génétiques capables de provoquer différents types de maladies.

Un exome est connu comme la partie du génome formée par les exons, qui sont les fractions d’ADN responsables du codage des protéines d’un organisme. Ainsi, l’étude de l’exome est l’un des moyens les plus complets et les plus complexes d’analyser notre ADN , car il existe de nombreuses maladies ou pathologies associées à des altérations ou des variantes.

Qu’est-ce que le séquençage d’exome?

Le séquençage de l’exome entier est une méthode de séquençage de masse (NGS) largement utilisée pour analyser l’ADN des régions codant pour les protéines du génome.

En chiffres, il faut tenir compte du fait que si l’exome humain représente moins de 2% du génome, il contient environ 85% des variantes connues liées aux pathologies .

De cette manière, le séquençage de l’exome devient l’une des méthodes les plus intéressantes de diagnostic clinique , sans avoir à recourir au séquençage du génome entier.

Avantages du séquençage des exomes

Le séquençage des exomes présente plusieurs avantages dans le domaine d’application clinique.

D’une part, il se distingue par sa rentabilité dans les cas où le séquençage de l’ensemble du génome n’est pas nécessaire . Ainsi, l’analyse unique des régions codantes du génome permet aux chercheurs de concentrer leurs efforts sur les gènes les plus susceptibles d’affecter la maladie et offre une combinaison efficace et rentable en termes de coût et de temps.

Un autre avantage à prendre en compte dans le séquençage des exomes est l’économie de l’information, en produisant un ensemble de données plus petit et plus gérable ce qui facilite les temps d’analyse pour être beaucoup plus courts par rapport à tests de séquençage du génome entier.

Dans le domaine de la recherche , le séquençage d’exome a également de multiples applications pour détecter des variantes génétiques pouvant conduire à l’apparition de maladies humaines , aussi bien dans le domaine du cancer, que dans les troubles mendéliens et l’hérédité plus complexe .
Dans le domaine du séquençage d’exome, Bioarray fonctionne avec la plate-forme Illumina NovaSeq, en utilisant le kit de capture Agilent SureSelect Human All Exon V6. Ces systèmes permettent une efficacité d’enrichissement la plus élevée, atteignant 90% d’uniformité de couverture et plus de 90% de nucléotides séquencés à une profondeur de 20X .

Cependant, nous comprenons l’importance de pouvoir indiquer le détail des résultats du séquençage de l’exome. Pour cela, chez Bioarray, nous proposons une étude bioinformatique complète du résultat du séquençage, avec toutes les variantes trouvées et la possibilité d’un impact clinique.

 

Nouveaux outils de séquençage d’exome

Ontologie du phénotype humain (HPO)

Il existe des milliers de maladies héréditaires chez l’homme, chacune ayant une combinaison spécifique de caractéristiques phénotypiques .

C’est pourquoi, depuis longtemps, les chercheurs et les professionnels de la recherche et de la santé recherchent des outils permettant d’analyser les corrélations phénotypiques des mutations génétiques pour découvrir les fonctions biologiques des gènes et avancer dans la recherche dans cette zone.

Aujourd’hui, grâce à la bioinformatique et aux outils d’analyse computationnelle, des plates-formes telles que l ‘ ontologie du phénotype humain (HPO) https://hpo.jax.org/app/ qui a été développé dans le but de couvrir toutes les anomalies phénotypiques couramment rencontrées dans les maladies monogéniques humaines.

Séquençage de l’exome pour la détection des CNV

Le développement de nouvelles bases de données et les progrès de la technologie ont permis à la bioinformatique d’utiliser les données du séquençage d’exome pour trouver des variantes du nombre de copies (CNV) , à la fois des suppressions et des duplications, qui bien qu’ils nécessitent une validation à l’aide d’autres techniques telles que MLPA ou microarrays, ils peuvent être montrés à partir de l’exome.

Le fait est que le séquençage des exomes est devenu l’un des outils les plus adaptés à l’analyse des CNV, car il permet d’obtenir une très bonne couverture des régions d’analyse à moindre coût.

De cette manière, le séquençage d’exome inaugure une nouvelle ère où la génétique et la bioinformatique deviendront des outils de guidage pour diagnostiquer les pathologies dans le secteur clinique et améliorer le domaine de la recherche, avec de nouvelles et meilleures avancées.

Exome Sequencing for Clinical Diagnosis

Exome sequencing is a key tool for clinical diagnosis, as it allows us to identify genetic variations which are capable of causing many types of inherited diseases.

The exome is the part of the genome which if formed by exons. These are fractions of DNA which are in charge of coding for proteins that make up an organism. Studying the exome is therefore one of the most thorough and complex ways of analysing a person’s DNA, as there are many genetic diseases or pathologies which are associated directly to mutations in the exome DNA.

What does Exome Sequencing Consist of?

Exome sequencing is a Next Generation Sequencing (NGS) method which is widely used for DNA analysis of the protein coding regions of the genome.

We must bear in mind that even though the human exome represents under 2% of the entire genome, it contains around 85% of the known variants related to pathologies.

Therefore, exome sequencing has become one of the most promising methods for clinical diagnosis, without needing to sequence the subject’s entire genome.

 

Advantages of Exome Sequencing

Exome sequencing has various advantages in the realm of clinical amplification.

Its profitability stands out in the cases where whole-genome sequencing is not necessary. Being able to exclusively analyse the coding regions allows investigators to focus their efforts on inspecting the genes with a much greater probability of being the cause of the disease. This therefore optimizes the cost-effectiveness of the whole process.

Another advantage we can consider is how concise the information is when obtained, meaning that the amount of data collected is smaller and more manageable. This shortens the time required for analysis compared to sequencing an entire genome.

In scientific investigation, exome sequencing also has multiple applications for detecting and analysing the genetic variants which lead to human diseases, such as those related to cancer, mendelian disorders, and others with more complex inheritance patterns.

Bioarray works with the Illumina NovaSeq platform for Exome Sequencing, using the Agilent SureSelect Human All Exon V6 capture kit. These systems allow for a greater enrichment efficiency, as they achieve 90% uniformity in coverage and over 90% nucleotides at 20X sequencing depth.

Nevertheless, we must understand the importance of showing the results in full detail. For this reason, Bioarray offers a complete bioinformatic analysis of the Exome Sequencing results.

 

 

New tools in Exome Sequencing

 

Human Phenotype Ontology (HPO)

There are thousands of hereditary diseases in human beings, each of which has its own specific combination of phenotypical characteristics.

For this reason, investigators and professionals have searched for tools to analyse the correlations between phenotypes and genetic mutations to discover the biological functions of certain genes.

Thanks to bioinformatics and new tools for computer analyses, platforms such as Human Phenotype Ontology (HPO)https://hpo.jax.org/app/ have been developed in order to cover all phenotypical anomalies.

 

Exome Sequencing for CNV detection

The development of new databases and technological advances have allowed bioinformatics to use data from Exome Sequencing to find Copy Number Variants (CNVs) : deletions or duplications which can be picked up with Exome sequencing and later verified with MLPA or microarrays.

Exome sequencing has become one of the most adequate tools for the analysis of CNVs, as we can obtain excellent coverage of the regions to be analysed for a more economic price than by other methods.

This way, Exome Sequencing has opened a new era in which genetics and bioinformatics become the key tools for diagnosis of clinical pathologies and improve the scientific investigation of these topics, helping with new discoveries.