Ana Bustamante Aragonés y Marta Rodríguez de Alba Freiría

November 21, 2022

"Research in biomedicine is building the medicine of tomorrow" (Dr. Ana Bustamante Aragonés).
"New advances in reproductive medicine allow for more comprehensive diagnoses and have helped many couples have healthy children" (Dr. Marta Rodríguez de Alba Freiría).

Dr. Ana Bustamante Aragonés graduated in Biology from the Complutense University of Madrid and later earned her PhD, with European doctorate distinction, from the Autonomous University of Madrid. She joined the Genetics Service of the Fundación Jiménez Díaz Health Research Institute (IIS-FJD) in 2003, first as a volunteer assistant and later as a "Conchita Rábago" fellow to develop her doctoral thesis on non-invasive prenatal diagnosis (NIPD) in maternal blood, under the supervision of Dr. Carmen Ramos.
Currently, she is an Associate Biologist in the Genetics Service and performs clinical work in the field of preimplantation, prenatal, and postnatal genetic diagnosis of genetic disorders. She holds the Human Genetics Accreditation from the Spanish Association of Human Genetics and the designation of Health Biologist Geneticist awarded by the Official College of Biologists of the Community of Madrid.
In the academic field, she has co-supervised a doctoral thesis, served on committees for two other doctoral theses, and supervised various undergraduate projects. She is an invited lecturer in the Molecular Biomedicine Master's program at the Autonomous University of Madrid and in courses and conferences organized by scientific associations and healthcare centers.
She has participated as the principal investigator and collaborator in various research projects and is the author of thirty publications in scientific journals, as well as numerous communications at national and international congresses, having been awarded three times in the Young Investigator Award category.

Dr. Marta Rodríguez de Alba Freiría graduated from the Faculty of Biological Sciences at the Complutense University of Madrid and earned her PhD from the same university. She joined the Genetics Service at IIS-FJD in 1996 as a volunteer assistant, and in 1997, she received the Conchita Rábago Foundation fellowship, which supported her doctoral thesis. After completing her PhD in 2002, she was appointed attending physician in the Genetics Service, and in 2022, she was named Associate Head of the service. She holds the Human Genetics Accreditation from the Spanish Association of Human Genetics and the designation of Health Biologist Geneticist from the Official College of Biologists of the Community of Madrid.
Throughout her career, she has combined clinical, research, and teaching work. Her clinical work is closely related to reproductive medicine, both prenatal and preimplantation, as well as the diagnosis of issues related to infertility/sterility. She has been responsible for the introduction of new diagnostic techniques, such as array-CGH, and new diagnostic processes, such as preimplantation genetic diagnosis of chromosomal rearrangements. She has been a principal investigator or a team member in numerous research projects, including the EUROGENTEST project, which aimed to establish the foundations for harmonizing genetic testing services for patients at the European level. As a result of this project, the external quality control program GenQA (formerly CEQAS) was established, and Dr. Rodríguez de Alba Freiría is an evaluator and a member of the expert advisory group and the organizational/directorial structure.
She has co-supervised a thesis and supervised several undergraduate theses. She has also participated as a speaker in numerous national and international meetings (Spanish Association of Human Genetics, Spanish Association of Prenatal Diagnosis, European Society for Human Genetics, European Cytogenetics Conference) and has participated in over 50 publications.
She has served as an external evaluator for international projects (The Netherlands Organization, Genome Canada), is a reviewer for international journals, and is an invited lecturer in the Department of Molecular Biology at the Autonomous University of Madrid, in training courses for technicians, and in professional update courses.

Summary of the Project and Clinical Relevance

Project: Implementation of Comprehensive Embryonic Genetic Diagnosis Technique

Preimplantation genetic testing (PGT) aims to select embryos free from a specific genetic alteration that causes disease, carried by one of the parents, to achieve a healthy pregnancy. To do so, a limited number of cells are extracted from the embryo in its early developmental stages (in vitro) to perform the necessary genetic studies. Currently, PGT represents one of the most requested reproductive alternatives for patients at high risk of transmitting a genetic disorder to their offspring.

The most common studies performed through PGT include: diagnosis of a monogenic disease (PGT-M) or chromosomal rearrangements (PGT-SR) present in one of the parents. It can also be used for aneuploidy screening (PGT-A), which involves determining the number of chromosomes in the embryo, particularly in cases where there is a high risk of chromosomal alterations not inherited from the parents (e.g., advanced maternal age, recurrent miscarriages, etc.).

Current technical approaches in PGT are designed for use in a single type of study. Additionally, PGT-M and PGT-SR require a personalized design based on the genetic basis of the pathology under investigation. However, there is an increasing need to combine these studies in a single embryo due to various factors such as the postponement of motherhood in modern society, which means that many patients requesting PGT are over the age of 35. In these cases, among others, performing both PGT-A and studying the family genetic alteration (PGT-M or PGT-SR) would allow the selection of embryos with the highest likelihood of proper implantation, as many potential alterations would be excluded, thus increasing the chances of a successful pregnancy. Furthermore, consumer-direct genetic diagnostic and screening studies are becoming more widespread, meaning that more patients are aware of being carriers of genetic or chromosomal alterations, making them potential candidates for PGT. This has led to the need to analyze more than one genetic pathology in the same embryo in up to 8% of PGT cases.

Advances in molecular biology techniques have enabled the development of new diagnostic strategies in this field. Among the latest advances in PGT, with widely demonstrated clinical application, is the use of next-generation sequencing (NGS), which allows the three types of studies—PGT-M, PGT-SR, and PGT-A—to be performed on the same embryonic sample. This is known as Comprehensive Preimplantation Genetic Testing.

To acquire the necessary knowledge to implement this simultaneous diagnostic technique at the Hospital Universitario Fundación Jiménez Díaz, Drs. Ana Bustamante Aragonés and Marta Rodríguez de Alba Freiría will undertake a one-week stay at the Laboratory of Cytogenetics and Genome at UZ Leuven Hospital (Belgium), a center with extensive experience in this type of diagnostic technique.

According to Drs. Ana Bustamante Aragonés and Marta Rodríguez de Alba Freiría, "The great benefit for patients from applying this integrated approach is performing a study that not only rules out the original pathology that led them to undergo PGT but also eliminates chromosomal alterations that could jeopardize pregnancy and the birth of a healthy child, offering patients a more comprehensive, robust, and versatile embryonic study."