Bioengineering in reproductive health

About

Our lab aims to study human embryo implantation and provide solutions to improve in vitro fertilization (IVF).

3D Transgenic embryo expressing fluorescent Oct4 fused to GFP. The blastocysts breaks out of the protective shield called zona pellucida (purple), in an event termed hatching.

The embryonic development of humans (and mammals in general) requires the implantation of the embryo into the walls of the mother uterus. Implantation involves the attachment of the embryo to the uterine lining, termed endometrium, and the invasion of the tissue to form the placenta.

This process is crucial for natural conception and especially for in vitro fertilization (IVF) as only 25% of IVF embryos successfully implant into the mother uterus’ and develop to term. However, despite the central role of implantation in human fertility, the process is still elusive to experimentation because of its inaccessibility.

In our lab we use bioengineering methods to create 3D environments that support embryonic development outside of the mother uterus. Our systems are accessible to imaging tools which allow us to interrogate the genetics, metabolomics and mechanics of the embryo in a high throughput manner. Using our systems we are capable to (i) improve embryo culture conditions and (ii) diagnose embryos with improved implantation potential.

Transgenic mouse embryo at blastocyst stage expressing the fluorescent protein tdTomato in the membrane and pa GFP in few selected cells.

Due to the high translational component of our research, we have established collaboration contracts with the pharma industry, hospitals and venture capital to bring our technology to the clinics and the market.

Our Open Lab is a multidisciplinary environment where biologists, biophysicists, clinicians and business developers synergize to create a unique environment shaped by science and entrepreneurship.

Staff

Samuel Ojosnegros Martos | Head of Bioengineering in Reproductive Health
Maria Demestre Viladevall | Senior Researcher
Anna Seriola Petit | Senior Researcher
Denitza Denkova | Postdoctoral Researcher
Amélie Luise Godeau | Postdoctoral Researcher
Albert Parra Martínez | PhD Student
Ester Aroca Bosque | Laboratory Technician
Marc Casals Sandoval | Laboratory Technician
Eduardo Sesma Herrero | Laboratory Technician

Mònica Valls · mvalls@ibecbarcelona.eu

 

 

 

 

 

Jobs/News

 

Study on decision making for embryo selection in IVF clinics

One out of seven couples suffers from sub-fertility problems. In vitro fertilization (IVF) is the most commonly used method to assist such couples. As only 30 % of the transferred embryos implant and develop to term, it is common to artificially increase the IVF success rate by transferring multiple embryos. This procedure has the undesirable side effect of multiple pregnancies, generating significant health complications, both for the mother (higher rates of hospitalizations and Caesarean delivery) and for the babies (prematurity, low weight, up to 40x increased risk of early infant death).

The current trend in IVF clinics is to transfer a single embryo and succeed a single pregnancy, as both unsuccessful and multiple pregnancies are physically, emotionally and economically traumatic. Improving the IVF success rate of single embryo transfer by recognizing which embryo has a higher chance to implant is one of the major challenges in ART.

The Bioengineering in Reproductive Health (BRH) group is currently developing a study to better understand in a quantitative way how do IVF clinics around the world make decisions regarding embryo selection for implantation. Due to the limited literature on the topic, the team has decided to request the collaboration of fertility specialists from prestigious clinics worldwide.

With this study, the group’s research goal is to discover which is the best way to help embryologists and fertility clinics in the critical process of selecting the best embryo to transfer to the mother’s uterus. By improving this process, the number of multiple embryo transfers and multiple births is going to decrease, thus increasing the efficacy and safety of IVF.

The best way to explore which is going to be the best way to collaborate in technological progress and help embryologists in this matter is to have a comprehensive understanding of the status quo of IVF decision making. This study will allow a two-fold benefit, providing information and knowledge both to the team and fertility specialists around the world.

 

 

Publications

Cutrale, Francesco, Rodriguez, Daniel, Hortigüela, Verónica, Chiu, Chi-Li, Otterstrom, Jason, Mieruszynski, Stephen, Seriola, Anna, Larrañaga, Enara, Raya, Angel, Lakadamyali, Melike, Fraser, Scott E., Martinez, Elena, Ojosnegros, Samuel, (2019). Using enhanced number and brightness to measure protein oligomerization dynamics in live cells Nature Protocols 14, 616-638

Protein dimerization and oligomerization are essential to most cellular functions, yet measurement of the size of these oligomers in live cells, especially when their size changes over time and space, remains a challenge. A commonly used approach for studying protein aggregates in cells is number and brightness (N&B), a fluorescence microscopy method that is capable of measuring the apparent average number of molecules and their oligomerization (brightness) in each pixel from a series of fluorescence microscopy images. We have recently expanded this approach in order to allow resampling of the raw data to resolve the statistical weighting of coexisting species within each pixel. This feature makes enhanced N&B (eN&B) optimal for capturing the temporal aspects of protein oligomerization when a distribution of oligomers shifts toward a larger central size over time. In this protocol, we demonstrate the application of eN&B by quantifying receptor clustering dynamics using electron-multiplying charge-coupled device (EMCCD)-based total internal reflection microscopy (TIRF) imaging. TIRF provides a superior signal-to-noise ratio, but we also provide guidelines for implementing eN&B in confocal microscopes. For each time point, eN&B requires the acquisition of 200 frames, and it takes a few seconds up to 2 min to complete a single time point. We provide an eN&B (and standard N&B) MATLAB software package amenable to any standard confocal or TIRF microscope. The software requires a high-RAM computer (64 Gb) to run and includes a photobleaching detrending algorithm, which allows extension of the live imaging for more than an hour.

 

Equipment

  • Micromanipulation-microinjection station
  • Embryo biopsy laser
  • Embryo culture laboratory
  • Cell culture laboratory

 

Entrepreneurship

  • Jorge Fuentes, Bussines Strategy
    A_Ventures, Barcelona, Spain

 

 

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