Sperm selection in a reproductive tract biomimetic environment
Assisted reproductive techniques (ARTs)(opens in new window) involve procedures such as in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes or embryos, and the use of fertility medication. Despite years of research, the clinical success of ARTs is low: approximately 35 %. A critical step in the process that determines ART success is the effective selection of high-quality sperm.
Sperm selection using microfluidics
Conventional sperm selection methods rely on sperm density and membrane surface charge and integrity, as well as overall morphology and motility. However, none of these techniques lead to consistent clinical success. Inspired by the natural swimming mechanisms of sperm, the MicroFSMA project focused on improving the analysis and isolation of quality sperm by developing a microfluidics-based(opens in new window) device. “Our system has been designed to mimic the physiology and micro-environment of the female reproductive tract,” explains project coordinator Shiva Shukla. In the mammalian reproductive tract, sperm cells have a major task: to find the unfertilised egg. This requires swimming against a light flow in a convoluted path through the vagina, cervical canal and uterus to ultimately reach the fallopian tube. Their asymmetrical bodies and flagella enable them to propel forward, while other parameters such as temperature and the biomolecules present in the follicular fluid also play a vital role. In essence, chemotaxis, thermotaxis and rheotaxis(opens in new window) are the major sperm guidance mechanisms. MicroFSMA also integrates a computational framework which delivers the automated kinematics of sperm cell swimming; it then assesses sperm quality based on characteristics such as velocity, linearity and beat frequency. The resulting analysis of sperm quality is more holistic, and includes count, motility and shape. “Although clinical validation is pending, we are confident our assay not only selects motile sperm, but also increases the population responsible for fertilisation,” emphasises Shukla.
MicroFSMA vs existing techniques
Existing techniques for sperm separation involve complex biological protocols and centrifugation that often cause DNA fragmentation. By contrast, the MicroFSMA assay maintains DNA integrity and is easy for clinicians to use. The microfluidic chip technology is suitable for simulating the geometry and fluid composition of the female reproductive tract. Moreover, it offers the potential for automation and reduced turnaround times for male infertility diagnosis and treatment. Improvement is also possible through the use of chemoattractants or feeder cells. MicroFSMA addresses a key technological challenge linked with high failure rates of ARTs. Implementation of the MicroFSMA assay promises to improve sperm selection and ART clinical success. This will greatly benefit women trying to get pregnant. For these women, ARTs represent a significant investment in terms of time, money and effort, not to mention the accompanying emotional and psychological stress and the biological risk associated with hormone injections. “The clinical validation of the developed technology is our primary goal onwards, and will be implemented by Béez Biotech,” concludes Shukla. Béez Biotech(opens in new window) will also patent the technology and bring it to the market.
