Douglas Carrell, Ph.D., H.C.L.D. - University of Utah, Salt Lake City, UT

Doug Carrell, Ph.D., H.C.L.D. is a tenured Professor of Surgery (Urology), with adjunct positions in the Department of Obstetrics and Gynecology and the Department of Human Genetics.  He is a board certified high complexity laboratory director and is the director of the In Vitro Fertilization and Andrology Laboratories at the University of Utah. Dr Carrell is active in numerous national and international societies, and is currently president-elect of the Society of Male Reproduction and Urology. He also serves as co-editor in chief of Andrology, the preeminent journal of male reproductive health, Dr Carrell’s research interests focus on genetic and epigenetic causes of male infertility, and the role of the sperm epigenome on early embryogenesis. His research spans from basic science of the sperm and embryo epigenomes to translation therapies and diagnostics for the infertile couple. He has published more than 190 manuscripts and chapters and has edited 7 books. Dr Carrell has directed several doctoral graduate students, as well as mentoring numerous research and clinical fellows.

Project: MicroElectrophoresis – A novel approach to select mature and genetically fit sperm

With the onset of clinical assisted reproduction 30 years ago, there has been a progressive increase in our understanding for the need of mature, genetically fit gametes for a successful outcome. Andrological research to understand the physiology of sperm has improved and more sophisticated techniques to separate functional sperm from those that are immotile have begun to be developed. Initially, starting from simple washing of sperm, separation techniques, based on different principles like migration, filtration, density gradient centrifugation, cell surface proteins or membrane charge, have evolved. However, the external appearance of sperm does not indicate the maturity or the genetic quality of the sperm. In addition, to measure DNA damage the sperm has to be lysed; after this process the sperm cannot be used for treatment. Therefore, novel concepts to isolate the best quality sperm are required to improve the assisted reproduction treatment outcomes.

In a normal and matured sperm, the membrane glycocalyx are rich in negatively charged sialic acid residues which prevent aggregation of ejaculated sperm, facilitates sperm interactions with ova, and also reflects normal spermatogenesis and maturation status of sperm. To identify the sperm with negative electrostatic potential, we have developed a microscopic electrophoresis unit. Using our novel sperm selection method, “MicroElectrophoresis” we are able to isolate mature sperm, and sperm with low levels of DNA damage, the two most important factors known to influence the success of assisted reproductive treatment.

During our preliminary studies the novel system of MicroElectrophoresis based sperm selection rapidly and effectively isolates human sperm exhibiting minimal DNA damage. There has been no controlled trial to prove the suitability of this novel method for clinical practice. Therefore, the objective of this prospective controlled clinical trial is to determine whether MicroElectrophoresis has advantages over morphologically based sperm selection for fertilizing oocytes with ICSI. The advantages would be determined by comparing fertilization rates, embryo cleavage rates, blastocyst development rates and quality, implantation, and clinical pregnancy outcomes. The aims of the study proposed here are:

1. Standardization of MicroElectrophoresis sperm selection protocol.
2. Perform a prospective controlled clinical trial using ICSI-Split where sibling oocytes are divided equally for insemination by sperm selected by density gradient separation (DGC)/morphology and MicroElectrophoresis techniques.
3. Evaluate the impact of sperm selection methods on ICSI outcomes using sperm DNA damage as a cofactor.
4. Analyse the efficiency of MicroElectrophoresis sperm selection technology on various subgroups of infertility.

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