Technologies to Advance Precision Medicine Diagnosis and Treatment of Infertility, Reproductive Tract and Gynecologic Disorders Affecting Fertility (R43/R44 Clinical Trial Optional)

Purpose The purpose of this initiative is to stimulate the small business community through the Small Business Innovation Research (SBIR) grant program to adapt discoveries in omics technologies such as genomics, epigenomics and metabolomics, as well as identification of disease biomarkers to the clinical diagnosis and treatment of couples with infertility. This initiative would foster collaborations of small businesses with scientists and clinicians in the fields of female and male reproductive medicine, infertility, andrology, and/or gynecology to develop and validate new procedures, assays, digital apps, devices or technologies to advance the application of precision medicine to clinical issues affecting reproduction. The goal of this program is to improve accuracy, safety, convenience and personalization of diagnostic evaluation and treatment of women and men with infertility and reproductive diseases and disorders that impact fertility. Proposed applications, tools and technologies are encouraged to incorporate existing standards and consider regulatory requirements where appropriate. Background The addition of precision medicine to the clinical practice of medicine has great promise to revolutionize diagnosis and treatment of many medical conditions. For example, the application of genomic and biomarker testing has optimized diagnosis, treatment and even prevention, for a variety of cancer conditions and improved individual treatment outcomes. Multiple genomic, epigenomic, proteomic, metabolomic and disease specific biomarkers are being discovered in reproductive medicine and for diseases that impact fertility. As has occurred in the cancer field, the translation of these discoveries into applications and technologies for clinical practice in reproductive medicine has the potential to personalize diagnosis, tailor management to the individual, lead to the identification of targeted treatments, reduce complications and improve patient outcomes. Delays in diagnosis, particularly in adolescents, have been identified for several conditions such as polycystic ovary syndrome and endometriosis, both of which are associated with infertility. The development of technological applications combining genomic and biomarker discoveries could hasten clinical diagnosis in an affected individual and enable more accurate diagnosis and more rapid treatment. The identification of markers that are associated with reduced efficacy of fertility treatments or increased complications, such as hyperstimulation or ectopic pregnancy, would allow clinicians to more efficiently diagnose underlying conditions, and select specific treatments associated with improved success and avoid treatments with adverse sequelae in at-risk individuals. Moreover, discoveries of differences in treatment response to fertility medications in individuals with specific genotypes would lead to more individualized prescription with the potential of improved safety and shorter time to pregnancy and live birth. A meeting on the topic of precision health sponsored by NICHD and NHGRI was held in April 2018 (https://www.genome.gov/27570856/genomic-medicine-for-reproductive-prenatal-and-neonatal-health/). The meeting participants emphasized genomics approaches to advance health. This FOA targets a specific clinical area that would benefit from application of discoveries in genomics that have already been made. Scope Specific areas of research could include, but are not limited to, the following examples: •A portable bio-chip device for DNA extraction and high-throughput genomic analyses, for genotype-guided infertility studies •Development of reliable assays for reproductive hormones and biomarkers •Methods to facilitate diagnosis of polycystic ovary syndrome, endometriosis, previous or chronic pelvic or urogenital infection, tubal blockage, impairment of implantation •In vitro diagnostic assays such as analytical tools for blood, saliva, or urine (e.g. lab-on-a-chip biosensors that allow remote performance of chemical and/or biological assays outside of a laboratory environment) •Point-of-care measurement of hormones in ranges tailored for reproductive aged males and females •Genomic characterization and prediction of treatment response to fertility medications. The proposed studies need to establish the accuracy and safety of the device or technology under varied clinical conditions. Studies may range from concept to developmental phases, with the goal of developing accurate devices/technologies that can be marketed and used in clinical settings. Applications that address methods for embryo selection will be considered non-responsive. See Section VIII. Other Information for award authorities and regulations.