Technologies to Advance Precision Medicine for Reproductive Health and Infertility (R43, R44 Clinical Trial Optional)

Purpose/Research Objectives The purpose of this FOA is to stimulate the small business community through the Small Business Innovation Research (SBIR) grant program to adapt discoveries in genomics, epigenomics and biomarker identification to the clinical diagnosis and treatment of couples with infertility, and diseases and disorders that affect fertility. This initiative would foster collaborations of 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 precision medicine as applied to clinical issues affecting reproduction. The research objectives of this initiative are to improve accuracy, safety, convenience and rapidity of diagnostic evaluation and treatment of women and men with infertility and reproductive diseases and disorders that impact fertility. Background The application 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 genotypes associated with differences in treatment response to fertility medications could lead to more individualized prescription with the potential of improved success and shorter time to pregnancy and live birth. Specific areas of research could include, but are not limited to, the following examples: Molecular markers for rapid assessment for precise timing of endometrial receptivity for successful implantation Non-invasive assessment of early pregnancy viability that distinguishes non-viable uterine pregnancy from persistent pregnancy of unknown location and early ectopic pregnancy Non-invasive assessment of male infertility and reproductive disorders Methods that improve assessment of ovulation and tubal blockage Molecular assessment of polycystic ovary syndrome Development of reliable salivary assays for reproductive hormones and biomarkers Molecular markers to facilitate diagnosis and treatment of polycystic ovary syndrome, male factor infertility, implantation failure, and early pregnancy loss Genomic characterization and prediction of treatment response to fertility medications Mobile apps for infertility diagnosis and treatment Rapid point-of-care measurement of reproductive hormones in ranges tailored for reproductive aged males and females Technologies to improve sperm processing for intrauterine insemination 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. Areas of low priority include: Methods for gamete creation