Inherent Biosciences Announces Podium Presentations at American Urological Association Annual Meeting 2022

By: Andy Olson

May 12, 2022

Salt Lake City, Utah — Inherent Biosciences, a biotechnology company pioneering epigenetic medicine, today announced Podium Presentations at American Urological Association Annual Meeting 2022 to discuss how we’re using epigenetic technology to revolutionize male reproductive health.
Details of the podium presentations are as follows:
Use of a new epigenetic sperm quality test (SpermQT) for men seeking fertility care
Larry Lipshultz, MD, Inherent Biosciences Clinical Advisor
Introduction: New technology and diagnostics are needed for better assessment of male infertility. The mainstay of male factor infertility diagnosis is the standard semen analysis (sperm concentration, motility, and morphology) has changed very little over the last several decades and has been shown to have limited value. Here we complete a prospective analysis of men seeking fertility care using a newly available epigenetic sperm quality test (SpermQT).
Methods: SpermQT was run on 50 sperm samples from consented patients at a single academic center. The SpermQT was developed and validated by a university associated bioscience company and is now available commercially. SpermQT looks specifically at DNA methylation sperm patterns at 10,000 promoters and has shown an 84% PPV for identifying men at high risk for no live birth from IUI or natural conception, and needing IVF with ICSI. Semen parameters, hormones, medications, health history, fertility treatments, and outcomes were analyzed for each sample, with 30 of the 50 samples having pregnancy data to date. Associations between the SpermQT results and the provided data were examined using standard statistical methods.
Results: Analysis was completed on all samples that passed the quality control measures of the SpermQT. In the 50 samples analyzed, 22% had the SpermQT high-risk (N=11) result. Of the 22% with a high-risk result, 73% of the men had normal semen parameters (concentration and motility). There was no statistically significant difference between the high-risk and low-risk between chronological ages, epigenetic sperm ages, % motility, smoking status, alcohol consumption, and BMI. However, for concentration the high-risk group had a statistically significant higher sperm concentration compared to the low-risk group (p=0.007) attesting to the unique quality of the epigenetic testing with SpermQT. Pregnancy outcomes were known for 30 out of the 50 patients, with 7% (N=2) achieving pregnancy to date. 100% of the pregnancies were from men with a low- risk result, and no man with a high-risk result has yet established a pregnancy.
Conclusions: Epigenetics is a growing field of scientific interest that is only starting to have an impact on the field of male infertility. Here we show the epigenetic sperm quality high-risk result is irrespective of semen quality. With continued collection of data for pregnancy outcomes we can further assess its utility in clinical care. The uniqueness of epigenetics is that it can be modified with
lifestyle, which is a feature that can be leveraged in future research and has potential for the treatment of patients.
Discovery of an epigenetic biomarker predictive of male infertility
Kristin Brogaard, PhD, Inherent Biosciences Chief Scientific Officer
Introduction: Herein we introduce the discovery of an epigenetic (DNA Methylation) biomarker that is predictive of sperm quality. Currently, the standard semen evaluation is the primary tool for the assessment of fertility potential. However, the semen analysis only provides a very superficial analysis of a man’s fertility potential. Reproductive Urologists and Endocrinologists need new and more powerful tools to better assess sperm quality. The optimization of the biomarker described here has potential to improve the current standard of care and will support more personalized and effective treatment plans for couples.
Methods: In phase 1 of this study, sperm DNA methylation patterns were analyzed from 122 men who were undergoing IVF treatment and 54 fertile sperm donor samples. For the 122 men, we collected semen analysis data, embryo quality, and pregnancy outcomes. Men with a female partner that had advanced maternal age, severe endometriosis, or PCOS were excluded from the study. Outcomes were divided up into four categories: 1) fertile, 2) good embryos with pregnancy, 3) poor embryos with pregnancy, and 4) poor embryos with no pregnancy. 10,000 promoters were analyzed for differential methylation values compared to a training set of fertile, donor controls. A cutoff of normal vs. unhealthy differential methylation was determined using a testing set of fertile donors, with the unhealthy men having an aberrant methylation pattern. Men with “unhealthy” differential methylation were designated to be at High-Risk for poor sperm quality. Utilizing the cut-offs defined in the phase 1 study, a phase 2 study was conducted analyzing the sperm DNA methylation patterns of 74 new men seeking infertility care compared with a new set of 60 fertile controls. Samples were blindly analyzed for the high-risk biomarker methylation pattern.
Results: For the phase 1 study there was a significant difference in the presence of the high-risk biomarker in fertile controls versus the men undergoing IVF (p=0.004). Prevalence of the high-risk biomarker increased with poorer outcomes as the high-risk biomarker was present in: 4% of the fertile donors, 38% of the good embryos with pregnancy, 38% of the poor embryos with pregnancy, and 44% of the poor embryos with no pregnancy. Of the men with a high-risk biomarker 94% of them had NORMAL semen parameters. In the phase 2 study, 5% of the fertile donor sperm sample had a high-risk biomarker while 38% of the men seeking fertility care had the high-risk biomarker (p=3.80 E -0.6).
Conclusions: In this study of 310 men with varying fertility outcomes (phase 1 and phase 2), we have identified a unique sperm DNA methylation pattern that can classify a subset of infertile men that would be missed by the standard semen analysis. Here we observe this biomarker to be associated with poor fertility outcomes and we found that it has very low prevalence in known fertile population. These findings introduce a new method for detection of male infertility.
About Inherent Biosciences
Inherent Biosciences, Inc. is a biotechnology company pioneering epigenetic medicine for complex diseases. Gene dysregulation, a hallmark of complex disease, has been difficult to detect and treat, until now. The company’s epigenetic platform detects dysregulation across multiple genes and related pathways to pioneer a new category of diagnostics and therapeutics that leverage epigenetics, biology’s inherent mechanism for gene regulation, to radically transform how we diagnose and treat complex diseases like infertility.
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