Path Fertility NIH Grant Backs New Male Infertility Test

Path Fertility has received a two million dollar Direct to Phase II Small Business Innovation Research grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health, to develop and clinically validate an epigenetic diagnostic for non-obstructive azoospermia, the most severe form of male infertility, and its associated cancer risk. The Path Fertility NIH grant was announced in Baltimore, where the company is presenting a pair of studies at the American Society for Reproductive Medicine congress, according to the announcement.

Non-obstructive azoospermia, known as NOA, leaves men with no sperm in the ejaculate because the testes produce too little sperm or none at all, and it is linked to higher risks of cancer and cardiovascular disease. Current tests, including karyotyping and Y-chromosome microdeletion testing, leave many cases without an explanation, which is why a molecular answer matters to patients who have spent months or years searching for one. Prior research by Dr. Dolores Lamb and collaborators, supported by Inherent Biosciences, found epigenetic changes called epimutations in MSH5, a DNA repair gene, in up to 19% of men with NOA, pointing to a pathway that may explain a large share of otherwise unexplained cases and connect failed sperm production to broader health risks.

Under the new award, Path Fertility will confirm how often those epimutations occur in a broader group of men with NOA through a multi-site clinical study, and it will develop a semen-based reflex test that removes the need for a separate blood draw. The team will also measure epimutations in 500 patients with colorectal cancer, a population known for DNA mismatch repair defects, and validate the assay in a CLIA-certified laboratory for commercial launch as a laboratory developed test. The work turns an earlier research finding into a test that clinics could actually order, rather than leaving the result as a laboratory observation.

The test will be incorporated into NOA Guide, Path Fertility's diagnostic that helps predict whether sperm can be retrieved surgically in men with NOA. NOA Guide also uses sperm-derived cell-free DNA technology that Path Fertility developed further under a prior NICHD grant and is presenting at the Baltimore meeting. According to co-founder and Chief Scientific Officer Kristin Brogaard, who is principal investigator on the award, men with NOA are often told there is no explanation for their infertility and rarely told it may signal risks to their overall health, and the award lets the team confirm the finding across clinical sites and turn it into a simple semen-based test that gives men an answer and flags health risks that deserve follow-up.

What the Baltimore studies showed

In one study, researchers followed 67 men with NOA who were undergoing surgical sperm retrieval and examined sperm-derived cell-free DNA in a semen sample. The amount of that DNA predicted whether sperm would be found, and the direction of the link depended on follicle-stimulating hormone level, so a reading that looked promising at one hormone level did not mean the same thing at another. In a subset of men with testicular pathology, the DNA measure distinguished maturation arrest with an AUC of 0.79, and no men with maturation arrest had sperm retrieved, which suggests a non-invasive semen test read alongside hormone level could help physicians counsel men and select candidates before surgery. The study was conducted with researchers at Baylor College of Medicine and Brigham Young University.

In a second study, researchers used real-world data from 537 men tested with SpermQT across 10 fertility clinics and 28 physicians, following 202 couples through intrauterine insemination over an average of 2.8 cycles. The cumulative pregnancy rate was 22.0% when the SpermQT result was Normal and 0% when it was Abnormal, even though age and total motile count were similar between the groups, and the result held after adjusting for physician and clinic. Co-authors included investigators from Baylor College of Medicine and a national fertility group, and the finding indicates that sperm epigenetics can predict insemination success regardless of where a couple is treated or which physician treats them. The Path Fertility NIH grant extends that platform to men facing the most severe infertility.

Why a semen test could change counseling

For men facing NOA, the current path can lead to surgery with no certainty about the outcome, and a reliable semen-based result before an operation would change how doctors and patients weigh that decision. A test that predicts retrieval could spare some men an operation that was unlikely to succeed, while giving others a clearer reason to proceed, and the same result could prompt follow-up care for health risks that might otherwise go unnoticed. The Path Fertility NIH grant ties those two purposes together, funding a fertility answer and a health signal in the same assay instead of treating them as separate problems.

Path Fertility is the commercial brand of Inherent Biosciences, based in Salt Lake City, Utah, and its flagship test, SpermQT, is a clinically validated epigenetic sperm quality test that analyzes DNA methylation across genes related to sperm function to help physicians and couples choose a treatment path. SpermQT is supported by three peer-reviewed studies and is ordered by fertility specialists across the United States, and the company is also developing epigenetic diagnostics for NOA and other areas of reproductive and men's health. According to co-founder and Chief Executive Andy Olson, the award is a strong vote of confidence in epigenetics as the foundation for better male fertility diagnostics, and the data presented in Baltimore show the same approach producing actionable answers across male fertility care, as reported by Newswire and ACCESS Newswire.

Source: Path Fertility awarded NIH grant to develop epigenetic test for severe male infertility