Jeremy Grushcow, PhD, on the questions the current IVF testing stack still can't answer and a new approach that's starting to fill in the gaps.

OPINION

This News Digest Story is paid featured content.

By Jeremy Grushcow, CEO, Juniper Genomics

Jeremy Grushcow is the Founder, CEO, and Acting Chief Scientific Officer of Juniper Genomics. His work focuses on reproductive genetics, embryo viability, and inherited disease risk beyond conventional IVF testing frameworks.

“A ‘negative’ carrier screen is widely interpreted as ‘no genetic risk,’ when it actually means ‘significantly reduced risk for the subset of conditions we looked for.’”

The Standard Workup Leaves Gaps That Matter

The standard genetic workup in IVF currently has two pillars: expanded carrier screening and PGT-A. Together, they are often treated as a comprehensive genetic evaluation, but in reality they leave clinically significant gaps.

Carrier screening is clinically validated and an important part of most genetic workups. But even the largest expanded panels cover under one thousand genes, even though OMIM lists more than 6,000 genes associated with Mendelian disease. This is because the panels are built around autosomal recessive conditions, which means dominant conditions are excluded by design and de novo variants are invisible to preconception screening entirely. A clean result on a 400-plus gene panel leaves hereditary cancer syndromes, polycystic kidney disease, familial hypercholesterolemia, hereditary cardiomyopathy and many other conditions completely unexamined. Not because the panel missed them, but because it was never built to look.

PGT-A screens for aneuploidy, but roughly 45% of euploid embryos still do not result in a live birth. Single-gene disorders, structural variants, and factors affecting developmental viability all sit outside what a ploidy screen evaluates. A euploid result answers one question. It leaves many others open.

Finally, PGT-P has recently entered the conversation as a way to rank embryos for complex traits, but it doesn't address whether any given embryo will implant or result in a live birth. If the top-ranked embryo fails to implant or miscarries, the family moves to the embryo PGT-P scored lower — with the same unanswered questions about why the first one failed or whether the next one will succeed.

These gaps compound. A family can complete carrier screening, run PGT-A on every embryo, layer PGT-P on top and still transfer an embryo carrying a single-gene disorder or a variant in a gene necessary for development that no test in their workup was designed to detect. More tests, but the same unanswered questions.

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PGT-G Was Built to Start Filling the Gaps

At Juniper Genomics, those structural blind spots shaped how we built PGT-G.

PGT-G combines whole genome and transcriptome analysis to screen for dominant, recessive, and de novo single-gene variants and to evaluate genetic factors associated with embryo viability, all without depending on a pre-built panel. It adds clinically relevant information that the current testing stack was never designed to provide.

The carrier screening gap alone has been significant. So far, PGT-G has identified disease-causing variants in over 10% of embryos that were previously unknown to the patients. These have included variants in BRCA2 (hereditary cancer risk), LDLR (familial hypercholesterolemia), TTN (cardiomyopathy), RP1 (progressive vision loss), and FBN1 (Marfan syndrome), among others. Every one of these variants fell outside the scope of the carrier panel the family had already completed. The tests didn’t miss them. They were never designed to find them.

“Optimization is not the bottleneck. Per-embryo success is.”

Beyond disease avoidance, Juniper identified what we call Reduced Viability Variants (RVVs) in over 30% of embryos tested. These are variants in genes implicated in embryonic development and placental function that a ploidy screen does not evaluate. These variants may help explain why euploid embryos fail, which is a question the current testing stack has no answer for.

In early transfer data, embryos without RVVs have shown a meaningful improvement in live birth rates compared to euploid embryos selected by PGT-A alone, even in a cohort enriched for recurrent implantation failure and recurrent pregnancy loss. We are currently collecting non-selection data to further validate these findings.

This information changes clinical decision-making. It changes how clinicians counsel patients on how many embryos they need to bank, which embryo to transfer first, when to consider third-party reproduction and begins to offer a framework for explaining euploid failures.