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About PreImplantation Factor (PIF)

PIF is pivotal for reproductive success and immune modulation. The discovery of PIF represents a paradigm shift in understanding mammalian pregnancy; its premise is that the burden of successful pregnancy resides not with the mother as previously thought, but with the embryo/fetus and its ability to secrete PIF.

While researching causative factors associated with early pregnancy, Dr. Eytan Barnea discovered PIF, a naturally occurring peptide secreted only by viable mammalian embryos. PIF is secreted and detected as early as the 2-cell stage, and it continues to do so throughout pregnancy. In non-viable embryos, PIF is either absent or negligible. The discovery of PIF helps to explain why, at the inception of and during pregnancy, the mother’s immune system does not reject the embryo. This event, at its very core, is a perfect transplant in a well-adapted immune environment. PIF enables maternal immunity to simultaneously tolerate the embryo and continue to protect both mother and embryo against disease.

The Barnea Research Group, a worldwide network of PIF researchers, quickly ascertained that PIF’s immune-modulatory effects offer potential therapeutic benefits across diverse disease areas in pregnancy, and extending into disorders of immunity and transplant. Synthetic PIF, currently used in clinical trials, was produced following the identification of native PIF. To date, PIF has been studied in more than 25 different mammalian pregnant and non-pregnant models, generating compelling evidence to establish PIF’s potential impact as a diagnostic and single therapeutic agent. PIF-based diagnostics for in vitro fertilization (IVF) viable embryo identification is currently in multicenter clinical trials. In parallel, research continues to study PIF’s mode of action, corroborating its comprehensive local and systemic regulatory role.

Possible PIF translational applications identified and studied to date include: pregnancy (i.e. embryo viability, recurrent pregnancy loss, premature labor / preeclampsia), immunity (i.e. disorders affecting the liver, gastrointestinal tract and skin), injury (i.e. traumatic brain injury, acute radiation syndrome), and transplant (i.e. bone marrow and organs).


Unlike immune suppressant drugs that are associated with serious side effects, PIF regulates local and systemic immune response through targeted effects in a safe, nontoxic manner. PIF represents a New Drug Entity (NDE), and given its potential and high safety margin, was awarded the coveted Fast-Track designation by the FDA.This discovery has broad translational therapeutic implications for treating pregnancy disorders, organ transplant rejection and immune diseases. PIF is at the center of numerous current and upcoming human clinical trials worldwide (www.clinicaltrials.gov).