Fertilin peptide decreases embryo resorption and improves live birth rate in mouse.

Abstract

Objective: To study the effect of the mouse Fertilin peptide, on mouse in vitro and in utero embryo development.

Design: The Fertilin peptide, a cyclic tripeptide derived from a loop of the ADAM2 protein, is already known to provide healthy pups over three generations of mice. The present prospective randomized study analyzes the in vitro and in vivo mouse embryo development using ultrasound examination, and birth rates, considering embryo resorption in mice as the equivalent of miscarriage in humans.

Subjects: B6CBA F1 female mice were crossed with C57BL6/J male mice. A total of 458 day 2 embryos were retrieved and involved in the study: 150 for in vitro study, 66 for immunofluorescence, and 242 were transferred in vivo. INTERVENTION (FOR RESEARCH CLINICAL TRIAL) OR EXPOSURE (FOR OBSERVATIONAL STUDIES): Two-cell embryos were incubated in an embryoscope without or with the Fertilin peptide at 100 μM. The embryos were then either followed up in vitro until blastocyst formation, or were transferred in utero on day 3. Their development was analyzed using ultrasound examination. Birth rates were registered.

Main outcome measures: The main outcomes are: (1) in vitro kinetics of embryo development in the control and Fertilin group, (2) in vivo development of embryos analyzed by ultrasound analysis. The pregnant female mice were kept separately so that newborns could be counted after they gave birth (3).

Results: In mice, Fertilin 100 μM accelerated blastocyst formation in vitro, and reduced embryo resorption in vivo from 48.6% to 33.0%. Consistently, the live birth rate was increased from 42% to 63%.

Conclusion: This study demonstrates that Fertilin peptide accelerates embryo development in vitro, reduces the resorption rate in utero, and increases the live birth rate in mice.

Interpretation: In the mouse model, Fertilin appears to be the first molecule able to significantly reduce miscarriage in vivo and improve live birth rate. The human molecule is currently being evaluated in an ongoing prospective, randomized, multicenter clinical trial (NCT:04954274).