Immunological determinants of human embryo implantation: an ex vivo model

Subfertility affects 15% of couples trying to conceive. Many underlying causes
of infertility can be overcome by assisted reproductive technologies (ART).
However, despite recent advances in in-vitro fertilisation (IVF) pregnancy
rates remain only 20-30% per embryo transfer procedure. Failure of implantation
therefore remains a major challenge. Implantation is a complex process in which
molecular cross-talk between embryo and endometrium occurs, resulting in
apposition, adhesion and invasion of the embryo into the endometrial stroma.
An accumulating body of evidence suggests that both implantation and uterine
receptivity are controlled primarily, although not exclusively, by locally
acting growth factors and cytokines. Further improvement of ART depends on
better understanding of the embryonic-uterine ensemble at the site of
implantation. The application of ex vivo models provides a powerful tool to
dissect the molecular, cellular and physiological mechanisms of embryo
implantation in the human. Here we propose to employ a newly developed model to
study stromal invasion of an embryo ex vivo.

We intend to employ an ex vivo model of human implantation to study the factors
involved in successful implantation. By linking parameters of successful
implantation with embryo quality markers, we aim to improve embryo selection
and IVF outcomes. It is our objective to improve embryonal screening methods,
achieve higher pregnancy rates and improve safety in women undergoing IVF.

The study design is a prospective, observational study. Firstly we will
establish and implement the newly developed ex vivo model, and then exploit it
for further experiments in the second stage.

Endometrial biopsy is a minimally invasive procedure that is practicable on an
out-patient basis. Previous studies have demonstrated that this procedure can
be safely performed in the luteal phase of the previous cycle, without
affecting pregnancy rates in IVF (Mercader 2003, Spandorfer 2004). This study
will not interfere with the standard IVF and embryo transfer procedures and
will only use surplus embryos. Therefore the study doesn*t affect pregnancy
success rates, nor will it risk the women*s or child*s health.