Nick Macklon & Søren Ziebe
Prof. Nick Macklon - Director Complete Fertility Centre; Chair in Obstetrics and Gynaecology , University of Southampton
Nick Macklon is Professor of Obstetrics and Gynaecology, and Director of Complete Fertility Centre at the University Hospital Southampton, UK. After training in Edinburgh and completing his doctoral research in Glasgow, he was appointed Senior Lecturer in Obstetrics and Gynaecology at the Erasmus University Medical Centre in Rotterdam. In 2004 he moved to Utrecht as Professor of Infertility and Periconceptional Medicine, before returning to the UK to his present position in 2009.
An active clinician, researcher and well known lecturer, he has published widely in the fields of ovarian stimulation, endometrial receptivity and periconceptional medicine, an area in which he has edited three books. In 2011 his group was awarded a GFI grant to investigate the endometrial factor in recurrent implantation failure. He currently holds visiting professorships in Adelaide and Copenhagen, where the preliminary work behind the current GFI award was carried out with Dr Morten Petersen and Dr Soeren Ziebe, his two collaborators on the study to be supported by GFI.
Prof. Søren Ziebe - Head of the Fertility department at the Juliane Marie Centre, Copenhagen University Hospital
Professor Søren Ziebe has a MSc in Biology , and DSc in medicine . He is the head of the Fertility department at the Juliane Marie Centre, Rigshospitalet, Copenhagen University Hospital and the University of Copenhagen, Denmark. Søren Ziebe is appointed as professor of clinical embryology by University of Copenhagen.
His main research areas are:
- Assisted Reproduction
- Embryonic development
- Gamete competence
He has previously been chairman of the National Danish Fertility Society, president of the Nordic Fertility Society, member of the Executive Committee of European Society of Human Reproduction and Embryology (ESHRE) and Coordinator for ESHRE SIG sub-committee – responsible for all training and educational activities of ESHRE 2007 – 2011. Further, he has been appointed Council of Europe expert.
Project: Embryo derived trypsin: A novel and simple marker of embryo viability
The trend to transfer fewer embryos has increased the importance of optimal embryo selection in vitro. Our group has recently identified a novel, simple, non-invasive embryo derived marker of implantation competence that has the potential to improve embryo selection in a cost effective and readily applicable way. Recently, it has been shown that the embryonic secreted serine protease trypsin serves as a key embryo derived signal of competence to the endometrium. We have shown that trypsin activity is readily measured in media conditioned by single cultured embryos, and our preliminary data indicates that trypsin activity provides additional functional prediction of viability independent of morphological parameters.
The main aims of the project, which will be carried out at the Fertility Clinic, Rigshospitalet, Copenhagen and the Complete Fertility Centre, University Hospital Southampton, are to:
- Further refine normogram curves generated by high implantation versus low implantation blastocysts in two laboratory settings, using two types of culture media.
- Analyse the most discerning differentiating characteristics of the graphs generated in order to optimise the sensitivity and specificity of the analysis of trypsin activity as a predictor of implantation potential.
- To determine the extent to which trypsin activity provides information regarding viability independent to that offered by morphological criteria.
Conditioned medium obtained from 300 individually cultured blastocysts of sufficient quality to transfer in which the clinical outcome is known, and patient characteristics such as age and number of oocytes obtained were recorded, will be subject to analysis of trypsin activity by a scientist blinded to clinical outcome after embryo transfer. In addition to recording trypsin activity in each drop of conditioned medium, extensive morphological scoring of the blastocyst will be performed.
Following generation of the curve analysis algorithm most predictive of implantation, a prospective validation study will be performed in both centres in which the data generated by 100 embryos is matched to the normative curves and scored as high or low implantation potential. Selection for transfer will be made on morphological criteria only, and the performance of the trypsin activity compared with morphological criteria compared, again using ROC curve analysis.
In order to discern to what extent trypsin activity provides additional prediction of IVF outcome, univariate and multivariate will be performed. External validation will be performed by comparing ROC curves generated in each centre using their own normative data, and then by comparing with the normative data generated in the other centre.
