Cover

Half-title

Title

Copyright

Contents

Participants

Preface

SECTION 1 PREPARATION FOR IMPLANTATION – THE UTERINE ENVIRONMENT

Chapter 1 Endocrine and paracrine signalling in the human endometrium: potential role for the prostanoid family in implantation

Introduction

Endocrine regulation of morphological and functional changes in endometrium during implantation

Genes involved in implantation

Prostaglandins as potential regulators of the implantation process

Role for paracrine regulation of implantation by COX2 and prostanoids

Paracrine signalling of COX2 in implantation

The role of COX2 and prostanoids in blastocyst adhesion and invasion

Angiogenesis is regulated by the COX/PG biosynthetic pathway during implantation

Programmed cell death is necessary for blastocyst implantation

Conclusion

References

Chapter 2 Immunology of implantation

Introduction

Immunological models

Anatomy of early placentation

Immunology of trophoblast

Differential expression of MHC proteins on trophoblast subpopulations

Decidualisation

Uterine mucosal lymphocytes

Uterine NK cells

Functions of uNK cells

NK cell receptors

Uterine NK cell recognition of trophoblast HLA

Immunology of pre-eclampsia

The outcome of recognition of trophoblast HLA by uNK cells

Conclusions

References

Chapter 3 Progestin-induced decidualisation promotes human endometrial haemostasis and vascular stability

Overview

Introduction

Decidualised HESCs are positioned to prevent bleeding during invasion and remodelling of endometrial vessels

Decidualised HESCs mediate haemostasis

Tissue-type plasminogen activator (tPA) and the type one plasminogen activator inhibitor (PAI-1) promote endometrial haemostasis

Decidualised HESCs promote endometrial vascular stability

Discussion

References

Chapter 4 Adhesion molecules and implantation

The timing of implantation

The embryo–endometrial dialogue

Hatching

The maternal barrier

Embryo attachment

Candidate adhesion molecules

Mouse genetic models

Adhesion molecules and the endometrial transcriptome

Endometrial receptivity in fertile and infertile women

Clinical and treatment implications

Conclusion

References

Chapter 5 Vascular Growth and Modelling in the

Changes in vascular structure during the menstrual cycle

Changes in vascular structure during the menstrual cycle

Development of functional receptive endometrium

Key factors regulating endometrial endothelial cell function

References

Chapter 6 Tissue Remodelling at the Fetal–Maternal Interface: the Regulation of Matrix Metalloproteinase 9 transcription

Introduction

Matrix metalloproteinases

Regulation of the MMP9 gene by transcription factors

Regulation of MMP9 gene by p53

References

Chapter 7 Embryo interactions in human implantation

Introduction

Chemokine receptors at the maternal–embryonic interface

Relevance of leptin and leptin receptor in human endometrium

Relaxin and relaxin receptor LGR7

Gene profiling

References

Chapter 8 Experimental models of implantation of the human embryo: reconstructing the endometrial–embryo dialogue in vitro

Implantation failure: a major challenge in in vitro fertilisation

Stages of human embryo implantation

Implantation in the human

Functional models for implantation in the human

Establishing models for human implantation

Conclusions

References

SECTION 2 THE EMBRYO

Chapter 9 What makes a good egg?

Introduction

Follicular growth and development

Oocyte growth and maturation

Gonadotrophin and steroid action within the ovary

Role of other factors in oocyte competence

Genomic imprinting

In vitro systems

Conclusion

References

Chapter 10 What makes ‘good sperm’?

Introduction

Defining ‘good sperm’

Concluding remarks

References

Chapter 11 Morphogenesis of the early mammalian embryo: cell lineage heterogeneity and developmental potential

Introduction

Origin of fetal and extra-embryonic cell lineages

Trophectoderm differentiation: progressive maturation of an epithelial phenotype

Cell contacts and the dynamic regulation of cell lineage allocation

Transcriptional factors and cell lineage diversification

Egg polarity, cell polarity and cell interactions

References

Chapter 12 Epigenetics in development and cloning by nuclear transfer: alternative approaches to nuclear reprogramming

Summary

Introduction

Factors associated with epigenetic remodelling

Nuclear reprogramming in cloned embryos

Cellular ‘plasticity’: can we ‘reprogramme’ the somatic nucleus?

Conclusions

References

Chapter 13 Risks associated with assisted reproduction: insights from animal studies

Introduction

Pregnancy outcomes following ART

Risk factors

Epigenetic modifications and genomic imprinting

Conclusions

References

Chapter 14 Pre-implantation genetic testing

Introduction

Pre-implantation genetic diagnosis (PGD)

Advances in pre-implantation genetic testing (PGT)

Future developments

Conclusion

References

SECTION 3 LESSONS FROM ANIMAL MODELS (TRANSGENICS) AND NOVEL TECHNOLOGIES

Chapter 15 To implant or not to implant: the role of leukaemia inhibitory factor

Introduction

LIF in humans

Regulation of LIF

Cellular targets of LIF in the uterus

Ultrastructural changes during the peri-implantation period in LIF nullmice

Molecular changes in the luminal epithelium of LIF-null animals

Molecular responses to LIF in the stroma

References

Chapter 16 Are gene arrays useful for the study of implantation?

Introduction

Analysis with microarrays

Use of arrays to identify genes involved in endometrial receptivity

Receptivity studies in women

Difficulties in comparing microarray experiments

Mifepristone and receptivity in women

Microarrays and endometriosis

Limitations of current microarray studies

Microarrays and the clinic

References

SECTION 4 CLINICAL SEQUELAE

Chapter 17 Sporadic early pregnancy loss: aetiology and management

Introduction

Terminology

Aetiology

Diagnosis

Patient examination

Treatment

Conclusions

References

Chapter 18 Recurrent miscarriage – the role of prothrombotic disorders

Definitions of pregnancy loss

Aetiology of recurrent miscarriage

Reproductive haemostasis

Evidence for adverse pregnancy outcome due to prothrombotic disorders

Established thrombophilic defects

Global markers of haemostatic abnormalities

Summary

References

Chapter 19 Reproductive disorders and pregnancy outcome

Summary

Introduction

Subfecundity and adverse feto-maternal outcome

In vitro fertilisation and pregnancy outcome

Reproductive disorders and adverse pregnancy outcome

Defective deep placentation and adverse pregnancy outcome

Reproductive disorders and adverse uterine milieu

Conclusions

References

Chapter 20 Risk factors for first-trimester miscarriage: summary of results from the National Women’s Health Study

Background

Methods

Results

Conclusions

References

Chapter 21 Single-embryo transfer

Introduction

Consequences of twin pregnancy

Strategies for prevention of twins

Evidence in favour of single-embryo transfer

Implementation

Conclusion

References

Chapter 22 Paediatric outcome after assisted reproductive technology

Difficulties with outcome studies looking at quality of life in children after ART conception

Literature review

Conclusion

Further reading

References

SECTION 5 CONSENSUS VIEWS

Chapter 23 Consensus views arising from the 48th Study Group: Implantation and Early Development

Future research

Clinical practice

Health policy/education

Index