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The endometrial factor in human embryo implantation
_________________________________________________
CAROLIEN M BOOMSMA

The endometrial factor in human embryo implantation

Thesis, Utrecht University, with a summary in Dutch. Proefschrift, Universiteit Utrecht, met een samenvatting in het Nederlands. ISBN Author Cover Lay-out & Print © 2009 Carolien Boomsma The author gratefullyacknowledges financial support for printing this thesis by: Division Women and Baby University Medical Center Utrecht, Jurriaanse Stichting, GlaxoSmithKline, Merck Serono, Clindia Benelux, BMA BV (Mosos), Medical Dynamics, Wyeth Pharmaceuticals, Ferring, Smiths Medical BV, Organon, Abbott BV. 978-90-393-49496 Carolien M. Boomsma Painting by Gertjan Scholte-Albers, www.scholte-albers.nl GildeprintDrukkerijen B.V. Enschede, The Netherlands

The endometrial factor in human embryo implantation
De endometrium factor in humane embryo implantatie
(met een samenvatting in het Nederlands)

Proefschrift

ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof. dr. J.C. Stoof, ingevolge het besluit van het college voor promoties in het openbaar teverdedigen op dinsdag 14 april 2009 des middags te 2.30 uur.

door Caroline Mariëtte Boomsma geboren op 13 februari 1979 te Amersfoort

Promotoren: Prof. dr. N.S. Macklon Prof. dr. C.J. Heijnen

Co-promotor: Dr. A. Kavelaars

Aim to achieve the mountain top, but don’t forget to enjoy the journey!

Contents ____________________________________________
Chapter 1 Introduction 9Chapter 2

Current clinical therapies to improve endometrial receptivity and embryo implantation in IVF

2.1

What can the clinician do to improve implantation? A literature review.

23

2.2

Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. A literature review and meta-analysis.

43

Chapter 3

Studying the endometrial factor: cytokineprofiling in endometrial secretions

3.1

Cytokine profiling in endometrial secretions: a non-invasive window on endometrial receptivity.

57

3.2

Analysis of the endometrial secretion cytokine profile to predict pregnancy in in-vitro fertilization.

75

3.3

Ovarian stimulation for in-vitro fertilization alters the intra-uterine cytokine, chemokine and growth factor milieuencountered by the embryo.

95

3.4

Is bacterial vaginosis associated with a pro-inflammatory cytokine profile in endometrial secretions of women undergoing IVF?

111

Chapter 4

The endometrial factor in recurrent implantation failure Determination of the peri-implantation endometrial transcript profile in women with recurrent implantation failure versus controls. 127

Chapter 5

GeneralDiscussion References Nederlandse Samenvatting List of publications List of authors and their affiliations Dankwoord Curriculum Vitae List of abbreviations

151 161 185 193 195 197 201 203

Chapter 1 ____________________________________________

General Introduction

10

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The endometrial factor in human embryo implantation

General introduction
In-vitro fertilization (IVF) is aprocess by which oocytes are fertilized by sperm outside the women’s womb, in vitro. It still represents one of the most exciting modern scientific developments and continues to have a tremendous impact on people's lives. One in six couples have an unwanted delay in conception and half of these couples remain subfertile or need complex treatment, such as IVF. In Europe this technology accountsfor 2-3 percent of births (The European IVF-monitoring program, 2005) and due to the current tendency of women to postpone their pregnancy until beyond their most fertile age, its use is increasing (Heffner et al. 2004; Wright et al. 2005).

Since the beginning of IVF, with the first baby born in 1978 (Steptoe and Edwards, 1978), much effort has been invested into developing techniques to...