Ovarian Stimulation and the Endometrium: New Approaches and Insights

When one considers the recognized 'causes' of infertility, problems with gamete quality and availability rank highly, as does the means of their transport, whether it be through the fallopian tubes in the female or vas deferens in the male. Conception is seen as the primary goal, and fertility therapies are currently focused on helping couples achieve this. In around 25% of couples with fertility problems, medical investigation reveals no such clear cause. It is now understood however, that while a couple may succeed in conception, implantation failure may be the underlying reason for their difficulties in achieving a pregnancy (Macklon et al., 2002). Implantations depend on the succesful interaction between the embryo and the endometrium of the uterus. Since the earliest days of in vitro fertilization (IVF) the focus of attention has been the embryo. In order to obtain multiple embryos to allow selection for transfer to the uterus, complex ovarian stimulation regimens have been devised which result in many oocytes being harvested for fertilization. In most women, these stimulation regimens succefully achieve this aim. Yet despite the ability to produce large numbers of embryos for selection for transfer, pregnancy rates from IVF remain around 25% per started cycle (ESHRE 2008). Once the embryo is transferred into the uterus, it must interact with the endometrium, and in the majority of treatment cycles, this is the moment in which failure occurs. The role played by the endometrium as a determinant factor of fertility treatment, and in particular IVF outcomes remains unclear. Moreover, the impact of ovarian stimulation on endometrial quality is only now beginning to be elucidated. In this introductory chapter, the hormonal control of endometrial development is reviewed, and current approaches for assessing the receptivity of the endometrium to the embryo are critically assessed (Chapter 1.1.1). The concept of the 'implantation window' is introduced (Chapter 1.1.2) and the molecular regulation of endometrial maturation and implantation is reviewed (Chapter 1.2), with emphasis on the most important of the described markers of receptivity (Chapter 1.3). The challenges of studying the impact of ovarian stimulation on endometrium are described (Chapter 1.4) as a prelude to introducing a novel means of addressing these by studying endometrial secretion fluid (Chapter 1.5). These considerations lead to the defining of the objectives of the research described in this thesis (Chapter 1.6).

• View at Worldcat

Free Full Text ( Final Version , 9mb )