consequences including the development of cardiovascular diseases, imprinting disorders and cancer should be further monitored for all ART children. INVITED SESSION Session 54: European IVF monitoring & ICMART data reports Wednesday 1 July 2009 08:30 – 09:30 O-206 Oral Assisted reproductive technology in Europe, 2006 O-207 Oral Preliminary global ART data for the year 2005 INVITED SESSION Session 55: Peri-implantation events and outcomes Wednesday 1 July 2009 08:30 – 09:30 O-208 Oral Defective decidualization and early pregnancy wastage J. Brosens 1 1 Imperial College London / Hammersmith Campus, Institute of Reproductive & Developmental Biology, London, United Kingdom Introduction: The maternal response to an implanting embryo is arguably the single most important factor in determining pregnancy outcome. This maternal response is termed decidualization, a process that occurs in all species where implantation involves breaching of the luminal endometrial epithelium. Pertur- bations in the decidual process inevitably result, depending on severity, in either early pregnancy failure or obstetrical complications caused by impaired placental function, such as fetal growth restriction and preeclampsia. Materials and methods: This presentation first reviews the molecular signals, pathways, and downstream transcription factors that control the differentiation of resident endometrial fibroblasts into secretory decidual cells, followed by an overview of the functions of these cells at the feto-maternal interface in normal and pathological pregnancies. Results: Based gene profiling studies, decidualization of endometrial stromal cells can be described as a process of sequential reprogramming of functionally related families of genes involved in cell adhesion, signal transduction, stress responses, extracellular matrix reorganization, cytoskeletal organization, metabolism, cell cycle progression, apoptosis and differentiation. It is now well established that initiation of the decidual process is dependent upon increased levels of the second messenger cyclic adenosine monophosphate and sustained activation of the protein kinase A pathway, which in turn sensi- tizes endometrial stromal cells to ovarian hormones, progesterone as well as androgens. Once initiated, decidualizing endometrial cells secrete various factors, including IL-15, activin A, somatostatin, ghrelin, PRL, IGFBP-1, and sphingosine-1-phosphate, capable of amplifying and modifying the differen- tiated phenotype in an autocrine or paracrine fashion. The process of endo- metrial decidualization has direct relevance to early implantation events as well as subsequent pregnancy outcome. Emerging evidence from co-culture studies suggest that decidualizing endometrial stromal cells play an important role in embryo recognition and selection. Moreover, decidualization of uterine tissues is essential for protection of the conceptus against environmental and immunological insults and to ensure hemostasis and tissue integrity during deep trophoblast invasion. Early pregnancy is a hyperinflammatory process, characterized by profound vascular remodelling and fluctuations in oxygen tension at the maternal-fetal interface. Of particular relevance to early preg- nancy loss is the ability of decidualizing endometrial stromal cells to resist oxi- dative cell death. Several components underpin this resistance upon decidualization, including increased free radical scavenging, selective silencing of stress MAPK pathways and inhibition of FOXO3a, a pro-apoptotic transcrip- tion factor that mediate oxidative cell death in undifferentiated stromal cells. Conclusions: The characterization of the gene networks that control endo- metrial stromal cell differentiation has yielded new insights into the functions of decidual cells at the maternal-fetal interface. In human beings, the decidual process is uniquely independent of an implanting embryo, raising the possi- bility that biochemical analysis of endometrial samples prior to conception may yield important cues for the prediction and understanding subsequent preg- nancy complications. O-209 Oral Defective implantation and the obstetrician E.R. Norwitz 1 1 Yale University School of Medicine, Department of Obstetrics Gynecology & Reproductive Sciences, New Haven CT, U.S.A. Human reproduction entails a fundamental paradox: although critical to the sur- vival of the species, the process is relatively inefficient. Fecundity (the prob- ability of pregnancy occurring within one menstrual cycle) peaks at around 30%, and only 50–60% of all conceptions advance beyond 20 weeks’ ges- tation. Few specimens exist that document the first weeks of embryonic devel- opment in humans. Analogous to events in several primate species, implantation in humans probably includes three stages. Initial adhesion of the blastocyst to the uterine wall, known as apposition, is unstable. Microvilli on the apical surface of syncytiotrophoblasts interdigitate with pinopodes on the apical surface of the uterine epithelium. The next stage, stable adhesion, is characterized by increased physical interaction between the blastocyst and the uterine epithelium. Shortly thereafter, invasion begins, and syncytiotropho- blasts penetrate the uterine epithelium. By day 10 post-conception, the blasto- cyst is completely embedded in stromal tissue of the uterus and the uterine epithelium has regrown to cover the implantation site. Thereafter, cytotropho- blasts change their adhesion molecule expression and stream out of the tropho- blast layer to invade the entire endometrium and the inner third of the myometrium (interstitial invasion) as well as the uterine vasculature (endovas- cular invasion). It is this latter process which establishes the definitive uteropla- cental circulation. At a functional level, the placenta must integrate maternal and fetal physiology, immunology, and endocrinology. Normal implantation and placentation is critical for successful pregnancy. While this has long been known to be true of spontaneous miscarriage, recent data suggest that complications of late pregnancy (such as preeclampsia, preterm premature rupture of membranes, and preterm labor) likely also result from abnormalities in early placental development. Cytotrophoblast invasion to the proper depth appears to be a major factor in determining pregnancy outcome. Excessive invasion can lead to deficient development of the decidua with abnormally firm attachment of the placenta directly onto the myo- metrium (placenta accreta), to extension into the myometrium (placenta increta), or to invasion through the myometrium to the uterine serosa and even into adjacent organs (placenta percreta). Inadequate invasion has been implicated in the pathophysiology of such conditions as preeclampsia (gesta- tional proteinuric hypertension), preterm premature rupture of membranes, preterm labor, and possibly intrauterine growth restriction. The characteristic pathologic lesion in such pregnancies is shallow interstitial cytotrophoblast invasion and, more consistently, restricted endovascular invasion. The molecular and cellular mechanisms responsible for defective implantation remain enigmatic. This presentation will include a review of human implantation followed by a discussion of recent studies that may shed light on the molecular mechanisms responsible for defective implantation and placentation including, among others, the identification and characteriz- ation of an endogenous inhibitor of prostaglandin production in the endome- trium/ decidua whose expression is regulated by progesterone and the role of first trimester decidual hemorrhage (thrombin) and hypoxia in regulating tro- phoblast invasion. An increased understanding of the molecular mechanisms responsible for abnormal implantation and placentation will likely improve clinicians’ ability to treat disorders that occur along this continuum, including recurrent pregnancy loss, preeclampsia, and preterm birth. i84 Abstracts of the 25th Annual Meeting of ESHRE, Amsterdam, the Netherlands, 28 June – 1 July, 2009 Downloaded from https://academic.oup.com/humrep/article-abstract/24/suppl_1/i84/740651 by guest on 25 May 2020