Embryo implantation is a complex process; primary step in implantation is the initiation of dialogue between free floating blastocyst and the receptive endometrium. This is followed by a stable adhesion of the blastocyst anchors to the endometrial basal lamina and stromal extracellular matrix. The last step is invasion of the embryo through the luminal epithelium and its basal lamina into the uterine stroma. Successful embryo implantation depends up on number of factors like steroid hormones (progesterone, estrogen), Cyclooxygenases, prostaglandins, cytokines, growth factors, transcription factors (HOXA-10 and HOXA-11), and adhesion molecules (integrins, selectins, cadherins, mucins) and receptive endometrium. Importantly, there is timely regulation of these factors and their cross talk which mediates the implantation process. Blastocyst is unable to implant successfully if there is deregulation in any of these factors leading to pregnancy loss. In this chapter we reviewed the information available till date to provide possible causes of implantation failure and its positive outcomes.

The success of Assisted Reproductive Technologies (ART) during the last decades has transformed the evaluation and treatment of infertility. Nonetheless, there are concerns about the risk for adverse pregnancy outcomes. Research on ART and perinatal outcomes faces several methodological challenges that need to be considered to allow reliable interpretation of results. Major perinatal risks are consequence of the high rate of multiple gestations associated with ART treatment. The improvement of embryo cryopreservation programmes and the development of elective Single Embryo Transfer policies will reduce significantly the number of multiple pregnancies while maintaining acceptable overall pregnancy rates. Although the great majority of singleton ART pregnancies are uncomplicated, numerous studies have raised questions concerning a range of adverse pregnancy outcomes in singleton ART pregnancies. Spontaneous abortion, first trimester vaginal bleeding, ectopic pregnancies, adnexal torsion, chromosomal abnormalities, imprinting disorders, preterm birth, low birth weight and small for gestational age infants, birth defects, preeclampsia, placenta praevia and placental abruption have been associated with ART. Nonetheless, questions remain about the underlying mechanisms. Maternal age is an important confounder, as well as the role of the underlying infertility in the observed adverse perinatal outcomes. There are many data gaps to date. Future research initiatives are emergently needed, with enhancing transdisciplinary collaboration.

Human placentation is characterized by the development of a hemochorial placenta and concomitantly by considerable changes in the vasculature of the uterus. The trophoblast is an essential tissue of the placenta. After blastocyst implantation, it differentiates into villous trophoblast, which ensures exchanges between mother and fetus as well as the endocrine functions of the placenta, and into invasive extravillous trophoblasts, which anchors the placenta in the uterus and participate to the implementation of the utero placental vascularization. We describe here the different stages of the placental morphogenesis and the physiological mechanisms responsible for uterine vascular remodeling. We then consider the main functions of the human placenta and in particular the qualitative and quantitative evolution along pregnancy of trophoblast hormonal functions from a paracrine role during the first trimester of pregnancy involved in the quality of placentation to an endocrine role that allows uterine quiescence and maternal adaptation to pregnancy.

Hypertensive disorders of pregnancy, and particularly preeclampsia, remain a leading cause of adverse pregnancy outcomes in both developing and developed countries. Identification of at-risk women, before the emergence of clinical signs, in order to implement preventive measures and early targeted interventions for improving short-and long-term outcomes for the mother and her child, remains a public health priority. The development of validated screening procedures using biological markers is hampered by the limited knowledge of the aetiology and pathophysiology of preeclampsia, despite continuous research efforts. However, recently discovered biochemical markers and ultrasonographic parameters, taken individually or in combination, have shown encouraging potential to better characterize and predict preeclampsia and its adverse outcomes. We provide in this chapter examples of potential markers in relation to their links to pathophysiological processes. We believe there is a need to investigate in large-scale population studies combinations of carefully-selected biochemical, biophysical and maternal determinants to identify early in pregnancy women at risk of developing preeclampsia and its adverse outcomes.

Pregnancy represents a semiallograft to a maternal host. To prevent semiallograft rejection, the maternal immune system dramatically changes to a unique immune system during pregnancy. Maladaptation of this system could cause implantation failure, recurrent spontaneous abortion, preeclampsia and preterm delivery. The objective of this report is to review the pathophysiology of these events in human pregnancy from the aspects of reproductive immunology.

Gestational diabetes mellitus occurs only during pregnancy, and usually disappears shortly after delivery. Although, GDM is a common disorder, its pathophysiology is not well understood. Impaired placental function is probably a contributing factor as the placenta hinders insulin signaling and produce increased levels of cytokines that affect placental transport and metabolism of glucose and lipids. This in turn negatively impacts on fetal growth and development with significantly increased risk of a number of short-and long-term adverse consequences for the fetus, and the most significant of which is a predisposition to the development of metabolic syndrome and Type 2 diabetes. This article will describe placental changes in gestational diabetes related to glucose and lipids following placental insulin and cytokines dysfunction, and subsequent effects on the offspring development.

Preeclampsia, a disorder of pregnancy, is a leading cause of maternal and infant illness and death affecting about 3-15 % of all pregnancies worldwide. It is characterized by high blood pressure and the presence of protein in the urine. It originates in the placenta and causes variable maternal and fetal problems. At its worst, it may threaten maternal and perinatal survival. Preeclampsia is defined as a syndrome (a pattern of clinical features) and is probably heterogeneous in its origin as it is in its presentation. To date, the only complete cure known for preeclampsia is delivery, accompanied by the removal of the placenta. As the complete etiology of preeclampsia is still unknown, researches are crucial in order to know more about this pathophysiology and to develop different treatments and prediction approaches. This chapter focuses on current knowledge and recent discoveries on preeclampsia, especially on the role of placenta in its physiopathology. The chapter also presents current knowledge concerning preeclampsia diagnosis, epidemiology, risk factors and pathogenesis with an emphasis on maternal and perinatal outcomes related to this most common cause of death for both children and mothers during pregnancy.

Epigenetic modifications regulate the expression of all genes, including those showing dynamic profile associated with cell differentiation and growth. Numerous lines of evidence have confirmed that epigenetic profile is sensitive to a variety of environmental and genetic factors, and that epigenetic mechanisms underpin most environmentally-mediated changes to gene expression. The dynamic process of epigenetic remodeling associated with early human development in utero is thought to be a particularly sensitive period for environmental perturbation and it is therefore not surprising that a variety of adverse pregnancy outcomes are now believed to involve some epigenetic disruption in the developing pregnancy (embryo, fetus, placenta). This chapter summarizes our current understanding of epigenetic mechanisms and the emerging evidence for a link between epigenetic change and pregnancy outcome.