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It is estimated that more than 4.5 million couples experience infertility each year, and more than 4 million babies have been born using IVF since 1978. However, assisted reproductive technologies continue to raise many medical, social, ethical, political and religious questions, often leading to controversial and sometimes inaccurate opinions about the outcomes of pregnancies resulting from these techniques. This is the first book dedicated to pregnancies arising from assisted reproductive technologies (ART). Chapters cover the most important management issues, from early pregnancy to outcome of children resulting from ART, including gynaecological, genetic and obstetric complications. Each chapter is written and edited by leading experts in the field of human reproduction. A timely, practical and evidence-based guide to the management of ART pregnancies, based on 30 years of clinical experience, this is essential reading for reproductive and maternal-fetal specialists as well as general obstetricians and gynaecologists.
Molar pregnancies result from disorders of human fertilisation. They are the most common form of gestational trophoblastic disease, which incorporates a wide spectrum of abnormalities of trophoblastic development. Hydatidiform moles were first described by Hippocrates in ancient Greece. The etymology is probably derived from the Greek word hydatis meaning ‘a drop of water’, referring to the watery content of the cysts, and the Persian word mylon meaning a misshapen thing (false conception). The modern medical term hydatidiform mole refers to a disorder of placental development in which the villous mesenchyme, vasculature and trophoblast are all affected and there is little or no fetal development.
Molar pregnancies are characterised by villous hydrops. Trophoblastic hyperplasia is the characteristic microscopic feature of true molar pregnancies. Biochemical analysis of the fluid from molar vesicles indicates that it is derived from the diffusion of maternal plasma but also contains specific trophoblastic proteins. These biochemical findings suggest that the hydropic (hydatidiform) transformation of the villous mesenchyme is caused by maldevelopment, regression or lack of the villous vasculature, which compromises the drainage of fluid produced by the trophoblast. Mild to moderate generalised villous oedema, which is often found following the demise of an embryo or early fetus, supports this concept and highlights the fact that hydropic villous changes are not exclusive to molar pregnancies. Hydatidiform transformation of villi is a non-specific feature of vascular dysfunction and only the hyperplastic microscopic appearance of the trophoblast is decisive for the diagnosis of molar pregnancy. Hyperplasia can be identified histologically before the hydropic villous changes are visible macroscopically.
This chapter reviews the key roles of the different layers of the maternofetal interface in supplying essential nutrients to the developing fetus before the placental circulations are fully established. Focal trophoblastic oxidative damage and progressive villous degeneration trigger the formation of the fetal membranes that remodel the uteroplacental interface. The distribution of the placental-specific protein human chorionic gonadotrophin (hCG) in yolk sac and coelomic fluid samples, and the absence of hCG mRNA expression in yolk sac tissue, suggests the secondary yolk sac (SYS) has an absorptive function. During the 10th week of gestation, the yolk sac starts to degenerate and rapidly ceases to function. The anatomy of the materno-fetal interface in the first trimester is the result of the need for a delicate balance between the metabolic requirements of the developing fetus and the potential harmful effects of oxygen during embryogenesis and organogenesis.
Impaired development of the early placenta has long been implicated in aberrations of placental shape at term. It has become possible to construct a hypothesis linking placental shape and complications of pregnancy based on oxidative and endoplasmic reticulum stress. The onset of maternal circulation is interlinked with remodelling of the chorion frondosum into the definitive placenta, and oxidative stress plays a key role in this process. This chapter proposes that a spectrum of defects may occur, ranging from variations at the physiological end in clinically 'normal' placentas that may relate to programming, to frank pathological changes associated with severe complications of pregnancy. It discusses spiral artery conversion, the onset of the maternal arterial circulation to the human placenta, abnormal villus regression, abnormal maternal blood flow, and the implications for developmental programming. Conversion of the spiral arteries is associated with invasion of the endometrium and the arterial walls by extravillous trophoblast.
Miscarriage is the most common complication of early pregnancy. This chapter summarizes the risk factors for first-trimester miscarriage. There is a strong relationship between infertility and miscarriage. Studies have shown that risk of miscarriage varies by socio-economic position, but the trends are unclear and most probably relate to exposure to environmental, occupational or behavioral risk factors. A very clear finding from the National Women's Health Study (NWHS) was the impact of stressful life events, a stressful job situation, and feelings of anxiety and depression on the risk of miscarriage. Most people seek an explanation of the cause of their miscarriage and treatment or guidance to prevent a recurrence. Efforts to gather research evidence have been hampered in the past by methodological difficulties and the lack of understanding by health professionals that at least a proportion of miscarriages are preventable.
Placental vasculature, in particular the relationship between maternal and fetal blood circulations, has been a contentious issue for a long time. In his magnificent Anatomy of the human gravid uterus William Hunter included the first drawing of spiral arteries (convoluted arteries), in what must have been the very first illustration of a human placental bed. The French anatomist Mathias Duval was probably the first to recognize the invasion of trophoblast into endometrial arteries, in this case in the rat. It it became clear that deep trophoblast invasion and associated spiral artery remodeling are essential for a healthy pregnancy. The actual depth of invasion was underrated for a long time, partly because of the increasing popularity of the decidual barrier concept. Early observations of trophoblast invasion into the spiral arteries set the stage for understanding the maternal blood supply to the placenta via the spiral arteries of the placental bed.