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Early Pregnancy
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Book description

Problems in early pregnancy are among the most common conditions in gynaecology and obstetrics, and in recent years have become an increasingly studied and important field of reproductive medicine. Early Pregnancy is the first book to embrace a multidisciplinary approach to this rapidly growing field. It combines the expertise of a wide range of internationally renowned authors to produce an authoritative reference on the subject, aiming to improve patient care in early pregnancy by making key recommendations for clinicians. The chapters cover a wide range of core subjects as well as addressing the latest developments by translating research into clinical practice. By bringing together essential elements of scientific research and clinical care Early Pregnancy sets a new benchmark for evidence-based patient care and will be essential reading for all clinicians, nurses, trainees and scientific researchers with an interest in early pregnancy.

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Contents


Page 1 of 2


  • Chapter 7 - Investigation of recurrent miscarriage
    pp 59-66
  • View abstract

    Summary

    In recent years ultrasound diagnosis and improved understanding of problems related to early pregnancy have led to the introduction of medical and expectant management of miscarriage and selected cases of ectopic pregnancy. The commonest early pregnancy complication of spontaneous miscarriage occurs in approximately 15-20% of all pregnancies, as recorded by hospital episode statistics. The embryonic period occupies the first 8 postfertilization weeks, during which organogenesis takes place. Gynecologists and ultrasonographers acknowledge the embryonic period by speaking about fetal heart action and fetal activity before the end of organogenesis. Between 1% and 2% of fertile women will experience recurring miscarriage (RM). Recent papers testify to the high rate of abnormal chromosome type when pregnancy loss has occurred. By actuarial analysis, the success rate for the next pregnancy can be reasonably predicted based on maternal age and number of losses. High-resolution transvaginal ultrasound provides surveillance and reassurance for the majority of women.
  • Chapter 8 - Molar pregnancy
    pp 67-74
  • View abstract

    Summary

    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.
  • Chapter 9 - Uterine natural killer cells and reproduction
    pp 75-84
  • View abstract

    Summary

    The majority of ectopic pregnancies occur within the Fallopian tube, with most implanted in the ampullary region. A number of risk factors have been identified for ectopic pregnancy. Transvaginal ultrasound (TVU) has now become the diagnostic technique of choice for ectopic pregnancy. Historically, laparotomy with salpingectomy was the standard treatment for ectopic pregnancy. Laparoscopic surgery has been shown to be superior to laparotomy, making it the surgical approach of choice. A number of drugs have been used for the treatment of ectopic pregnancy including potassium chloride, prostaglandins, hyperosmolar glucose, mifepristone and actinomycin D. However, the most commonly used drug in clinical practice for the treatment of ectopic pregnancy is methotrexate. The reported success rates for expectant management range between 48-100%. Subsequent hysterosalpingography has shown patency for the affected tube in up to 93% of cases of ectopic pregnancy managed expectantly.
  • Chapter 10 - Cytogenetic factors in recurrent early pregnancy loss
    pp 85-90
  • View abstract

    Summary

    The incidence of congenital uterine anomalies in the general population is between 0. 4% and 3. 2%. This chapter describes the principles of ultrasound diagnosis of uterine anomalies and compares the results with other available diagnostic modalities. The gold standard in the diagnosis of congenital uterine anomalies used to be a simultaneous laparotomy/ laparoscopy and hysteroscopy to visualize the serosal surface of the uterus and the endometrial cavity. The real breakthrough in ultrasound assessment of congenital uterine anomalies was the development of three-dimensional transvaginal probes. This technique involves the acquisition and storage of a volume of ultrasound information. Magnetic resonance imaging (MRI) has been shown to be effective for the diagnosis of congenital uterine anomalies with sensitivity and specificity up to 100%. The advent of three-dimensional ultrasound has greatly enhanced the ability to diagnose congenital uterine anomalies in an outpatient setting.
  • Chapter 11 - Parental chromosome testing
    pp 91-102
  • View abstract

    Summary

    Ultrasound is an integral part of early pregnancy assessment. This chapter covers the normal findings in early pregnancy, the ultrasound diagnosis of early pregnancy failure, and the spectrum of appearances of perigestational hemorrhage. It discusses the first-trimester evaluation of chorionicity and amnionicity in multiple gestations. Chorionicity is the most important prognostic indicator in multiple gestations therefore it is vital to make an accurate determination of this any time a multiple pregnancy is seen. Monochorionic diamniotic twins are at risk for specific complications such as twin-twin transfusion syndrome; this makes the prognosis worse than for dichorionic twins. Knowledge of the normal imaging findings and expected developmental milestones is vital for accurate interpretation. Recognition of monochorionic pregnancies and significant anomalies allows for appropriate early referral for specialist evaluation. Ultrasound is the most accurate way to triage patients with pain and/or bleeding in the first trimester.
  • Chapter 12 - Embryoscopy
    pp 103-112
  • View abstract

    Summary

    Only about 30% of successfully fertilized oocytes result in the delivery of a living child. This chapter summarizes current knowledge on the epidemiology, diagnosis, and treatment of first-trimester pregnancy loss. First-trimester pregnancy loss is a common event, experienced by about 25% of all women during their reproductive career. Clinical characteristics of women presenting with first-trimester bleeding are of little value in correctly predicting a miscarriage. The most constant sonographic findings indicative of a miscarriage are those of an empty gestational sac, where no yolk sac and no embryonic pole are present, or the finding of an embryo or fetus without cardiac activity. More recently, progesterone has also been applied in the prevention of miscarriages. At present, three different treatment options are being used in managing first-trimester miscarriages: expectant, surgical and medical management. The available knowledge from randomized controlled trials comparing various treatment options for miscarriages has been systematically reviewed.
  • Chapter 13 - Acquired thrombophilia and recurrent early pregnancy loss
    pp 113-130
  • View abstract

    Summary

    Recurrent miscarriage (RM) affects between 1-2% of fertile couples and is a clinical condition of heterogeneous etiology. Parental structural chromosome rearrangements are reported in 3-8% of couples suffering recurrent miscarriage and testing of both partners is therefore recommended. Conventional cytogenetic analysis of miscarriage tissue from women with a history of RM has detected a 26-57% abnormality rate. In the RM population, the prevalence of reported uterine malformations range widely from between 1.8% to 37.6%. Diagnostic tools for detecting uterine anomalies include two- and three-dimensional ultrasound, hysteroscopy, laparoscopy and magnetic resonance imaging (MRI). The antiphospholipid syndrome (APS) remains entrenched as one of the most studied factors associated with RM. Natural killer (NK) cells are found in peripheral blood and within the endometrium and have been associated with RM. Presently, many of the RM investigations are controversial because of limited studies, inconsistent terminology and small and poorly designed treatment studies.
  • Chapter 14 - Inherited thrombophilia and early pregnancy
    pp 131-142
  • View abstract

    Summary

    Molar pregnancies are characterized by gross water logging and villous cistern formation. Villous trophoblastic hyperplasia is the microscopic characteristic feature of true molar pregnancies. This chapter reviews the role of ultrasound in early pregnancy in the screening for molar pregnancy. Complete moles are almost always diploid with their chromosomes totally derived from the paternal genome resulting from endoreduplication after monospermic fertilization or more rarely dispermic fertilization of an anucleate oocyte. Usually, the ultrasonographic description of complete hydatidiform moles (CHM) applies to pregnancies between 9 and 12 weeks of amenorrhea. In early pregnancy and in particular in missed miscarriage, independently of the presence of a chromosomal abnormality, the progressive disappearance of the villous vasculature after embryonic death leads to villous hydrops. Overall, the risk of persistent Gestational trophoblastic disorder (pGTD) developing from a histologically confirmed non-molar hydropic miscarriage is considered to be less than 1 in 50,000.
  • Chapter 15 - Thrombosis, air travel and early pregnancy
    pp 143-150
  • View abstract

    Summary

    Uterine natural killer cells exert their function by production of high levels of cytokines such as granulocyte-macrophage colony stimulating factor (GM-CSF), colony stimulating factor-1 (CSF-1) and interleukin-2 (IL-2). Recurrent miscarriage (RM) is a stressful condition for both patients and clinicians. As uterine natural killer (uNK) cells share many similar properties with peripheral blood NK cells, their population in the blood has been reported to be associated with RM. Steroids are used as anti-inflammatory agents to try to improve success of implantation, as aside from the immunology of pregnancy, there could be other inflammatory processes in the practice of in-vitro fertilization (IVF) such as stimulation from the intrauterine catheter during embryo transfer. As with RM, immunomodulation therapies have been tried to suppress NK cell activity. A recent meta-analysis of three trials shows that IvIg treatment significantly increases the live-birth rate in patients who fail IVF.
  • Chapter 16 - Immunotherapy and early pregnancy
    pp 151-160
  • View abstract

    Summary

    Human reproduction appears to be an inefficient process, primarily because of chromosome errors in gametes and the resultant embryos. This chapter discusses the cytogenetic factors involved in miscarriage in the general population and in couples with recurrent pregnancy loss. It reviews the process of meiosis in gametogenesis and highlights the importance and limitations of cytogenetic analyses of miscarriage tissue. Recently, recurrent aneuploidy has been suggested as a factor associated with a history of recurrent pregnancy loss. Cytogenetic analyses can be performed on miscarriage tissue using several techniques, including cell culture followed by chromosome banding, microsatellite testing and comparative genomic hybridization. Comparative genomic hybridization followed by flow cytometry may prove a powerful technique to provide chromosome results on paraffin-stored miscarriage tissue. The possibility of recurring chromosome errors as etiologic for recurring pregnancy loss, has led to the recent application of pre-implantation genetic screening (PGS) for management of idiopathic recurrent miscarriage.
  • Chapter 17 - Endometrial receptivity
    pp 161-170
  • View abstract

    Summary

    For many years, it has been good clinical practice to offer chromosome testing to women with recurrent miscarriage. This chapter addresses parental chromosome testing and describes couples carrying a structural chromosome abnormality ascertained through recurrent miscarriage work-up. Conventional parental chromosome testing is offered to couples after they have experienced recurrent miscarriage. If one of the partners carries a structural chromosome abnormality, products of conception can have a normal karyotype, the same karyotype as the carrier parent, or an unbalanced karyotype. The latter can lead to miscarriage, stillbirth or the birth of a child with major congenital impairments. Molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) are improving all the time and could play a role in the future in establishing submicroscopic chromosome abnormalities, resulting in another way of assessing abnormalities which play a role in couples with recurring miscarriage (RM).
  • Chapter 18 - Clinical assessment of the endometrium
    pp 171-198
  • View abstract

    Summary

    This chapter describes the technique and various embryoscopic findings in cases of early intrauterine death. Embryoscopy is a stepwise investigation. The steps have to be performed cautiously in order to avoid bleeding that would obscure the examiner's vision. A comprehensive examination of the conceptus includes visualization of the head, face, dorsal and ventral walls, limbs and umbilical cord. Transcervical embryoscopy permits selective and reliable sampling of chorionic tissues with minimal potential for maternal contamination. Localized developmental defects may be isolated or combined. They are similar to the malformations seen in fetuses and newborns. Embryoscopy should be offered to a patient when a reliable cytogenetic evaluation of the abortus is indicated. Loss of pregnancy may be due to maternal or fetal factors. Embryonic growth disorganization possibly resulting from an aneuploidy/polyploidy suggests that there may be a genetic cause which cannot be identified by current cytogenetic techniques.
  • Chapter 19 - Implantation events
    pp 199-212
  • View abstract

    Summary

    A thrombophilic defect is an abnormality in the coagulation system that predisposes an individual to thrombosis. This chapter examines the role that the acquired thrombophilic defects play in the magnitude of early pregnancy loss, with particular reference to Primary Antiphospholipid syndrome, hyperhomocysteinemia and Acquired protein C resistance. Antiphospholipid syndrome (APS) is now recognized to be the most important treatable cause of recurrent miscarriage. The potential of thromboelastography as a clinical tool to overcome many of the above limitations in hemostasis testing in our recurrent pregnancy-loss population is promising. The success of thromboprophylactic treatment for women with recurrent miscarriage associated with APS has resulted in women with unexplained recurrent miscarriage frequently demanding similar treatment. Recurrent miscarriage is a distressing condition that affects at least 1% of couples trying to achieve a successful pregnancy. Recurrent miscarriage is a heterogeneous condition and no single abnormality will account for all cases.
  • Chapter 20 - Recurrent implantation failure
    pp 213-226
  • View abstract

    Summary

    This chapter focuses on the primary antiphospholipid syndrome, that is, in the absence of systemic lupus erythematodes. Women with thrombophilia have an increased baseline risk of venous thromboembolism. In antiphospholipid syndrome, lupus anticoagulant is more strongly related to venous thrombosis and pregnancy complications than antibodies against phospholipids. The chapter reviews the evidence regarding potential clinical implications of acquired and inherited thrombophilia for both venous thromboembolism and for pregnancy failure. Treatment guidelines vary with regard to the administration of heparin for antiphospholipid syndrome and recurrent miscarriage. For women with antiphospholipid syndrome, the evidence regarding the efficacy of aspirin with or without the addition of low-molecular-weight heparin is not solid, whereas two small trials have shown a clear benefit of unfractionated heparin. For women with inherited thrombophilia, low-molecular-weight heparin to prevent pregnancy loss is definitely experimental as solid evidence is not yet available.
  • Chapter 21 - Trophoblast biology and early pregnancy
    pp 227-236
  • View abstract

    Summary

    Venous thromboembolism (VTE) has a multifactorial pathogenesis involving genetic predisposition, acquired diseases and conditions, and lifestyle and environmental factors. Although the level of risk of VTE associated with air travel has been exaggerated through sensationalized reporting in the mass media, it has nevertheless been established now that long-haul flights represent a risk factor for deep vein thrombosis and pulmonary embolism, including fatal events. Potentially effective measures to reduce the risk of travel-related VTE include enhanced mobility, use of graduated compression hosiery and pharmacological interventions. Low molecular weight heparin (LMWH) is effective in reducing the incidence of VTE post-operatively (by 50-60%) as well as in hospitalized subjects more generally, with little increased risk of bleeding. Based on the low absolute risk of travel-related VTE in the overwhelming majority of women during early pregnancy, pharmacological thromboprophylaxis with LMWH can be justified.
  • Chapter 22 - Implantation failure:
    pp 237-244
  • an embryologist’s view
  • View abstract

    Summary

    Three immunotherapeutic approaches have been tested in recurrent miscarriage (RM): prednisone, active immunization with allogeneic lymphocytes from the partner or third-party donors, and intravenous immunoglobulin (IvIg). The thought that allogeneic leukocyte immunization therapy (ALT) could be beneficial in RM arose from the observation that injections of paternal lymphocytes into pregnant female mice in crosses of strains with a high fetal resorption rate could decrease the resorption rate. The placebo-controlled trial (PCTs) included in the Cochrane meta-analysis of ALT were very heterogeneous with respect to the frequency of secondary RM patients. Intravenous immunoglobulin (IvIg) is prepared by extracting the IgG fraction from plasma from normal blood donors. More PCTs in the potential main target group with primary RM should be undertaken to get better documentation for the benefit and more information about the optimal doses and methods of administration and about harm effects.
  • Chapter 23 - Embryo reduction in multiple pregnancies
    pp 245-254
  • View abstract

    Summary

    This chapter summarizes the hormonal regulation and molecular bases of endometrial receptivity, its clinical implication and the possible models to study this complex process and to develop functional assays in vitro. Cyclic changes of the endometrium have been well described at the light microscopy level. A large amount of research worldwide has been focused on the problem of finding a specific marker(s) of uterine (endometrial) receptivity-biomarkers that can be useful for the diagnosis and treatment of couples with infertility of endometrial origin. The main techniques used to study the features of the receptive endometrium include microscopy for endometrial morphology, quantitative PCR, in situ hybridization and gene expression microarrays in endometrial biopsy. The ultimate in vitro model to study endometrial receptivity and embryonic implantation would contain all the cell types of the endometrium so that the complex interactions between the maternal tissue and the blastocyst could be characterized.
  • Chapter 24 - Miscarriage after in-vitro fertilization
    pp 255-266
  • View abstract

    Summary

    This chapter reviews the available literature on the clinical assessment of the endometrium. It focuses on the tools available to diagnose and treat both infertility and pregnancy loss. Infertility and recurrent pregnancy loss are often attributable to implantation failure. The mechanism of implantation varies widely between species, reflecting the evolving conflicts between maternal and embryonic interests. Serum progesterone measurements are a mainstay of hormonal assessment to document ovulation and appear to correlate well with endometrial biopsy results. Doppler flow studies are non-invasive ultrasound methods used to evaluate the blood flow to the uterus and endometrium. Causes of repeat in-vitro fertilization (IVF) failure that are related to endometrial receptivity defects have recently been reviewed. Cost and side effects of treatments will be reduced as clinical assessment of the endometrium yields more information about the causes of infertility or pregnancy loss.

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