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12 results

  • 10A - Natural Killer Cell Assay in the Blood Is a Useless Investigation

  • from Section II - IVF Add-ons
  • Edited by Roy Homburg, Adam H. Balen, Robert F. Casper
  • Book:
    50 Big Debates in Reproductive Medicine
    Published online:
    25 November 2021
    Print publication:
    16 December 2021, pp 51-52

  • Summary

    There are many commercial tests for blood immune cell tests looking at NK cell numbers, cell cytotoxicity or associated cytokine levels. Despite the lack of evidence, patients with recurrent pregnancy loss and implantation failure are often advised to have these tests and are subsequently offered immunotherapies, not backed by trial evidence to treat apparently abnormal results. Blood NK cells are innate immune cells and a first line of host defence against pathogens and tumour cells. Uterine NK cells are phenotypically different to blood NK cells and function when activated to promote normal placentation when pregnancy occurs. Despite a lack of biological plausibility, meta-analyses have been suggestive of altered blood NK cells in subfertility and recurrent pregnancy loss. However they have not shown that blood NK cells have an impact on pregnancy outcome. It is imperative that we offer patients tests and treatment based on robust evidence rather than poor science.

  • Chapter 12 - Recurrent Pregnancy Loss in the First and Second Trimesters

  • from Section 3 - Reproductive Endocrinology and Infertility
  • Edited by Tahir Mahmood, Charles Savona-Ventura, Ioannis Messinis, Sambit Mukhopadhyay
  • Book:
    The EBCOG Postgraduate Textbook of Obstetrics & Gynaecology
    Published online:
    24 November 2021
    Print publication:
    02 December 2021, pp 101-107

  • Summary

    Recurrent pregnancy loss (RPL) is defined as the consecutive or non-consecutive loss of two or more pregnancies before viability. Established, contributory and postulated causes for RPL include advanced maternal age, anti-TPO antibodies, antiphospholipid antibodies, Müllerian anomalies, parental chromosomal aberrations, inherited thrombophilia and alloimmunity. Recommended investigations include thyroid screening, testing for antiphospholipid antibodies and imaging of the uterus. A thorough reproductive history can guide investigation to include tailored tests (e.g. metabolic and genetic profile). Despite investigation, no cause is found in about 50% of RPL cases.

    Thyroid dysfunction should be treated, antiphospholipid antibodies are managed with low-dose aspirin and heparin in a subsequent pregnancy and an intrauterine septum should be resected.

    Maternal age and number of prior losses are the major determinants for the prognosis of a subsequent pregnancy. Pregnancies after RPL should be managed as high-risk.

  • Chapter 19 - Implantation events

  • Edited by Roy G. Farquharson, University of Liverpool, Mary D. Stephenson, University of Chicago
  • Book:
    Early Pregnancy
    Published online:
    05 October 2010
    Print publication:
    09 September 2010, pp 199-212

  • 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 22 - Implantation failure:

  • Edited by Roy G. Farquharson, University of Liverpool, Mary D. Stephenson, University of Chicago
  • Book:
    Early Pregnancy
    Published online:
    05 October 2010
    Print publication:
    09 September 2010, pp 237-244

  • 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 20 - Recurrent implantation failure

  • Edited by Roy G. Farquharson, University of Liverpool, Mary D. Stephenson, University of Chicago
  • Book:
    Early Pregnancy
    Published online:
    05 October 2010
    Print publication:
    09 September 2010, pp 213-226

  • 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 15 - Thrombosis, air travel and early pregnancy

  • Edited by Roy G. Farquharson, University of Liverpool, Mary D. Stephenson, University of Chicago
  • Book:
    Early Pregnancy
    Published online:
    05 October 2010
    Print publication:
    09 September 2010, pp 143-150

  • 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 13 - Acquired thrombophilia and recurrent early pregnancy loss

  • Edited by Roy G. Farquharson, University of Liverpool, Mary D. Stephenson, University of Chicago
  • Book:
    Early Pregnancy
    Published online:
    05 October 2010
    Print publication:
    09 September 2010, pp 113-130

  • 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 16 - Recommendations

  • Edited by Tahir Mahmood, Allan Templeton, University of Aberdeen, Charnjit Dhillon
  • Book:
    Models of Care in Women's Health
    Published online:
    05 July 2014
    Print publication:
    01 June 2009, pp 150-156

  • Summary

    The Royal College of Obstetricians and Gynaecologists (RCOG) published its document Standards for Gynaecology in 2008 and is being used widely by commissioners, providers and policy makers. It sets out the principles of quality assured gynaecological services. The recommendations cover issues such as gynaecological services, early pregnancy loss, ectopic pregnancy, recurrent miscarriage, infertility, urogynaecology, colposcopy, termination of pregnancy and laparoscopic surgery. All emotional and psychological counselling requirements should be provided within the early pregnancy assessment unit. All units should audit patient choice and uptake rates for medical, surgical and conservative management of miscarriage, together with complications and failure rates. Clear information on choice of anonymised testing, treatment and contact tracing through genitourinary medicine should be available. Counselling and advice on sterilisation procedures (both vasectomy and tubal occlusion) should be provided in the context of services providing a full range of information about and access to long-term reversible methods of contraception.

  • CHAPTER 2 - Early pregnancy loss, including ectopic pregnancy and recurrent miscarriage

  • Edited by Tahir Mahmood, Allan Templeton, University of Aberdeen, Charnjit Dhillon
  • Book:
    Models of Care in Women's Health
    Published online:
    05 July 2014
    Print publication:
    01 June 2009, pp 6-23

  • Summary

    Early pregnancy problems form a major part of all gynaecological emergencies. Approximately one in five pregnancies will end in pregnancy loss. The model of care for all early pregnancy events and complications provides the timeline base along which the core standards of care elements, care pathways and clinical protocols can support the care provision for best patient experience. Many agents, including prostaglandins, mifepristone, potassium chloride and dactinomycin, have all been used for the medical management of ectopic pregnancy. It is vital that only appropriately trained and competent staff should perform transabdominal and transvaginal early pregnancy scans. As an essential component of clinical governance, all early pregnancy assessment units and recurrent miscarriage clinics should have regular meetings to review clinical guidelines and protocols. This would provide an ideal opportunity to discuss audits, to generate research ideas and discuss recruitment to national or international multicentre trials.

  • Chapter 18: - Preimplantation genetic diagnosis: the future

  • from Section 3 - Ethics and the future
  • Edited by Joyce Harper, University College London
  • Book:
    Preimplantation Genetic Diagnosis
    Published online:
    09 November 2009
    Print publication:
    28 May 2009, pp 274-285

  • Summary

    The incidence of chromosomal abnormalities in cleavage-stage embryos produced in vitro, 50-70 percent depending on maternal age, is considerably higher than that of spontaneous abortions, indicating that a sizeable percentage of chromosomally abnormal embryos are eliminated before any prenatal diagnosis. In most in vitro fertilization (IVF) laboratories one of the powerful tools to improve results is embryo selection, based on morphological and developmental characteristics. FISH is currently the best method to analyze polar bodies and blastomeres since the former have poor quality metaphases and in the latter metaphases are produced in low rates even after culture. Mosaicism rates vary in the literature. Some of the differences between centers are attributed to the population; others to hormonal stimulation and the general quality of embryos produced in those centers. Recurrent miscarriage (RM) in patients with normal karyotype is defined as three or more consecutive spontaneous abortions of less than 20-28 weeks gestation.

  • 18 - Recurrent miscarriage – the role of prothrombotic disorders

  • from SECTION 4 - CLINICAL SEQUELAE
  • Edited by Hilary Critchley, University of Edinburgh, Iain Cameron, University of Southampton, Stephen Smith
  • Book:
    Implantation and Early Development
    Published online:
    05 June 2014
    Print publication:
    01 June 2005, pp 229-239

  • Summary

    This chapter develops the hypothesis that some women with a history of recurrent miscarriage (RM) are in a prothrombotic state outside of pregnancy. The causes of RM have been grouped into six main categories: genetic, anatomical, infective, endocrinological, immunological and unexplained. The thrombophilic disorders play a part in the aetiology of recurrent pregnancy loss at various gestations. Haemostasis in vivo is a balancing act between the coagulation and fibrinolytic pathways, and plays a vital role in the establishment and maintenance of pregnancy. Prospective studies have shown an increased prevalence of acquired thrombophilic disorders in women with a history of RM. Women with a history of RM are at greater risk of later pregnancy complications such as pre-eclampsia, fetal growth restriction and intrauterine death. Revised criteria for the diagnosis of Primary antiphospholipid syndrome (PAPS) recognise the obstetric manifestations of antiphospholipid antibodies (aPL), such as a history of pre-eclampsia and preterm labour.

  • 9 - Early pregnancy complications after assisted reproductive technology

  • Edited by Paul Serhal, Caroline Overton
  • Book:
    Good Clinical Practice in Assisted Reproduction
    Published online:
    22 October 2009
    Print publication:
    01 July 2004, pp 167-185

  • Summary

    The different forms of early pregnancy loss (EPL) are: threatened miscarriage, inevitable miscarriage, missed miscarriage and recurrent miscarriage. Gestational trophoblastic disease (GTD) is a term commonly applied to a spectrum of interrelated diseases originating from the placental trophoblast. The main categories of GTD are complete hydatidiform mole, partial hydatidiform mole and choriocarcinoma. Studies have described the outcome of assisted reproductive technology (ART) pregnancies following prenatal diagnosis but there appear to be no cytogenetic data regarding pregnancy loss before 11 weeks of gestation. Molar pregnancies may be complete (diploid and androgenetic usually arising from fertilization by a haploid sperm which doubles its chromosomes and takes over the ovum) or partial (triploid and predominantly genetically male). Progesterone and human chorionic gonadotrophin (HCG) have been used in the diagnosis, management and treatment of abnormal early pregnancy. This chapter discusses management of multiple gestation pregnancy (MGP) after ART, and multifetal pregnancy reduction (MFPR).