Recurent miscarriage

Department of Obstetrics and Gynaecology, St Mary's Campus, Imperial College London, Mint Wing, South Wharf Road, London W2 1PG, UK.
The Lancet (Impact Factor: 45.22). 09/2006; 368(9535):601-11. DOI: 10.1016/S0140-6736(06)69204-0
Source: PubMed

ABSTRACT Many human conceptions are genetically abnormal and end in miscarriage, which is the commonest complication of pregnancy. Recurrent miscarriage, the loss of three or more consecutive pregnancies, affects 1% of couples trying to conceive. It is associated with psychological morbidity, and has often proven to be frustrating for both patient and clinician. A third of women attending specialist clinics are clinically depressed, and one in five have levels of anxiety that are similar to those in psychiatric outpatient populations. Many conventional beliefs about the cause and treatment of women with recurrent miscarriage have not withstood scrutiny, but progress has been made. Research has emphasised the importance of recurrent miscarriage in the range of reproductive failure linking subfertility and late pregnancy complications and has allowed us to reject practice based on anecdotal evidence in favour of evidence-based management.

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Available from: Lesley Regan, Jan 07, 2014
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    • "Infertility and recurrent pregnancy loss (RPL) are important reproductive phenotypes of multifactorial origin that affect up to 30% and 5– 15% of couples of reproductive age attempting a pregnancy, respectively (Rai and Regan, 2006; Boivin et al., 2007; Smith et al., 2011). Maternal comorbidities along with maternal and fetal genetic factors play a role in the etiology of these conditions, but despite extensive research, a cause cannot be identified in up to 13% (SART, 2010) of cases with unexplained infertility and 40 –50% (Allison and Schust, 2009) with RPL. "
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    ABSTRACT: Are mutations in NLRP2/7 (NACHT, LRR and PYD domains-containing protein 2/7) or KHDC3L (KH Domain Containing 3 Like) associated with recurrent pregnancy loss (RPL) or infertility?
    Human Reproduction 11/2014; DOI:10.1093/humrep/deu296 · 4.59 Impact Factor
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    • "Defined as the occurrence of two or more consecutive pregnancy losses, recurrent pregnancy loss (RPL) occurs before 24 weeks of pregnancy [1] [2] and affects approximately 5% of couples of who are in the reproductive period [3]. The most common risk factors for RPL include genetic, morphological, hormonal, metabolic, infectious, environmental, and immunological factors, as well as thrombophilia and advanced maternal age [4]. "
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    ABSTRACT: Recent studies have investigated the role of the p53 gene family in reproductive processes. Each member of the gene family acts through different mechanisms: p53 is involved in genomic stability and regulation of blastocyst implantation; p63 acts as a regulator of the quality and maturation of oocytes; and p73 controls the meiotic spindle. Polymorphisms in the genes of the p53 family have been associated with female infertility. One polymorphism in MDM2, the main regulator of the p53 family, has also been associated with this condition. Although polymorphisms in the TP53 gene have been related to recurrent pregnancy loss (RPL), there have been no studies associating polymorphisms in p63 and p73 with RPL. Therefore, the aim of this study was to evaluate the role of polymorphisms in the TP63 (rs17506395), TP73 (rs2273953, rs1801173), and MDM2 (SNP309, rs2279744) genes as risk factors for RPL.
    European Journal of Obstetrics & Gynecology and Reproductive Biology 08/2014; 182C:7-10. DOI:10.1016/j.ejogrb.2014.07.044 · 1.63 Impact Factor
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    • "It is a distressing condition for affected couples as each subsequent miscarriage leads to elevated risk of experiencing further pregnancy loss [Ogasawara et al., 2000] and increased probability of other pregnancy complications such as preterm delivery or small for gestational age newborns [Jivraj et al., 2001; van Oppenraaij et al., 2009]. Although a spectrum of factors is known to increase the risk to RM, including immune system dysfunction and thrombophilic disorders, the underlying etiology remains undetermined in about half of the cases [Rai and Regan, 2006; Allison and Schust, 2009]. A familial segregation of RM has been observed highlighting the contribution of the genetic predisposition to the disease [Christiansen et al., 1990; Kolte et al., 2011]. "
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    ABSTRACT: Recurrent miscarriage (RM) is a multifactorial disorder with acknowledged genetic heritability that affects ∼3% of couples aiming at childbirth. As Copy Number Variants (CNVs) have been shown to contribute to reproductive disease susceptibility, we aimed to describe genome-wide profile of CNVs and identify common rearrangements modulating risk to RM. Genome-wide screening of Estonian RM patients and fertile controls identified excessive cumulative burden of CNVs (5.4 and 6.1 Mb/genome) in two RM cases possibly increasing their individual disease risk. Functional profiling of all rearranged genes within RM study group revealed significant enrichment of loci related to innate immunity and immunoregulatory pathways essential for immune tolerance at feto-maternal interface. As a major finding, we report a multicopy duplication (61.6 kb) at 5p13.3 conferring increased maternal risk to RM in Estonia and Denmark (meta-analysis, n = 309/205, OR = 4.82, P = 0.012). Comparison to Estonian population-based EGCUT cohort (total, n = 1000) confirmed the risk for Estonian female cases (P = 7.9×10−4). Datasets of four cohorts from the Database of Genomic Variants (total, n = 5846 subjects) exhibited similar low duplication prevalence worldwide (0.7%-1.2%) compared to RM cases of this study (6.6%-7.5%). The CNV disrupts PDZD2 and GOLPH3 genes predominantly expressed in placenta and it may represent a novel risk factor for pregnancy complications.This article is protected by copyright. All rights reserved
    Human Mutation 08/2014; 35(8). DOI:10.1002/humu.22589 · 5.05 Impact Factor
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