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      New insights into mechanisms behind miscarriage

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          Abstract

          Sporadic miscarriage is the most common complication of early pregnancy. Two or three consecutive pregnancy losses is a less common phenomenon, and this is considered a distinct disease entity. Sporadic miscarriages are considered to primarily represent failure of abnormal embryos to progress to viability. Recurrent miscarriage is thought to have multiple etiologies, including parental chromosomal anomalies, maternal thrombophilic disorders, immune dysfunction and various endocrine disturbances. However, none of these conditions is specific to recurrent miscarriage or always associated with repeated early pregnancy loss. In recent years, new theories about the mechanisms behind sporadic and recurrent miscarriage have emerged. Epidemiological and genetic studies suggest a multifactorial background where immunological dysregulation in pregnancy may play a role, as well as lifestyle factors and changes in sperm DNA integrity. Recent experimental evidence has led to the concept that the decidualized endometrium acts as biosensor of embryo quality, which if disrupted, may lead to implantation of embryos destined to miscarry. These new insights into the mechanisms behind miscarriage offer the prospect of novel effective interventions that may prevent this distressing condition.

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          Most cited references76

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          Chromosome instability is common in human cleavage-stage embryos.

          Chromosome instability is a hallmark of tumorigenesis. This study establishes that chromosome instability is also common during early human embryogenesis. A new array-based method allowed screening of genome-wide copy number and loss of heterozygosity in single cells. This revealed not only mosaicism for whole-chromosome aneuploidies and uniparental disomies in most cleavage-stage embryos but also frequent segmental deletions, duplications and amplifications that were reciprocal in sister blastomeres, implying the occurrence of breakage-fusion-bridge cycles. This explains the low human fecundity and identifies post-zygotic chromosome instability as a leading cause of constitutional chromosomal disorders.
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            Evaluation and treatment of recurrent pregnancy loss: a committee opinion.

            (2012)
            The majority of miscarriages are sporadic and most result from genetic causes that are greatly influenced by maternal age. Recurrent pregnancy loss (RPL) is defined by two or more failed clinical pregnancies, and up to 50% of cases of RPL will not have a clearly defined etiology. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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              Maternal age and fetal loss: population based register linkage study.

              To estimate the association between maternal age and fetal death (spontaneous abortion, ectopic pregnancy, stillbirth), taking into account a woman's reproductive history. Prospective register linkage study. All women with a reproductive outcome (live birth, stillbirth, spontaneous abortion leading to admission to hospital, induced abortion, ectopic pregnancy, or hydatidiform mole) in Denmark from 1978 to 1992; a total of 634 272 women and 1 221 546 pregnancy outcomes. Age related risk of fetal loss, ectopic pregnancy, and stillbirth, and age related risk of spontaneous abortion stratified according to parity and previous spontaneous abortions. Overall, 13.5% of the pregnancies intended to be carried to term ended with fetal loss. At age 42 years, more than half of such pregnancies resulted in fetal loss. The risk of a spontaneous abortion was 8.9% in women aged 20-24 years and 74.7% in those aged 45 years or more. High maternal age was a significant risk factor for spontaneous abortion irrespective of the number of previous miscarriages, parity, or calendar period. The risk of an ectopic pregnancy and stillbirth also increased with increasing maternal age. Fetal loss is high in women in their late 30s or older, irrespective of reproductive history. This should be taken into consideration in pregnancy planning and counselling.
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                Author and article information

                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central
                1741-7015
                2013
                26 June 2013
                : 11
                : 154
                Affiliations
                [1 ]The Fertility Clinic, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
                [2 ]Department of Obstetrics and Gynaecology, Aalborg Hospital, Aalborg, Denmark
                [3 ]Division of Human Development and Health, University of Southampton, Southampton, UK
                [4 ]Obstetrics and Gynaecology, Academic Unit of Human Development and Health, University of Southampton, Southampton, UK
                [5 ]Complete Fertility Centre Southampton, Princess Anne Hospital, Coxford Road, Southampton, SO16 5YA, UK
                Article
                1741-7015-11-154
                10.1186/1741-7015-11-154
                3699442
                23803387
                5ab91794-6800-4282-822f-52549272a88d
                Copyright ©2013 Larsen et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 March 2013
                : 29 May 2013
                Categories
                Review

                Medicine
                embryo selection,epidemiology,genetics,immunology,miscarriage,recurrent miscarriage,sperm dna integrity

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