Recurrent 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


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?
    Full-text · Article · Nov 2014 · Human Reproduction
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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: Objective: 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. Study design: A case-control study was conducted in 153 women with RPL and 143 fertile women with at least two living children and no history of pregnancy loss. Molecular analysis was performed by TaqMan Allelic Discrimination assay. The statistical analysis was performed using SPSS software version 20.0 and the chi-square test, Student's t-test, Mann-Whitney test and logistic regression to compare the evaluated characteristics between both groups and RPL outcome. Results: The allelic and genotypic frequencies did not differ between the groups when analyzed separately, however, the interaction between the TP63 TT and MDM2 TT genotypes was shown to increase the risk of RPL (OR=2.19, CI 95%: 1.28-3.75, p=0.004), even when adjusted for alcohol consumption, smoking, number of pregnancies and ethnicity (OR=1.97, CI 95%: 1.27-3.58, p=0.025). Conclusions: Our results suggest that genes from the p53 family proteins, evaluated here, have an influence on the risk of RPL.
    Full-text · Article · Aug 2014 · European Journal of Obstetrics & Gynecology and Reproductive Biology
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    • "Thus, a miscarriage results in great sorrow, loss of life quality, and personal concern. In particular, RM is extremely stressful [2]. It is, therefore, very important to conduct research in this area. "
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    ABSTRACT: Background Recurrent miscarriage is generally defined as three or more miscarriages before gestational week 20. Recurrent miscarriage affects 1% of all women and the condition can only be explained by parental chromosome abnormalities, uterine malformations, or endocrine or thrombophilic disturbances to a limited extent. Immunological disturbances are hypothesised to play an important role in recurrent miscarriage and, therefore, various types of immunologically-based therapies have been tested in recurrent miscarriage patients including intravenous immunoglobulins. So far, at least eight randomised placebo-controlled trials, with opposing results, investigating intravenous immunoglobulins with a total of 324 recurrent miscarriage patients have been published. Methods/Design We will include randomised clinical trials irrespective of publication date, publication type, publication language, and publication status investigating infusions with immunoglobulins in relation to pregnancy compared to placebo, no intervention, or treatment as usual for assessments of benefits and harms. The relevant published literature will be searched using the following databases: Cochrane Central Register of Controlled Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, and Ovid Medline In-Process and Other Non-Indexed Citations databases. Two review authors will independently extract data and assess risk of bias. We will undertake meta-analyses according to the recommendations stated in the Cochrane Handbook for Systematic Reviews of Interventions. Further, we will conduct trial sequential analyses and individual patient data meta-analyses. Discussion A miscarriage results in great sorrow, loss of life quality, and personal concern. In particular, recurrent miscarriage is extremely stressful and burdensome. It is, therefore, very important to conduct research in this area. There is currently no evidence-based treatment for women with recurrent miscarriage which significantly improves their ability to give live birth. Therefore, a comprehensive up-to-date systematic review is needed. By using individual patient data, it will be possible to provide new knowledge about the benefits and harms of intravenous immunoglobulins and try to identify the subgroup in which the treatment will have the highest impact. This systematic review protocol was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42014007112.
    Full-text · Article · Aug 2014 · Systematic Reviews
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