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      Women with a History of Recurrent Pregnancy Loss Are a High-Risk Population for Adverse Obstetrical Outcome: A Retrospective Cohort Study

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          Abstract

          Recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, is hypothesized to share some of the same pathogenic factors as placenta-associated disorders. It has been hypothesized that a defect implantation causes pregnancy loss, while a partially impaired implantation may lead to late pregnancy complications. The aim of this retrospective register-based cohort study was to study the association between RPL and such disorders including pre-eclampsia, stillbirth, small for gestational age (SGA) birth, preterm birth and placental abruption. Women registered with childbirth(s) in the Swedish Medical Birth Register (MFR) were included in the cohort. Pregnancies of women diagnosed with RPL (exposed) in the National Patient Register (NPR), were compared with pregnancies of women without RPL (unexposed/reference). Obstetrical outcomes, in the first pregnancy subsequent to the diagnosis of RPL ( n = 4971), were compared with outcomes in reference-pregnancies ( n = 57,410). Associations between RPL and placental dysfunctional disorders were estimated by odds ratios (AORs) adjusting for confounders, with logistic regression. RPL women had an increased risk for pre-eclampsia (AOR 1.45; 95% CI; 1.24–1.69), stillbirth <37 gestational weeks (GWs) (AOR 1.92; 95% CI; 1.22–3.02), SGA birth (AOR 1.97; 95% CI; 1.42–2.74), preterm birth (AOR 1.46; 95% CI; 1.20–1.77), and placental abruption <37 GWs (AOR 2.47; 95% CI; 1.62–3.76) compared with pregnancies by women without RPL. Women with RPL had an increased risk of pregnancy complications associated with placental dysfunction. This risk population is, therefore, in need of improved antenatal surveillance.

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          The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research

          Swedish health care and national health registers are dependent on the presence of a unique identifier. This paper describes the Swedish personal identity number (PIN) and explores ethical issues of its use in medical research. A ten-digit-PIN is maintained by the National Tax Board for all individuals that have resided in Sweden since 1947. Until January 2008, an estimated 75,638 individuals have changed PIN. The most common reasons for change of PIN are incorrect recording of date of birth or sex among immigrants or newborns. Although uncommon, change of sex always leads to change of PIN since the PIN is sex-specific. The most common reasons for re-use of PIN (n = 15,887), is when immigrants are assigned a PIN that has previously been assigned to someone else. This is sometimes necessary since there is a shortage of certain PIN combinations referring to dates of birth in the 1950s and 1960s. Several ethical issues can be raised pro and con the use of PIN in medical research. The Swedish PIN is a useful tool for linkages between medical registers and allows for virtually 100% coverage of the Swedish health care system. We suggest that matching of registers through PIN and matching of national health registers without the explicit approval of the individual patient is to the benefit for both the individual patient and for society.
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            Recurrent miscarriage.

            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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              ESHRE guideline: recurrent pregnancy loss

              Abstract STUDY QUESTION What is the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature? SUMMARY ANSWER The guideline development group formulated 77 recommendations answering 18 key questions on investigations and treatments for RPL, and on how care should be organized. WHAT IS KNOWN ALREADY A previous guideline for the investigation and medical treatment of recurrent miscarriage was published in 2006 and is in need of an update. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 31 March 2017 and written in English were included. Cumulative live birth rate, live birth rate and pregnancy loss rate (or miscarriage rate) were considered the critical outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE The guideline provides 38 recommendations on risk factors, prevention and investigations in couples with RPL, and 39 recommendations on treatments. These include 60 evidence-based recommendations – of which 31 were formulated as strong recommendations and 29 as conditional – and 17 good practice points. The evidence supporting investigations and treatment of couples with RPL is limited and of moderate quality. Of the evidence-based recommendations, only 10 (16.3%) were supported by moderate quality evidence. The remaining recommendations were supported by low (35 recommendations: 57.4%), or very low quality evidence (16 recommendations: 26.2%). There were no recommendations based on high quality evidence. Owing to the lack of evidence-based investigations and treatments in RPL care, the guideline also clearly mentions investigations and treatments that should not be used for couples with RPL. LIMITATIONS, REASONS FOR CAUTION Several investigations and treatments are offered to couples with RPL, but most of them are not well studied. For most of these investigations and treatments, a recommendation against the intervention or treatment was formulated based on insufficient evidence. Future studies may require these recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in RPL, based on the best evidence available. In addition, a list of research recommendations is provided to stimulate further studies in RPL. One of the most important consequences of the limited evidence is the absence of evidence for a definition of RPL. STUDY FUNDING/COMPETING INTEREST(S) The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. J.E. reports position funding from CARE Fertility. S.L. reports position funding from SpermComet Ltd. S.M. reports research grants, consulting and speaker’s fees from GSK, BMS/Pfizer, Sanquin, Aspen, Bayer and Daiichi Sankyo. S.Q. reports speaker’s fees from Ferring. The other authors report no conflicts of interest. ESHRE Pages are not externally peer reviewed. This article has been approved by the Executive Committee of ESHRE.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                06 January 2021
                January 2021
                : 10
                : 2
                : 179
                Affiliations
                [1 ]Institute of Clinical Sciences Lund, Lund University, 22100 Lund, Sweden; karin.kallen@ 123456med.lu.se (K.K.); stefan.hansson@ 123456med.lu.se (S.R.H.)
                [2 ]Department of Obstetrics and Gynaecology, Skåne University Hospital, Jan Waldenströmsgatan 47, 20502 Malmö, Sweden
                [3 ]Centre for Recurrent Pregnancy Loss of Western Denmark, Department of Obstetrics and Gynaecology, Aalborg University Hospital, Clinical Institute at Aalborg University, 9220 Aalborg, Denmark; olbc@ 123456rn.dk
                Author notes
                [* ]Correspondence: emma.rasmark_ropke@ 123456med.lu.se ; Tel.: +46-452-346-0721
                Author information
                https://orcid.org/0000-0002-7838-9074
                Article
                jcm-10-00179
                10.3390/jcm10020179
                7825424
                33419111
                923b6308-a6bd-4baa-88f0-2a3ab4552e4b
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 November 2020
                : 27 December 2020
                Categories
                Article

                recurrent pregnancy loss,pre-eclampsia,intrauterine growth restriction,preterm birth,stillbirth,placental abruption

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