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      Endometriosis and adverse maternal, fetal and neonatal outcomes, a systematic review and meta-analysis

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          Abstract

          STUDY QUESTION

          How is endometriosis associated with adverse maternal, fetal and neonatal outcomes of pregnancy?

          SUMMARY ANSWER

          Women with endometriosis are at elevated risk for serious and important adverse maternal (pre-eclampsia, gestational diabetes, placenta praevia and Cesarean section) and fetal or neonatal outcomes (preterm birth, PPROM, small for gestational age, stillbirth and neonatal death).

          WHAT IS KNOWN ALREADY

          A number of studies have shown an association between endometriosis and certain adverse maternal and fetal outcomes, but the results have been conflicting with potential for confounding by the use of assisted reproductive technology.

          STUDY DESIGN, SIZE, DURATION

          A systematic review and meta-analysis of observational studies (1 January 1990–31 December 2017) that evaluated the effect of endometriosis on maternal, fetal and neonatal outcomes was conducted.

          PARTICIPANTS/MATERIALS, SETTING, METHODS

          Studies were considered for inclusion if they were prospective or retrospective cohort or case–control studies; included women greater than 20 weeks gestational age with endometriosis; included a control group of gravid women without endometriosis; and, reported at least one of the outcomes of interest. Each study was reviewed for inclusion, data were extracted and risk of bias was assessed by two independent reviewers.

          MAIN RESULTS AND THE ROLE OF CHANCE

          The search strategy identified 33 studies (sample size, n = 3 280 488) for inclusion. Compared with women without endometriosis, women with endometriosis had higher odds of pre-eclampsia (odds ratio [OR] = 1.18 [1.01–1.39]), gestational hypertension and/or pre-eclampsia (OR = 1.21 [1.05–1.39]), gestational diabetes (OR = 1.26 [1.03–1.55]), gestational cholestasis (OR = 4.87 [1.85–12.83]), placenta praevia (OR = 3.31 [2.37, 4.63]), antepartum hemorrhage (OR = 1.69 [1.38–2.07]), antepartum hospital admissions (OR = 3.18 [2.60–3.87]), malpresentation (OR = 1.71 [1.34, 2.18]), labor dystocia (OR = 1.45 [1.04–2.01]) and cesarean section (OR = 1.86 [1.51–2.29]). Fetuses and neonates of women with endometriosis were also more likely to have preterm premature rupture of membranes (OR = 2.33 [1.39–3.90]), preterm birth (OR = 1.70 [1.40–2.06]), small for gestational age <10th% (OR = 1.28 [1.11–1.49]), NICU admission (OR = 1.39 [1.08–1.78]), stillbirth (OR = 1.29 [1.10, 1.52]) and neonatal death (MOR = 1.78 [1.46–2.16]). Among the subgroup of women who conceived spontaneously, endometriosis was found to be associated with placenta praevia, cesarean section, preterm birth and low birth weight. Among the subgroup of women who conceived with the use of assisted reproductive technology, endometriosis was found to be associated with placenta praevia and preterm birth.

          LIMITATIONS, REASONS FOR CAUTION

          As with any systematic review, the review is limited by the quality of the included studies. The diagnosis for endometriosis and the selection of comparison groups were not uniform across studies. However, the effect of potential misclassification would be bias towards the null hypothesis.

          WIDER IMPLICATIONS OF THE FINDINGS

          The association between endometriosis with the important and serious pregnancy outcomes observed in our meta-analysis, in particular stillbirth and neonatal death, is concerning and warrants further studies to elucidate the mechanisms for the observed findings.

          STUDY FUNDING/COMPETING INTEREST(S)

          Dr Shifana Lalani is supported by a Physicians’ Services Incorporated Foundation Research Grant, and Dr Innie Chen is supported by a University of Ottawa Clinical Research Chair in Reproductive Population Health and Health Services. Dr Singh declares conflicts of interests with Bayer, Abvie, Allergan and Cooper Surgical. All other authors have no conflicts of interests to declare.

          REGISTRATION NUMBER

          PROSPERO CRD42015013911.

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          Most cited references28

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          The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis.

          Endometriosis is found in 0.5-5% of fertile women and 25-40% of infertile women. It is known that endometriosis is associated with infertility, but there is uncertainty whether women with endometriosis have adverse pregnancy outcomes in in vitro fertilisation (IVF) treatment. To explore the association between endometriosis and IVF outcome. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science (inception, December 2012) in all languages, together with reference lists of retrieved papers. Studies comparing IVF outcome in women with endometriosis with women without endometriosis. Patients were classified by stage of endometriosis. The outcomes were fertilisation, implantation, clinical pregnancy and live birth rates. Study selection was conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. Data extraction was conducted independently by two reviewers. Relative risks from individual studies were meta-analysed. Twenty-seven observational studies were included, comprising 8984 women. Meta-analysis of these studies showed that fertilisation rates were reduced in stage I/II of endometriosis (relative risk [RR] = 0.93, 95% confidence interval [95% CI] 0.87-0.99, P = 0.03). There was a decrease in the implantation rate (RR = 0.79, 95% CI 0.67-0.93, P = 0.006) and clinical pregnancy rate (RR = 0.79, 95% CI 0.69-0.91, P = 0.0008) in women with stage III/IV endometriosis undergoing IVF treatment. The presence of severe endometriosis (stage III/IV) is associated with poor implantation and clinical pregnancy rates in women undergoing IVF treatment. © 2013 RCOG.
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            Pathophysiology of hypertension in pre-eclampsia: a lesson in integrative physiology.

            Despite being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of pre-eclampsia have yet to be fully elucidated. However, it is evident that this is a complex disorder involving multiple organ systems, and by using integrative approaches, enormous progress has been made towards understanding the pathophysiology of pre-eclampsia. Growing evidence supports the concept that the placenta plays a central role in the pathogenesis of pre-eclampsia and that reduced uteroplacental perfusion, which develops as a result of abnormal cytotrophoblast invasion of spiral arterioles, triggers the cascade of events leading to the maternal disorder. Placental ischaemia leads to release of soluble placental factors, many of which are classified as anti-angiogenic or pro-inflammatory. Once these ischaemic placental factors reach the maternal circulation, they cause widespread activation and dysfunction of the maternal vascular endothelium that results in enhanced formation of endothelin-1 and superoxide, increased vascular sensitivity to angiotensin II and decreased formation of vasodilators such as nitric oxide. This review highlights these links between placental ischaemia, maternal endothelial activation and renal dysfunction in the pathogenesis of hypertension in pre-eclampsia. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
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              • Article: not found

              The epidemiology of endometriosis.

              The epidemiologic study of endometriosis presents researchers with unique challenges. As a result, few well-designed studies have been published. The authors briefly describe the primary pathogenic hypotheses, discuss methodologic issues specific to endometriosis, and review the small body of literature addressing risk factors. Finally, they offer a brief interpretation of these findings and suggest hypotheses for future research.
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                Author and article information

                Journal
                Hum Reprod
                Hum. Reprod
                humrep
                Human Reproduction (Oxford, England)
                Oxford University Press
                0268-1161
                1460-2350
                October 2018
                17 September 2018
                17 September 2018
                : 33
                : 10
                : 1854-1865
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, University of Ottawa/The Ottawa Hospital, 501 Smyth Road, Ottawa, ON, Canada
                [2 ]Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, Canada
                Author notes
                Correspondence address.1967 Riverside Drive, Rm 7236-3, Ottawa, Ontario, Canada K1H 7W9. Tel. +1-613-738-8400x81740; E-mail: ichen@ 123456toh.on.ca
                Article
                dey269
                10.1093/humrep/dey269
                6145420
                30239732
                a34c9569-6131-46c9-be78-b6de64fc67b6
                © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 07 April 2018
                : 04 June 2018
                : 04 September 2018
                Page count
                Pages: 14
                Categories
                Meta-Analysis
                Gynaecology

                Human biology
                endometriosis,pregnancy outcomes,assisted reproduction,stillbirth,meta-analysis
                Human biology
                endometriosis, pregnancy outcomes, assisted reproduction, stillbirth, meta-analysis

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