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Recently, immune pathways have been implicated in the pathophysiology of <jats:styled-content style=\"fixed-case\">RSA<\/jats:styled-content>. Immune tolerance of the fetal\u2013placental unit and placental angiogenesis are mandatory for a successful pregnancy outcome. Unscheduled dysregulation of the placental vasculature is thought to be the pathophysiologic mechanisms underlying an array of pregnancy complications like infertility, miscarriage, pre\u2010eclampsia, and fetal growth restriction and death. Investigations on mechanisms and management of <jats:styled-content style=\"fixed-case\">RSA<\/jats:styled-content> are mired by substandard design and lack of optimal randomized clinical trials and have resulted in disagreement on guidelines for evaluation and treatments for patients with multiple pregnancy losses of unknown etiology. The present review focuses on evidence\u2010based research discussion with immunologic causes, and immune\u2010regulatory therapies recommended for helping patients with a history of <jats:styled-content style=\"fixed-case\">RSA<\/jats:styled-content>. We highlight data that might support revalidation of low molecular weight heparin as a protective therapy in <jats:styled-content style=\"fixed-case\">RSA<\/jats:styled-content>. Newly launched growth factors, <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>, and potentially novel agents to suppress inflammatory rejection, including regulatory T cells, human chorionic gonadotropin, and M\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010, may work in concert with tender\u2010loving\u2010care therapy and give hope to couples with multiple pregnancy losses.<\/jats:p>","DOI":"10.1111\/j.1600-0897.2012.01121.x","type":"journal-article","created":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T11:26:06Z","timestamp":1330601166000},"page":"334-340","source":"Crossref","is-referenced-by-count":59,"title":["Multiple Pregnancy Failures: An Immunological Paradigm"],"prefix":"10.1111","volume":"67","author":[{"given":"Leif","family":"Matthiesen","sequence":"first","affiliation":[{"name":"Department Obstetrics and Gynecology Helsingborg Hospital, Affiliated Lunds University Helsingborg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyan","family":"Kalkunte","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Women and Infants Hospital\u2013Warren Alpert Medical School Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surendra","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Women and Infants Hospital\u2013Warren Alpert Medical School Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92159-F"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92215-4"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.gco.0000194112.86051.26"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-004-0706-y"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69204-0"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.01753.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511777851.012"},{"key":"e_1_2_6_9_1","unstructured":"Royal College of Obstetricians and Gynecologist (RCOG).The investigation and treatment of couples with recurrent spontaneous miscarriage. 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