title: Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome.
abstract: BACKGROUND
  Reproductive disorders and infertility are associated with the risk of obstetric complications and have a negative impact on pregnancy outcome. Affected patients often require assisted reproductive technologies (ART) to conceive, and advanced maternal age is a further confounding factor. The challenge is to dissect causation, correlation and confounders in determining how infertility and reproductive disorders individually or together predispose women to poor pregnancy outcomes.
  
  
  METHODS
  The published literature, to June 2015, was searched using PubMed, summarizing all evidences concerning the perinatal outcome of women with infertility and reproductive disorders and the potential mechanisms that may influence poor pregnancy outcome.
  
  
  RESULTS
  Reproductive disorders (endometriosis, adenomyosis, polycystic ovary syndrome and uterine fibroids) and unexplained infertility share inflammatory pathways, hormonal aberrations, decidual senescence and vascular abnormalities that may impair pregnancy success through common mechanisms. Either in combination or alone, these disorders results in an increased risk of preterm birth, fetal growth restriction, placental pathologies and hypertensive disorders. Systemic hormonal aberrations, and inflammatory and metabolic factors acting on endometrium, myometrium, cervix and placenta are all associated with an aberrant milieu during implantation and pregnancy, thus contributing to the genesis of obstetric complications. Some of these features have been also described in placentas from ART.
  
  
  CONCLUSIONS
  Reproductive disorders are common in women of childbearing age and rarely occur in isolation. Inflammatory, endocrine and metabolic mechanisms associated with these disorders are responsible for an increased incidence of obstetric complications. These patients should be recognized as 'high risk' for poor pregnancy outcomes and monitored with specialized follow-up. There is a real need for development of evidence-based recommendations about clinical management and specific obstetric care pathways for the introduction of prompt preventative care measures.
authors.affiliation: Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vannuccini
authors.affiliation: Robinson Research Institute, University of Adelaide, Adelaide, Australia.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Clifton
authors.affiliation: Department of Obstetrics and Gynaecology, Center for Women's Health, University of New South Wales, Sydney, Australia.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Fraser
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, CT, USA.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Hilary
authors.initials: H
authors.lastname: Critchley
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, 550 16th Street, Floor 7, Box 0132, San Francisco, CA 94143, USA linda.giudice@ucsf.edu.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Giudice
authors.affiliation: Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, Siena, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D002584:Cervix Uteri / Q000502:physiology; D005260:Female; D052776:Female Urogenital Diseases / Q000209:etiology*; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D007247:Infertility, Female / Q000209:etiology*; D007249:Inflammation / Q000503:physiopathology; D007889:Leiomyoma / Q000209:etiology; D008423:Maternal Age; D010920:Placenta / Q000502:physiology; D011085:Polycystic Ovary Syndrome / Q000150:complications; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology*; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000209:etiology; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects; D015398:Signal Transduction
chemical_list: D012739:Gonadal Steroid Hormones
keywords: assisted reproductive technologies; endometriosis; inflammation; placenta; polycystic ovary syndrome; pre-eclampsia; preterm birth; sex steroids; unexplained infertility; uterine fibroids