title: Angiogenic markers in pregnancies conceived through in vitro fertilization.
abstract: OBJECTIVE
  Pregnancies that have been conceived through in vitro fertilization (IVF) have been associated with higher rates of preeclampsia and other complications that are associated with placental dysfunction. We evaluated whether IVF pregnancies, when compared with those conceived spontaneously, would be associated with alterations in serum angiogenic markers.
  
  
  METHODS
  This was a retrospective cohort study from 3 US academic institutions (2006-2008). Women with singleton pregnancies who conceived via IVF or spontaneously were included. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 4 time points throughout gestation. Pregnancy outcomes that included diagnosis of preeclampsia or other obstetric complications were ascertained from the medical record. The relationship among IVF status, PlGF, and sFlt-1 were modeled over gestation and stratified by clinical pregnancy outcome.
  
  
  RESULTS
  Of the included 2392 singleton pregnancies, 4.5% (108 pregnancies) were conceived though IVF. IVF pregnancies were significantly more likely to be complicated by preeclampsia (15.7% vs 7.7%). IVF pregnancies had significantly higher levels of sFlt-1 at 18, 26, and 35 weeks of gestation (P = .04, P = .004, P < .0001, respectively) and lower levels of PlGF at 18 and 35 weeks of gestation (P = .007 and .0006, respectively). These differences persisted even after being controlled for maternal comorbidities or obstetric outcomes such as preeclampsia.
  
  
  CONCLUSIONS
  Pregnancies conceived via IVF were found to have an increased antiangiogenic profile (elevated sFlt-1 and decreased PlGF) at multiple time points throughout gestation when compared with spontaneously conceived pregnancies. Alterations in the angiogenic profile persisted even after we controlled for maternal comorbidities of clinically evident disorders of abnormal placentation such as preeclampsia. The increased antiangiogenic profile suggests fundamentally aberrant placentation related to in vitro fertilization, which may warrant closer fetal surveillance in these pregnancies.
authors: Brigham and Women's Hospital/Massachusetts General Hospital Integrated Residency Program in Obstetrics and Gynecology, Boston, MA; Harvard Medical School, Boston, MA. Electronic address: mlee33@partners.org.
authors: Malinda S
authors: MS
authors: Lee
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors: David
authors: D
authors: Cantonwine
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors: Sarah E
authors: SE
authors: Little
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors: Thomas F
authors: TF
authors: McElrath
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors: Samuel I
authors: SI
authors: Parry
authors: Harvard Medical School, Boston, MA; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA.
authors: Kee-Hak
authors: KH
authors: Lim
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors: Louise E
authors: LE
authors: Wilkins-Haug
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D018919:Neovascularization, Physiologic; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000453:epidemiology / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: angiogenic marker; in vitro fertilization; placental growth factor; preeclampsia; soluble fms-like tyrosine kinase-1