title: Midpregnancy Doppler ultrasound of the uterine artery in metformin- versus placebo-treated PCOS women: a randomized trial.
abstract: BACKGROUND
  Metformin is used to reduce pregnancy complications in women with polycystic ovary syndrome (PCOS), although it is not approved for this indication and solid evidence is lacking. Midpregnancy Doppler ultrasound is one of the best methods for prediction of adverse pregnancy outcome.
  
  
  OBJECTIVE
  The objectives of the study were to investigate the following: 1) whether metformin treatment influenced the midpregnancy pulsatility index (PI) of the uterine artery; 2) whether metabolic or endocrine factors affect the PI of the uterine artery of PCOS women; and 3) whether PI predicted adverse pregnancy outcome in PCOS woman.
  
  
  METHODS
  This is a substudy of a randomized, placebo-controlled, double-blind, multicenter study conducted at 11 secondary care centers. We randomly assigned 273 pregnancies to receive metformin or placebo, from the first trimester of pregnancy to delivery. In the present substudy, 231 pregnancies are included, ie, those who completed the ultrasound examinations.
  
  
  METHODS
  Midpregnancy PI in the uterine artery related to metformin use, androgen levels, an oral glucose tolerance test, and insulin levels was measured. We found no difference in the PI between the metformin and placebo groups. In multivariate analyses, fasting serum glucose of the first and second trimester correlated positively to the midpregnancy PI. Only in univariate analyses a weak correlation between androstenedione and PI was seen.
  
  
  CONCLUSIONS
  Metformin treatment did not affect uterine artery blood flow, measured by PI. High fasting blood glucose correlated inversely to uterine artery blood flow. The midpregnancy PI correlated positively to preeclampsia, hypertension, and gestational diabetes mellitus in PCOS pregnancies. Androgen levels correlated only to PI in univariate analyses.
authors.affiliation: Departments of Obstetrics and Gynecology (S.S., I.C., E.V.) and Endocrinology (S.M.C.), St Olav's Hospital, Trondheim University Hospital, 7006 Trondheim, Norway; and Department for Laboratory Medicine (S.S., E.V.), Children's and Women's Health, and Unit for Applied Clinical Research (S.M.C., Ø.S.), Department for Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
authors.forename: Solhild
authors.initials: S
authors.lastname: Stridsklev
authors.forename: Sven M
authors.initials: SM
authors.lastname: Carlsen
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Salvesen
authors.forename: Ilka
authors.initials: I
authors.lastname: Clemens
authors.forename: Eszter
authors.initials: E
authors.lastname: Vanky
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos / Q000627:therapeutic use; D011085:Polycystic Ovary Syndrome / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011256:Pregnancy Outcome / Q000453:epidemiology; D011262:Pregnancy Trimester, Second / Q000187:drug effects; D018608:Ultrasonography, Doppler; D055988:Uterine Artery / Q000000981:diagnostic imaging* / Q000187:drug effects*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D010919:Placebos; D008687:Metformin