title: The Effects of Intravenous Immunoglobulins in Women with Recurrent Miscarriages: A Systematic Review of Randomised Trials with Meta-Analyses and Trial Sequential Analyses Including Individual Patient Data.
abstract: BACKGROUND
  Immunological disturbances are hypothesised to play a role in recurrent miscarriage (RM) and therefore intravenous immunoglubulins (IVIg) have been tested in RM patients.
  
  
  OBJECTIVE
  The objectives were to investigate the benefits and harms of IVIg versus placebo, no intervention, or treatment as usual in women with RM.
  
  
  METHODS
  We searched the published literature in all relevant databases.
  
  
  METHODS
  Randomised trials investigating IVIg versus placebo, no intervention, or treatment as usual in women with RM.
  
  
  METHODS
  We undertook meta-analyses of aggregated data and individual patient data using a two-step approach, and we conducted bias domain assessments and trial sequential analyses to assess the risks of systematic and random errors.
  
  
  RESULTS
  We identified 11 randomised clinical trials. No significant difference in the frequency of no live birth was found when IVIg was compared with placebo or treatment as usual (RR 0.92, 95% CI 0.75-1.12, p = 0.42). Trial sequential analysis showed that the required information size of 1,008 participants was not obtained. IVIg compared with placebo seems to increase the risk of adverse events. Subgroup analysis suggests that women with RM after a birth (secondary RM) seemed most likely to obtain a potential beneficial effect of IVIg (RR for no live birth 0.77, 95%CI 0.58-1.02, p = 0.06), however, trial sequential analysis showed that insufficient information is presently accrued.
  
  
  CONCLUSIONS
  We cannot recommend or refute IVIg in women with RM. IVIg should therefore be assessed in further randomised clinical trials with positive outcomes before any clinical use is considered.
authors.affiliation: The Fertility Department, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Egerup
authors.affiliation: The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jane
authors.initials: J
authors.lastname: Lindschou
authors.affiliation: The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.affiliation: The Fertility Department, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Obstetrics and Gynaecology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Ole Bjarne
authors.initials: OB
authors.lastname: Christiansen
mesh_terms: D000026:Abortion, Habitual / Q000453:epidemiology* / Q000517:prevention & control; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors