title: Assisted hatching of human embryos: a systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Assisted hatching (AH) is a manipulation of zona pellucida aiming to facilitate embryo implantation.
  
  
  METHODS
  Systematic review and meta-analysis of medical literature was used to evaluate the effect of AH on assisted reproduction outcomes: clinical pregnancy, live birth, multiple pregnancy and miscarriage. Additional analysis was performed in these subgroups: (i) fresh embryos transferred to unselected or non-poor prognosis women; (ii) fresh embryos transferred to women with previous repeated failure; (iii) fresh embryos transferred to women of advanced age; (iv) frozen-thawed embryos transferred to unselected or non-poor prognosis women. Analyses were based on risk ratio and 95% confidence intervals (RR, 95% CIs) using Mantel-Haenszel random effects model.
  
  
  RESULTS
  There were 28 studies (5507 participants) included. AH was related to a trend toward increased clinical pregnancy for all participants (RR = 1.11, 95% CI = 1.00-1.24), with a significant increase in subgroups 2 (RR = 1.73; 95% CI = 1.37-2.17) and 4 (RR = 1.36; 95% CI = 1.08-1.72, P< 0.01), but not for subgroups 1 and 3. For multiple pregnancy, a significant increase was observed for all participants (RR = 1.45; 95% CI = 1.11-1.90) and for subgroups 2 (RR = 2.53; 95% CI = 1.23-5.21) and 4 (RR = 3.40; 95% CI = 1.93-6.01). No significant heterogeneity was observed in subgroup analysis.
  
  
  CONCLUSIONS
  AH was related to increased clinical pregnancy and multiple pregnancy rates in women with previous repeated failure or frozen-thawed embryos. However, AH is unlikely to increase clinical pregnancy rates when performed in fresh embryos transferred to unselected or non-poor prognosis women or to women of advanced age. Due to the small sample evaluated by the pool of included studies, no proper conclusions could be drawn regarding miscarriage or live birth.
authors.affiliation: Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto da, Universidade de São Paulo, Av. dos Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, Brazil. wpmartins@gmail.com
authors.forename: Wellington P
authors.initials: WP
authors.lastname: Martins
authors.forename: Isa A
authors.initials: IA
authors.lastname: Rocha
authors.forename: Rui A
authors.initials: RA
authors.lastname: Ferriani
authors.forename: Carolina O
authors.initials: CO
authors.lastname: Nastri
mesh_terms: D000022:Abortion, Spontaneous; D000328:Adult; D010064:Embryo Implantation; D004624:Embryo Transfer / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D011272:Pregnancy, Multiple; D016032:Randomized Controlled Trials as Topic; D015044:Zona Pellucida / Q000502:physiology*