title: Recombinant human follicle-stimulating hormone (r-hFSH) plus recombinant luteinizing hormone versus r-hFSH alone for ovarian stimulation during assisted reproductive technology: systematic review and meta-analysis.
abstract: BACKGROUND
  The potential benefit of adding recombinant human luteinizing hormone (r-hLH) to recombinant human follicle-stimulating hormone (r-hFSH) during ovarian stimulation is a subject of debate, although there is evidence that it may benefit certain subpopulations, e.g. poor responders.
  
  
  METHODS
  A systematic review and a meta-analysis were performed. Three databases (MEDLINE, Embase and CENTRAL) were searched (from 1990 to 2011). Prospective, parallel-, comparative-group randomized controlled trials (RCTs) in women aged 18-45 years undergoing in vitro fertilization, intracytoplasmic sperm injection or both, treated with gonadotrophin-releasing hormone analogues and r-hFSH plus r-hLH or r-hFSH alone were included. The co-primary endpoints were number of oocytes retrieved and clinical pregnancy rate. Analyses were conducted for the overall population and for prospectively identified patient subgroups, including patients with poor ovarian response (POR).
  
  
  RESULTS
  In total, 40 RCTs (6443 patients) were included in the analysis. Data on the number of oocytes retrieved were reported in 41 studies and imputed in two studies. Therefore, data were available from 43 studies (r-hFSH plus r-hLH, n=3113; r-hFSH, n=3228) in the intention-to-treat (ITT) population (all randomly allocated patients, including imputed data). Overall, no significant difference in the number of oocytes retrieved was found between the r-hFSH plus r-hLH and r-hFSH groups (weighted mean difference -0.03; 95% confidence interval [CI] -0.41 to 0.34). However, in poor responders, significantly more oocytes were retrieved with r-hFSH plus r-hLH versus r-hFSH alone (n=1077; weighted mean difference +0.75 oocytes; 95% CI 0.14-1.36). Significantly higher clinical pregnancy rates were observed with r-hFSH plus r-hLH versus r-hFSH alone in the overall population analysed in this review (risk ratio [RR] 1.09; 95% CI 1.01-1.18) and in poor responders (n=1179; RR 1.30; 95% CI 1.01-1.67; ITT population); the observed difference was more pronounced in poor responders.
  
  
  CONCLUSIONS
  These data suggest that there is a relative increase in the clinical pregnancy rates of 9% in the overall population and 30% in poor responders. In conclusion, this meta-analysis suggests that the addition of r-hLH to r-hFSH may be beneficial for women with POR.
authors.affiliation: Faculty of Economics, Université Catholique de Louvain (UCL Mons), 7000 Mons, Belgium. philippe.lehert@gmail.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lehert
authors.forename: Efstratios M
authors.initials: EM
authors.lastname: Kolibianakis
authors.forename: Christos A
authors.initials: CA
authors.lastname: Venetis
authors.forename: Joan
authors.initials: J
authors.lastname: Schertz
authors.forename: Helen
authors.initials: H
authors.lastname: Saunders
authors.forename: Pablo
authors.initials: P
authors.lastname: Arriagada
authors.forename: Samuel
authors.initials: S
authors.lastname: Copt
authors.forename: Basil
authors.initials: B
authors.lastname: Tarlatzis
mesh_terms: D004359:Drug Therapy, Combination; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy / Q000453:epidemiology; D007986:Luteinizing Hormone / Q000008:administration & dosage*; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D018873:Pregnancy Rate / Q000639:trends; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; D007986:Luteinizing Hormone