title: Should an intrauterine insemination with donor semen be performed 1 or 2 days after the spontaneous LH rise? A prospective RCT.
abstract: OBJECTIVE
  What is the impact on pregnancy rates when intrauterine insemination (IUI) is performed 1 or 2 days after the spontaneous LH rise?
  
  
  CONCLUSIONS
  IUI 1 day after the spontaneous LH rise results in significantly higher clinical pregnancy rates compared with IUI performed 2 days after the LH rise.
  
  
  BACKGROUND
  IUI is scheduled within a limited time interval during which successful conception can be expected. Data about the optimal timing of IUI are based on inseminations following ovarian stimulation. There is no available evidence regarding the correct timing of IUI in a natural menstrual cycle following the occurrence of a spontaneous LH rise.
  
  
  METHODS
  A prospective RCT, including patients undergoing IUI with donor sperm in a natural menstrual cycle. IUI cycles (n = 435) were randomized between October 2010 and April 2013, of which 23 were excluded owing to protocol deviation and 412 received the allocated intervention.
  
  
  METHODS
  Serial serum LH concentrations were analysed in samples taken between 07:00 and 09:00 h to detect an LH rise from Day 11 of the cycle onwards. The subjects were randomized to receive insemination either 1 or 2 days after the observed LH rise. In the final analysis, there were 213 cycles in the group receiving IUI 1 day after the LH rise and 199 cycles in the group receiving IUI 2 days after the LH rise.
  
  
  RESULTS
  Significantly higher clinical pregnancy rates per IUI cycle were observed in patients undergoing IUI 1 day after the LH rise when compared with patients undergoing IUI 2 days after the LH rise [19.7 (42/213) versus 11.1% (22/199), P = 0.02]. In view of the timing of sampling for LH, the inseminations were performed at 27 h (±2 h) and 51 h (±2 h) after detection of the LH rise. The risk ratio of achieving a clinical pregnancy if IUI was scheduled 1 day after the LH rise compared with 2 days was 1.78 [95% confidence interval (CI), 1.11-2.88]. This points towards a gain of one additional clinical pregnancy for every 12 cycles performed 1 day instead of 2 days after the LH rise. When analysing the results per patient, including only women who underwent their first treatment cycle of insemination, the outcome was in line with the per cycle analysis, demonstrating an 8% difference in pregnancy rate in favour of the early group (20.5 versus 12.2%), however, this difference was not significant.
  
  
  CONCLUSIONS
  Optimal monitoring for the occurrence of the LH rise involves several daily LH measurements, which is not always amenable to everyday clinical practice, however, daily sampling was sufficient to detect a significant difference in pregnancy rate. The strict inclusion of a highly selected population of patients who underwent IUI in a natural cycle may have been a limitation. IUI in a natural menstrual cycle confers lower success rates compared with IUI following ovarian stimulation and is not suitable for patients with ovulatory dysfunction. Furthermore, a similar study in a larger number of women is required to confirm the result in terms of pregnancy rate per patient.
  
  
  CONCLUSIONS
  This is the first RCT to show that timing of IUI in a natural menstrual cycle is important and that IUI should be performed 1 day after the LH rise, rather than 2 days post-LH rise. Daily monitoring of the rise in LH, as performed in our study, can be adopted to achieve a higher pregnancy rate per IUI cycle.
  
  
  BACKGROUND
  No funding was received for this study. All authors declare to have no conflict of interest with regard to this trial.
  
  
  BACKGROUND
  The trial was registered at clinicaltrials.gov (NCT01622023).
authors.affiliation: Centrum voor Reproductieve Geneeskunde, Universitair Ziekenhuis Brussel, Brussel, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Blockeel
authors.forename: J
authors.initials: J
authors.lastname: Knez
authors.forename: N P
authors.initials: NP
authors.lastname: Polyzos
authors.forename: M
authors.initials: M
authors.lastname: De Vos
authors.forename: M
authors.initials: M
authors.lastname: Camus
authors.forename: H
authors.initials: H
authors.lastname: Tournaye
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007316:Insemination, Artificial, Heterologous / Q000379:methods*; D007986:Luteinizing Hormone / Q000097:blood*; D016017:Odds Ratio; D011247:Pregnancy; D018873:Pregnancy Rate; D013997:Time Factors
chemical_list: D007986:Luteinizing Hormone
keywords: LH rise; intrauterine insemination; natural cycle; timing