title: Timed intercourse for couples trying to conceive.
abstract: BACKGROUND
  Fertility problems are very common, as subfertility affects about 10% to 15% of couples trying to conceive. There are many factors that may impact a couple's ability to conceive and one of these may be incorrect timing of intercourse. Conception is only possible from approximately five days before up to several hours after ovulation. Therefore, to be effective, intercourse must take place during this fertile period. 'Timed intercourse' is the practice of prospectively identifying ovulation and, thus, the fertile period to increase the likelihood of conception. Whilst timed intercourse may increase conception rates and reduce unnecessary intervention and costs, there may be associated adverse aspects including time consumption and stress. Ovulation prediction methods used for timing intercourse include urinary hormone measurement (luteinizing hormone (LH), estrogen), tracking basal body temperatures, cervical mucus investigation, calendar charting and ultrasonography. This review considered the evidence from randomised controlled trials for the use of timed intercourse on positive pregnancy outcomes.
  
  
  OBJECTIVE
  To assess the benefits and risks of ovulation prediction methods for timing intercourse on conception in couples trying to conceive.
  
  
  METHODS
  We searched the following sources to identify relevant randomised controlled trials, the Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, PubMed, LILACS, Web of Knowledge, the World Health Organization (WHO) Clinical Trials Register Platform and ClinicalTrials.gov. Furthermore, we manually searched the references of relevant articles. The search was not restricted by language or publication status. The last search was on 5 August 2014.
  
  
  METHODS
  We included randomised controlled trials (RCTs) comparing timed intercourse versus intercourse without ovulation prediction or comparing different methods of ovulation prediction for timing intercourse against each other in couples trying to conceive.
  
  
  METHODS
  Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The primary review outcomes were cumulative live birth and adverse events (such as quality of life, depression and stress). Secondary outcomes were clinical pregnancy, pregnancy (clinical or self-reported pregnancy, not yet confirmed by ultrasound) and time to conception. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods.
  
  
  RESULTS
  We included five RCTs (2840 women or couples) comparing timed intercourse versus intercourse without ovulation prediction. Unfortunately one large study (n = 1453) reporting live birth and pregnancy had not published outcome data by randomised group and therefore could not be analysed. Consequently, four RCTs (n = 1387) were included in the meta-analysis. The evidence was of low to very low quality. Main limitations for downgrading the evidence included imprecision, lack of reporting clinically relevant outcomes and the high risk of publication bias.One study reported live birth, but the sample size was too small to draw any relevant conclusions on the effect of timed intercourse (RR 0.75, 95% CI 0.16 to 3.41, 1 RCT, n = 17, very low quality).One study reported stress as an adverse event. There was no evidence of a difference in levels of stress (mean difference 1.98, 95 CI% -0.87 to 4.83, 1 RCT, n = 77, low level evidence). No other studies reported adverse events.Two studies reported clinical pregnancy. There was no evidence of a difference in clinical pregnancy rates (RR 1.10, 95% CI 0.57 to 2.12, 2 RCTs, n = 177, I(2) = 0%, low level evidence). This suggested that if the chance of a clinical pregnancy following intercourse without ovulation prediction is assumed to be 16%, the chance of success following timed intercourse would be between 9% and 33%.Four studies reported pregnancy rate (clinical or self-reported pregnancy). Timed intercourse was associated with higher pregnancy rates compared to intercourse without ovulation prediction in couples trying to conceive (RR 1.35, 95% CI 1.06 to 1.71, 4 RCTs, n = 1387, I(2) = 0%, very low level evidence). This suggests that if the chance of a pregnancy following intercourse without ovulation prediction is assumed to be 13%, the chance following timed intercourse would be between 14% and 23%. Subgroup analysis by duration of subfertility showed no difference in effect between couples trying to conceive for < 12 months versus couples trying for ≥ 12 months. One trial reported time to conception data and showed no evidence of a difference in time to conception.
  
  
  CONCLUSIONS
  There are insufficient data available to draw conclusions on the effectiveness of timed intercourse for the outcomes of live birth, adverse events and clinical pregnancy. Timed intercourse may improve pregnancy rates (clinical or self-reported pregnancy, not yet confirmed by ultrasound) compared to intercourse without ovulation prediction. The quality of this evidence is low to very low and therefore findings should be regarded with caution. There is a high risk of publication bias, as one large study remains unpublished 8 years after recruitment finished. Further research is required, reporting clinically relevant outcomes (live birth, clinical pregnancy rates and adverse effects), to determine if timed intercourse is safe and effective in couples trying to conceive.
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
authors.forename: Marlies
authors.initials: M
authors.lastname: Manders
authors.forename: Luke
authors.initials: L
authors.lastname: McLindon
authors.forename: Brittany
authors.initials: B
authors.lastname: Schulze
authors.forename: Michael M
authors.initials: MM
authors.lastname: Beckmann
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Kremer
authors.forename: Cindy
authors.initials: C
authors.lastname: Farquhar
mesh_terms: D000328:Adult; D003075:Coitus; D005260:Female; D005306:Fertilization; D006801:Humans; D007246:Infertility; D050498:Live Birth; D010061:Ovulation Detection / Q000379:methods; D044384:Ovulation Prediction / Q000379:methods* / Q000706:statistics & numerical data; D011247:Pregnancy; D018873:Pregnancy Rate; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors