Abstract: 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, I2 = 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, I2 = 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. 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.

Plain-language summary: We found five randomised controlled trials comparing timed intercourse versus intercourse without ovulation prediction, in a total of 2840 women or couples trying to conceive. The evidence was current to August 2014. One large included study (1453 women) has not published usable results and could therefore not be analysed. One study reported live birth rates and found no evidence of a difference; however, the study was too small to have any clinical value. Only one study reported levels of stress and showed no evidence of a difference between timed intercourse with urinary fertility monitoring and intercourse without urinary fertility monitoring. No other adverse events were reported. Only two studies reported clinical pregnancy rates, and showed no evidence of a difference in pregnancy rates in couples with subfertility. The evidence suggested that if the chance of a clinical pregnancy following intercourse without ovulation prediction was assumed to be 16%, the chance of a clinical pregnancy following timed intercourse would be between 9% and 33%. However, if including self-reported pregnancies (not confirmed by ultrasound), pregnancy rates were higher after timed intercourse. The evidence suggested that if the chance of a pregnancy following intercourse without ovulation prediction was 13%, the chance following timed intercourse would be between 14% and 23%. No difference in effect was found between couples trying to conceive for less than 12 months versus 12 months or more. One trial reported time to conception data and showed no evidence of a difference in time to conception. The overall quality of the evidence ranged from low to very low for all outcomes. The main limitations of the evidence were imprecision, poor reporting of clinically relevant outcomes and a high risk of publication bias, as one large study remains unpublished. Therefore, the findings should be regarded with caution.