Abstract: Six randomised controlled trials with a total of 788 women were included. The largest of these trials included 396 women eligible for this review. No evidence of a statistically significant difference was found between natural cycle and standard IVF in live birth rates (OR 0.68, 95% CI 0.46 to 1.01, two studies, 425 women, I2= 0%, moderate quality evidence). The evidence suggests that for a woman with a 53% chance of live birth using standard IVF, the chance using natural cycle IVF would range from 34% to 53%. There was no evidence of a statistically significant difference between natural cycle and standard IVF in rates of OHSS (OR 0.19, 95% CI 0.01 to 4.06, one study, 60 women, very low quality evidence), clinical pregnancy (OR 0.52 95% CI 0.17 to 1.61, 4 studies, 351 women, I2=63%, low quality evidence), ongoing pregnancy (OR 0.72, 95% CI 0.50 to 1.05, three studies, 485 women, I2=0%, moderate quality evidence), multiple pregnancy (OR 0.76, 95% CI 0.25 to 2.31, 2 studies, 527 women, I2=0%, very low quality evidence), gestational abnormalities (OR 0.44 95% CI 0.03 to 5.93, 1 study, 18 women, very low quality evidence) or cycle cancellations (OR 8.98, 95% CI 0.20 to 393.66, 2 studies, 159 women, I2=83%, very low quality evidence). One trial reported that the oocyte retrieval rate was significantly lower in the natural cycle group (MD -4.40, 95% CI -7.87 to -0.93, 60 women, very low quality evidence). There were insufficient data to draw any conclusions about rates of treatment cancellation. Findings on treatment costs were inconsistent and more data are awaited. The evidence was limited by imprecision. Findings for pregnancy rate and for cycle cancellation were sensitive to the choice of statistical model: for these outcomes, use of a fixed effect model suggested a benefit for the standard IVF group. Moreover the largest trial has not yet completed follow up, though data have been reported for over 95% of women. Further evidence from well conducted large trials is awaited on natural cycle IVF treatment. Future trials should compare natural cycle IVF with standard IVF. Outcomes should include cumulative live birth and pregnancy rates, the number of treatment cycles necessary to reach live birth, treatment costs and adverse effects.

Plain-language summary: Six trials were included, with a total of 788 women undergoing an IVF treatment. The evidence is current to 31st July 2013. The largest trial in the review (with 396 women) has not yet reported full results. The evidence suggested that for a woman with a 53% chance of live birth using standard IVF, the chance using natural cycle IVF ranges from 34% to 53%. No significant difference was found in rates of clinical pregnancy, ongoing pregnancy, multiple pregnancy, incidence of ovarian hyperstimulation syndrome, gestational abnormalities or cancellations of treatment. However findings were imprecise for all outcomes and further evidence from larger studies is awaited. There was evidence from single studies that a lower number of oocytes was retrieved in the natural cycle group. Findings on cost-effectiveness were inconsistent. Quality ratings for the evidence ranged from very low to moderate, the main limitation being imprecision due to insufficient data. When the review authors checked the effect of using an alternative method of analysis the findings suggested higher rates of clinical pregnancy with standard IVF than with natural cycle IVF.