Abstract: Sixteen studies were eligible for inclusion (n = 1811 participants), 12 (n = 1366 participants) of which were suitable for meta-analysis. No significant heterogeneity was detected. There were no significant differences between depot GnRHa and daily GnRHa in live birth/ongoing pregnancy rates (OR 0.95, 95% CI 0.70 to 1.31, seven studies, 873 women), but substantial differences could not be ruled out. Thus for a woman with a 24% chance of achieving a live birth or ongoing pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 18% and 29%. There was no significant difference between the groups in clinical pregnancy rate (OR 0.96, 95% CI 0.75 to 1.23, 11 studies, 1259 women). For a woman with a 30% chance of achieving clinical pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 25% and 35%. There was no significant difference between the groups in the rate of severe OHSS (OR 0.84, 95% CI 0.29 to 2.42, five studies, 570 women), but substantial differences could not be ruled out. For a woman with a 3% chance of severe OHSS using daily GnRHa injections, the corresponding risk using GnRHa depot would be between 1% and 6%. Compared to women using daily GnRHa, those on depot administration required significantly more gonadotrophin units for ovarian stimulation (standardised mean difference (SMD) 0.26, 95% CI 0.08 to 0.43, 11 studies, 1143 women) and a significantly longer duration of gonadotrophin use (mean difference (MD) 0.65, 95% CI 0.46 to 0.84, 10 studies, 1033 women). Study quality was unclear due to poor reporting. Only four studies reported live births as an outcome and only five described adequate methods for concealment of allocation. We found no evidence of a significant difference between depot and daily GnRHa use for pituitary down regulation in IVF cycles using the long protocol, but substantial differences could not be ruled out. Since depot GnRHa requires more gonadotrophins and a longer duration of use, it may increase the overall costs of IVF treatment.

Plain-language summary: The review of 16 randomised controlled trials found no evidence that depot versus daily GnRHa injections produce different rates of live birth/ongoing pregnancy, clinical pregnancy or ovarian hyperstimulation syndrome (OHSS). However, substantial differences could not be ruled out. For example, for a woman with a 25% chance of achieving a live birth or ongoing pregnancy using GnRHa depot, the corresponding chance using daily injection would be between 16% and 30%. For a woman with a 25% risk of severe OHSS using GnRHa depot, the corresponding risk using daily injection would be between 4% and 89%. For a woman with a 25% chance of achieving a live birth or ongoing pregnancy using daily GnRHa injections, the corresponding chance using a depot injection would be between 19% and 30% . For a woman with a 25 % chance of severe OHSS using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 9 % and 45 % . Depot GnRHa may increase the cost of an IVF cycle, because it lengthens the period to ovulation and requires the use of higher doses of other hormone drugs. The quality of the studies was unclear due to poor reporting, and only four studies reported live births.