Meta-analysis of GnRH antagonist protocols: do they reduce the risk of OHSS in PCOS?

This systematic review and meta-analysis investigated whether gonadotrophin-releasing hormone (GnRH) antagonist protocols reduce the risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovary syndrome undergoing IVF compared with the long agonist protocol. Searches were conducted on MEDLINE, EMBASE, Cochrane Library, National Research Register and ISI Conference Proceedings. Primary outcome was OHSS incidence. Secondary outcomes were total duration and dose of gonadotrophin, number of oocytes retrieved and clinical pregnancy and miscarriage rates. A total of 966 women were included in nine randomized controlled trials. There was inconsistency in definition, classification of severity and reporting of the OHSS rate. There was no difference in the incidence of severe OHSS in the antagonist group compared with the long agonist group (relative risk 0.61; 95% CI 0.23 to 1.64). However, when all moderate and severe OHSS cases were pooled, the antagonist protocol was associated with significantly lower risk of OHSS (relative risk 0.60; 95% CI 0.48–0.76; P < 0.0001). A possible reduction in the incidence of severe OHSS with the GnRH antagonist protocol should be viewed with caution since the data is inconclusive. Larger randomized trials with adequate sample size and standardized definition, classification and diagnosis of OHSS remain necessary.Many trials have evaluated the use of gonadotrophin-releasing hormone (GnRH) antagonist and GnRH long agonist protocols to look at the pregnancy outcome and risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovarian syndrome (PCOS) undergoing IVF. We conducted a systematic review and meta-analysis of the trials, which compared these protocols in women with PCOS, with the aim to see whether GnRH antagonist protocols reduce the risk of OHSS compared with long agonist protocols. Searches were conducted in all major databases and all randomized controlled trials were included in our study (up to August 2010). Study selection, quality appraisal and data extraction were performed independently and in duplicate. The main outcome measure was the risk of OHSS. The secondary outcome measures were total duration and dose of gonadotrophin, number of oocytes retrieved, clinical pregnancy rate and miscarriage rates. A total of 966 women with PCOS undergoing IVF/intracytoplasmic sperm injection treatment were included in nine randomized controlled trials. There was inconsistency in definition, classification of severity and reporting of the OHSS rate amongst the included studies. GnRH antagonist protocol is associated with shorter duration of stimulation, lower total dose of gonadotrophins used and comparable clinical pregnancy and miscarriage rates. The incidence of moderate and severe OHSS is possibly reduced with antagonist protocol as compared with the GnRH long agonist protocol; however, the data is inconclusive. Larger randomized trials with adequate sample size and standardized definition, classification and diagnosis of OHSS along with economic evaluation and live-birth rates remain necessary.